TheSpecificandNonspecificEffectsofTaiChiandItsPossible ...the intervention. e metrics of HRV include...

9
ResearchArticle The Specific and Nonspecific Effects of Tai Chi and Its Possible Central Responses: A Protocol of Neuroimaging Study Tianyu Liu , 1,2 Yuke Teng , 2,3 Sha Yang , 2,3 Yuyi Guo, 2,3 Tao Yin, 2,3 Jingwen Chen, 2,3 Rongtao Ying , 3 Zhaoxuan He , 2,3 Shuguang Yu, 3 Jianwei Wu , 4 and Fang Zeng 2,3 1 School of Sport, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China 2 Acupuncture and Brain Science Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China 3 SchoolofAcupunctureandTuina,e3rdTeachingHospital,ChengduUniversityofTraditionalChineseMedicine,Chengdu, Sichuan, China 4 School of Chinese Classics, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China Correspondence should be addressed to Jianwei Wu; [email protected] and Fang Zeng; [email protected] Received 6 September 2020; Revised 12 January 2021; Accepted 18 January 2021; Published 19 February 2021 Academic Editor: Liye Zou Copyright © 2021 Tianyu Liu et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Tai Chi has been proven to be a safe and effective assistant therapy for healthcare and disease treatment. However, whether the adjuvant therapeutic effect of Tai Chi is general or disease-oriented remains uncertain. is trial focuses on exploring the specific and nonspecific effects of Tai Chi and its potential central responses. e results will deepen our understanding of the char- acteristics of Tai Chi exercise for adjuvant therapeutic effects and promote its application in the clinic. In this neuroimaging trial, 40 functional constipation (FC) patients and 40 healthy subjects (HS) will be recruited and will receive 10 weeks of Tai Chi exercise. e motor function, respiratory function, stool-related symptoms, quality of life, and emotional state of the participants will be evaluated at the baseline, the 5-week Tai Chi practice, and the end of practice. e potential changes in the heart rate variability and the cerebral function will be recorded by the 24 h dynamic electrocardiogram at the baseline and the functional magnetic resonance imaging at the end of practice. e possible correlations among the clinical variables, the heart rate variability, and the cerebral activity alterations in FC patients and HS will be analyzed. e healthcare and therapeutic effects of Tai Chi exercise might consist of the specific and nonspecific effects. is study provides not only a new perspective for understanding Tai Chi but also a new approach for investigating the mind-body exercise. is trial was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj33243) on 28 November 2018 (registration number: ChiCTR1800019781; protocol version number: V1.0). is trial is currently in the stage of recruiting patients. e first patient was included on 1 December 2018. To date, 18 FC patients and 20 HS have been included. Recruitment will be completed in December 2020. 1. Introduction Tai Chi is a traditional mind-body exercise, which originated from ancient China and widely spread all over the world. It is reported that there are 5 and 150 million Tai Chi practi- tioners in China and the whole world, respectively. Tai Chi has dual effects on healthcare and treatment. For healthy subjects (HS), the healthcare effects of Tai Chi in strengthening muscle strength [1], improving physical flexibility [2], enhancing the ability to balance and control [2], increasing vital capacity [3], reducing stress [4], and others have long been identified. For patients, the thera- peutic effects of Tai Chi for treating multiple chronic diseases including osteoarthritis [5], hypertension [6], type 2 diabetes mellitus [7], coronary heart disease [8], and chronic ob- structive pulmonary disease [9] have also been proven by a number of studies. ese studies indicated that Tai Chi was widely involved in the prevention, treatment, and rehabil- itation of various diseases. Does Tai Chi have different effects on the same organ/system in different practitioners? For example, a systematic review and meta-analysis showed that mind-body interventions, including Tai Chi, were effective Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2021, Article ID 8883460, 9 pages https://doi.org/10.1155/2021/8883460

Transcript of TheSpecificandNonspecificEffectsofTaiChiandItsPossible ...the intervention. e metrics of HRV include...

Page 1: TheSpecificandNonspecificEffectsofTaiChiandItsPossible ...the intervention. e metrics of HRV include standard deviation of NN intervals (SDNN), standard deviation of sequential 5-min

Research ArticleThe Specific and Nonspecific Effects of Tai Chi and Its PossibleCentral Responses A Protocol of Neuroimaging Study

Tianyu Liu 12 Yuke Teng 23 Sha Yang 23 Yuyi Guo23 Tao Yin23 Jingwen Chen23

Rongtao Ying 3 Zhaoxuan He 23 Shuguang Yu3 Jianwei Wu 4 and Fang Zeng 23

1School of Sport Chengdu University of Traditional Chinese Medicine Chengdu Sichuan China2Acupuncture and Brain Science Research Center Chengdu University of Traditional Chinese Medicine ChengduSichuan China3School of Acupuncture and Tuina e 3rd Teaching Hospital Chengdu University of Traditional Chinese Medicine ChengduSichuan China4School of Chinese Classics Chengdu University of Traditional Chinese Medicine Chengdu Sichuan China

Correspondence should be addressed to Jianwei Wu wujianweicdutcmeducn and Fang Zeng zeng_fang126com

Received 6 September 2020 Revised 12 January 2021 Accepted 18 January 2021 Published 19 February 2021

Academic Editor Liye Zou

Copyright copy 2021 Tianyu Liu et al is is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Tai Chi has been proven to be a safe and effective assistant therapy for healthcare and disease treatment However whether theadjuvant therapeutic effect of Tai Chi is general or disease-oriented remains uncertain is trial focuses on exploring the specificand nonspecific effects of Tai Chi and its potential central responses e results will deepen our understanding of the char-acteristics of Tai Chi exercise for adjuvant therapeutic effects and promote its application in the clinic In this neuroimaging trial40 functional constipation (FC) patients and 40 healthy subjects (HS) will be recruited and will receive 10 weeks of Tai Chiexercise e motor function respiratory function stool-related symptoms quality of life and emotional state of the participantswill be evaluated at the baseline the 5-week Tai Chi practice and the end of practice e potential changes in the heart ratevariability and the cerebral function will be recorded by the 24 h dynamic electrocardiogram at the baseline and the functionalmagnetic resonance imaging at the end of practicee possible correlations among the clinical variables the heart rate variabilityand the cerebral activity alterations in FC patients and HS will be analyzed e healthcare and therapeutic effects of Tai Chiexercise might consist of the specific and nonspecific effects is study provides not only a new perspective for understanding TaiChi but also a new approach for investigating the mind-body exercise is trial was registered in the Chinese Clinical TrialRegistry (httpwwwchictrorgcnshowprojaspxproj33243) on 28 November 2018 (registration number ChiCTR1800019781protocol version number V10) is trial is currently in the stage of recruiting patients e first patient was included on 1December 2018 To date 18 FC patients and 20 HS have been included Recruitment will be completed in December 2020

1 Introduction

Tai Chi is a traditional mind-body exercise which originatedfrom ancient China and widely spread all over the world It isreported that there are 5 and 150 million Tai Chi practi-tioners in China and the whole world respectively Tai Chihas dual effects on healthcare and treatment For healthysubjects (HS) the healthcare effects of Tai Chi instrengthening muscle strength [1] improving physicalflexibility [2] enhancing the ability to balance and control[2] increasing vital capacity [3] reducing stress [4] and

others have long been identified For patients the thera-peutic effects of Tai Chi for treatingmultiple chronic diseasesincluding osteoarthritis [5] hypertension [6] type 2 diabetesmellitus [7] coronary heart disease [8] and chronic ob-structive pulmonary disease [9] have also been proven by anumber of studies ese studies indicated that Tai Chi waswidely involved in the prevention treatment and rehabil-itation of various diseases Does Tai Chi have different effectson the same organsystem in different practitioners Forexample a systematic review and meta-analysis showed thatmind-body interventions including Tai Chi were effective

HindawiEvidence-Based Complementary and Alternative MedicineVolume 2021 Article ID 8883460 9 pageshttpsdoiorg10115520218883460

in alleviating gastrointestinal symptoms and improving thequality of life (QOL) of patients [10] Does Tai Chi havedifferent gastrointestinal modulation effects between pa-tients with gastrointestinal disorders and HS In otherwords is the gastrointestinal regulation of Tai Chi disease-oriented and influenced by individual physical conditionHowever majority of the Tai Chi-related studies wereperformed either on patients or HS and few studies wereperformed on both patients and HS to investigate the in-fluence of physical conditions on the effect of Tai Chi

On the basis of the characteristics of Tai Chi and pre-vious researches we predict that the effects of Tai Chi in-clude two aspects the relatively specific effects andnonspecific effectse nonspecific effects mainly refer to themodulating effects on human motor function (musclestrength physical flexibility etc) and respiratory functionespecially vital capacity e nonspecific effects might alsomanifest as maintaining the normal function of organssystems keeping the body in a relatively balanced and co-ordinated state While the relatively specific effects of Tai Chiare disease-oriented meaning that when the body is in apathological state Tai Chi practice might reduce the hy-peractive function to improve the hypoactive function

To test the hypothesis we design this neuroimagingstudy In this study both functional constipation (FC) pa-tients and HS were selected as participants to investigate thespecific effects (gastrointestinal function) and nonspecificeffects (motor function and respiratory function) of Tai ChiFC is a common functional gastrointestinal disorder (FGID)with high prevalence It is characterized by various con-stipation-related symptoms including reduced defecationdefecation stress hard stools and uncomfortable abdominalmuscle in the absence of evident organic or structuralreasons for these symptoms A randomized control trialindicated that Tai Chi practice could significantly improvethe constipation symptom of patients with chronic FC [11]

is study aims to (1) investigate the nonspecific effectsof Tai Chi by comparing the influence of Tai Chi practice onmotor function and respiratory function between FC pa-tients and HS using the lower-extremity muscle strengthtest functional balance tests and vital capacity test (2)investigate the specific effects of Tai Chi from three aspectsincluding gastrointestinal symptom autonomic nervousactivity and emotional state and (3) explore the potentialcentral responses of Tai Chirsquos specific and nonspecific effectsby functional magnetic resonance imaging (fMRI)

2 Methods and Analysis

21 Study Design e trial is designed as a neuroimagingtrial that focuses on specific and nonspecific effects of Tai Chiand its potential central responses A total of 40 FC patientsand 40 HS will be recruited Fifteen participants in eachgroup will be randomly selected to undergo MRI scan estudy procedure is outlined in Figure 1

22 Sample Size Calculation We will investigate the thera-peutic effects of Tai Chi for FC patients According to our

preliminary study from which we recruited 10 FC patientswith the Tai Chi intervention the mean improvement ofweekly complete spontaneous bowel movements (CSBMs) ofTai Chi was 167plusmn 089 times A systematic review [12] fo-cusing on the management of FC reported the mean im-provement of weekly CSBMs of polyethylene glycol (the first-line medication of FC) was 18 times We hypothesize that thetherapeutic effects of Tai Chi are not less than the polyethyleneglycol Considering α 005 1minus β 08 the study designrequired a sample size of 36 for each group with the one-sample noninferiority test [13] with a drop-out rate of 10 Atotal of 40 patients with FC and 40HS will be finally recruited

N σZ1minus α + Z1minus β

μ minus μo minus δ1113888 1113889

2

(1)

23 Patients with FC Patients who match the inclusioncriteria will be recruited FC patients will be diagnosed by twogastroenterologists in the digestion department of the Hos-pital of CDUTCM according to the Rome IV DiagnosticCriteria for FC [14] Each FC patient will undergo a carefulphysical examination including a routine blood test routineurine test routine stool test blood biochemical test (ALTAST BUN Scr) transabdominal ultrasound and dynamicelectrocardiogram e inclusion criteria and exclusion cri-teria of FC patients were as same as our previous study [15]

231 Inclusion Criteria Patients will be included in thestudy if they (1) reach the Rome IV Diagnostic Criteria forFC [14] (2) are right-handers and the age range is between18 and 35 (3) have less than three CSBMs every week (4) theCleveland Constipation Score (CCS) scoregt10 and (5)provide a written informed consent form

232 Exclusion Criteria Patients will be excluded from thestudy if they (1) are pregnant women or plan to be pregnantwithin 3 months or are breast-feeding women (2) are in-capable of sports (3) have a history of head trauma and lossof consciousness (4) have diabetes or serious cardiovascularneurological psychiatric renal or respiratory disease (5)have moderate or serious depression and anxiety (6) cannotkeep silent for 20 minutes while lying down (7) have anycontraindications to fMRI scanning including the presenceof metal stent metal denture or claustrophobia (8) havetaken other exercises (including meditation and yoga) thatmay improve constipation over 30 minutes every week in thelast 3 months (9) have taken gastrointestinal motilitymedicine nonsteroidal anti-inflammatory medicine andsteroids in the last 15 days (10) have received other treat-ments (including surgery diet modification biofeedback orprobiotics) in the last month or (11) have participated in anyother clinical trials in the past 3 months

24 Healthy Subjects ose who match the inclusion cri-teria will be recruited and will receive the same physicalexamination with the FC patients

2 Evidence-Based Complementary and Alternative Medicine

241 Inclusion Criteria Subjects will be included if they (1)are right-handers and aged 18ndash35 years (2) have no ab-normalities during the physical examinations (3) havepassed the National Student Physical Health Standard testand (4) provide written informed consent

242 Exclusion Criteria e exclusion criteria for HS arethe same as the criteria for FC patients (see Section 232)Moreover those who have possible organic diseases psy-chological disorders and gastrointestinal symptoms andsigns are also excluded

25 Recruitment Strategy e participants will be recruitedfrom the Chengdu University of Traditional ChineseMedicine (CDUTCM) by delivering leaflets inside thecampus posting advertisements in billboards posting atAcupuncture and Brain Science Research Center andCDUTCM (httpcdutcmeducn) websites and posting inour WeChat public account

26 Intervention e participants will undergo 40 sessionswith 24-style Tai Chi e exercise of Tai Chi will be per-formed four times a week (Monday Tuesday ursday andFriday) and will last for 10 weeks [15] Each exercise sessionlasts for an hour including 10-minute warm-up 40-minuteTai Chi exercise and 10-minute relaxation

Before the formal intervention participants were in-volved in motor learning and strength training under theguidance of two professional Tai Chi instructors During theintervention they exercise strictly under the 24-style Tai Chiexercise standard operating procedure (SOP) which wasformulated by two Tai Chi experts In each session of theexercise the instant heart rate will be counted both at the

pre- and posttrial and the sports self-rating scale will also befilled out Participants who did not come will be recordede training will be considered effective when the rating ofperceived exertion (RPE) of the subjects reaches 4ndash6 levels ineach session and training times must not be less than 80(32 times) of total training times

During the treatment period participants are usually notrecommended to use concomitant care or interventionsHowever if required (such as aggravation of the patientrsquoscondition) participants will be permitted to use extra os-motic laxatives e type and dosage of medication usedshould be recorded in the case report forms (CRFs)

27 Outcome Measurements Measurements will be evalu-ated by independent assessors who have been trained priorto the study All results will be recorded whether or not theparticipants completed the studye outcome assessors willbe independent of the research team and will not be toldabout group allocation so as to ensure the object evaluationsof the trial

271 General Information Collection Same as our previousstudy [15] general information including the demographicdata and vital signs will be collected e demographic datainclude age gender education level nationality and bodymass index (BMI) e vital signs include body temperatureheart rate respiratory rate and blood pressure Amongthem the BMI will be calculated at the baseline and the endof the invention whereas the vital signs of each patient willbe immediately recorded after every training

According to our hypothesis the nonspecific effects ofTai Chi include motor function vital capacity and psy-chological state regulation and the specific effects of Tai Chi

FC and HSscreen inclusion exclusion

FC group (n = 40) HS group (n = 40)

2nd motor functionrespiratory function

1st symptoms and theQOL measurements

1st psychological stateevaluation

1st autonomicnerve function 1st MRI scan

Tai Chi training 10 weeks

2nd MRI scan

Data collection and statistical analysis

1st motor functionrespiratory function

2nd symptoms and theQOL measurements

2nd psychological stateevaluation

2nd autonomicnerve function

Figure 1 Study flowchart is is a neuroimaging trial which focuses on specific and nonspecific effects of Tai Chi and its potential centralresponses Totally 40 eligible FC patients and 40 HS will be recruited Fifteen participants in each group will be randomly selected toundergo functional magnetic resonance imaging (fMRI) scan

Evidence-Based Complementary and Alternative Medicine 3

for FC patients reflects in relieving gastrointestinal symp-toms and modulating autonomic nerve function

272 Nonspecific Effects Motor Function Vital Capacityand Psychological State e lower-extremity musclestrength functional balance tests and the vital capacity testwill be collected at the baseline the median of intervention(after 5 weeks of exercise) and at the end of the interventione lower-extremity muscle strength will be measured usinga hand-held isometric dynamometer (Micro FET3 HogganHealth Industries Draper UT United States) Functionalbalance tests include the Berg Balance Scale (BBS) [16]timed up-and-go (TUG) test and functional reach test [17]

During the vital capacity test the forced expiratoryvolume in one second (FEV1) forced vital capacity (FVC)and FEV1FVC ratio will be measured using a Super Spirospirometer (MicroMedical Rochester Kent UK) in restingstatus e peak expiratory flow rate (PEFR) will be assayedusing a peak flow meter

To assess the psychological state of all participants wecollected the following metrics at the baseline the median ofintervention and the end of intervention the self-ratingdepression scale (SDS) [18] the self-rating anxiety scale(SAS) [19] and the Eysenck Personality Questionnaire(EPQ) [20]

273 Specific Effects Gastrointestinal Symptoms and Auto-nomic Nerve Function To evaluate the changes of thegastrointestinal symptoms and QOL of participants weperformed the following measurements at the baseline themedian of intervention and the end of intervention CCS[21] patient assessment of constipation symptoms (PAC-SYM) [22] patient assessment of constipation QOL ques-tionnaire (PAC-QOL) [23] RPE [24] and MOS 36-itemshort-form health survey (SF-36) [25] Also the evaluationof constipation diary including CSBMs per week the fecalcharacter and the difficulty degree of defecation will bemeasured once a week for 10 times

To evaluate the autonomic nervous function we selectedthe heart rate variability (HRV) All participants will beassessed during the 24-h HRV at the baseline and the end ofthe intervention e metrics of HRV include standarddeviation of NN intervals (SDNN) standard deviation ofsequential 5-min RR interval means (SDANN) and rootmean square successive difference (RMSSD) e deviceused is a dynamic electrocardiogram (ct-086S BENEWARE Hangzhou China)

28 MRI Data Acquisition MRI data will be collected on 15participants in each group at the baseline and the end ofintervention e acquisition parameter will be consistentwith our previous article [15]

e MRI scan includes three sequences a high-resolu-tion 3-dimensional T1-weighted imaging (3D-T1W1) ablood oxygenation level-dependent functional MRI (BOLD-fMRI) and a diffusion tensor imaging (DTI) sequenceScanning will start in the morning after overnight fasting

Subjects who are selected will undergoMRI scan with a 30 Tmagnetic resonance scanner (Siemens Germany) e 3D-T1WI scan parameters will be as follows repetition timeecho time 1900ms226ms slice thickness 1mm slicenumber 176 matrix size 128times128 and the view field256times 256mm2e BOLD-fMRI scanning parameters are asfollows repetition timeecho time 2000ms30ms flip angle90deg slice number 30 matrix size 128times128 view field240times 240mm2 slice thickness 5mm and total volume 240DTI data are as follows view field 240times 240mm2 repetitiontimeecho time 6800ms93ms matrix size 128times128 andslice thickness 3mm seamless Two diffusion-weightedsequences will be acquired using gradient values b 1000 smm2 and b 0 with diffusion-sensitizing gradients used in 64noncollinear directions

29 Data Management e clinical data will be managedwith printed and electronic CRFs CRFs will be enteredparallelly and will only be available to the outcome assessorse Evidence-based Medicine Center of the CDUTCM willbe responsible for monitoring the study and data every 3months

210 Statistical Analysis

2101 Clinical Data Analysis Clinical data will be analyzedby independent statisticians who do not know the testprocedure based on the principles of intention to treat (ITT)and per protocol e statistical significance threshold has p

value lt005 e results of the participants who failed tocomplete the study will be considered no different from thebaseline data in ITTanalysis All continuous variables will bepresented as meanplusmn standard deviation e categoricalvariables will be described in percentage () e clinicaldata in the two groups (FC group and HS group) will becompared with two-sample t-tests and the comparisons ofthe baseline and after intervention in each group will becompared with a paired sample t-test Nonparametric tests(MannndashWhitney U test) will be used to compare non-normally distributed clinical data and the χ2 test or Fisherrsquostest will be used to compare categorical variables

2102 Functional MRI Data Analysis For fMRI scans allpreprocessing steps will be performed using DPABI softwarebased on MATLAB e main analytical methods includethe amplitude of low-frequency fluctuation amplitude(ALFF) and seed-based functional connectivity

After preprocessing the data the ALFF will be calculatedto compare the whole-brain spontaneous activity patternbefore and after intervention in each group as well as be-tween patients with FC and HS following 10-week Tai Chipractices e different regions obtained at ALFF analysiswill be selected as the region of interest (ROI) also calledseed to perform the seed-based functional connectivityanalysis and to explore the functional synchronization ofROI and other regionse thresholds of plt 005 with a falsediscovery rate correlation will be applied to all analyses

4 Evidence-Based Complementary and Alternative Medicine

2103 Correlation Analysis To investigate the associationsbetween nonspecific effects and central responses underdifferent physical conditions we performed the correlationanalysis between the clinical data including motor functionrespiratory function psychological state and cerebralfunction in patients with FC and HS In order to furtherexplain the regulation mechanism of Tai Chi on the brain-gut interaction disorder the correlation analysis amonggastrointestinal symptoms heart rate variability and brainfunction activities in FC patients will also be carried out

2104 Safety Assessments Adverse events might happenduring Tai Chi practice including strain sprain nausea anddizziness If any these adverse events occur the instructorwill take appropriate treatment according to clinicianrsquosadvice and record the processing detail in the CRFs esafety assessments will be monitored by the EthicsCommittee

e schedule of the study including enrollment inter-ventions assessments and visits for participants is shown inTable 1

3 Discussion

As a popular physicalndashmind exercise Tai Chi is widely usedin the prevention treatment and rehabilitation of variousdiseases On the basis of the characteristics and relatedstudies on Tai Chi we put forward the original hypothesisthat Tai Chi practice can produce relative specific effects andnonspecific effects on the human body

e main purposes of this study include two aspectsFirst this study tries to explore the physiological andpsychological existence of the specific and nonspecific ef-fects of Tai Chi by comparing the differences in the motorfunction respiratory function gastrointestinal symptomspsychological manifestations and HRV between FC pa-tients and HS after Tai Chi practice Second this study triesto explore the potential central mechanism of the specificand nonspecific effects of Tai Chi practice by analyzing thepotential cerebral activity changes induced by Tai Chi andtheir correlation with clinical variables e study willprovide a new approach for investigating the mind-bodyexercise and the results might deepen our knowledge aboutTai Chi

31 Specific and Nonspecific Effects of Tai Chi Tai Chi is acomplex sport that requires the coordination of spiritbreathing postures and movements It can produce a sig-nificant impact on almost all human systems such as motorsystem cardiovascular system respiratory system and di-gestive system e impact is far beyond the physiologicaland psychological changes brought by a simple physicalexercise us Tai Chi is not only widely used in publichealthcare but also involved in disease treatment andrehabilitation

On the basis of the characteristics of Tai Chi andrelated studies we put forward that there are two types ofeffects of Tai Chi One is the specific effect which mainly

indicates the therapeutic effects of Tai Chi practice on thepathological status and has obvious disease orientationFor instance Tai Chi practice could produce a specific-regulating effect on the abnormal gastrointestinal (GI)function of patients with GI disorders specifically im-prove the cognitive function of patients with Alzheimerrsquosdisease [26] and significantly relieve the depressionsymptoms of patients with depression [27] A systematicreview and meta-analysis demonstrated that Tai Chi andother mind-body interventions were effective in allevi-ating GI symptoms and improving several aspects of thedisease-related QOL including interference with activitybody image health worry food avoidance and socialreaction [10]

e second aspect is the nonspecific effects whichmainly refers to the benefits for the motor system respi-ratory system and others No matter Tai Chi practice orother forms of physical exercises can produce it enonspecific effects might be a promoting effect on the motorsystem and respiratory system for not only the patients butalso the HS For example studies demonstrated that Tai Chiexercises could increase the muscle strength in the lowerextremities improve balance control and reduce the risk offalls for both healthy elderly people [28 29] and Parkinsonrsquosand stroke patients [30 31] However it should be em-phasized that the specific effects of Tai Chi are relative andconditional e nonspecific effects are the more widely usedand fundamental effect of Tai Chi

32 Potential Central Responses of Tai Chi As a typicalphysical and mental exercise Tai Chi not only emphasizesphysical movement but also requires the state of unity ofbody and mind e positive effects of meditation andaerobic exercise on cognitive function including memoryand decision-making abilities have been widely accepted[32 33] Recent studies further identified the influence of TaiChi practice on the cerebral structure and function ofpractitioners [34] For example MRI studies showed that TaiChi training evoked significant changes in the brain whitematter network [35] brain volume [36] and spontaneousbrain functional activities [37] in older people ese studiesindicated that Tai Chi practice could influence not only thecerebral function but also the brain structure It might be thecentral mechanism of the specific and nonspecific effects ofTai Chi

In this study FC patients will be enrolled to investigatethe specific effects of Tai Chi-modulating GI function FCas a typical FGID the dysfunction of the gut-brain axisplays an essential role in its pathogenesis [38] Recentneuroimaging studies identified the abnormality in thecerebral function and structure in FC patients comparedwith the healthy controls For example an fMRI studydemonstrated that FC patients showed significant dif-ferences in baseline brain activities in several brain re-gions implicated in emotional process modulationsomatic and sensory processing and motor control re-gions [39] Considering the existence of cerebral struc-tural and functional abnormalities in FC patients it is

Evidence-Based Complementary and Alternative Medicine 5

feasible to explore the mechanism of Tai Chirsquos specificeffects on GI function of FC patients

In this study fMRI will be selected as the neuroimagingtechnique to investigate the cerebral activity changes elicitedby Tai Chi practice fMRI is the most commonly used brainimaging technique and has been widely used in the studieson the central mechanism of Tai Chi intervention[35 40 41] For example using fMRI people found thatinfluencing the resting-state functional connectivity alter-ation between the cognitive control network and rostralanterior cingulate cortex and medial prefrontal cortex mightbe the central mechanism of Tai Chi intervention forfibromyalgia [41] ese studies indicated that it was reliable

to use fMRI to explore the central mechanism of Tai Chiintervention for FC

Furthermore to ensure the reliability and repeatabilityof the results we will establish a strict quality controlprogram which includes the participant selection the SOPof Tai Chi practice the SOP of neuroimaging scan and theoutcome measures For example for the selection of par-ticipants the freshmen who never practice Tai Chi and haveno physical exercise frequently will be taken into consid-eration In the implementation of Tai Chi intervention theSOP of 24-style Tai Chi is established which covers therequirement on the movements breathing and ideas of theparticipant

Table 1 Study period

Study period

Enrollment Allocation Postallocation

Timepointlowastlowast minus14 days minus7 days 0 day(baseline)

35 days(middle of intervention)

70 days(after intervention) Etc

EnrollmentEligibility screen 7

Informed consent 7

Demographics 7

Diagnosis 7

Past medical history 7

Physical examination 7

Allocation 7

InterventionsGroup A (FC patients) 7 7 7

Group B (HS) 7 7 7

AssessmentsBMI 7 7

HRV 7 7

Lower-extremity muscle 7 7 7

Functional balance 7 7 7

Vital capacity 7 7 7

Exercise self-rating scale 7 7 7

CCS 7 7 7

PAC-QOL 7 7 7

PAC-SYM 7 7 7

Stool diary 7 7 7

SDS SAS 7 7 7

EPQ 7 7 7

SF-36 7 7 7

MRI 7 7

Safety observationBlood routine test 7

Urine routine test 7

Stool routine test 7

Adverse events 7

is is a neuroimaging trial that includes a 2-week baseline period and a 10-week treatment period In the baseline period recruited patients will be screenedaccording to the inclusion criteria and exclusion criteria and then eligible FC patients and HS will sign an informed consent form and receive a physicalexamination After allocation the FC patients and HS will be recruited and will receive 10 weeks of Tai Chi exercise Schedule of enrollment interventionsand assessments at the baseline the median of intervention (5 weeks of exercise) and the end of the intervention (10 weeks of exercise) Among them lower-extremity muscle strength was measured using a hand-held isometric dynamometer (Micro FET3 Hoggan Health Industries) Functional balance testsinclude BBS TUG test and functional reach test During the vital capacity test FEV1 FVC and FEV1FVC ratio were measured using a MicroMedical SuperSpiro spirometer in resting status PEFR was assayed using a peak flowmetere stool diary CCS and PAC-SYMwill be used to evaluate the clinical efficacyof different interventions the PAC-QOL will be used to assess the health-related QOL the SDS SAS EPQ and Mini-Mental State Examinations will be usedto consider the effect of psychological factors on the patientsrsquo symptoms All participants will be assessed during the 24 h HRV to evaluate the autonomicnervous function at the baseline and the end of the 10-week intervention fMRI scans will be performed to detect the cerebral functional changes in 15 patientsin each group both at the baseline and the end of the intervention

6 Evidence-Based Complementary and Alternative Medicine

4 Conclusions

In conclusion Tai Chi is a safe and effective assistant therapy formany diseases However whether the therapeutic effects of TaiChi are disease-oriented remains uncertain is trial is the firstto investigate the existence of the specific and nonspecific effectsof Tai Chi and to explore their potential central responses It willprovide a new perspective for understanding Tai Chi and a newapproach for studying mind-body exercise

Abbreviations

HS Healthy subjectFC Functional constipationFGID Functional gastrointestinal diseaseQOL Quality of lifeGI GastrointestinalfMRI Functional magnetic resonance imagingCDUTCM Chengdu University of Traditional Chinese

MedicineCSBMs Complete spontaneous bowel movementsCCS Cleveland Constipation ScoreRPE Rating of perceived exertionPAC-SYM Patient Assessment of Constipation SymptomPAC-QOL Patient Assessment of Constipation Quality of

Life QuestionnaireRPE Rating of perceived exertionSF-36 e MOS 36-item short-form health surveyBBS Berg Balance ScaleTUG Timed up-and-goFEV1 Forced expiratory volume in one secondFVC Forced vital capacitySDS Self-Rating Depression ScaleSAS Self-Rating Anxiety ScaleEPQ Eysenck Personality QuestionnairesHRV Heart rate variability3D-T1WI 3-dimensional T1-weighted imagingBOLD-fMRI

Blood oxygenation level-dependent fMRI

DTI Diffusion tensor imagingCRF Case report formITT Intention to treatPP Per protocolReHo Regional homogeneityALFF Amplitude of low-frequency fluctuation

amplitude

Data Availability

is is a protocol for a clinical trial and no original data areincluded

Ethical Approval

e procedures have been approved by the Sichuan RegionalEthics Review Committee on Traditional Chinese Medicine(no 2018KL-047) and conformed to the Declaration ofHelsinki In addition all researchers were trained and signeda pledge to protect the confidentiality of study participants

Consent

All enrolled subjects signed an informed consent form

Disclosure

Tianyu Liu Yuke Teng and Sha Yang are the co-firstauthors

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Tianyu Liu Yuke Teng and Sha Yang contributed equally tothis article FZ and JW were responsible for this study TLYT SY FZ JW ZH and SY conceived and designed thestudy TL YT and SY participated in drafting the trialprotocol and preparing the manuscript YG TY JC and RYparticipated in data collection and were in charge of re-cruitment and treatment of patients All authors read andapproved the final manuscript

Acknowledgments

is study was supported by the Humanities and SocialSciences Youth Project of theMinistry of Education of China(19YJC890027) e trial was financially supported by theTen-ousand Talents Program of China (W02020595) andthe China Postdoctoral Science Foundation(2020M673562XB)

References

[1] C Lan J-S Lai S-Y Chen andM-K Wong ldquoTai Chi Chuanto improve muscular strength and endurance in elderly in-dividuals a pilot studyrdquo Archives of Physical Medicine andRehabilitation vol 81 no 5 pp 604ndash607 2000

[2] A M K Wong and C Lan ldquoTai Chi and balance controlrdquoMedicine and Sport Science vol 52 pp 115ndash123 2008

[3] L Sun L P Zhuang X Z Li J Zheng andW FWu ldquoTai Chican prevent cardiovascular disease and improve cardiopul-monary function of adults with obesity aged 50 years andolder a long-term follow-up studyrdquoMedicine vol 98 no 42Article ID e17509 2019

[4] C E Rogers L K Larkey and C Keller ldquoA review of clinicaltrials of Tai Chi and Qigong in older adultsrdquoWestern Journalof Nursing Research vol 31 no 2 pp 245ndash279 2009

[5] J H Yan W J Gu J Sun W X Zhang B W Li and L PanldquoEfficacy of Tai Chi on pain stiffness and function in patientswith osteoarthritis a meta-analysisrdquo PLoS One vol 8 no 4Article ID e61672 2013

[6] C Wang J P Collet and J Lau ldquoe effect of Tai Chi onhealth outcomes in patients with chronic conditions a sys-tematic reviewrdquo Archives of Internal Medicine vol 164 no 5pp 493ndash501 2004

[7] M Chao C Wang X Dong and M Ding ldquoe effects of taichi on type 2 diabetes mellitus a meta-analysisrdquo Journal ofDiabetes Research vol 2018 Article ID 7350567 9 pages2018

Evidence-Based Complementary and Alternative Medicine 7

[8] E Salmoirago-Blotcher P M Wayne S Dunsiger et al ldquoTaiChi is a promising exercise option for patients with coronaryheart disease declining cardiac rehabilitationrdquo Journal of theAmerican Heart Association vol 6 no 10 2017

[9] L Wang KWu X Chen and Q Liu ldquoe effects of tai chi onlung function exercise capacity and health related quality oflife for patients with chronic obstructive pulmonary disease apilot studyrdquo Heart Lung and Circulation vol 28 no 8pp 1206ndash1212 2019

[10] W Wang F Wang F Fan A C Sedas and J Wang ldquoMind-body interventions for irritable bowel syndrome patients inthe Chinese population a systematic review and meta-anal-ysisrdquo International Journal of Behavioral Medicine vol 24no 2 pp 191ndash204 2017

[11] Y Zhou L Liang L I Hong and L Jing ldquoAbout the con-valescent influence of 24-Pattern Shadowboxing to the pa-tients with chronic functional constipationrdquo Liaoning SportScience and Technology vol 2 pp 52ndash54 2015

[12] P Katelaris V Naganathan K Liu G Krassas andJ Gullotta ldquoComparison of the effectiveness of polyethyleneglycol with and without electrolytes in constipation a sys-tematic review and network meta-analysisrdquo BMC Gastroen-terology vol 16 no 1 p 42 2016

[13] S C Chow J Shao and H Wang Sample Size Calculations inClinical Research Wiley Hoboken NJ USA 2003

[14] D A Drossman and W L Hasler ldquoRome IV-functional GIdisorders disorders of gut-brain interactionrdquo Gastroenter-ology vol 150 no 6 pp 1257ndash1261 2016

[15] S Yang J Chen Y Guo et al ldquoComparison of Taiji andaerobic exercise for functional constipation study protocolfor a randomised controlled neuroimaging trialrdquo BMJ Openvol 9 no 8 Article ID e031089 2019

[16] K Berg S Wood-Dauphinee and J I Williams ldquoe balancescale reliability assessment with elderly residents and patientswith an acute strokerdquo Scandinavian Journal of RehabilitationMedicine vol 27 no 1 pp 27ndash36 1995

[17] P W Duncan D K Weiner J Chandler and S StudenskildquoFunctional reach a new clinical measure of balancerdquo Journalof Gerontology vol 45 no 6 pp M192ndashM197 1990

[18] W W K Zung ldquoA self-rating depression scalerdquo Archives ofGeneral Psychiatry vol 12 no 1 pp 63ndash70 1965

[19] W W K Zung ldquoA rating instrument for anxiety disordersrdquoPsychosomatics vol 12 no 6 pp 371ndash379 1971

[20] D Schuldberg ldquoEysenck personality questionnaire scales andpaper-and-pencil tests related to creativityrdquo PsychologicalReports vol 97 no 1 pp 180ndash182 2005

[21] F Agachan T Chen J Pfeifer P Reissman andS D Wexner ldquoA constipation scoring system to simplifyevaluation andmanagement of constipated patientsrdquoDiseasesof the Colon amp Rectum vol 39 no 6 pp 681ndash685 1996

[22] L Frank L Kleinman C Farup L Taylor and P Miner JrldquoPsychometric validation of a constipation symptom assess-ment questionnairerdquo Scandinavian Journal of Gastroenter-ology vol 34 no 9 pp 870ndash877 1999

[23] P Marquis C De La Loge D Dubois A McDermott andO Chassany ldquoDevelopment and validation of the patientAssessment of constipation quality of life questionnairerdquoScandinavian Journal of Gastroenterology vol 40 no 5pp 540ndash551 2005

[24] S Morishita A Tsubaki T Takabayashi and J B Fu ldquoRe-lationship between the rating of perceived exertion scale andthe load intensity of resistance trainingrdquo Strength and Con-ditioning Journal vol 40 no 2 pp 94ndash109 2018

[25] A Kelly J Rush E Shafonsky et al ldquoDetecting short-termchange and variation in health-related quality of life within-and between-person factor structure of the SF-36 healthsurveyrdquo Health and Quality of Life Outcomes vol 13 no 1p 199 2015

[26] P J Klein ldquoTai Chi Chuan in the management of Parkinsonrsquosdisease and Alzheimerrsquos diseaserdquo Medicine and Sport Sciencevol 52 pp 173ndash181 2008

[27] J Kong G Wilson J Park K Pereira C Walpole andA Yeung ldquoTreating depression with Tai Chi state of the artand future perspectivesrdquo Front Psychiatry vol 10 p 2372019

[28] W W N Tsang and C W Y Hui-Chan ldquoEffect of 4- and 8-wk intensive Tai Chi training on balance control in the el-derlyrdquoMedicine amp Science in Sports amp Exercise vol 36 no 4pp 648ndash657 2004

[29] Z G Huang Y H Feng Y H Li and C S Lv ldquoSystematicreview and meta-analysis Tai Chi for preventing falls in olderadultsrdquo BMJ Open vol 7 no 2 Article ID e013661 2017

[30] F Li P Harmer K Fitzgerald et al ldquoTai Chi and posturalstability in patients with Parkinsonrsquos diseaserdquo New EnglandJournal of Medicine vol 366 no 6 pp 511ndash519 2012

[31] I Hwang R Song S Ahn M-A Lee P M Wayne andM K Sohn ldquoExploring the adaptability of Tai Chi to strokerehabilitationrdquo Rehabilitation Nursing vol 44 no 4pp 221ndash229 2019

[32] S Deepeshwar S A Vinchurkar N K Visweswaraiah andH R Nagendra ldquoHemodynamic responses on prefrontalcortex related to meditation and attentional taskrdquo Frontiers inSystems Neuroscience vol 8 p 252 2014

[33] T Moriarty K Bourbeau B Bellovary and M N ZuhlldquoExercise intensity influences prefrontal cortex oxygenationduring cognitive testingrdquo Behavioral Sciences vol 9 no 8p 83 2019

[34] R Silveira R C R Prado C Brietzke et al ldquoPrefrontal cortexasymmetry and psychological responses to exercise a sys-tematic reviewrdquo Physiology amp Behavior vol 208 p 1125802019

[35] C Yue L Zou J Mei et al ldquoTai Chi training evokes sig-nificant changes in brain white matter network in olderwomenrdquo Healthcare vol 8 no 1 p 57 2020

[36] M Adcock M Fankhauser J Post et al ldquoEffects of an in-home multicomponent exergame training on physical func-tions cognition and brain volume of older adults a ran-domized controlled trialrdquo Frontiers in Medicine vol 6 p 3212019

[37] Z Zheng X Zhu S Yin et al ldquoCombined cognitive-psy-chological-physical intervention induces reorganization ofintrinsic functional brain architecture in older adultsrdquo NeuralPlasticity vol 2015 Article ID 713104 11 pages 2015

[38] M Equit J Niemczyk A Kluth C omas M Rubly andA von Gontard ldquoCentral nervous system processing ofemotions in children with fecal incontinence and con-stipationrdquo Zeitschrift fur Kinder- und Jugendpsychiatrie undPsychotherapie vol 47 no 1 pp 67ndash71 2019

[39] Q Zhu W Cai J Zheng et al ldquoDistinct resting-state brainactivity in patients with functional constipationrdquo Neurosci-ence Letters vol 632 pp 141ndash146 2016

[40] J Kong E Wolcott Z Wang et al ldquoAltered resting statefunctional connectivity of the cognitive control network infibromyalgia and the modulation effect of mind-body inter-ventionrdquo Brain Imaging and Behavior vol 13 no 2pp 482ndash492 2019

8 Evidence-Based Complementary and Alternative Medicine

[41] R Jalilianhasanpour E Beheshtian G Sherbaf S Sahraianand H I Sair ldquoFunctional connectivity in neurodegenerativedisorders Alzheimerrsquos disease and frontotemporal dementiardquoTopics in Magnetic Resonance Imaging vol 28 no 6pp 317ndash324 2019

Evidence-Based Complementary and Alternative Medicine 9

Page 2: TheSpecificandNonspecificEffectsofTaiChiandItsPossible ...the intervention. e metrics of HRV include standard deviation of NN intervals (SDNN), standard deviation of sequential 5-min

in alleviating gastrointestinal symptoms and improving thequality of life (QOL) of patients [10] Does Tai Chi havedifferent gastrointestinal modulation effects between pa-tients with gastrointestinal disorders and HS In otherwords is the gastrointestinal regulation of Tai Chi disease-oriented and influenced by individual physical conditionHowever majority of the Tai Chi-related studies wereperformed either on patients or HS and few studies wereperformed on both patients and HS to investigate the in-fluence of physical conditions on the effect of Tai Chi

On the basis of the characteristics of Tai Chi and pre-vious researches we predict that the effects of Tai Chi in-clude two aspects the relatively specific effects andnonspecific effectse nonspecific effects mainly refer to themodulating effects on human motor function (musclestrength physical flexibility etc) and respiratory functionespecially vital capacity e nonspecific effects might alsomanifest as maintaining the normal function of organssystems keeping the body in a relatively balanced and co-ordinated state While the relatively specific effects of Tai Chiare disease-oriented meaning that when the body is in apathological state Tai Chi practice might reduce the hy-peractive function to improve the hypoactive function

To test the hypothesis we design this neuroimagingstudy In this study both functional constipation (FC) pa-tients and HS were selected as participants to investigate thespecific effects (gastrointestinal function) and nonspecificeffects (motor function and respiratory function) of Tai ChiFC is a common functional gastrointestinal disorder (FGID)with high prevalence It is characterized by various con-stipation-related symptoms including reduced defecationdefecation stress hard stools and uncomfortable abdominalmuscle in the absence of evident organic or structuralreasons for these symptoms A randomized control trialindicated that Tai Chi practice could significantly improvethe constipation symptom of patients with chronic FC [11]

is study aims to (1) investigate the nonspecific effectsof Tai Chi by comparing the influence of Tai Chi practice onmotor function and respiratory function between FC pa-tients and HS using the lower-extremity muscle strengthtest functional balance tests and vital capacity test (2)investigate the specific effects of Tai Chi from three aspectsincluding gastrointestinal symptom autonomic nervousactivity and emotional state and (3) explore the potentialcentral responses of Tai Chirsquos specific and nonspecific effectsby functional magnetic resonance imaging (fMRI)

2 Methods and Analysis

21 Study Design e trial is designed as a neuroimagingtrial that focuses on specific and nonspecific effects of Tai Chiand its potential central responses A total of 40 FC patientsand 40 HS will be recruited Fifteen participants in eachgroup will be randomly selected to undergo MRI scan estudy procedure is outlined in Figure 1

22 Sample Size Calculation We will investigate the thera-peutic effects of Tai Chi for FC patients According to our

preliminary study from which we recruited 10 FC patientswith the Tai Chi intervention the mean improvement ofweekly complete spontaneous bowel movements (CSBMs) ofTai Chi was 167plusmn 089 times A systematic review [12] fo-cusing on the management of FC reported the mean im-provement of weekly CSBMs of polyethylene glycol (the first-line medication of FC) was 18 times We hypothesize that thetherapeutic effects of Tai Chi are not less than the polyethyleneglycol Considering α 005 1minus β 08 the study designrequired a sample size of 36 for each group with the one-sample noninferiority test [13] with a drop-out rate of 10 Atotal of 40 patients with FC and 40HS will be finally recruited

N σZ1minus α + Z1minus β

μ minus μo minus δ1113888 1113889

2

(1)

23 Patients with FC Patients who match the inclusioncriteria will be recruited FC patients will be diagnosed by twogastroenterologists in the digestion department of the Hos-pital of CDUTCM according to the Rome IV DiagnosticCriteria for FC [14] Each FC patient will undergo a carefulphysical examination including a routine blood test routineurine test routine stool test blood biochemical test (ALTAST BUN Scr) transabdominal ultrasound and dynamicelectrocardiogram e inclusion criteria and exclusion cri-teria of FC patients were as same as our previous study [15]

231 Inclusion Criteria Patients will be included in thestudy if they (1) reach the Rome IV Diagnostic Criteria forFC [14] (2) are right-handers and the age range is between18 and 35 (3) have less than three CSBMs every week (4) theCleveland Constipation Score (CCS) scoregt10 and (5)provide a written informed consent form

232 Exclusion Criteria Patients will be excluded from thestudy if they (1) are pregnant women or plan to be pregnantwithin 3 months or are breast-feeding women (2) are in-capable of sports (3) have a history of head trauma and lossof consciousness (4) have diabetes or serious cardiovascularneurological psychiatric renal or respiratory disease (5)have moderate or serious depression and anxiety (6) cannotkeep silent for 20 minutes while lying down (7) have anycontraindications to fMRI scanning including the presenceof metal stent metal denture or claustrophobia (8) havetaken other exercises (including meditation and yoga) thatmay improve constipation over 30 minutes every week in thelast 3 months (9) have taken gastrointestinal motilitymedicine nonsteroidal anti-inflammatory medicine andsteroids in the last 15 days (10) have received other treat-ments (including surgery diet modification biofeedback orprobiotics) in the last month or (11) have participated in anyother clinical trials in the past 3 months

24 Healthy Subjects ose who match the inclusion cri-teria will be recruited and will receive the same physicalexamination with the FC patients

2 Evidence-Based Complementary and Alternative Medicine

241 Inclusion Criteria Subjects will be included if they (1)are right-handers and aged 18ndash35 years (2) have no ab-normalities during the physical examinations (3) havepassed the National Student Physical Health Standard testand (4) provide written informed consent

242 Exclusion Criteria e exclusion criteria for HS arethe same as the criteria for FC patients (see Section 232)Moreover those who have possible organic diseases psy-chological disorders and gastrointestinal symptoms andsigns are also excluded

25 Recruitment Strategy e participants will be recruitedfrom the Chengdu University of Traditional ChineseMedicine (CDUTCM) by delivering leaflets inside thecampus posting advertisements in billboards posting atAcupuncture and Brain Science Research Center andCDUTCM (httpcdutcmeducn) websites and posting inour WeChat public account

26 Intervention e participants will undergo 40 sessionswith 24-style Tai Chi e exercise of Tai Chi will be per-formed four times a week (Monday Tuesday ursday andFriday) and will last for 10 weeks [15] Each exercise sessionlasts for an hour including 10-minute warm-up 40-minuteTai Chi exercise and 10-minute relaxation

Before the formal intervention participants were in-volved in motor learning and strength training under theguidance of two professional Tai Chi instructors During theintervention they exercise strictly under the 24-style Tai Chiexercise standard operating procedure (SOP) which wasformulated by two Tai Chi experts In each session of theexercise the instant heart rate will be counted both at the

pre- and posttrial and the sports self-rating scale will also befilled out Participants who did not come will be recordede training will be considered effective when the rating ofperceived exertion (RPE) of the subjects reaches 4ndash6 levels ineach session and training times must not be less than 80(32 times) of total training times

During the treatment period participants are usually notrecommended to use concomitant care or interventionsHowever if required (such as aggravation of the patientrsquoscondition) participants will be permitted to use extra os-motic laxatives e type and dosage of medication usedshould be recorded in the case report forms (CRFs)

27 Outcome Measurements Measurements will be evalu-ated by independent assessors who have been trained priorto the study All results will be recorded whether or not theparticipants completed the studye outcome assessors willbe independent of the research team and will not be toldabout group allocation so as to ensure the object evaluationsof the trial

271 General Information Collection Same as our previousstudy [15] general information including the demographicdata and vital signs will be collected e demographic datainclude age gender education level nationality and bodymass index (BMI) e vital signs include body temperatureheart rate respiratory rate and blood pressure Amongthem the BMI will be calculated at the baseline and the endof the invention whereas the vital signs of each patient willbe immediately recorded after every training

According to our hypothesis the nonspecific effects ofTai Chi include motor function vital capacity and psy-chological state regulation and the specific effects of Tai Chi

FC and HSscreen inclusion exclusion

FC group (n = 40) HS group (n = 40)

2nd motor functionrespiratory function

1st symptoms and theQOL measurements

1st psychological stateevaluation

1st autonomicnerve function 1st MRI scan

Tai Chi training 10 weeks

2nd MRI scan

Data collection and statistical analysis

1st motor functionrespiratory function

2nd symptoms and theQOL measurements

2nd psychological stateevaluation

2nd autonomicnerve function

Figure 1 Study flowchart is is a neuroimaging trial which focuses on specific and nonspecific effects of Tai Chi and its potential centralresponses Totally 40 eligible FC patients and 40 HS will be recruited Fifteen participants in each group will be randomly selected toundergo functional magnetic resonance imaging (fMRI) scan

Evidence-Based Complementary and Alternative Medicine 3

for FC patients reflects in relieving gastrointestinal symp-toms and modulating autonomic nerve function

272 Nonspecific Effects Motor Function Vital Capacityand Psychological State e lower-extremity musclestrength functional balance tests and the vital capacity testwill be collected at the baseline the median of intervention(after 5 weeks of exercise) and at the end of the interventione lower-extremity muscle strength will be measured usinga hand-held isometric dynamometer (Micro FET3 HogganHealth Industries Draper UT United States) Functionalbalance tests include the Berg Balance Scale (BBS) [16]timed up-and-go (TUG) test and functional reach test [17]

During the vital capacity test the forced expiratoryvolume in one second (FEV1) forced vital capacity (FVC)and FEV1FVC ratio will be measured using a Super Spirospirometer (MicroMedical Rochester Kent UK) in restingstatus e peak expiratory flow rate (PEFR) will be assayedusing a peak flow meter

To assess the psychological state of all participants wecollected the following metrics at the baseline the median ofintervention and the end of intervention the self-ratingdepression scale (SDS) [18] the self-rating anxiety scale(SAS) [19] and the Eysenck Personality Questionnaire(EPQ) [20]

273 Specific Effects Gastrointestinal Symptoms and Auto-nomic Nerve Function To evaluate the changes of thegastrointestinal symptoms and QOL of participants weperformed the following measurements at the baseline themedian of intervention and the end of intervention CCS[21] patient assessment of constipation symptoms (PAC-SYM) [22] patient assessment of constipation QOL ques-tionnaire (PAC-QOL) [23] RPE [24] and MOS 36-itemshort-form health survey (SF-36) [25] Also the evaluationof constipation diary including CSBMs per week the fecalcharacter and the difficulty degree of defecation will bemeasured once a week for 10 times

To evaluate the autonomic nervous function we selectedthe heart rate variability (HRV) All participants will beassessed during the 24-h HRV at the baseline and the end ofthe intervention e metrics of HRV include standarddeviation of NN intervals (SDNN) standard deviation ofsequential 5-min RR interval means (SDANN) and rootmean square successive difference (RMSSD) e deviceused is a dynamic electrocardiogram (ct-086S BENEWARE Hangzhou China)

28 MRI Data Acquisition MRI data will be collected on 15participants in each group at the baseline and the end ofintervention e acquisition parameter will be consistentwith our previous article [15]

e MRI scan includes three sequences a high-resolu-tion 3-dimensional T1-weighted imaging (3D-T1W1) ablood oxygenation level-dependent functional MRI (BOLD-fMRI) and a diffusion tensor imaging (DTI) sequenceScanning will start in the morning after overnight fasting

Subjects who are selected will undergoMRI scan with a 30 Tmagnetic resonance scanner (Siemens Germany) e 3D-T1WI scan parameters will be as follows repetition timeecho time 1900ms226ms slice thickness 1mm slicenumber 176 matrix size 128times128 and the view field256times 256mm2e BOLD-fMRI scanning parameters are asfollows repetition timeecho time 2000ms30ms flip angle90deg slice number 30 matrix size 128times128 view field240times 240mm2 slice thickness 5mm and total volume 240DTI data are as follows view field 240times 240mm2 repetitiontimeecho time 6800ms93ms matrix size 128times128 andslice thickness 3mm seamless Two diffusion-weightedsequences will be acquired using gradient values b 1000 smm2 and b 0 with diffusion-sensitizing gradients used in 64noncollinear directions

29 Data Management e clinical data will be managedwith printed and electronic CRFs CRFs will be enteredparallelly and will only be available to the outcome assessorse Evidence-based Medicine Center of the CDUTCM willbe responsible for monitoring the study and data every 3months

210 Statistical Analysis

2101 Clinical Data Analysis Clinical data will be analyzedby independent statisticians who do not know the testprocedure based on the principles of intention to treat (ITT)and per protocol e statistical significance threshold has p

value lt005 e results of the participants who failed tocomplete the study will be considered no different from thebaseline data in ITTanalysis All continuous variables will bepresented as meanplusmn standard deviation e categoricalvariables will be described in percentage () e clinicaldata in the two groups (FC group and HS group) will becompared with two-sample t-tests and the comparisons ofthe baseline and after intervention in each group will becompared with a paired sample t-test Nonparametric tests(MannndashWhitney U test) will be used to compare non-normally distributed clinical data and the χ2 test or Fisherrsquostest will be used to compare categorical variables

2102 Functional MRI Data Analysis For fMRI scans allpreprocessing steps will be performed using DPABI softwarebased on MATLAB e main analytical methods includethe amplitude of low-frequency fluctuation amplitude(ALFF) and seed-based functional connectivity

After preprocessing the data the ALFF will be calculatedto compare the whole-brain spontaneous activity patternbefore and after intervention in each group as well as be-tween patients with FC and HS following 10-week Tai Chipractices e different regions obtained at ALFF analysiswill be selected as the region of interest (ROI) also calledseed to perform the seed-based functional connectivityanalysis and to explore the functional synchronization ofROI and other regionse thresholds of plt 005 with a falsediscovery rate correlation will be applied to all analyses

4 Evidence-Based Complementary and Alternative Medicine

2103 Correlation Analysis To investigate the associationsbetween nonspecific effects and central responses underdifferent physical conditions we performed the correlationanalysis between the clinical data including motor functionrespiratory function psychological state and cerebralfunction in patients with FC and HS In order to furtherexplain the regulation mechanism of Tai Chi on the brain-gut interaction disorder the correlation analysis amonggastrointestinal symptoms heart rate variability and brainfunction activities in FC patients will also be carried out

2104 Safety Assessments Adverse events might happenduring Tai Chi practice including strain sprain nausea anddizziness If any these adverse events occur the instructorwill take appropriate treatment according to clinicianrsquosadvice and record the processing detail in the CRFs esafety assessments will be monitored by the EthicsCommittee

e schedule of the study including enrollment inter-ventions assessments and visits for participants is shown inTable 1

3 Discussion

As a popular physicalndashmind exercise Tai Chi is widely usedin the prevention treatment and rehabilitation of variousdiseases On the basis of the characteristics and relatedstudies on Tai Chi we put forward the original hypothesisthat Tai Chi practice can produce relative specific effects andnonspecific effects on the human body

e main purposes of this study include two aspectsFirst this study tries to explore the physiological andpsychological existence of the specific and nonspecific ef-fects of Tai Chi by comparing the differences in the motorfunction respiratory function gastrointestinal symptomspsychological manifestations and HRV between FC pa-tients and HS after Tai Chi practice Second this study triesto explore the potential central mechanism of the specificand nonspecific effects of Tai Chi practice by analyzing thepotential cerebral activity changes induced by Tai Chi andtheir correlation with clinical variables e study willprovide a new approach for investigating the mind-bodyexercise and the results might deepen our knowledge aboutTai Chi

31 Specific and Nonspecific Effects of Tai Chi Tai Chi is acomplex sport that requires the coordination of spiritbreathing postures and movements It can produce a sig-nificant impact on almost all human systems such as motorsystem cardiovascular system respiratory system and di-gestive system e impact is far beyond the physiologicaland psychological changes brought by a simple physicalexercise us Tai Chi is not only widely used in publichealthcare but also involved in disease treatment andrehabilitation

On the basis of the characteristics of Tai Chi andrelated studies we put forward that there are two types ofeffects of Tai Chi One is the specific effect which mainly

indicates the therapeutic effects of Tai Chi practice on thepathological status and has obvious disease orientationFor instance Tai Chi practice could produce a specific-regulating effect on the abnormal gastrointestinal (GI)function of patients with GI disorders specifically im-prove the cognitive function of patients with Alzheimerrsquosdisease [26] and significantly relieve the depressionsymptoms of patients with depression [27] A systematicreview and meta-analysis demonstrated that Tai Chi andother mind-body interventions were effective in allevi-ating GI symptoms and improving several aspects of thedisease-related QOL including interference with activitybody image health worry food avoidance and socialreaction [10]

e second aspect is the nonspecific effects whichmainly refers to the benefits for the motor system respi-ratory system and others No matter Tai Chi practice orother forms of physical exercises can produce it enonspecific effects might be a promoting effect on the motorsystem and respiratory system for not only the patients butalso the HS For example studies demonstrated that Tai Chiexercises could increase the muscle strength in the lowerextremities improve balance control and reduce the risk offalls for both healthy elderly people [28 29] and Parkinsonrsquosand stroke patients [30 31] However it should be em-phasized that the specific effects of Tai Chi are relative andconditional e nonspecific effects are the more widely usedand fundamental effect of Tai Chi

32 Potential Central Responses of Tai Chi As a typicalphysical and mental exercise Tai Chi not only emphasizesphysical movement but also requires the state of unity ofbody and mind e positive effects of meditation andaerobic exercise on cognitive function including memoryand decision-making abilities have been widely accepted[32 33] Recent studies further identified the influence of TaiChi practice on the cerebral structure and function ofpractitioners [34] For example MRI studies showed that TaiChi training evoked significant changes in the brain whitematter network [35] brain volume [36] and spontaneousbrain functional activities [37] in older people ese studiesindicated that Tai Chi practice could influence not only thecerebral function but also the brain structure It might be thecentral mechanism of the specific and nonspecific effects ofTai Chi

In this study FC patients will be enrolled to investigatethe specific effects of Tai Chi-modulating GI function FCas a typical FGID the dysfunction of the gut-brain axisplays an essential role in its pathogenesis [38] Recentneuroimaging studies identified the abnormality in thecerebral function and structure in FC patients comparedwith the healthy controls For example an fMRI studydemonstrated that FC patients showed significant dif-ferences in baseline brain activities in several brain re-gions implicated in emotional process modulationsomatic and sensory processing and motor control re-gions [39] Considering the existence of cerebral struc-tural and functional abnormalities in FC patients it is

Evidence-Based Complementary and Alternative Medicine 5

feasible to explore the mechanism of Tai Chirsquos specificeffects on GI function of FC patients

In this study fMRI will be selected as the neuroimagingtechnique to investigate the cerebral activity changes elicitedby Tai Chi practice fMRI is the most commonly used brainimaging technique and has been widely used in the studieson the central mechanism of Tai Chi intervention[35 40 41] For example using fMRI people found thatinfluencing the resting-state functional connectivity alter-ation between the cognitive control network and rostralanterior cingulate cortex and medial prefrontal cortex mightbe the central mechanism of Tai Chi intervention forfibromyalgia [41] ese studies indicated that it was reliable

to use fMRI to explore the central mechanism of Tai Chiintervention for FC

Furthermore to ensure the reliability and repeatabilityof the results we will establish a strict quality controlprogram which includes the participant selection the SOPof Tai Chi practice the SOP of neuroimaging scan and theoutcome measures For example for the selection of par-ticipants the freshmen who never practice Tai Chi and haveno physical exercise frequently will be taken into consid-eration In the implementation of Tai Chi intervention theSOP of 24-style Tai Chi is established which covers therequirement on the movements breathing and ideas of theparticipant

Table 1 Study period

Study period

Enrollment Allocation Postallocation

Timepointlowastlowast minus14 days minus7 days 0 day(baseline)

35 days(middle of intervention)

70 days(after intervention) Etc

EnrollmentEligibility screen 7

Informed consent 7

Demographics 7

Diagnosis 7

Past medical history 7

Physical examination 7

Allocation 7

InterventionsGroup A (FC patients) 7 7 7

Group B (HS) 7 7 7

AssessmentsBMI 7 7

HRV 7 7

Lower-extremity muscle 7 7 7

Functional balance 7 7 7

Vital capacity 7 7 7

Exercise self-rating scale 7 7 7

CCS 7 7 7

PAC-QOL 7 7 7

PAC-SYM 7 7 7

Stool diary 7 7 7

SDS SAS 7 7 7

EPQ 7 7 7

SF-36 7 7 7

MRI 7 7

Safety observationBlood routine test 7

Urine routine test 7

Stool routine test 7

Adverse events 7

is is a neuroimaging trial that includes a 2-week baseline period and a 10-week treatment period In the baseline period recruited patients will be screenedaccording to the inclusion criteria and exclusion criteria and then eligible FC patients and HS will sign an informed consent form and receive a physicalexamination After allocation the FC patients and HS will be recruited and will receive 10 weeks of Tai Chi exercise Schedule of enrollment interventionsand assessments at the baseline the median of intervention (5 weeks of exercise) and the end of the intervention (10 weeks of exercise) Among them lower-extremity muscle strength was measured using a hand-held isometric dynamometer (Micro FET3 Hoggan Health Industries) Functional balance testsinclude BBS TUG test and functional reach test During the vital capacity test FEV1 FVC and FEV1FVC ratio were measured using a MicroMedical SuperSpiro spirometer in resting status PEFR was assayed using a peak flowmetere stool diary CCS and PAC-SYMwill be used to evaluate the clinical efficacyof different interventions the PAC-QOL will be used to assess the health-related QOL the SDS SAS EPQ and Mini-Mental State Examinations will be usedto consider the effect of psychological factors on the patientsrsquo symptoms All participants will be assessed during the 24 h HRV to evaluate the autonomicnervous function at the baseline and the end of the 10-week intervention fMRI scans will be performed to detect the cerebral functional changes in 15 patientsin each group both at the baseline and the end of the intervention

6 Evidence-Based Complementary and Alternative Medicine

4 Conclusions

In conclusion Tai Chi is a safe and effective assistant therapy formany diseases However whether the therapeutic effects of TaiChi are disease-oriented remains uncertain is trial is the firstto investigate the existence of the specific and nonspecific effectsof Tai Chi and to explore their potential central responses It willprovide a new perspective for understanding Tai Chi and a newapproach for studying mind-body exercise

Abbreviations

HS Healthy subjectFC Functional constipationFGID Functional gastrointestinal diseaseQOL Quality of lifeGI GastrointestinalfMRI Functional magnetic resonance imagingCDUTCM Chengdu University of Traditional Chinese

MedicineCSBMs Complete spontaneous bowel movementsCCS Cleveland Constipation ScoreRPE Rating of perceived exertionPAC-SYM Patient Assessment of Constipation SymptomPAC-QOL Patient Assessment of Constipation Quality of

Life QuestionnaireRPE Rating of perceived exertionSF-36 e MOS 36-item short-form health surveyBBS Berg Balance ScaleTUG Timed up-and-goFEV1 Forced expiratory volume in one secondFVC Forced vital capacitySDS Self-Rating Depression ScaleSAS Self-Rating Anxiety ScaleEPQ Eysenck Personality QuestionnairesHRV Heart rate variability3D-T1WI 3-dimensional T1-weighted imagingBOLD-fMRI

Blood oxygenation level-dependent fMRI

DTI Diffusion tensor imagingCRF Case report formITT Intention to treatPP Per protocolReHo Regional homogeneityALFF Amplitude of low-frequency fluctuation

amplitude

Data Availability

is is a protocol for a clinical trial and no original data areincluded

Ethical Approval

e procedures have been approved by the Sichuan RegionalEthics Review Committee on Traditional Chinese Medicine(no 2018KL-047) and conformed to the Declaration ofHelsinki In addition all researchers were trained and signeda pledge to protect the confidentiality of study participants

Consent

All enrolled subjects signed an informed consent form

Disclosure

Tianyu Liu Yuke Teng and Sha Yang are the co-firstauthors

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Tianyu Liu Yuke Teng and Sha Yang contributed equally tothis article FZ and JW were responsible for this study TLYT SY FZ JW ZH and SY conceived and designed thestudy TL YT and SY participated in drafting the trialprotocol and preparing the manuscript YG TY JC and RYparticipated in data collection and were in charge of re-cruitment and treatment of patients All authors read andapproved the final manuscript

Acknowledgments

is study was supported by the Humanities and SocialSciences Youth Project of theMinistry of Education of China(19YJC890027) e trial was financially supported by theTen-ousand Talents Program of China (W02020595) andthe China Postdoctoral Science Foundation(2020M673562XB)

References

[1] C Lan J-S Lai S-Y Chen andM-K Wong ldquoTai Chi Chuanto improve muscular strength and endurance in elderly in-dividuals a pilot studyrdquo Archives of Physical Medicine andRehabilitation vol 81 no 5 pp 604ndash607 2000

[2] A M K Wong and C Lan ldquoTai Chi and balance controlrdquoMedicine and Sport Science vol 52 pp 115ndash123 2008

[3] L Sun L P Zhuang X Z Li J Zheng andW FWu ldquoTai Chican prevent cardiovascular disease and improve cardiopul-monary function of adults with obesity aged 50 years andolder a long-term follow-up studyrdquoMedicine vol 98 no 42Article ID e17509 2019

[4] C E Rogers L K Larkey and C Keller ldquoA review of clinicaltrials of Tai Chi and Qigong in older adultsrdquoWestern Journalof Nursing Research vol 31 no 2 pp 245ndash279 2009

[5] J H Yan W J Gu J Sun W X Zhang B W Li and L PanldquoEfficacy of Tai Chi on pain stiffness and function in patientswith osteoarthritis a meta-analysisrdquo PLoS One vol 8 no 4Article ID e61672 2013

[6] C Wang J P Collet and J Lau ldquoe effect of Tai Chi onhealth outcomes in patients with chronic conditions a sys-tematic reviewrdquo Archives of Internal Medicine vol 164 no 5pp 493ndash501 2004

[7] M Chao C Wang X Dong and M Ding ldquoe effects of taichi on type 2 diabetes mellitus a meta-analysisrdquo Journal ofDiabetes Research vol 2018 Article ID 7350567 9 pages2018

Evidence-Based Complementary and Alternative Medicine 7

[8] E Salmoirago-Blotcher P M Wayne S Dunsiger et al ldquoTaiChi is a promising exercise option for patients with coronaryheart disease declining cardiac rehabilitationrdquo Journal of theAmerican Heart Association vol 6 no 10 2017

[9] L Wang KWu X Chen and Q Liu ldquoe effects of tai chi onlung function exercise capacity and health related quality oflife for patients with chronic obstructive pulmonary disease apilot studyrdquo Heart Lung and Circulation vol 28 no 8pp 1206ndash1212 2019

[10] W Wang F Wang F Fan A C Sedas and J Wang ldquoMind-body interventions for irritable bowel syndrome patients inthe Chinese population a systematic review and meta-anal-ysisrdquo International Journal of Behavioral Medicine vol 24no 2 pp 191ndash204 2017

[11] Y Zhou L Liang L I Hong and L Jing ldquoAbout the con-valescent influence of 24-Pattern Shadowboxing to the pa-tients with chronic functional constipationrdquo Liaoning SportScience and Technology vol 2 pp 52ndash54 2015

[12] P Katelaris V Naganathan K Liu G Krassas andJ Gullotta ldquoComparison of the effectiveness of polyethyleneglycol with and without electrolytes in constipation a sys-tematic review and network meta-analysisrdquo BMC Gastroen-terology vol 16 no 1 p 42 2016

[13] S C Chow J Shao and H Wang Sample Size Calculations inClinical Research Wiley Hoboken NJ USA 2003

[14] D A Drossman and W L Hasler ldquoRome IV-functional GIdisorders disorders of gut-brain interactionrdquo Gastroenter-ology vol 150 no 6 pp 1257ndash1261 2016

[15] S Yang J Chen Y Guo et al ldquoComparison of Taiji andaerobic exercise for functional constipation study protocolfor a randomised controlled neuroimaging trialrdquo BMJ Openvol 9 no 8 Article ID e031089 2019

[16] K Berg S Wood-Dauphinee and J I Williams ldquoe balancescale reliability assessment with elderly residents and patientswith an acute strokerdquo Scandinavian Journal of RehabilitationMedicine vol 27 no 1 pp 27ndash36 1995

[17] P W Duncan D K Weiner J Chandler and S StudenskildquoFunctional reach a new clinical measure of balancerdquo Journalof Gerontology vol 45 no 6 pp M192ndashM197 1990

[18] W W K Zung ldquoA self-rating depression scalerdquo Archives ofGeneral Psychiatry vol 12 no 1 pp 63ndash70 1965

[19] W W K Zung ldquoA rating instrument for anxiety disordersrdquoPsychosomatics vol 12 no 6 pp 371ndash379 1971

[20] D Schuldberg ldquoEysenck personality questionnaire scales andpaper-and-pencil tests related to creativityrdquo PsychologicalReports vol 97 no 1 pp 180ndash182 2005

[21] F Agachan T Chen J Pfeifer P Reissman andS D Wexner ldquoA constipation scoring system to simplifyevaluation andmanagement of constipated patientsrdquoDiseasesof the Colon amp Rectum vol 39 no 6 pp 681ndash685 1996

[22] L Frank L Kleinman C Farup L Taylor and P Miner JrldquoPsychometric validation of a constipation symptom assess-ment questionnairerdquo Scandinavian Journal of Gastroenter-ology vol 34 no 9 pp 870ndash877 1999

[23] P Marquis C De La Loge D Dubois A McDermott andO Chassany ldquoDevelopment and validation of the patientAssessment of constipation quality of life questionnairerdquoScandinavian Journal of Gastroenterology vol 40 no 5pp 540ndash551 2005

[24] S Morishita A Tsubaki T Takabayashi and J B Fu ldquoRe-lationship between the rating of perceived exertion scale andthe load intensity of resistance trainingrdquo Strength and Con-ditioning Journal vol 40 no 2 pp 94ndash109 2018

[25] A Kelly J Rush E Shafonsky et al ldquoDetecting short-termchange and variation in health-related quality of life within-and between-person factor structure of the SF-36 healthsurveyrdquo Health and Quality of Life Outcomes vol 13 no 1p 199 2015

[26] P J Klein ldquoTai Chi Chuan in the management of Parkinsonrsquosdisease and Alzheimerrsquos diseaserdquo Medicine and Sport Sciencevol 52 pp 173ndash181 2008

[27] J Kong G Wilson J Park K Pereira C Walpole andA Yeung ldquoTreating depression with Tai Chi state of the artand future perspectivesrdquo Front Psychiatry vol 10 p 2372019

[28] W W N Tsang and C W Y Hui-Chan ldquoEffect of 4- and 8-wk intensive Tai Chi training on balance control in the el-derlyrdquoMedicine amp Science in Sports amp Exercise vol 36 no 4pp 648ndash657 2004

[29] Z G Huang Y H Feng Y H Li and C S Lv ldquoSystematicreview and meta-analysis Tai Chi for preventing falls in olderadultsrdquo BMJ Open vol 7 no 2 Article ID e013661 2017

[30] F Li P Harmer K Fitzgerald et al ldquoTai Chi and posturalstability in patients with Parkinsonrsquos diseaserdquo New EnglandJournal of Medicine vol 366 no 6 pp 511ndash519 2012

[31] I Hwang R Song S Ahn M-A Lee P M Wayne andM K Sohn ldquoExploring the adaptability of Tai Chi to strokerehabilitationrdquo Rehabilitation Nursing vol 44 no 4pp 221ndash229 2019

[32] S Deepeshwar S A Vinchurkar N K Visweswaraiah andH R Nagendra ldquoHemodynamic responses on prefrontalcortex related to meditation and attentional taskrdquo Frontiers inSystems Neuroscience vol 8 p 252 2014

[33] T Moriarty K Bourbeau B Bellovary and M N ZuhlldquoExercise intensity influences prefrontal cortex oxygenationduring cognitive testingrdquo Behavioral Sciences vol 9 no 8p 83 2019

[34] R Silveira R C R Prado C Brietzke et al ldquoPrefrontal cortexasymmetry and psychological responses to exercise a sys-tematic reviewrdquo Physiology amp Behavior vol 208 p 1125802019

[35] C Yue L Zou J Mei et al ldquoTai Chi training evokes sig-nificant changes in brain white matter network in olderwomenrdquo Healthcare vol 8 no 1 p 57 2020

[36] M Adcock M Fankhauser J Post et al ldquoEffects of an in-home multicomponent exergame training on physical func-tions cognition and brain volume of older adults a ran-domized controlled trialrdquo Frontiers in Medicine vol 6 p 3212019

[37] Z Zheng X Zhu S Yin et al ldquoCombined cognitive-psy-chological-physical intervention induces reorganization ofintrinsic functional brain architecture in older adultsrdquo NeuralPlasticity vol 2015 Article ID 713104 11 pages 2015

[38] M Equit J Niemczyk A Kluth C omas M Rubly andA von Gontard ldquoCentral nervous system processing ofemotions in children with fecal incontinence and con-stipationrdquo Zeitschrift fur Kinder- und Jugendpsychiatrie undPsychotherapie vol 47 no 1 pp 67ndash71 2019

[39] Q Zhu W Cai J Zheng et al ldquoDistinct resting-state brainactivity in patients with functional constipationrdquo Neurosci-ence Letters vol 632 pp 141ndash146 2016

[40] J Kong E Wolcott Z Wang et al ldquoAltered resting statefunctional connectivity of the cognitive control network infibromyalgia and the modulation effect of mind-body inter-ventionrdquo Brain Imaging and Behavior vol 13 no 2pp 482ndash492 2019

8 Evidence-Based Complementary and Alternative Medicine

[41] R Jalilianhasanpour E Beheshtian G Sherbaf S Sahraianand H I Sair ldquoFunctional connectivity in neurodegenerativedisorders Alzheimerrsquos disease and frontotemporal dementiardquoTopics in Magnetic Resonance Imaging vol 28 no 6pp 317ndash324 2019

Evidence-Based Complementary and Alternative Medicine 9

Page 3: TheSpecificandNonspecificEffectsofTaiChiandItsPossible ...the intervention. e metrics of HRV include standard deviation of NN intervals (SDNN), standard deviation of sequential 5-min

241 Inclusion Criteria Subjects will be included if they (1)are right-handers and aged 18ndash35 years (2) have no ab-normalities during the physical examinations (3) havepassed the National Student Physical Health Standard testand (4) provide written informed consent

242 Exclusion Criteria e exclusion criteria for HS arethe same as the criteria for FC patients (see Section 232)Moreover those who have possible organic diseases psy-chological disorders and gastrointestinal symptoms andsigns are also excluded

25 Recruitment Strategy e participants will be recruitedfrom the Chengdu University of Traditional ChineseMedicine (CDUTCM) by delivering leaflets inside thecampus posting advertisements in billboards posting atAcupuncture and Brain Science Research Center andCDUTCM (httpcdutcmeducn) websites and posting inour WeChat public account

26 Intervention e participants will undergo 40 sessionswith 24-style Tai Chi e exercise of Tai Chi will be per-formed four times a week (Monday Tuesday ursday andFriday) and will last for 10 weeks [15] Each exercise sessionlasts for an hour including 10-minute warm-up 40-minuteTai Chi exercise and 10-minute relaxation

Before the formal intervention participants were in-volved in motor learning and strength training under theguidance of two professional Tai Chi instructors During theintervention they exercise strictly under the 24-style Tai Chiexercise standard operating procedure (SOP) which wasformulated by two Tai Chi experts In each session of theexercise the instant heart rate will be counted both at the

pre- and posttrial and the sports self-rating scale will also befilled out Participants who did not come will be recordede training will be considered effective when the rating ofperceived exertion (RPE) of the subjects reaches 4ndash6 levels ineach session and training times must not be less than 80(32 times) of total training times

During the treatment period participants are usually notrecommended to use concomitant care or interventionsHowever if required (such as aggravation of the patientrsquoscondition) participants will be permitted to use extra os-motic laxatives e type and dosage of medication usedshould be recorded in the case report forms (CRFs)

27 Outcome Measurements Measurements will be evalu-ated by independent assessors who have been trained priorto the study All results will be recorded whether or not theparticipants completed the studye outcome assessors willbe independent of the research team and will not be toldabout group allocation so as to ensure the object evaluationsof the trial

271 General Information Collection Same as our previousstudy [15] general information including the demographicdata and vital signs will be collected e demographic datainclude age gender education level nationality and bodymass index (BMI) e vital signs include body temperatureheart rate respiratory rate and blood pressure Amongthem the BMI will be calculated at the baseline and the endof the invention whereas the vital signs of each patient willbe immediately recorded after every training

According to our hypothesis the nonspecific effects ofTai Chi include motor function vital capacity and psy-chological state regulation and the specific effects of Tai Chi

FC and HSscreen inclusion exclusion

FC group (n = 40) HS group (n = 40)

2nd motor functionrespiratory function

1st symptoms and theQOL measurements

1st psychological stateevaluation

1st autonomicnerve function 1st MRI scan

Tai Chi training 10 weeks

2nd MRI scan

Data collection and statistical analysis

1st motor functionrespiratory function

2nd symptoms and theQOL measurements

2nd psychological stateevaluation

2nd autonomicnerve function

Figure 1 Study flowchart is is a neuroimaging trial which focuses on specific and nonspecific effects of Tai Chi and its potential centralresponses Totally 40 eligible FC patients and 40 HS will be recruited Fifteen participants in each group will be randomly selected toundergo functional magnetic resonance imaging (fMRI) scan

Evidence-Based Complementary and Alternative Medicine 3

for FC patients reflects in relieving gastrointestinal symp-toms and modulating autonomic nerve function

272 Nonspecific Effects Motor Function Vital Capacityand Psychological State e lower-extremity musclestrength functional balance tests and the vital capacity testwill be collected at the baseline the median of intervention(after 5 weeks of exercise) and at the end of the interventione lower-extremity muscle strength will be measured usinga hand-held isometric dynamometer (Micro FET3 HogganHealth Industries Draper UT United States) Functionalbalance tests include the Berg Balance Scale (BBS) [16]timed up-and-go (TUG) test and functional reach test [17]

During the vital capacity test the forced expiratoryvolume in one second (FEV1) forced vital capacity (FVC)and FEV1FVC ratio will be measured using a Super Spirospirometer (MicroMedical Rochester Kent UK) in restingstatus e peak expiratory flow rate (PEFR) will be assayedusing a peak flow meter

To assess the psychological state of all participants wecollected the following metrics at the baseline the median ofintervention and the end of intervention the self-ratingdepression scale (SDS) [18] the self-rating anxiety scale(SAS) [19] and the Eysenck Personality Questionnaire(EPQ) [20]

273 Specific Effects Gastrointestinal Symptoms and Auto-nomic Nerve Function To evaluate the changes of thegastrointestinal symptoms and QOL of participants weperformed the following measurements at the baseline themedian of intervention and the end of intervention CCS[21] patient assessment of constipation symptoms (PAC-SYM) [22] patient assessment of constipation QOL ques-tionnaire (PAC-QOL) [23] RPE [24] and MOS 36-itemshort-form health survey (SF-36) [25] Also the evaluationof constipation diary including CSBMs per week the fecalcharacter and the difficulty degree of defecation will bemeasured once a week for 10 times

To evaluate the autonomic nervous function we selectedthe heart rate variability (HRV) All participants will beassessed during the 24-h HRV at the baseline and the end ofthe intervention e metrics of HRV include standarddeviation of NN intervals (SDNN) standard deviation ofsequential 5-min RR interval means (SDANN) and rootmean square successive difference (RMSSD) e deviceused is a dynamic electrocardiogram (ct-086S BENEWARE Hangzhou China)

28 MRI Data Acquisition MRI data will be collected on 15participants in each group at the baseline and the end ofintervention e acquisition parameter will be consistentwith our previous article [15]

e MRI scan includes three sequences a high-resolu-tion 3-dimensional T1-weighted imaging (3D-T1W1) ablood oxygenation level-dependent functional MRI (BOLD-fMRI) and a diffusion tensor imaging (DTI) sequenceScanning will start in the morning after overnight fasting

Subjects who are selected will undergoMRI scan with a 30 Tmagnetic resonance scanner (Siemens Germany) e 3D-T1WI scan parameters will be as follows repetition timeecho time 1900ms226ms slice thickness 1mm slicenumber 176 matrix size 128times128 and the view field256times 256mm2e BOLD-fMRI scanning parameters are asfollows repetition timeecho time 2000ms30ms flip angle90deg slice number 30 matrix size 128times128 view field240times 240mm2 slice thickness 5mm and total volume 240DTI data are as follows view field 240times 240mm2 repetitiontimeecho time 6800ms93ms matrix size 128times128 andslice thickness 3mm seamless Two diffusion-weightedsequences will be acquired using gradient values b 1000 smm2 and b 0 with diffusion-sensitizing gradients used in 64noncollinear directions

29 Data Management e clinical data will be managedwith printed and electronic CRFs CRFs will be enteredparallelly and will only be available to the outcome assessorse Evidence-based Medicine Center of the CDUTCM willbe responsible for monitoring the study and data every 3months

210 Statistical Analysis

2101 Clinical Data Analysis Clinical data will be analyzedby independent statisticians who do not know the testprocedure based on the principles of intention to treat (ITT)and per protocol e statistical significance threshold has p

value lt005 e results of the participants who failed tocomplete the study will be considered no different from thebaseline data in ITTanalysis All continuous variables will bepresented as meanplusmn standard deviation e categoricalvariables will be described in percentage () e clinicaldata in the two groups (FC group and HS group) will becompared with two-sample t-tests and the comparisons ofthe baseline and after intervention in each group will becompared with a paired sample t-test Nonparametric tests(MannndashWhitney U test) will be used to compare non-normally distributed clinical data and the χ2 test or Fisherrsquostest will be used to compare categorical variables

2102 Functional MRI Data Analysis For fMRI scans allpreprocessing steps will be performed using DPABI softwarebased on MATLAB e main analytical methods includethe amplitude of low-frequency fluctuation amplitude(ALFF) and seed-based functional connectivity

After preprocessing the data the ALFF will be calculatedto compare the whole-brain spontaneous activity patternbefore and after intervention in each group as well as be-tween patients with FC and HS following 10-week Tai Chipractices e different regions obtained at ALFF analysiswill be selected as the region of interest (ROI) also calledseed to perform the seed-based functional connectivityanalysis and to explore the functional synchronization ofROI and other regionse thresholds of plt 005 with a falsediscovery rate correlation will be applied to all analyses

4 Evidence-Based Complementary and Alternative Medicine

2103 Correlation Analysis To investigate the associationsbetween nonspecific effects and central responses underdifferent physical conditions we performed the correlationanalysis between the clinical data including motor functionrespiratory function psychological state and cerebralfunction in patients with FC and HS In order to furtherexplain the regulation mechanism of Tai Chi on the brain-gut interaction disorder the correlation analysis amonggastrointestinal symptoms heart rate variability and brainfunction activities in FC patients will also be carried out

2104 Safety Assessments Adverse events might happenduring Tai Chi practice including strain sprain nausea anddizziness If any these adverse events occur the instructorwill take appropriate treatment according to clinicianrsquosadvice and record the processing detail in the CRFs esafety assessments will be monitored by the EthicsCommittee

e schedule of the study including enrollment inter-ventions assessments and visits for participants is shown inTable 1

3 Discussion

As a popular physicalndashmind exercise Tai Chi is widely usedin the prevention treatment and rehabilitation of variousdiseases On the basis of the characteristics and relatedstudies on Tai Chi we put forward the original hypothesisthat Tai Chi practice can produce relative specific effects andnonspecific effects on the human body

e main purposes of this study include two aspectsFirst this study tries to explore the physiological andpsychological existence of the specific and nonspecific ef-fects of Tai Chi by comparing the differences in the motorfunction respiratory function gastrointestinal symptomspsychological manifestations and HRV between FC pa-tients and HS after Tai Chi practice Second this study triesto explore the potential central mechanism of the specificand nonspecific effects of Tai Chi practice by analyzing thepotential cerebral activity changes induced by Tai Chi andtheir correlation with clinical variables e study willprovide a new approach for investigating the mind-bodyexercise and the results might deepen our knowledge aboutTai Chi

31 Specific and Nonspecific Effects of Tai Chi Tai Chi is acomplex sport that requires the coordination of spiritbreathing postures and movements It can produce a sig-nificant impact on almost all human systems such as motorsystem cardiovascular system respiratory system and di-gestive system e impact is far beyond the physiologicaland psychological changes brought by a simple physicalexercise us Tai Chi is not only widely used in publichealthcare but also involved in disease treatment andrehabilitation

On the basis of the characteristics of Tai Chi andrelated studies we put forward that there are two types ofeffects of Tai Chi One is the specific effect which mainly

indicates the therapeutic effects of Tai Chi practice on thepathological status and has obvious disease orientationFor instance Tai Chi practice could produce a specific-regulating effect on the abnormal gastrointestinal (GI)function of patients with GI disorders specifically im-prove the cognitive function of patients with Alzheimerrsquosdisease [26] and significantly relieve the depressionsymptoms of patients with depression [27] A systematicreview and meta-analysis demonstrated that Tai Chi andother mind-body interventions were effective in allevi-ating GI symptoms and improving several aspects of thedisease-related QOL including interference with activitybody image health worry food avoidance and socialreaction [10]

e second aspect is the nonspecific effects whichmainly refers to the benefits for the motor system respi-ratory system and others No matter Tai Chi practice orother forms of physical exercises can produce it enonspecific effects might be a promoting effect on the motorsystem and respiratory system for not only the patients butalso the HS For example studies demonstrated that Tai Chiexercises could increase the muscle strength in the lowerextremities improve balance control and reduce the risk offalls for both healthy elderly people [28 29] and Parkinsonrsquosand stroke patients [30 31] However it should be em-phasized that the specific effects of Tai Chi are relative andconditional e nonspecific effects are the more widely usedand fundamental effect of Tai Chi

32 Potential Central Responses of Tai Chi As a typicalphysical and mental exercise Tai Chi not only emphasizesphysical movement but also requires the state of unity ofbody and mind e positive effects of meditation andaerobic exercise on cognitive function including memoryand decision-making abilities have been widely accepted[32 33] Recent studies further identified the influence of TaiChi practice on the cerebral structure and function ofpractitioners [34] For example MRI studies showed that TaiChi training evoked significant changes in the brain whitematter network [35] brain volume [36] and spontaneousbrain functional activities [37] in older people ese studiesindicated that Tai Chi practice could influence not only thecerebral function but also the brain structure It might be thecentral mechanism of the specific and nonspecific effects ofTai Chi

In this study FC patients will be enrolled to investigatethe specific effects of Tai Chi-modulating GI function FCas a typical FGID the dysfunction of the gut-brain axisplays an essential role in its pathogenesis [38] Recentneuroimaging studies identified the abnormality in thecerebral function and structure in FC patients comparedwith the healthy controls For example an fMRI studydemonstrated that FC patients showed significant dif-ferences in baseline brain activities in several brain re-gions implicated in emotional process modulationsomatic and sensory processing and motor control re-gions [39] Considering the existence of cerebral struc-tural and functional abnormalities in FC patients it is

Evidence-Based Complementary and Alternative Medicine 5

feasible to explore the mechanism of Tai Chirsquos specificeffects on GI function of FC patients

In this study fMRI will be selected as the neuroimagingtechnique to investigate the cerebral activity changes elicitedby Tai Chi practice fMRI is the most commonly used brainimaging technique and has been widely used in the studieson the central mechanism of Tai Chi intervention[35 40 41] For example using fMRI people found thatinfluencing the resting-state functional connectivity alter-ation between the cognitive control network and rostralanterior cingulate cortex and medial prefrontal cortex mightbe the central mechanism of Tai Chi intervention forfibromyalgia [41] ese studies indicated that it was reliable

to use fMRI to explore the central mechanism of Tai Chiintervention for FC

Furthermore to ensure the reliability and repeatabilityof the results we will establish a strict quality controlprogram which includes the participant selection the SOPof Tai Chi practice the SOP of neuroimaging scan and theoutcome measures For example for the selection of par-ticipants the freshmen who never practice Tai Chi and haveno physical exercise frequently will be taken into consid-eration In the implementation of Tai Chi intervention theSOP of 24-style Tai Chi is established which covers therequirement on the movements breathing and ideas of theparticipant

Table 1 Study period

Study period

Enrollment Allocation Postallocation

Timepointlowastlowast minus14 days minus7 days 0 day(baseline)

35 days(middle of intervention)

70 days(after intervention) Etc

EnrollmentEligibility screen 7

Informed consent 7

Demographics 7

Diagnosis 7

Past medical history 7

Physical examination 7

Allocation 7

InterventionsGroup A (FC patients) 7 7 7

Group B (HS) 7 7 7

AssessmentsBMI 7 7

HRV 7 7

Lower-extremity muscle 7 7 7

Functional balance 7 7 7

Vital capacity 7 7 7

Exercise self-rating scale 7 7 7

CCS 7 7 7

PAC-QOL 7 7 7

PAC-SYM 7 7 7

Stool diary 7 7 7

SDS SAS 7 7 7

EPQ 7 7 7

SF-36 7 7 7

MRI 7 7

Safety observationBlood routine test 7

Urine routine test 7

Stool routine test 7

Adverse events 7

is is a neuroimaging trial that includes a 2-week baseline period and a 10-week treatment period In the baseline period recruited patients will be screenedaccording to the inclusion criteria and exclusion criteria and then eligible FC patients and HS will sign an informed consent form and receive a physicalexamination After allocation the FC patients and HS will be recruited and will receive 10 weeks of Tai Chi exercise Schedule of enrollment interventionsand assessments at the baseline the median of intervention (5 weeks of exercise) and the end of the intervention (10 weeks of exercise) Among them lower-extremity muscle strength was measured using a hand-held isometric dynamometer (Micro FET3 Hoggan Health Industries) Functional balance testsinclude BBS TUG test and functional reach test During the vital capacity test FEV1 FVC and FEV1FVC ratio were measured using a MicroMedical SuperSpiro spirometer in resting status PEFR was assayed using a peak flowmetere stool diary CCS and PAC-SYMwill be used to evaluate the clinical efficacyof different interventions the PAC-QOL will be used to assess the health-related QOL the SDS SAS EPQ and Mini-Mental State Examinations will be usedto consider the effect of psychological factors on the patientsrsquo symptoms All participants will be assessed during the 24 h HRV to evaluate the autonomicnervous function at the baseline and the end of the 10-week intervention fMRI scans will be performed to detect the cerebral functional changes in 15 patientsin each group both at the baseline and the end of the intervention

6 Evidence-Based Complementary and Alternative Medicine

4 Conclusions

In conclusion Tai Chi is a safe and effective assistant therapy formany diseases However whether the therapeutic effects of TaiChi are disease-oriented remains uncertain is trial is the firstto investigate the existence of the specific and nonspecific effectsof Tai Chi and to explore their potential central responses It willprovide a new perspective for understanding Tai Chi and a newapproach for studying mind-body exercise

Abbreviations

HS Healthy subjectFC Functional constipationFGID Functional gastrointestinal diseaseQOL Quality of lifeGI GastrointestinalfMRI Functional magnetic resonance imagingCDUTCM Chengdu University of Traditional Chinese

MedicineCSBMs Complete spontaneous bowel movementsCCS Cleveland Constipation ScoreRPE Rating of perceived exertionPAC-SYM Patient Assessment of Constipation SymptomPAC-QOL Patient Assessment of Constipation Quality of

Life QuestionnaireRPE Rating of perceived exertionSF-36 e MOS 36-item short-form health surveyBBS Berg Balance ScaleTUG Timed up-and-goFEV1 Forced expiratory volume in one secondFVC Forced vital capacitySDS Self-Rating Depression ScaleSAS Self-Rating Anxiety ScaleEPQ Eysenck Personality QuestionnairesHRV Heart rate variability3D-T1WI 3-dimensional T1-weighted imagingBOLD-fMRI

Blood oxygenation level-dependent fMRI

DTI Diffusion tensor imagingCRF Case report formITT Intention to treatPP Per protocolReHo Regional homogeneityALFF Amplitude of low-frequency fluctuation

amplitude

Data Availability

is is a protocol for a clinical trial and no original data areincluded

Ethical Approval

e procedures have been approved by the Sichuan RegionalEthics Review Committee on Traditional Chinese Medicine(no 2018KL-047) and conformed to the Declaration ofHelsinki In addition all researchers were trained and signeda pledge to protect the confidentiality of study participants

Consent

All enrolled subjects signed an informed consent form

Disclosure

Tianyu Liu Yuke Teng and Sha Yang are the co-firstauthors

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Tianyu Liu Yuke Teng and Sha Yang contributed equally tothis article FZ and JW were responsible for this study TLYT SY FZ JW ZH and SY conceived and designed thestudy TL YT and SY participated in drafting the trialprotocol and preparing the manuscript YG TY JC and RYparticipated in data collection and were in charge of re-cruitment and treatment of patients All authors read andapproved the final manuscript

Acknowledgments

is study was supported by the Humanities and SocialSciences Youth Project of theMinistry of Education of China(19YJC890027) e trial was financially supported by theTen-ousand Talents Program of China (W02020595) andthe China Postdoctoral Science Foundation(2020M673562XB)

References

[1] C Lan J-S Lai S-Y Chen andM-K Wong ldquoTai Chi Chuanto improve muscular strength and endurance in elderly in-dividuals a pilot studyrdquo Archives of Physical Medicine andRehabilitation vol 81 no 5 pp 604ndash607 2000

[2] A M K Wong and C Lan ldquoTai Chi and balance controlrdquoMedicine and Sport Science vol 52 pp 115ndash123 2008

[3] L Sun L P Zhuang X Z Li J Zheng andW FWu ldquoTai Chican prevent cardiovascular disease and improve cardiopul-monary function of adults with obesity aged 50 years andolder a long-term follow-up studyrdquoMedicine vol 98 no 42Article ID e17509 2019

[4] C E Rogers L K Larkey and C Keller ldquoA review of clinicaltrials of Tai Chi and Qigong in older adultsrdquoWestern Journalof Nursing Research vol 31 no 2 pp 245ndash279 2009

[5] J H Yan W J Gu J Sun W X Zhang B W Li and L PanldquoEfficacy of Tai Chi on pain stiffness and function in patientswith osteoarthritis a meta-analysisrdquo PLoS One vol 8 no 4Article ID e61672 2013

[6] C Wang J P Collet and J Lau ldquoe effect of Tai Chi onhealth outcomes in patients with chronic conditions a sys-tematic reviewrdquo Archives of Internal Medicine vol 164 no 5pp 493ndash501 2004

[7] M Chao C Wang X Dong and M Ding ldquoe effects of taichi on type 2 diabetes mellitus a meta-analysisrdquo Journal ofDiabetes Research vol 2018 Article ID 7350567 9 pages2018

Evidence-Based Complementary and Alternative Medicine 7

[8] E Salmoirago-Blotcher P M Wayne S Dunsiger et al ldquoTaiChi is a promising exercise option for patients with coronaryheart disease declining cardiac rehabilitationrdquo Journal of theAmerican Heart Association vol 6 no 10 2017

[9] L Wang KWu X Chen and Q Liu ldquoe effects of tai chi onlung function exercise capacity and health related quality oflife for patients with chronic obstructive pulmonary disease apilot studyrdquo Heart Lung and Circulation vol 28 no 8pp 1206ndash1212 2019

[10] W Wang F Wang F Fan A C Sedas and J Wang ldquoMind-body interventions for irritable bowel syndrome patients inthe Chinese population a systematic review and meta-anal-ysisrdquo International Journal of Behavioral Medicine vol 24no 2 pp 191ndash204 2017

[11] Y Zhou L Liang L I Hong and L Jing ldquoAbout the con-valescent influence of 24-Pattern Shadowboxing to the pa-tients with chronic functional constipationrdquo Liaoning SportScience and Technology vol 2 pp 52ndash54 2015

[12] P Katelaris V Naganathan K Liu G Krassas andJ Gullotta ldquoComparison of the effectiveness of polyethyleneglycol with and without electrolytes in constipation a sys-tematic review and network meta-analysisrdquo BMC Gastroen-terology vol 16 no 1 p 42 2016

[13] S C Chow J Shao and H Wang Sample Size Calculations inClinical Research Wiley Hoboken NJ USA 2003

[14] D A Drossman and W L Hasler ldquoRome IV-functional GIdisorders disorders of gut-brain interactionrdquo Gastroenter-ology vol 150 no 6 pp 1257ndash1261 2016

[15] S Yang J Chen Y Guo et al ldquoComparison of Taiji andaerobic exercise for functional constipation study protocolfor a randomised controlled neuroimaging trialrdquo BMJ Openvol 9 no 8 Article ID e031089 2019

[16] K Berg S Wood-Dauphinee and J I Williams ldquoe balancescale reliability assessment with elderly residents and patientswith an acute strokerdquo Scandinavian Journal of RehabilitationMedicine vol 27 no 1 pp 27ndash36 1995

[17] P W Duncan D K Weiner J Chandler and S StudenskildquoFunctional reach a new clinical measure of balancerdquo Journalof Gerontology vol 45 no 6 pp M192ndashM197 1990

[18] W W K Zung ldquoA self-rating depression scalerdquo Archives ofGeneral Psychiatry vol 12 no 1 pp 63ndash70 1965

[19] W W K Zung ldquoA rating instrument for anxiety disordersrdquoPsychosomatics vol 12 no 6 pp 371ndash379 1971

[20] D Schuldberg ldquoEysenck personality questionnaire scales andpaper-and-pencil tests related to creativityrdquo PsychologicalReports vol 97 no 1 pp 180ndash182 2005

[21] F Agachan T Chen J Pfeifer P Reissman andS D Wexner ldquoA constipation scoring system to simplifyevaluation andmanagement of constipated patientsrdquoDiseasesof the Colon amp Rectum vol 39 no 6 pp 681ndash685 1996

[22] L Frank L Kleinman C Farup L Taylor and P Miner JrldquoPsychometric validation of a constipation symptom assess-ment questionnairerdquo Scandinavian Journal of Gastroenter-ology vol 34 no 9 pp 870ndash877 1999

[23] P Marquis C De La Loge D Dubois A McDermott andO Chassany ldquoDevelopment and validation of the patientAssessment of constipation quality of life questionnairerdquoScandinavian Journal of Gastroenterology vol 40 no 5pp 540ndash551 2005

[24] S Morishita A Tsubaki T Takabayashi and J B Fu ldquoRe-lationship between the rating of perceived exertion scale andthe load intensity of resistance trainingrdquo Strength and Con-ditioning Journal vol 40 no 2 pp 94ndash109 2018

[25] A Kelly J Rush E Shafonsky et al ldquoDetecting short-termchange and variation in health-related quality of life within-and between-person factor structure of the SF-36 healthsurveyrdquo Health and Quality of Life Outcomes vol 13 no 1p 199 2015

[26] P J Klein ldquoTai Chi Chuan in the management of Parkinsonrsquosdisease and Alzheimerrsquos diseaserdquo Medicine and Sport Sciencevol 52 pp 173ndash181 2008

[27] J Kong G Wilson J Park K Pereira C Walpole andA Yeung ldquoTreating depression with Tai Chi state of the artand future perspectivesrdquo Front Psychiatry vol 10 p 2372019

[28] W W N Tsang and C W Y Hui-Chan ldquoEffect of 4- and 8-wk intensive Tai Chi training on balance control in the el-derlyrdquoMedicine amp Science in Sports amp Exercise vol 36 no 4pp 648ndash657 2004

[29] Z G Huang Y H Feng Y H Li and C S Lv ldquoSystematicreview and meta-analysis Tai Chi for preventing falls in olderadultsrdquo BMJ Open vol 7 no 2 Article ID e013661 2017

[30] F Li P Harmer K Fitzgerald et al ldquoTai Chi and posturalstability in patients with Parkinsonrsquos diseaserdquo New EnglandJournal of Medicine vol 366 no 6 pp 511ndash519 2012

[31] I Hwang R Song S Ahn M-A Lee P M Wayne andM K Sohn ldquoExploring the adaptability of Tai Chi to strokerehabilitationrdquo Rehabilitation Nursing vol 44 no 4pp 221ndash229 2019

[32] S Deepeshwar S A Vinchurkar N K Visweswaraiah andH R Nagendra ldquoHemodynamic responses on prefrontalcortex related to meditation and attentional taskrdquo Frontiers inSystems Neuroscience vol 8 p 252 2014

[33] T Moriarty K Bourbeau B Bellovary and M N ZuhlldquoExercise intensity influences prefrontal cortex oxygenationduring cognitive testingrdquo Behavioral Sciences vol 9 no 8p 83 2019

[34] R Silveira R C R Prado C Brietzke et al ldquoPrefrontal cortexasymmetry and psychological responses to exercise a sys-tematic reviewrdquo Physiology amp Behavior vol 208 p 1125802019

[35] C Yue L Zou J Mei et al ldquoTai Chi training evokes sig-nificant changes in brain white matter network in olderwomenrdquo Healthcare vol 8 no 1 p 57 2020

[36] M Adcock M Fankhauser J Post et al ldquoEffects of an in-home multicomponent exergame training on physical func-tions cognition and brain volume of older adults a ran-domized controlled trialrdquo Frontiers in Medicine vol 6 p 3212019

[37] Z Zheng X Zhu S Yin et al ldquoCombined cognitive-psy-chological-physical intervention induces reorganization ofintrinsic functional brain architecture in older adultsrdquo NeuralPlasticity vol 2015 Article ID 713104 11 pages 2015

[38] M Equit J Niemczyk A Kluth C omas M Rubly andA von Gontard ldquoCentral nervous system processing ofemotions in children with fecal incontinence and con-stipationrdquo Zeitschrift fur Kinder- und Jugendpsychiatrie undPsychotherapie vol 47 no 1 pp 67ndash71 2019

[39] Q Zhu W Cai J Zheng et al ldquoDistinct resting-state brainactivity in patients with functional constipationrdquo Neurosci-ence Letters vol 632 pp 141ndash146 2016

[40] J Kong E Wolcott Z Wang et al ldquoAltered resting statefunctional connectivity of the cognitive control network infibromyalgia and the modulation effect of mind-body inter-ventionrdquo Brain Imaging and Behavior vol 13 no 2pp 482ndash492 2019

8 Evidence-Based Complementary and Alternative Medicine

[41] R Jalilianhasanpour E Beheshtian G Sherbaf S Sahraianand H I Sair ldquoFunctional connectivity in neurodegenerativedisorders Alzheimerrsquos disease and frontotemporal dementiardquoTopics in Magnetic Resonance Imaging vol 28 no 6pp 317ndash324 2019

Evidence-Based Complementary and Alternative Medicine 9

Page 4: TheSpecificandNonspecificEffectsofTaiChiandItsPossible ...the intervention. e metrics of HRV include standard deviation of NN intervals (SDNN), standard deviation of sequential 5-min

for FC patients reflects in relieving gastrointestinal symp-toms and modulating autonomic nerve function

272 Nonspecific Effects Motor Function Vital Capacityand Psychological State e lower-extremity musclestrength functional balance tests and the vital capacity testwill be collected at the baseline the median of intervention(after 5 weeks of exercise) and at the end of the interventione lower-extremity muscle strength will be measured usinga hand-held isometric dynamometer (Micro FET3 HogganHealth Industries Draper UT United States) Functionalbalance tests include the Berg Balance Scale (BBS) [16]timed up-and-go (TUG) test and functional reach test [17]

During the vital capacity test the forced expiratoryvolume in one second (FEV1) forced vital capacity (FVC)and FEV1FVC ratio will be measured using a Super Spirospirometer (MicroMedical Rochester Kent UK) in restingstatus e peak expiratory flow rate (PEFR) will be assayedusing a peak flow meter

To assess the psychological state of all participants wecollected the following metrics at the baseline the median ofintervention and the end of intervention the self-ratingdepression scale (SDS) [18] the self-rating anxiety scale(SAS) [19] and the Eysenck Personality Questionnaire(EPQ) [20]

273 Specific Effects Gastrointestinal Symptoms and Auto-nomic Nerve Function To evaluate the changes of thegastrointestinal symptoms and QOL of participants weperformed the following measurements at the baseline themedian of intervention and the end of intervention CCS[21] patient assessment of constipation symptoms (PAC-SYM) [22] patient assessment of constipation QOL ques-tionnaire (PAC-QOL) [23] RPE [24] and MOS 36-itemshort-form health survey (SF-36) [25] Also the evaluationof constipation diary including CSBMs per week the fecalcharacter and the difficulty degree of defecation will bemeasured once a week for 10 times

To evaluate the autonomic nervous function we selectedthe heart rate variability (HRV) All participants will beassessed during the 24-h HRV at the baseline and the end ofthe intervention e metrics of HRV include standarddeviation of NN intervals (SDNN) standard deviation ofsequential 5-min RR interval means (SDANN) and rootmean square successive difference (RMSSD) e deviceused is a dynamic electrocardiogram (ct-086S BENEWARE Hangzhou China)

28 MRI Data Acquisition MRI data will be collected on 15participants in each group at the baseline and the end ofintervention e acquisition parameter will be consistentwith our previous article [15]

e MRI scan includes three sequences a high-resolu-tion 3-dimensional T1-weighted imaging (3D-T1W1) ablood oxygenation level-dependent functional MRI (BOLD-fMRI) and a diffusion tensor imaging (DTI) sequenceScanning will start in the morning after overnight fasting

Subjects who are selected will undergoMRI scan with a 30 Tmagnetic resonance scanner (Siemens Germany) e 3D-T1WI scan parameters will be as follows repetition timeecho time 1900ms226ms slice thickness 1mm slicenumber 176 matrix size 128times128 and the view field256times 256mm2e BOLD-fMRI scanning parameters are asfollows repetition timeecho time 2000ms30ms flip angle90deg slice number 30 matrix size 128times128 view field240times 240mm2 slice thickness 5mm and total volume 240DTI data are as follows view field 240times 240mm2 repetitiontimeecho time 6800ms93ms matrix size 128times128 andslice thickness 3mm seamless Two diffusion-weightedsequences will be acquired using gradient values b 1000 smm2 and b 0 with diffusion-sensitizing gradients used in 64noncollinear directions

29 Data Management e clinical data will be managedwith printed and electronic CRFs CRFs will be enteredparallelly and will only be available to the outcome assessorse Evidence-based Medicine Center of the CDUTCM willbe responsible for monitoring the study and data every 3months

210 Statistical Analysis

2101 Clinical Data Analysis Clinical data will be analyzedby independent statisticians who do not know the testprocedure based on the principles of intention to treat (ITT)and per protocol e statistical significance threshold has p

value lt005 e results of the participants who failed tocomplete the study will be considered no different from thebaseline data in ITTanalysis All continuous variables will bepresented as meanplusmn standard deviation e categoricalvariables will be described in percentage () e clinicaldata in the two groups (FC group and HS group) will becompared with two-sample t-tests and the comparisons ofthe baseline and after intervention in each group will becompared with a paired sample t-test Nonparametric tests(MannndashWhitney U test) will be used to compare non-normally distributed clinical data and the χ2 test or Fisherrsquostest will be used to compare categorical variables

2102 Functional MRI Data Analysis For fMRI scans allpreprocessing steps will be performed using DPABI softwarebased on MATLAB e main analytical methods includethe amplitude of low-frequency fluctuation amplitude(ALFF) and seed-based functional connectivity

After preprocessing the data the ALFF will be calculatedto compare the whole-brain spontaneous activity patternbefore and after intervention in each group as well as be-tween patients with FC and HS following 10-week Tai Chipractices e different regions obtained at ALFF analysiswill be selected as the region of interest (ROI) also calledseed to perform the seed-based functional connectivityanalysis and to explore the functional synchronization ofROI and other regionse thresholds of plt 005 with a falsediscovery rate correlation will be applied to all analyses

4 Evidence-Based Complementary and Alternative Medicine

2103 Correlation Analysis To investigate the associationsbetween nonspecific effects and central responses underdifferent physical conditions we performed the correlationanalysis between the clinical data including motor functionrespiratory function psychological state and cerebralfunction in patients with FC and HS In order to furtherexplain the regulation mechanism of Tai Chi on the brain-gut interaction disorder the correlation analysis amonggastrointestinal symptoms heart rate variability and brainfunction activities in FC patients will also be carried out

2104 Safety Assessments Adverse events might happenduring Tai Chi practice including strain sprain nausea anddizziness If any these adverse events occur the instructorwill take appropriate treatment according to clinicianrsquosadvice and record the processing detail in the CRFs esafety assessments will be monitored by the EthicsCommittee

e schedule of the study including enrollment inter-ventions assessments and visits for participants is shown inTable 1

3 Discussion

As a popular physicalndashmind exercise Tai Chi is widely usedin the prevention treatment and rehabilitation of variousdiseases On the basis of the characteristics and relatedstudies on Tai Chi we put forward the original hypothesisthat Tai Chi practice can produce relative specific effects andnonspecific effects on the human body

e main purposes of this study include two aspectsFirst this study tries to explore the physiological andpsychological existence of the specific and nonspecific ef-fects of Tai Chi by comparing the differences in the motorfunction respiratory function gastrointestinal symptomspsychological manifestations and HRV between FC pa-tients and HS after Tai Chi practice Second this study triesto explore the potential central mechanism of the specificand nonspecific effects of Tai Chi practice by analyzing thepotential cerebral activity changes induced by Tai Chi andtheir correlation with clinical variables e study willprovide a new approach for investigating the mind-bodyexercise and the results might deepen our knowledge aboutTai Chi

31 Specific and Nonspecific Effects of Tai Chi Tai Chi is acomplex sport that requires the coordination of spiritbreathing postures and movements It can produce a sig-nificant impact on almost all human systems such as motorsystem cardiovascular system respiratory system and di-gestive system e impact is far beyond the physiologicaland psychological changes brought by a simple physicalexercise us Tai Chi is not only widely used in publichealthcare but also involved in disease treatment andrehabilitation

On the basis of the characteristics of Tai Chi andrelated studies we put forward that there are two types ofeffects of Tai Chi One is the specific effect which mainly

indicates the therapeutic effects of Tai Chi practice on thepathological status and has obvious disease orientationFor instance Tai Chi practice could produce a specific-regulating effect on the abnormal gastrointestinal (GI)function of patients with GI disorders specifically im-prove the cognitive function of patients with Alzheimerrsquosdisease [26] and significantly relieve the depressionsymptoms of patients with depression [27] A systematicreview and meta-analysis demonstrated that Tai Chi andother mind-body interventions were effective in allevi-ating GI symptoms and improving several aspects of thedisease-related QOL including interference with activitybody image health worry food avoidance and socialreaction [10]

e second aspect is the nonspecific effects whichmainly refers to the benefits for the motor system respi-ratory system and others No matter Tai Chi practice orother forms of physical exercises can produce it enonspecific effects might be a promoting effect on the motorsystem and respiratory system for not only the patients butalso the HS For example studies demonstrated that Tai Chiexercises could increase the muscle strength in the lowerextremities improve balance control and reduce the risk offalls for both healthy elderly people [28 29] and Parkinsonrsquosand stroke patients [30 31] However it should be em-phasized that the specific effects of Tai Chi are relative andconditional e nonspecific effects are the more widely usedand fundamental effect of Tai Chi

32 Potential Central Responses of Tai Chi As a typicalphysical and mental exercise Tai Chi not only emphasizesphysical movement but also requires the state of unity ofbody and mind e positive effects of meditation andaerobic exercise on cognitive function including memoryand decision-making abilities have been widely accepted[32 33] Recent studies further identified the influence of TaiChi practice on the cerebral structure and function ofpractitioners [34] For example MRI studies showed that TaiChi training evoked significant changes in the brain whitematter network [35] brain volume [36] and spontaneousbrain functional activities [37] in older people ese studiesindicated that Tai Chi practice could influence not only thecerebral function but also the brain structure It might be thecentral mechanism of the specific and nonspecific effects ofTai Chi

In this study FC patients will be enrolled to investigatethe specific effects of Tai Chi-modulating GI function FCas a typical FGID the dysfunction of the gut-brain axisplays an essential role in its pathogenesis [38] Recentneuroimaging studies identified the abnormality in thecerebral function and structure in FC patients comparedwith the healthy controls For example an fMRI studydemonstrated that FC patients showed significant dif-ferences in baseline brain activities in several brain re-gions implicated in emotional process modulationsomatic and sensory processing and motor control re-gions [39] Considering the existence of cerebral struc-tural and functional abnormalities in FC patients it is

Evidence-Based Complementary and Alternative Medicine 5

feasible to explore the mechanism of Tai Chirsquos specificeffects on GI function of FC patients

In this study fMRI will be selected as the neuroimagingtechnique to investigate the cerebral activity changes elicitedby Tai Chi practice fMRI is the most commonly used brainimaging technique and has been widely used in the studieson the central mechanism of Tai Chi intervention[35 40 41] For example using fMRI people found thatinfluencing the resting-state functional connectivity alter-ation between the cognitive control network and rostralanterior cingulate cortex and medial prefrontal cortex mightbe the central mechanism of Tai Chi intervention forfibromyalgia [41] ese studies indicated that it was reliable

to use fMRI to explore the central mechanism of Tai Chiintervention for FC

Furthermore to ensure the reliability and repeatabilityof the results we will establish a strict quality controlprogram which includes the participant selection the SOPof Tai Chi practice the SOP of neuroimaging scan and theoutcome measures For example for the selection of par-ticipants the freshmen who never practice Tai Chi and haveno physical exercise frequently will be taken into consid-eration In the implementation of Tai Chi intervention theSOP of 24-style Tai Chi is established which covers therequirement on the movements breathing and ideas of theparticipant

Table 1 Study period

Study period

Enrollment Allocation Postallocation

Timepointlowastlowast minus14 days minus7 days 0 day(baseline)

35 days(middle of intervention)

70 days(after intervention) Etc

EnrollmentEligibility screen 7

Informed consent 7

Demographics 7

Diagnosis 7

Past medical history 7

Physical examination 7

Allocation 7

InterventionsGroup A (FC patients) 7 7 7

Group B (HS) 7 7 7

AssessmentsBMI 7 7

HRV 7 7

Lower-extremity muscle 7 7 7

Functional balance 7 7 7

Vital capacity 7 7 7

Exercise self-rating scale 7 7 7

CCS 7 7 7

PAC-QOL 7 7 7

PAC-SYM 7 7 7

Stool diary 7 7 7

SDS SAS 7 7 7

EPQ 7 7 7

SF-36 7 7 7

MRI 7 7

Safety observationBlood routine test 7

Urine routine test 7

Stool routine test 7

Adverse events 7

is is a neuroimaging trial that includes a 2-week baseline period and a 10-week treatment period In the baseline period recruited patients will be screenedaccording to the inclusion criteria and exclusion criteria and then eligible FC patients and HS will sign an informed consent form and receive a physicalexamination After allocation the FC patients and HS will be recruited and will receive 10 weeks of Tai Chi exercise Schedule of enrollment interventionsand assessments at the baseline the median of intervention (5 weeks of exercise) and the end of the intervention (10 weeks of exercise) Among them lower-extremity muscle strength was measured using a hand-held isometric dynamometer (Micro FET3 Hoggan Health Industries) Functional balance testsinclude BBS TUG test and functional reach test During the vital capacity test FEV1 FVC and FEV1FVC ratio were measured using a MicroMedical SuperSpiro spirometer in resting status PEFR was assayed using a peak flowmetere stool diary CCS and PAC-SYMwill be used to evaluate the clinical efficacyof different interventions the PAC-QOL will be used to assess the health-related QOL the SDS SAS EPQ and Mini-Mental State Examinations will be usedto consider the effect of psychological factors on the patientsrsquo symptoms All participants will be assessed during the 24 h HRV to evaluate the autonomicnervous function at the baseline and the end of the 10-week intervention fMRI scans will be performed to detect the cerebral functional changes in 15 patientsin each group both at the baseline and the end of the intervention

6 Evidence-Based Complementary and Alternative Medicine

4 Conclusions

In conclusion Tai Chi is a safe and effective assistant therapy formany diseases However whether the therapeutic effects of TaiChi are disease-oriented remains uncertain is trial is the firstto investigate the existence of the specific and nonspecific effectsof Tai Chi and to explore their potential central responses It willprovide a new perspective for understanding Tai Chi and a newapproach for studying mind-body exercise

Abbreviations

HS Healthy subjectFC Functional constipationFGID Functional gastrointestinal diseaseQOL Quality of lifeGI GastrointestinalfMRI Functional magnetic resonance imagingCDUTCM Chengdu University of Traditional Chinese

MedicineCSBMs Complete spontaneous bowel movementsCCS Cleveland Constipation ScoreRPE Rating of perceived exertionPAC-SYM Patient Assessment of Constipation SymptomPAC-QOL Patient Assessment of Constipation Quality of

Life QuestionnaireRPE Rating of perceived exertionSF-36 e MOS 36-item short-form health surveyBBS Berg Balance ScaleTUG Timed up-and-goFEV1 Forced expiratory volume in one secondFVC Forced vital capacitySDS Self-Rating Depression ScaleSAS Self-Rating Anxiety ScaleEPQ Eysenck Personality QuestionnairesHRV Heart rate variability3D-T1WI 3-dimensional T1-weighted imagingBOLD-fMRI

Blood oxygenation level-dependent fMRI

DTI Diffusion tensor imagingCRF Case report formITT Intention to treatPP Per protocolReHo Regional homogeneityALFF Amplitude of low-frequency fluctuation

amplitude

Data Availability

is is a protocol for a clinical trial and no original data areincluded

Ethical Approval

e procedures have been approved by the Sichuan RegionalEthics Review Committee on Traditional Chinese Medicine(no 2018KL-047) and conformed to the Declaration ofHelsinki In addition all researchers were trained and signeda pledge to protect the confidentiality of study participants

Consent

All enrolled subjects signed an informed consent form

Disclosure

Tianyu Liu Yuke Teng and Sha Yang are the co-firstauthors

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Tianyu Liu Yuke Teng and Sha Yang contributed equally tothis article FZ and JW were responsible for this study TLYT SY FZ JW ZH and SY conceived and designed thestudy TL YT and SY participated in drafting the trialprotocol and preparing the manuscript YG TY JC and RYparticipated in data collection and were in charge of re-cruitment and treatment of patients All authors read andapproved the final manuscript

Acknowledgments

is study was supported by the Humanities and SocialSciences Youth Project of theMinistry of Education of China(19YJC890027) e trial was financially supported by theTen-ousand Talents Program of China (W02020595) andthe China Postdoctoral Science Foundation(2020M673562XB)

References

[1] C Lan J-S Lai S-Y Chen andM-K Wong ldquoTai Chi Chuanto improve muscular strength and endurance in elderly in-dividuals a pilot studyrdquo Archives of Physical Medicine andRehabilitation vol 81 no 5 pp 604ndash607 2000

[2] A M K Wong and C Lan ldquoTai Chi and balance controlrdquoMedicine and Sport Science vol 52 pp 115ndash123 2008

[3] L Sun L P Zhuang X Z Li J Zheng andW FWu ldquoTai Chican prevent cardiovascular disease and improve cardiopul-monary function of adults with obesity aged 50 years andolder a long-term follow-up studyrdquoMedicine vol 98 no 42Article ID e17509 2019

[4] C E Rogers L K Larkey and C Keller ldquoA review of clinicaltrials of Tai Chi and Qigong in older adultsrdquoWestern Journalof Nursing Research vol 31 no 2 pp 245ndash279 2009

[5] J H Yan W J Gu J Sun W X Zhang B W Li and L PanldquoEfficacy of Tai Chi on pain stiffness and function in patientswith osteoarthritis a meta-analysisrdquo PLoS One vol 8 no 4Article ID e61672 2013

[6] C Wang J P Collet and J Lau ldquoe effect of Tai Chi onhealth outcomes in patients with chronic conditions a sys-tematic reviewrdquo Archives of Internal Medicine vol 164 no 5pp 493ndash501 2004

[7] M Chao C Wang X Dong and M Ding ldquoe effects of taichi on type 2 diabetes mellitus a meta-analysisrdquo Journal ofDiabetes Research vol 2018 Article ID 7350567 9 pages2018

Evidence-Based Complementary and Alternative Medicine 7

[8] E Salmoirago-Blotcher P M Wayne S Dunsiger et al ldquoTaiChi is a promising exercise option for patients with coronaryheart disease declining cardiac rehabilitationrdquo Journal of theAmerican Heart Association vol 6 no 10 2017

[9] L Wang KWu X Chen and Q Liu ldquoe effects of tai chi onlung function exercise capacity and health related quality oflife for patients with chronic obstructive pulmonary disease apilot studyrdquo Heart Lung and Circulation vol 28 no 8pp 1206ndash1212 2019

[10] W Wang F Wang F Fan A C Sedas and J Wang ldquoMind-body interventions for irritable bowel syndrome patients inthe Chinese population a systematic review and meta-anal-ysisrdquo International Journal of Behavioral Medicine vol 24no 2 pp 191ndash204 2017

[11] Y Zhou L Liang L I Hong and L Jing ldquoAbout the con-valescent influence of 24-Pattern Shadowboxing to the pa-tients with chronic functional constipationrdquo Liaoning SportScience and Technology vol 2 pp 52ndash54 2015

[12] P Katelaris V Naganathan K Liu G Krassas andJ Gullotta ldquoComparison of the effectiveness of polyethyleneglycol with and without electrolytes in constipation a sys-tematic review and network meta-analysisrdquo BMC Gastroen-terology vol 16 no 1 p 42 2016

[13] S C Chow J Shao and H Wang Sample Size Calculations inClinical Research Wiley Hoboken NJ USA 2003

[14] D A Drossman and W L Hasler ldquoRome IV-functional GIdisorders disorders of gut-brain interactionrdquo Gastroenter-ology vol 150 no 6 pp 1257ndash1261 2016

[15] S Yang J Chen Y Guo et al ldquoComparison of Taiji andaerobic exercise for functional constipation study protocolfor a randomised controlled neuroimaging trialrdquo BMJ Openvol 9 no 8 Article ID e031089 2019

[16] K Berg S Wood-Dauphinee and J I Williams ldquoe balancescale reliability assessment with elderly residents and patientswith an acute strokerdquo Scandinavian Journal of RehabilitationMedicine vol 27 no 1 pp 27ndash36 1995

[17] P W Duncan D K Weiner J Chandler and S StudenskildquoFunctional reach a new clinical measure of balancerdquo Journalof Gerontology vol 45 no 6 pp M192ndashM197 1990

[18] W W K Zung ldquoA self-rating depression scalerdquo Archives ofGeneral Psychiatry vol 12 no 1 pp 63ndash70 1965

[19] W W K Zung ldquoA rating instrument for anxiety disordersrdquoPsychosomatics vol 12 no 6 pp 371ndash379 1971

[20] D Schuldberg ldquoEysenck personality questionnaire scales andpaper-and-pencil tests related to creativityrdquo PsychologicalReports vol 97 no 1 pp 180ndash182 2005

[21] F Agachan T Chen J Pfeifer P Reissman andS D Wexner ldquoA constipation scoring system to simplifyevaluation andmanagement of constipated patientsrdquoDiseasesof the Colon amp Rectum vol 39 no 6 pp 681ndash685 1996

[22] L Frank L Kleinman C Farup L Taylor and P Miner JrldquoPsychometric validation of a constipation symptom assess-ment questionnairerdquo Scandinavian Journal of Gastroenter-ology vol 34 no 9 pp 870ndash877 1999

[23] P Marquis C De La Loge D Dubois A McDermott andO Chassany ldquoDevelopment and validation of the patientAssessment of constipation quality of life questionnairerdquoScandinavian Journal of Gastroenterology vol 40 no 5pp 540ndash551 2005

[24] S Morishita A Tsubaki T Takabayashi and J B Fu ldquoRe-lationship between the rating of perceived exertion scale andthe load intensity of resistance trainingrdquo Strength and Con-ditioning Journal vol 40 no 2 pp 94ndash109 2018

[25] A Kelly J Rush E Shafonsky et al ldquoDetecting short-termchange and variation in health-related quality of life within-and between-person factor structure of the SF-36 healthsurveyrdquo Health and Quality of Life Outcomes vol 13 no 1p 199 2015

[26] P J Klein ldquoTai Chi Chuan in the management of Parkinsonrsquosdisease and Alzheimerrsquos diseaserdquo Medicine and Sport Sciencevol 52 pp 173ndash181 2008

[27] J Kong G Wilson J Park K Pereira C Walpole andA Yeung ldquoTreating depression with Tai Chi state of the artand future perspectivesrdquo Front Psychiatry vol 10 p 2372019

[28] W W N Tsang and C W Y Hui-Chan ldquoEffect of 4- and 8-wk intensive Tai Chi training on balance control in the el-derlyrdquoMedicine amp Science in Sports amp Exercise vol 36 no 4pp 648ndash657 2004

[29] Z G Huang Y H Feng Y H Li and C S Lv ldquoSystematicreview and meta-analysis Tai Chi for preventing falls in olderadultsrdquo BMJ Open vol 7 no 2 Article ID e013661 2017

[30] F Li P Harmer K Fitzgerald et al ldquoTai Chi and posturalstability in patients with Parkinsonrsquos diseaserdquo New EnglandJournal of Medicine vol 366 no 6 pp 511ndash519 2012

[31] I Hwang R Song S Ahn M-A Lee P M Wayne andM K Sohn ldquoExploring the adaptability of Tai Chi to strokerehabilitationrdquo Rehabilitation Nursing vol 44 no 4pp 221ndash229 2019

[32] S Deepeshwar S A Vinchurkar N K Visweswaraiah andH R Nagendra ldquoHemodynamic responses on prefrontalcortex related to meditation and attentional taskrdquo Frontiers inSystems Neuroscience vol 8 p 252 2014

[33] T Moriarty K Bourbeau B Bellovary and M N ZuhlldquoExercise intensity influences prefrontal cortex oxygenationduring cognitive testingrdquo Behavioral Sciences vol 9 no 8p 83 2019

[34] R Silveira R C R Prado C Brietzke et al ldquoPrefrontal cortexasymmetry and psychological responses to exercise a sys-tematic reviewrdquo Physiology amp Behavior vol 208 p 1125802019

[35] C Yue L Zou J Mei et al ldquoTai Chi training evokes sig-nificant changes in brain white matter network in olderwomenrdquo Healthcare vol 8 no 1 p 57 2020

[36] M Adcock M Fankhauser J Post et al ldquoEffects of an in-home multicomponent exergame training on physical func-tions cognition and brain volume of older adults a ran-domized controlled trialrdquo Frontiers in Medicine vol 6 p 3212019

[37] Z Zheng X Zhu S Yin et al ldquoCombined cognitive-psy-chological-physical intervention induces reorganization ofintrinsic functional brain architecture in older adultsrdquo NeuralPlasticity vol 2015 Article ID 713104 11 pages 2015

[38] M Equit J Niemczyk A Kluth C omas M Rubly andA von Gontard ldquoCentral nervous system processing ofemotions in children with fecal incontinence and con-stipationrdquo Zeitschrift fur Kinder- und Jugendpsychiatrie undPsychotherapie vol 47 no 1 pp 67ndash71 2019

[39] Q Zhu W Cai J Zheng et al ldquoDistinct resting-state brainactivity in patients with functional constipationrdquo Neurosci-ence Letters vol 632 pp 141ndash146 2016

[40] J Kong E Wolcott Z Wang et al ldquoAltered resting statefunctional connectivity of the cognitive control network infibromyalgia and the modulation effect of mind-body inter-ventionrdquo Brain Imaging and Behavior vol 13 no 2pp 482ndash492 2019

8 Evidence-Based Complementary and Alternative Medicine

[41] R Jalilianhasanpour E Beheshtian G Sherbaf S Sahraianand H I Sair ldquoFunctional connectivity in neurodegenerativedisorders Alzheimerrsquos disease and frontotemporal dementiardquoTopics in Magnetic Resonance Imaging vol 28 no 6pp 317ndash324 2019

Evidence-Based Complementary and Alternative Medicine 9

Page 5: TheSpecificandNonspecificEffectsofTaiChiandItsPossible ...the intervention. e metrics of HRV include standard deviation of NN intervals (SDNN), standard deviation of sequential 5-min

2103 Correlation Analysis To investigate the associationsbetween nonspecific effects and central responses underdifferent physical conditions we performed the correlationanalysis between the clinical data including motor functionrespiratory function psychological state and cerebralfunction in patients with FC and HS In order to furtherexplain the regulation mechanism of Tai Chi on the brain-gut interaction disorder the correlation analysis amonggastrointestinal symptoms heart rate variability and brainfunction activities in FC patients will also be carried out

2104 Safety Assessments Adverse events might happenduring Tai Chi practice including strain sprain nausea anddizziness If any these adverse events occur the instructorwill take appropriate treatment according to clinicianrsquosadvice and record the processing detail in the CRFs esafety assessments will be monitored by the EthicsCommittee

e schedule of the study including enrollment inter-ventions assessments and visits for participants is shown inTable 1

3 Discussion

As a popular physicalndashmind exercise Tai Chi is widely usedin the prevention treatment and rehabilitation of variousdiseases On the basis of the characteristics and relatedstudies on Tai Chi we put forward the original hypothesisthat Tai Chi practice can produce relative specific effects andnonspecific effects on the human body

e main purposes of this study include two aspectsFirst this study tries to explore the physiological andpsychological existence of the specific and nonspecific ef-fects of Tai Chi by comparing the differences in the motorfunction respiratory function gastrointestinal symptomspsychological manifestations and HRV between FC pa-tients and HS after Tai Chi practice Second this study triesto explore the potential central mechanism of the specificand nonspecific effects of Tai Chi practice by analyzing thepotential cerebral activity changes induced by Tai Chi andtheir correlation with clinical variables e study willprovide a new approach for investigating the mind-bodyexercise and the results might deepen our knowledge aboutTai Chi

31 Specific and Nonspecific Effects of Tai Chi Tai Chi is acomplex sport that requires the coordination of spiritbreathing postures and movements It can produce a sig-nificant impact on almost all human systems such as motorsystem cardiovascular system respiratory system and di-gestive system e impact is far beyond the physiologicaland psychological changes brought by a simple physicalexercise us Tai Chi is not only widely used in publichealthcare but also involved in disease treatment andrehabilitation

On the basis of the characteristics of Tai Chi andrelated studies we put forward that there are two types ofeffects of Tai Chi One is the specific effect which mainly

indicates the therapeutic effects of Tai Chi practice on thepathological status and has obvious disease orientationFor instance Tai Chi practice could produce a specific-regulating effect on the abnormal gastrointestinal (GI)function of patients with GI disorders specifically im-prove the cognitive function of patients with Alzheimerrsquosdisease [26] and significantly relieve the depressionsymptoms of patients with depression [27] A systematicreview and meta-analysis demonstrated that Tai Chi andother mind-body interventions were effective in allevi-ating GI symptoms and improving several aspects of thedisease-related QOL including interference with activitybody image health worry food avoidance and socialreaction [10]

e second aspect is the nonspecific effects whichmainly refers to the benefits for the motor system respi-ratory system and others No matter Tai Chi practice orother forms of physical exercises can produce it enonspecific effects might be a promoting effect on the motorsystem and respiratory system for not only the patients butalso the HS For example studies demonstrated that Tai Chiexercises could increase the muscle strength in the lowerextremities improve balance control and reduce the risk offalls for both healthy elderly people [28 29] and Parkinsonrsquosand stroke patients [30 31] However it should be em-phasized that the specific effects of Tai Chi are relative andconditional e nonspecific effects are the more widely usedand fundamental effect of Tai Chi

32 Potential Central Responses of Tai Chi As a typicalphysical and mental exercise Tai Chi not only emphasizesphysical movement but also requires the state of unity ofbody and mind e positive effects of meditation andaerobic exercise on cognitive function including memoryand decision-making abilities have been widely accepted[32 33] Recent studies further identified the influence of TaiChi practice on the cerebral structure and function ofpractitioners [34] For example MRI studies showed that TaiChi training evoked significant changes in the brain whitematter network [35] brain volume [36] and spontaneousbrain functional activities [37] in older people ese studiesindicated that Tai Chi practice could influence not only thecerebral function but also the brain structure It might be thecentral mechanism of the specific and nonspecific effects ofTai Chi

In this study FC patients will be enrolled to investigatethe specific effects of Tai Chi-modulating GI function FCas a typical FGID the dysfunction of the gut-brain axisplays an essential role in its pathogenesis [38] Recentneuroimaging studies identified the abnormality in thecerebral function and structure in FC patients comparedwith the healthy controls For example an fMRI studydemonstrated that FC patients showed significant dif-ferences in baseline brain activities in several brain re-gions implicated in emotional process modulationsomatic and sensory processing and motor control re-gions [39] Considering the existence of cerebral struc-tural and functional abnormalities in FC patients it is

Evidence-Based Complementary and Alternative Medicine 5

feasible to explore the mechanism of Tai Chirsquos specificeffects on GI function of FC patients

In this study fMRI will be selected as the neuroimagingtechnique to investigate the cerebral activity changes elicitedby Tai Chi practice fMRI is the most commonly used brainimaging technique and has been widely used in the studieson the central mechanism of Tai Chi intervention[35 40 41] For example using fMRI people found thatinfluencing the resting-state functional connectivity alter-ation between the cognitive control network and rostralanterior cingulate cortex and medial prefrontal cortex mightbe the central mechanism of Tai Chi intervention forfibromyalgia [41] ese studies indicated that it was reliable

to use fMRI to explore the central mechanism of Tai Chiintervention for FC

Furthermore to ensure the reliability and repeatabilityof the results we will establish a strict quality controlprogram which includes the participant selection the SOPof Tai Chi practice the SOP of neuroimaging scan and theoutcome measures For example for the selection of par-ticipants the freshmen who never practice Tai Chi and haveno physical exercise frequently will be taken into consid-eration In the implementation of Tai Chi intervention theSOP of 24-style Tai Chi is established which covers therequirement on the movements breathing and ideas of theparticipant

Table 1 Study period

Study period

Enrollment Allocation Postallocation

Timepointlowastlowast minus14 days minus7 days 0 day(baseline)

35 days(middle of intervention)

70 days(after intervention) Etc

EnrollmentEligibility screen 7

Informed consent 7

Demographics 7

Diagnosis 7

Past medical history 7

Physical examination 7

Allocation 7

InterventionsGroup A (FC patients) 7 7 7

Group B (HS) 7 7 7

AssessmentsBMI 7 7

HRV 7 7

Lower-extremity muscle 7 7 7

Functional balance 7 7 7

Vital capacity 7 7 7

Exercise self-rating scale 7 7 7

CCS 7 7 7

PAC-QOL 7 7 7

PAC-SYM 7 7 7

Stool diary 7 7 7

SDS SAS 7 7 7

EPQ 7 7 7

SF-36 7 7 7

MRI 7 7

Safety observationBlood routine test 7

Urine routine test 7

Stool routine test 7

Adverse events 7

is is a neuroimaging trial that includes a 2-week baseline period and a 10-week treatment period In the baseline period recruited patients will be screenedaccording to the inclusion criteria and exclusion criteria and then eligible FC patients and HS will sign an informed consent form and receive a physicalexamination After allocation the FC patients and HS will be recruited and will receive 10 weeks of Tai Chi exercise Schedule of enrollment interventionsand assessments at the baseline the median of intervention (5 weeks of exercise) and the end of the intervention (10 weeks of exercise) Among them lower-extremity muscle strength was measured using a hand-held isometric dynamometer (Micro FET3 Hoggan Health Industries) Functional balance testsinclude BBS TUG test and functional reach test During the vital capacity test FEV1 FVC and FEV1FVC ratio were measured using a MicroMedical SuperSpiro spirometer in resting status PEFR was assayed using a peak flowmetere stool diary CCS and PAC-SYMwill be used to evaluate the clinical efficacyof different interventions the PAC-QOL will be used to assess the health-related QOL the SDS SAS EPQ and Mini-Mental State Examinations will be usedto consider the effect of psychological factors on the patientsrsquo symptoms All participants will be assessed during the 24 h HRV to evaluate the autonomicnervous function at the baseline and the end of the 10-week intervention fMRI scans will be performed to detect the cerebral functional changes in 15 patientsin each group both at the baseline and the end of the intervention

6 Evidence-Based Complementary and Alternative Medicine

4 Conclusions

In conclusion Tai Chi is a safe and effective assistant therapy formany diseases However whether the therapeutic effects of TaiChi are disease-oriented remains uncertain is trial is the firstto investigate the existence of the specific and nonspecific effectsof Tai Chi and to explore their potential central responses It willprovide a new perspective for understanding Tai Chi and a newapproach for studying mind-body exercise

Abbreviations

HS Healthy subjectFC Functional constipationFGID Functional gastrointestinal diseaseQOL Quality of lifeGI GastrointestinalfMRI Functional magnetic resonance imagingCDUTCM Chengdu University of Traditional Chinese

MedicineCSBMs Complete spontaneous bowel movementsCCS Cleveland Constipation ScoreRPE Rating of perceived exertionPAC-SYM Patient Assessment of Constipation SymptomPAC-QOL Patient Assessment of Constipation Quality of

Life QuestionnaireRPE Rating of perceived exertionSF-36 e MOS 36-item short-form health surveyBBS Berg Balance ScaleTUG Timed up-and-goFEV1 Forced expiratory volume in one secondFVC Forced vital capacitySDS Self-Rating Depression ScaleSAS Self-Rating Anxiety ScaleEPQ Eysenck Personality QuestionnairesHRV Heart rate variability3D-T1WI 3-dimensional T1-weighted imagingBOLD-fMRI

Blood oxygenation level-dependent fMRI

DTI Diffusion tensor imagingCRF Case report formITT Intention to treatPP Per protocolReHo Regional homogeneityALFF Amplitude of low-frequency fluctuation

amplitude

Data Availability

is is a protocol for a clinical trial and no original data areincluded

Ethical Approval

e procedures have been approved by the Sichuan RegionalEthics Review Committee on Traditional Chinese Medicine(no 2018KL-047) and conformed to the Declaration ofHelsinki In addition all researchers were trained and signeda pledge to protect the confidentiality of study participants

Consent

All enrolled subjects signed an informed consent form

Disclosure

Tianyu Liu Yuke Teng and Sha Yang are the co-firstauthors

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Tianyu Liu Yuke Teng and Sha Yang contributed equally tothis article FZ and JW were responsible for this study TLYT SY FZ JW ZH and SY conceived and designed thestudy TL YT and SY participated in drafting the trialprotocol and preparing the manuscript YG TY JC and RYparticipated in data collection and were in charge of re-cruitment and treatment of patients All authors read andapproved the final manuscript

Acknowledgments

is study was supported by the Humanities and SocialSciences Youth Project of theMinistry of Education of China(19YJC890027) e trial was financially supported by theTen-ousand Talents Program of China (W02020595) andthe China Postdoctoral Science Foundation(2020M673562XB)

References

[1] C Lan J-S Lai S-Y Chen andM-K Wong ldquoTai Chi Chuanto improve muscular strength and endurance in elderly in-dividuals a pilot studyrdquo Archives of Physical Medicine andRehabilitation vol 81 no 5 pp 604ndash607 2000

[2] A M K Wong and C Lan ldquoTai Chi and balance controlrdquoMedicine and Sport Science vol 52 pp 115ndash123 2008

[3] L Sun L P Zhuang X Z Li J Zheng andW FWu ldquoTai Chican prevent cardiovascular disease and improve cardiopul-monary function of adults with obesity aged 50 years andolder a long-term follow-up studyrdquoMedicine vol 98 no 42Article ID e17509 2019

[4] C E Rogers L K Larkey and C Keller ldquoA review of clinicaltrials of Tai Chi and Qigong in older adultsrdquoWestern Journalof Nursing Research vol 31 no 2 pp 245ndash279 2009

[5] J H Yan W J Gu J Sun W X Zhang B W Li and L PanldquoEfficacy of Tai Chi on pain stiffness and function in patientswith osteoarthritis a meta-analysisrdquo PLoS One vol 8 no 4Article ID e61672 2013

[6] C Wang J P Collet and J Lau ldquoe effect of Tai Chi onhealth outcomes in patients with chronic conditions a sys-tematic reviewrdquo Archives of Internal Medicine vol 164 no 5pp 493ndash501 2004

[7] M Chao C Wang X Dong and M Ding ldquoe effects of taichi on type 2 diabetes mellitus a meta-analysisrdquo Journal ofDiabetes Research vol 2018 Article ID 7350567 9 pages2018

Evidence-Based Complementary and Alternative Medicine 7

[8] E Salmoirago-Blotcher P M Wayne S Dunsiger et al ldquoTaiChi is a promising exercise option for patients with coronaryheart disease declining cardiac rehabilitationrdquo Journal of theAmerican Heart Association vol 6 no 10 2017

[9] L Wang KWu X Chen and Q Liu ldquoe effects of tai chi onlung function exercise capacity and health related quality oflife for patients with chronic obstructive pulmonary disease apilot studyrdquo Heart Lung and Circulation vol 28 no 8pp 1206ndash1212 2019

[10] W Wang F Wang F Fan A C Sedas and J Wang ldquoMind-body interventions for irritable bowel syndrome patients inthe Chinese population a systematic review and meta-anal-ysisrdquo International Journal of Behavioral Medicine vol 24no 2 pp 191ndash204 2017

[11] Y Zhou L Liang L I Hong and L Jing ldquoAbout the con-valescent influence of 24-Pattern Shadowboxing to the pa-tients with chronic functional constipationrdquo Liaoning SportScience and Technology vol 2 pp 52ndash54 2015

[12] P Katelaris V Naganathan K Liu G Krassas andJ Gullotta ldquoComparison of the effectiveness of polyethyleneglycol with and without electrolytes in constipation a sys-tematic review and network meta-analysisrdquo BMC Gastroen-terology vol 16 no 1 p 42 2016

[13] S C Chow J Shao and H Wang Sample Size Calculations inClinical Research Wiley Hoboken NJ USA 2003

[14] D A Drossman and W L Hasler ldquoRome IV-functional GIdisorders disorders of gut-brain interactionrdquo Gastroenter-ology vol 150 no 6 pp 1257ndash1261 2016

[15] S Yang J Chen Y Guo et al ldquoComparison of Taiji andaerobic exercise for functional constipation study protocolfor a randomised controlled neuroimaging trialrdquo BMJ Openvol 9 no 8 Article ID e031089 2019

[16] K Berg S Wood-Dauphinee and J I Williams ldquoe balancescale reliability assessment with elderly residents and patientswith an acute strokerdquo Scandinavian Journal of RehabilitationMedicine vol 27 no 1 pp 27ndash36 1995

[17] P W Duncan D K Weiner J Chandler and S StudenskildquoFunctional reach a new clinical measure of balancerdquo Journalof Gerontology vol 45 no 6 pp M192ndashM197 1990

[18] W W K Zung ldquoA self-rating depression scalerdquo Archives ofGeneral Psychiatry vol 12 no 1 pp 63ndash70 1965

[19] W W K Zung ldquoA rating instrument for anxiety disordersrdquoPsychosomatics vol 12 no 6 pp 371ndash379 1971

[20] D Schuldberg ldquoEysenck personality questionnaire scales andpaper-and-pencil tests related to creativityrdquo PsychologicalReports vol 97 no 1 pp 180ndash182 2005

[21] F Agachan T Chen J Pfeifer P Reissman andS D Wexner ldquoA constipation scoring system to simplifyevaluation andmanagement of constipated patientsrdquoDiseasesof the Colon amp Rectum vol 39 no 6 pp 681ndash685 1996

[22] L Frank L Kleinman C Farup L Taylor and P Miner JrldquoPsychometric validation of a constipation symptom assess-ment questionnairerdquo Scandinavian Journal of Gastroenter-ology vol 34 no 9 pp 870ndash877 1999

[23] P Marquis C De La Loge D Dubois A McDermott andO Chassany ldquoDevelopment and validation of the patientAssessment of constipation quality of life questionnairerdquoScandinavian Journal of Gastroenterology vol 40 no 5pp 540ndash551 2005

[24] S Morishita A Tsubaki T Takabayashi and J B Fu ldquoRe-lationship between the rating of perceived exertion scale andthe load intensity of resistance trainingrdquo Strength and Con-ditioning Journal vol 40 no 2 pp 94ndash109 2018

[25] A Kelly J Rush E Shafonsky et al ldquoDetecting short-termchange and variation in health-related quality of life within-and between-person factor structure of the SF-36 healthsurveyrdquo Health and Quality of Life Outcomes vol 13 no 1p 199 2015

[26] P J Klein ldquoTai Chi Chuan in the management of Parkinsonrsquosdisease and Alzheimerrsquos diseaserdquo Medicine and Sport Sciencevol 52 pp 173ndash181 2008

[27] J Kong G Wilson J Park K Pereira C Walpole andA Yeung ldquoTreating depression with Tai Chi state of the artand future perspectivesrdquo Front Psychiatry vol 10 p 2372019

[28] W W N Tsang and C W Y Hui-Chan ldquoEffect of 4- and 8-wk intensive Tai Chi training on balance control in the el-derlyrdquoMedicine amp Science in Sports amp Exercise vol 36 no 4pp 648ndash657 2004

[29] Z G Huang Y H Feng Y H Li and C S Lv ldquoSystematicreview and meta-analysis Tai Chi for preventing falls in olderadultsrdquo BMJ Open vol 7 no 2 Article ID e013661 2017

[30] F Li P Harmer K Fitzgerald et al ldquoTai Chi and posturalstability in patients with Parkinsonrsquos diseaserdquo New EnglandJournal of Medicine vol 366 no 6 pp 511ndash519 2012

[31] I Hwang R Song S Ahn M-A Lee P M Wayne andM K Sohn ldquoExploring the adaptability of Tai Chi to strokerehabilitationrdquo Rehabilitation Nursing vol 44 no 4pp 221ndash229 2019

[32] S Deepeshwar S A Vinchurkar N K Visweswaraiah andH R Nagendra ldquoHemodynamic responses on prefrontalcortex related to meditation and attentional taskrdquo Frontiers inSystems Neuroscience vol 8 p 252 2014

[33] T Moriarty K Bourbeau B Bellovary and M N ZuhlldquoExercise intensity influences prefrontal cortex oxygenationduring cognitive testingrdquo Behavioral Sciences vol 9 no 8p 83 2019

[34] R Silveira R C R Prado C Brietzke et al ldquoPrefrontal cortexasymmetry and psychological responses to exercise a sys-tematic reviewrdquo Physiology amp Behavior vol 208 p 1125802019

[35] C Yue L Zou J Mei et al ldquoTai Chi training evokes sig-nificant changes in brain white matter network in olderwomenrdquo Healthcare vol 8 no 1 p 57 2020

[36] M Adcock M Fankhauser J Post et al ldquoEffects of an in-home multicomponent exergame training on physical func-tions cognition and brain volume of older adults a ran-domized controlled trialrdquo Frontiers in Medicine vol 6 p 3212019

[37] Z Zheng X Zhu S Yin et al ldquoCombined cognitive-psy-chological-physical intervention induces reorganization ofintrinsic functional brain architecture in older adultsrdquo NeuralPlasticity vol 2015 Article ID 713104 11 pages 2015

[38] M Equit J Niemczyk A Kluth C omas M Rubly andA von Gontard ldquoCentral nervous system processing ofemotions in children with fecal incontinence and con-stipationrdquo Zeitschrift fur Kinder- und Jugendpsychiatrie undPsychotherapie vol 47 no 1 pp 67ndash71 2019

[39] Q Zhu W Cai J Zheng et al ldquoDistinct resting-state brainactivity in patients with functional constipationrdquo Neurosci-ence Letters vol 632 pp 141ndash146 2016

[40] J Kong E Wolcott Z Wang et al ldquoAltered resting statefunctional connectivity of the cognitive control network infibromyalgia and the modulation effect of mind-body inter-ventionrdquo Brain Imaging and Behavior vol 13 no 2pp 482ndash492 2019

8 Evidence-Based Complementary and Alternative Medicine

[41] R Jalilianhasanpour E Beheshtian G Sherbaf S Sahraianand H I Sair ldquoFunctional connectivity in neurodegenerativedisorders Alzheimerrsquos disease and frontotemporal dementiardquoTopics in Magnetic Resonance Imaging vol 28 no 6pp 317ndash324 2019

Evidence-Based Complementary and Alternative Medicine 9

Page 6: TheSpecificandNonspecificEffectsofTaiChiandItsPossible ...the intervention. e metrics of HRV include standard deviation of NN intervals (SDNN), standard deviation of sequential 5-min

feasible to explore the mechanism of Tai Chirsquos specificeffects on GI function of FC patients

In this study fMRI will be selected as the neuroimagingtechnique to investigate the cerebral activity changes elicitedby Tai Chi practice fMRI is the most commonly used brainimaging technique and has been widely used in the studieson the central mechanism of Tai Chi intervention[35 40 41] For example using fMRI people found thatinfluencing the resting-state functional connectivity alter-ation between the cognitive control network and rostralanterior cingulate cortex and medial prefrontal cortex mightbe the central mechanism of Tai Chi intervention forfibromyalgia [41] ese studies indicated that it was reliable

to use fMRI to explore the central mechanism of Tai Chiintervention for FC

Furthermore to ensure the reliability and repeatabilityof the results we will establish a strict quality controlprogram which includes the participant selection the SOPof Tai Chi practice the SOP of neuroimaging scan and theoutcome measures For example for the selection of par-ticipants the freshmen who never practice Tai Chi and haveno physical exercise frequently will be taken into consid-eration In the implementation of Tai Chi intervention theSOP of 24-style Tai Chi is established which covers therequirement on the movements breathing and ideas of theparticipant

Table 1 Study period

Study period

Enrollment Allocation Postallocation

Timepointlowastlowast minus14 days minus7 days 0 day(baseline)

35 days(middle of intervention)

70 days(after intervention) Etc

EnrollmentEligibility screen 7

Informed consent 7

Demographics 7

Diagnosis 7

Past medical history 7

Physical examination 7

Allocation 7

InterventionsGroup A (FC patients) 7 7 7

Group B (HS) 7 7 7

AssessmentsBMI 7 7

HRV 7 7

Lower-extremity muscle 7 7 7

Functional balance 7 7 7

Vital capacity 7 7 7

Exercise self-rating scale 7 7 7

CCS 7 7 7

PAC-QOL 7 7 7

PAC-SYM 7 7 7

Stool diary 7 7 7

SDS SAS 7 7 7

EPQ 7 7 7

SF-36 7 7 7

MRI 7 7

Safety observationBlood routine test 7

Urine routine test 7

Stool routine test 7

Adverse events 7

is is a neuroimaging trial that includes a 2-week baseline period and a 10-week treatment period In the baseline period recruited patients will be screenedaccording to the inclusion criteria and exclusion criteria and then eligible FC patients and HS will sign an informed consent form and receive a physicalexamination After allocation the FC patients and HS will be recruited and will receive 10 weeks of Tai Chi exercise Schedule of enrollment interventionsand assessments at the baseline the median of intervention (5 weeks of exercise) and the end of the intervention (10 weeks of exercise) Among them lower-extremity muscle strength was measured using a hand-held isometric dynamometer (Micro FET3 Hoggan Health Industries) Functional balance testsinclude BBS TUG test and functional reach test During the vital capacity test FEV1 FVC and FEV1FVC ratio were measured using a MicroMedical SuperSpiro spirometer in resting status PEFR was assayed using a peak flowmetere stool diary CCS and PAC-SYMwill be used to evaluate the clinical efficacyof different interventions the PAC-QOL will be used to assess the health-related QOL the SDS SAS EPQ and Mini-Mental State Examinations will be usedto consider the effect of psychological factors on the patientsrsquo symptoms All participants will be assessed during the 24 h HRV to evaluate the autonomicnervous function at the baseline and the end of the 10-week intervention fMRI scans will be performed to detect the cerebral functional changes in 15 patientsin each group both at the baseline and the end of the intervention

6 Evidence-Based Complementary and Alternative Medicine

4 Conclusions

In conclusion Tai Chi is a safe and effective assistant therapy formany diseases However whether the therapeutic effects of TaiChi are disease-oriented remains uncertain is trial is the firstto investigate the existence of the specific and nonspecific effectsof Tai Chi and to explore their potential central responses It willprovide a new perspective for understanding Tai Chi and a newapproach for studying mind-body exercise

Abbreviations

HS Healthy subjectFC Functional constipationFGID Functional gastrointestinal diseaseQOL Quality of lifeGI GastrointestinalfMRI Functional magnetic resonance imagingCDUTCM Chengdu University of Traditional Chinese

MedicineCSBMs Complete spontaneous bowel movementsCCS Cleveland Constipation ScoreRPE Rating of perceived exertionPAC-SYM Patient Assessment of Constipation SymptomPAC-QOL Patient Assessment of Constipation Quality of

Life QuestionnaireRPE Rating of perceived exertionSF-36 e MOS 36-item short-form health surveyBBS Berg Balance ScaleTUG Timed up-and-goFEV1 Forced expiratory volume in one secondFVC Forced vital capacitySDS Self-Rating Depression ScaleSAS Self-Rating Anxiety ScaleEPQ Eysenck Personality QuestionnairesHRV Heart rate variability3D-T1WI 3-dimensional T1-weighted imagingBOLD-fMRI

Blood oxygenation level-dependent fMRI

DTI Diffusion tensor imagingCRF Case report formITT Intention to treatPP Per protocolReHo Regional homogeneityALFF Amplitude of low-frequency fluctuation

amplitude

Data Availability

is is a protocol for a clinical trial and no original data areincluded

Ethical Approval

e procedures have been approved by the Sichuan RegionalEthics Review Committee on Traditional Chinese Medicine(no 2018KL-047) and conformed to the Declaration ofHelsinki In addition all researchers were trained and signeda pledge to protect the confidentiality of study participants

Consent

All enrolled subjects signed an informed consent form

Disclosure

Tianyu Liu Yuke Teng and Sha Yang are the co-firstauthors

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Tianyu Liu Yuke Teng and Sha Yang contributed equally tothis article FZ and JW were responsible for this study TLYT SY FZ JW ZH and SY conceived and designed thestudy TL YT and SY participated in drafting the trialprotocol and preparing the manuscript YG TY JC and RYparticipated in data collection and were in charge of re-cruitment and treatment of patients All authors read andapproved the final manuscript

Acknowledgments

is study was supported by the Humanities and SocialSciences Youth Project of theMinistry of Education of China(19YJC890027) e trial was financially supported by theTen-ousand Talents Program of China (W02020595) andthe China Postdoctoral Science Foundation(2020M673562XB)

References

[1] C Lan J-S Lai S-Y Chen andM-K Wong ldquoTai Chi Chuanto improve muscular strength and endurance in elderly in-dividuals a pilot studyrdquo Archives of Physical Medicine andRehabilitation vol 81 no 5 pp 604ndash607 2000

[2] A M K Wong and C Lan ldquoTai Chi and balance controlrdquoMedicine and Sport Science vol 52 pp 115ndash123 2008

[3] L Sun L P Zhuang X Z Li J Zheng andW FWu ldquoTai Chican prevent cardiovascular disease and improve cardiopul-monary function of adults with obesity aged 50 years andolder a long-term follow-up studyrdquoMedicine vol 98 no 42Article ID e17509 2019

[4] C E Rogers L K Larkey and C Keller ldquoA review of clinicaltrials of Tai Chi and Qigong in older adultsrdquoWestern Journalof Nursing Research vol 31 no 2 pp 245ndash279 2009

[5] J H Yan W J Gu J Sun W X Zhang B W Li and L PanldquoEfficacy of Tai Chi on pain stiffness and function in patientswith osteoarthritis a meta-analysisrdquo PLoS One vol 8 no 4Article ID e61672 2013

[6] C Wang J P Collet and J Lau ldquoe effect of Tai Chi onhealth outcomes in patients with chronic conditions a sys-tematic reviewrdquo Archives of Internal Medicine vol 164 no 5pp 493ndash501 2004

[7] M Chao C Wang X Dong and M Ding ldquoe effects of taichi on type 2 diabetes mellitus a meta-analysisrdquo Journal ofDiabetes Research vol 2018 Article ID 7350567 9 pages2018

Evidence-Based Complementary and Alternative Medicine 7

[8] E Salmoirago-Blotcher P M Wayne S Dunsiger et al ldquoTaiChi is a promising exercise option for patients with coronaryheart disease declining cardiac rehabilitationrdquo Journal of theAmerican Heart Association vol 6 no 10 2017

[9] L Wang KWu X Chen and Q Liu ldquoe effects of tai chi onlung function exercise capacity and health related quality oflife for patients with chronic obstructive pulmonary disease apilot studyrdquo Heart Lung and Circulation vol 28 no 8pp 1206ndash1212 2019

[10] W Wang F Wang F Fan A C Sedas and J Wang ldquoMind-body interventions for irritable bowel syndrome patients inthe Chinese population a systematic review and meta-anal-ysisrdquo International Journal of Behavioral Medicine vol 24no 2 pp 191ndash204 2017

[11] Y Zhou L Liang L I Hong and L Jing ldquoAbout the con-valescent influence of 24-Pattern Shadowboxing to the pa-tients with chronic functional constipationrdquo Liaoning SportScience and Technology vol 2 pp 52ndash54 2015

[12] P Katelaris V Naganathan K Liu G Krassas andJ Gullotta ldquoComparison of the effectiveness of polyethyleneglycol with and without electrolytes in constipation a sys-tematic review and network meta-analysisrdquo BMC Gastroen-terology vol 16 no 1 p 42 2016

[13] S C Chow J Shao and H Wang Sample Size Calculations inClinical Research Wiley Hoboken NJ USA 2003

[14] D A Drossman and W L Hasler ldquoRome IV-functional GIdisorders disorders of gut-brain interactionrdquo Gastroenter-ology vol 150 no 6 pp 1257ndash1261 2016

[15] S Yang J Chen Y Guo et al ldquoComparison of Taiji andaerobic exercise for functional constipation study protocolfor a randomised controlled neuroimaging trialrdquo BMJ Openvol 9 no 8 Article ID e031089 2019

[16] K Berg S Wood-Dauphinee and J I Williams ldquoe balancescale reliability assessment with elderly residents and patientswith an acute strokerdquo Scandinavian Journal of RehabilitationMedicine vol 27 no 1 pp 27ndash36 1995

[17] P W Duncan D K Weiner J Chandler and S StudenskildquoFunctional reach a new clinical measure of balancerdquo Journalof Gerontology vol 45 no 6 pp M192ndashM197 1990

[18] W W K Zung ldquoA self-rating depression scalerdquo Archives ofGeneral Psychiatry vol 12 no 1 pp 63ndash70 1965

[19] W W K Zung ldquoA rating instrument for anxiety disordersrdquoPsychosomatics vol 12 no 6 pp 371ndash379 1971

[20] D Schuldberg ldquoEysenck personality questionnaire scales andpaper-and-pencil tests related to creativityrdquo PsychologicalReports vol 97 no 1 pp 180ndash182 2005

[21] F Agachan T Chen J Pfeifer P Reissman andS D Wexner ldquoA constipation scoring system to simplifyevaluation andmanagement of constipated patientsrdquoDiseasesof the Colon amp Rectum vol 39 no 6 pp 681ndash685 1996

[22] L Frank L Kleinman C Farup L Taylor and P Miner JrldquoPsychometric validation of a constipation symptom assess-ment questionnairerdquo Scandinavian Journal of Gastroenter-ology vol 34 no 9 pp 870ndash877 1999

[23] P Marquis C De La Loge D Dubois A McDermott andO Chassany ldquoDevelopment and validation of the patientAssessment of constipation quality of life questionnairerdquoScandinavian Journal of Gastroenterology vol 40 no 5pp 540ndash551 2005

[24] S Morishita A Tsubaki T Takabayashi and J B Fu ldquoRe-lationship between the rating of perceived exertion scale andthe load intensity of resistance trainingrdquo Strength and Con-ditioning Journal vol 40 no 2 pp 94ndash109 2018

[25] A Kelly J Rush E Shafonsky et al ldquoDetecting short-termchange and variation in health-related quality of life within-and between-person factor structure of the SF-36 healthsurveyrdquo Health and Quality of Life Outcomes vol 13 no 1p 199 2015

[26] P J Klein ldquoTai Chi Chuan in the management of Parkinsonrsquosdisease and Alzheimerrsquos diseaserdquo Medicine and Sport Sciencevol 52 pp 173ndash181 2008

[27] J Kong G Wilson J Park K Pereira C Walpole andA Yeung ldquoTreating depression with Tai Chi state of the artand future perspectivesrdquo Front Psychiatry vol 10 p 2372019

[28] W W N Tsang and C W Y Hui-Chan ldquoEffect of 4- and 8-wk intensive Tai Chi training on balance control in the el-derlyrdquoMedicine amp Science in Sports amp Exercise vol 36 no 4pp 648ndash657 2004

[29] Z G Huang Y H Feng Y H Li and C S Lv ldquoSystematicreview and meta-analysis Tai Chi for preventing falls in olderadultsrdquo BMJ Open vol 7 no 2 Article ID e013661 2017

[30] F Li P Harmer K Fitzgerald et al ldquoTai Chi and posturalstability in patients with Parkinsonrsquos diseaserdquo New EnglandJournal of Medicine vol 366 no 6 pp 511ndash519 2012

[31] I Hwang R Song S Ahn M-A Lee P M Wayne andM K Sohn ldquoExploring the adaptability of Tai Chi to strokerehabilitationrdquo Rehabilitation Nursing vol 44 no 4pp 221ndash229 2019

[32] S Deepeshwar S A Vinchurkar N K Visweswaraiah andH R Nagendra ldquoHemodynamic responses on prefrontalcortex related to meditation and attentional taskrdquo Frontiers inSystems Neuroscience vol 8 p 252 2014

[33] T Moriarty K Bourbeau B Bellovary and M N ZuhlldquoExercise intensity influences prefrontal cortex oxygenationduring cognitive testingrdquo Behavioral Sciences vol 9 no 8p 83 2019

[34] R Silveira R C R Prado C Brietzke et al ldquoPrefrontal cortexasymmetry and psychological responses to exercise a sys-tematic reviewrdquo Physiology amp Behavior vol 208 p 1125802019

[35] C Yue L Zou J Mei et al ldquoTai Chi training evokes sig-nificant changes in brain white matter network in olderwomenrdquo Healthcare vol 8 no 1 p 57 2020

[36] M Adcock M Fankhauser J Post et al ldquoEffects of an in-home multicomponent exergame training on physical func-tions cognition and brain volume of older adults a ran-domized controlled trialrdquo Frontiers in Medicine vol 6 p 3212019

[37] Z Zheng X Zhu S Yin et al ldquoCombined cognitive-psy-chological-physical intervention induces reorganization ofintrinsic functional brain architecture in older adultsrdquo NeuralPlasticity vol 2015 Article ID 713104 11 pages 2015

[38] M Equit J Niemczyk A Kluth C omas M Rubly andA von Gontard ldquoCentral nervous system processing ofemotions in children with fecal incontinence and con-stipationrdquo Zeitschrift fur Kinder- und Jugendpsychiatrie undPsychotherapie vol 47 no 1 pp 67ndash71 2019

[39] Q Zhu W Cai J Zheng et al ldquoDistinct resting-state brainactivity in patients with functional constipationrdquo Neurosci-ence Letters vol 632 pp 141ndash146 2016

[40] J Kong E Wolcott Z Wang et al ldquoAltered resting statefunctional connectivity of the cognitive control network infibromyalgia and the modulation effect of mind-body inter-ventionrdquo Brain Imaging and Behavior vol 13 no 2pp 482ndash492 2019

8 Evidence-Based Complementary and Alternative Medicine

[41] R Jalilianhasanpour E Beheshtian G Sherbaf S Sahraianand H I Sair ldquoFunctional connectivity in neurodegenerativedisorders Alzheimerrsquos disease and frontotemporal dementiardquoTopics in Magnetic Resonance Imaging vol 28 no 6pp 317ndash324 2019

Evidence-Based Complementary and Alternative Medicine 9

Page 7: TheSpecificandNonspecificEffectsofTaiChiandItsPossible ...the intervention. e metrics of HRV include standard deviation of NN intervals (SDNN), standard deviation of sequential 5-min

4 Conclusions

In conclusion Tai Chi is a safe and effective assistant therapy formany diseases However whether the therapeutic effects of TaiChi are disease-oriented remains uncertain is trial is the firstto investigate the existence of the specific and nonspecific effectsof Tai Chi and to explore their potential central responses It willprovide a new perspective for understanding Tai Chi and a newapproach for studying mind-body exercise

Abbreviations

HS Healthy subjectFC Functional constipationFGID Functional gastrointestinal diseaseQOL Quality of lifeGI GastrointestinalfMRI Functional magnetic resonance imagingCDUTCM Chengdu University of Traditional Chinese

MedicineCSBMs Complete spontaneous bowel movementsCCS Cleveland Constipation ScoreRPE Rating of perceived exertionPAC-SYM Patient Assessment of Constipation SymptomPAC-QOL Patient Assessment of Constipation Quality of

Life QuestionnaireRPE Rating of perceived exertionSF-36 e MOS 36-item short-form health surveyBBS Berg Balance ScaleTUG Timed up-and-goFEV1 Forced expiratory volume in one secondFVC Forced vital capacitySDS Self-Rating Depression ScaleSAS Self-Rating Anxiety ScaleEPQ Eysenck Personality QuestionnairesHRV Heart rate variability3D-T1WI 3-dimensional T1-weighted imagingBOLD-fMRI

Blood oxygenation level-dependent fMRI

DTI Diffusion tensor imagingCRF Case report formITT Intention to treatPP Per protocolReHo Regional homogeneityALFF Amplitude of low-frequency fluctuation

amplitude

Data Availability

is is a protocol for a clinical trial and no original data areincluded

Ethical Approval

e procedures have been approved by the Sichuan RegionalEthics Review Committee on Traditional Chinese Medicine(no 2018KL-047) and conformed to the Declaration ofHelsinki In addition all researchers were trained and signeda pledge to protect the confidentiality of study participants

Consent

All enrolled subjects signed an informed consent form

Disclosure

Tianyu Liu Yuke Teng and Sha Yang are the co-firstauthors

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Tianyu Liu Yuke Teng and Sha Yang contributed equally tothis article FZ and JW were responsible for this study TLYT SY FZ JW ZH and SY conceived and designed thestudy TL YT and SY participated in drafting the trialprotocol and preparing the manuscript YG TY JC and RYparticipated in data collection and were in charge of re-cruitment and treatment of patients All authors read andapproved the final manuscript

Acknowledgments

is study was supported by the Humanities and SocialSciences Youth Project of theMinistry of Education of China(19YJC890027) e trial was financially supported by theTen-ousand Talents Program of China (W02020595) andthe China Postdoctoral Science Foundation(2020M673562XB)

References

[1] C Lan J-S Lai S-Y Chen andM-K Wong ldquoTai Chi Chuanto improve muscular strength and endurance in elderly in-dividuals a pilot studyrdquo Archives of Physical Medicine andRehabilitation vol 81 no 5 pp 604ndash607 2000

[2] A M K Wong and C Lan ldquoTai Chi and balance controlrdquoMedicine and Sport Science vol 52 pp 115ndash123 2008

[3] L Sun L P Zhuang X Z Li J Zheng andW FWu ldquoTai Chican prevent cardiovascular disease and improve cardiopul-monary function of adults with obesity aged 50 years andolder a long-term follow-up studyrdquoMedicine vol 98 no 42Article ID e17509 2019

[4] C E Rogers L K Larkey and C Keller ldquoA review of clinicaltrials of Tai Chi and Qigong in older adultsrdquoWestern Journalof Nursing Research vol 31 no 2 pp 245ndash279 2009

[5] J H Yan W J Gu J Sun W X Zhang B W Li and L PanldquoEfficacy of Tai Chi on pain stiffness and function in patientswith osteoarthritis a meta-analysisrdquo PLoS One vol 8 no 4Article ID e61672 2013

[6] C Wang J P Collet and J Lau ldquoe effect of Tai Chi onhealth outcomes in patients with chronic conditions a sys-tematic reviewrdquo Archives of Internal Medicine vol 164 no 5pp 493ndash501 2004

[7] M Chao C Wang X Dong and M Ding ldquoe effects of taichi on type 2 diabetes mellitus a meta-analysisrdquo Journal ofDiabetes Research vol 2018 Article ID 7350567 9 pages2018

Evidence-Based Complementary and Alternative Medicine 7

[8] E Salmoirago-Blotcher P M Wayne S Dunsiger et al ldquoTaiChi is a promising exercise option for patients with coronaryheart disease declining cardiac rehabilitationrdquo Journal of theAmerican Heart Association vol 6 no 10 2017

[9] L Wang KWu X Chen and Q Liu ldquoe effects of tai chi onlung function exercise capacity and health related quality oflife for patients with chronic obstructive pulmonary disease apilot studyrdquo Heart Lung and Circulation vol 28 no 8pp 1206ndash1212 2019

[10] W Wang F Wang F Fan A C Sedas and J Wang ldquoMind-body interventions for irritable bowel syndrome patients inthe Chinese population a systematic review and meta-anal-ysisrdquo International Journal of Behavioral Medicine vol 24no 2 pp 191ndash204 2017

[11] Y Zhou L Liang L I Hong and L Jing ldquoAbout the con-valescent influence of 24-Pattern Shadowboxing to the pa-tients with chronic functional constipationrdquo Liaoning SportScience and Technology vol 2 pp 52ndash54 2015

[12] P Katelaris V Naganathan K Liu G Krassas andJ Gullotta ldquoComparison of the effectiveness of polyethyleneglycol with and without electrolytes in constipation a sys-tematic review and network meta-analysisrdquo BMC Gastroen-terology vol 16 no 1 p 42 2016

[13] S C Chow J Shao and H Wang Sample Size Calculations inClinical Research Wiley Hoboken NJ USA 2003

[14] D A Drossman and W L Hasler ldquoRome IV-functional GIdisorders disorders of gut-brain interactionrdquo Gastroenter-ology vol 150 no 6 pp 1257ndash1261 2016

[15] S Yang J Chen Y Guo et al ldquoComparison of Taiji andaerobic exercise for functional constipation study protocolfor a randomised controlled neuroimaging trialrdquo BMJ Openvol 9 no 8 Article ID e031089 2019

[16] K Berg S Wood-Dauphinee and J I Williams ldquoe balancescale reliability assessment with elderly residents and patientswith an acute strokerdquo Scandinavian Journal of RehabilitationMedicine vol 27 no 1 pp 27ndash36 1995

[17] P W Duncan D K Weiner J Chandler and S StudenskildquoFunctional reach a new clinical measure of balancerdquo Journalof Gerontology vol 45 no 6 pp M192ndashM197 1990

[18] W W K Zung ldquoA self-rating depression scalerdquo Archives ofGeneral Psychiatry vol 12 no 1 pp 63ndash70 1965

[19] W W K Zung ldquoA rating instrument for anxiety disordersrdquoPsychosomatics vol 12 no 6 pp 371ndash379 1971

[20] D Schuldberg ldquoEysenck personality questionnaire scales andpaper-and-pencil tests related to creativityrdquo PsychologicalReports vol 97 no 1 pp 180ndash182 2005

[21] F Agachan T Chen J Pfeifer P Reissman andS D Wexner ldquoA constipation scoring system to simplifyevaluation andmanagement of constipated patientsrdquoDiseasesof the Colon amp Rectum vol 39 no 6 pp 681ndash685 1996

[22] L Frank L Kleinman C Farup L Taylor and P Miner JrldquoPsychometric validation of a constipation symptom assess-ment questionnairerdquo Scandinavian Journal of Gastroenter-ology vol 34 no 9 pp 870ndash877 1999

[23] P Marquis C De La Loge D Dubois A McDermott andO Chassany ldquoDevelopment and validation of the patientAssessment of constipation quality of life questionnairerdquoScandinavian Journal of Gastroenterology vol 40 no 5pp 540ndash551 2005

[24] S Morishita A Tsubaki T Takabayashi and J B Fu ldquoRe-lationship between the rating of perceived exertion scale andthe load intensity of resistance trainingrdquo Strength and Con-ditioning Journal vol 40 no 2 pp 94ndash109 2018

[25] A Kelly J Rush E Shafonsky et al ldquoDetecting short-termchange and variation in health-related quality of life within-and between-person factor structure of the SF-36 healthsurveyrdquo Health and Quality of Life Outcomes vol 13 no 1p 199 2015

[26] P J Klein ldquoTai Chi Chuan in the management of Parkinsonrsquosdisease and Alzheimerrsquos diseaserdquo Medicine and Sport Sciencevol 52 pp 173ndash181 2008

[27] J Kong G Wilson J Park K Pereira C Walpole andA Yeung ldquoTreating depression with Tai Chi state of the artand future perspectivesrdquo Front Psychiatry vol 10 p 2372019

[28] W W N Tsang and C W Y Hui-Chan ldquoEffect of 4- and 8-wk intensive Tai Chi training on balance control in the el-derlyrdquoMedicine amp Science in Sports amp Exercise vol 36 no 4pp 648ndash657 2004

[29] Z G Huang Y H Feng Y H Li and C S Lv ldquoSystematicreview and meta-analysis Tai Chi for preventing falls in olderadultsrdquo BMJ Open vol 7 no 2 Article ID e013661 2017

[30] F Li P Harmer K Fitzgerald et al ldquoTai Chi and posturalstability in patients with Parkinsonrsquos diseaserdquo New EnglandJournal of Medicine vol 366 no 6 pp 511ndash519 2012

[31] I Hwang R Song S Ahn M-A Lee P M Wayne andM K Sohn ldquoExploring the adaptability of Tai Chi to strokerehabilitationrdquo Rehabilitation Nursing vol 44 no 4pp 221ndash229 2019

[32] S Deepeshwar S A Vinchurkar N K Visweswaraiah andH R Nagendra ldquoHemodynamic responses on prefrontalcortex related to meditation and attentional taskrdquo Frontiers inSystems Neuroscience vol 8 p 252 2014

[33] T Moriarty K Bourbeau B Bellovary and M N ZuhlldquoExercise intensity influences prefrontal cortex oxygenationduring cognitive testingrdquo Behavioral Sciences vol 9 no 8p 83 2019

[34] R Silveira R C R Prado C Brietzke et al ldquoPrefrontal cortexasymmetry and psychological responses to exercise a sys-tematic reviewrdquo Physiology amp Behavior vol 208 p 1125802019

[35] C Yue L Zou J Mei et al ldquoTai Chi training evokes sig-nificant changes in brain white matter network in olderwomenrdquo Healthcare vol 8 no 1 p 57 2020

[36] M Adcock M Fankhauser J Post et al ldquoEffects of an in-home multicomponent exergame training on physical func-tions cognition and brain volume of older adults a ran-domized controlled trialrdquo Frontiers in Medicine vol 6 p 3212019

[37] Z Zheng X Zhu S Yin et al ldquoCombined cognitive-psy-chological-physical intervention induces reorganization ofintrinsic functional brain architecture in older adultsrdquo NeuralPlasticity vol 2015 Article ID 713104 11 pages 2015

[38] M Equit J Niemczyk A Kluth C omas M Rubly andA von Gontard ldquoCentral nervous system processing ofemotions in children with fecal incontinence and con-stipationrdquo Zeitschrift fur Kinder- und Jugendpsychiatrie undPsychotherapie vol 47 no 1 pp 67ndash71 2019

[39] Q Zhu W Cai J Zheng et al ldquoDistinct resting-state brainactivity in patients with functional constipationrdquo Neurosci-ence Letters vol 632 pp 141ndash146 2016

[40] J Kong E Wolcott Z Wang et al ldquoAltered resting statefunctional connectivity of the cognitive control network infibromyalgia and the modulation effect of mind-body inter-ventionrdquo Brain Imaging and Behavior vol 13 no 2pp 482ndash492 2019

8 Evidence-Based Complementary and Alternative Medicine

[41] R Jalilianhasanpour E Beheshtian G Sherbaf S Sahraianand H I Sair ldquoFunctional connectivity in neurodegenerativedisorders Alzheimerrsquos disease and frontotemporal dementiardquoTopics in Magnetic Resonance Imaging vol 28 no 6pp 317ndash324 2019

Evidence-Based Complementary and Alternative Medicine 9

Page 8: TheSpecificandNonspecificEffectsofTaiChiandItsPossible ...the intervention. e metrics of HRV include standard deviation of NN intervals (SDNN), standard deviation of sequential 5-min

[8] E Salmoirago-Blotcher P M Wayne S Dunsiger et al ldquoTaiChi is a promising exercise option for patients with coronaryheart disease declining cardiac rehabilitationrdquo Journal of theAmerican Heart Association vol 6 no 10 2017

[9] L Wang KWu X Chen and Q Liu ldquoe effects of tai chi onlung function exercise capacity and health related quality oflife for patients with chronic obstructive pulmonary disease apilot studyrdquo Heart Lung and Circulation vol 28 no 8pp 1206ndash1212 2019

[10] W Wang F Wang F Fan A C Sedas and J Wang ldquoMind-body interventions for irritable bowel syndrome patients inthe Chinese population a systematic review and meta-anal-ysisrdquo International Journal of Behavioral Medicine vol 24no 2 pp 191ndash204 2017

[11] Y Zhou L Liang L I Hong and L Jing ldquoAbout the con-valescent influence of 24-Pattern Shadowboxing to the pa-tients with chronic functional constipationrdquo Liaoning SportScience and Technology vol 2 pp 52ndash54 2015

[12] P Katelaris V Naganathan K Liu G Krassas andJ Gullotta ldquoComparison of the effectiveness of polyethyleneglycol with and without electrolytes in constipation a sys-tematic review and network meta-analysisrdquo BMC Gastroen-terology vol 16 no 1 p 42 2016

[13] S C Chow J Shao and H Wang Sample Size Calculations inClinical Research Wiley Hoboken NJ USA 2003

[14] D A Drossman and W L Hasler ldquoRome IV-functional GIdisorders disorders of gut-brain interactionrdquo Gastroenter-ology vol 150 no 6 pp 1257ndash1261 2016

[15] S Yang J Chen Y Guo et al ldquoComparison of Taiji andaerobic exercise for functional constipation study protocolfor a randomised controlled neuroimaging trialrdquo BMJ Openvol 9 no 8 Article ID e031089 2019

[16] K Berg S Wood-Dauphinee and J I Williams ldquoe balancescale reliability assessment with elderly residents and patientswith an acute strokerdquo Scandinavian Journal of RehabilitationMedicine vol 27 no 1 pp 27ndash36 1995

[17] P W Duncan D K Weiner J Chandler and S StudenskildquoFunctional reach a new clinical measure of balancerdquo Journalof Gerontology vol 45 no 6 pp M192ndashM197 1990

[18] W W K Zung ldquoA self-rating depression scalerdquo Archives ofGeneral Psychiatry vol 12 no 1 pp 63ndash70 1965

[19] W W K Zung ldquoA rating instrument for anxiety disordersrdquoPsychosomatics vol 12 no 6 pp 371ndash379 1971

[20] D Schuldberg ldquoEysenck personality questionnaire scales andpaper-and-pencil tests related to creativityrdquo PsychologicalReports vol 97 no 1 pp 180ndash182 2005

[21] F Agachan T Chen J Pfeifer P Reissman andS D Wexner ldquoA constipation scoring system to simplifyevaluation andmanagement of constipated patientsrdquoDiseasesof the Colon amp Rectum vol 39 no 6 pp 681ndash685 1996

[22] L Frank L Kleinman C Farup L Taylor and P Miner JrldquoPsychometric validation of a constipation symptom assess-ment questionnairerdquo Scandinavian Journal of Gastroenter-ology vol 34 no 9 pp 870ndash877 1999

[23] P Marquis C De La Loge D Dubois A McDermott andO Chassany ldquoDevelopment and validation of the patientAssessment of constipation quality of life questionnairerdquoScandinavian Journal of Gastroenterology vol 40 no 5pp 540ndash551 2005

[24] S Morishita A Tsubaki T Takabayashi and J B Fu ldquoRe-lationship between the rating of perceived exertion scale andthe load intensity of resistance trainingrdquo Strength and Con-ditioning Journal vol 40 no 2 pp 94ndash109 2018

[25] A Kelly J Rush E Shafonsky et al ldquoDetecting short-termchange and variation in health-related quality of life within-and between-person factor structure of the SF-36 healthsurveyrdquo Health and Quality of Life Outcomes vol 13 no 1p 199 2015

[26] P J Klein ldquoTai Chi Chuan in the management of Parkinsonrsquosdisease and Alzheimerrsquos diseaserdquo Medicine and Sport Sciencevol 52 pp 173ndash181 2008

[27] J Kong G Wilson J Park K Pereira C Walpole andA Yeung ldquoTreating depression with Tai Chi state of the artand future perspectivesrdquo Front Psychiatry vol 10 p 2372019

[28] W W N Tsang and C W Y Hui-Chan ldquoEffect of 4- and 8-wk intensive Tai Chi training on balance control in the el-derlyrdquoMedicine amp Science in Sports amp Exercise vol 36 no 4pp 648ndash657 2004

[29] Z G Huang Y H Feng Y H Li and C S Lv ldquoSystematicreview and meta-analysis Tai Chi for preventing falls in olderadultsrdquo BMJ Open vol 7 no 2 Article ID e013661 2017

[30] F Li P Harmer K Fitzgerald et al ldquoTai Chi and posturalstability in patients with Parkinsonrsquos diseaserdquo New EnglandJournal of Medicine vol 366 no 6 pp 511ndash519 2012

[31] I Hwang R Song S Ahn M-A Lee P M Wayne andM K Sohn ldquoExploring the adaptability of Tai Chi to strokerehabilitationrdquo Rehabilitation Nursing vol 44 no 4pp 221ndash229 2019

[32] S Deepeshwar S A Vinchurkar N K Visweswaraiah andH R Nagendra ldquoHemodynamic responses on prefrontalcortex related to meditation and attentional taskrdquo Frontiers inSystems Neuroscience vol 8 p 252 2014

[33] T Moriarty K Bourbeau B Bellovary and M N ZuhlldquoExercise intensity influences prefrontal cortex oxygenationduring cognitive testingrdquo Behavioral Sciences vol 9 no 8p 83 2019

[34] R Silveira R C R Prado C Brietzke et al ldquoPrefrontal cortexasymmetry and psychological responses to exercise a sys-tematic reviewrdquo Physiology amp Behavior vol 208 p 1125802019

[35] C Yue L Zou J Mei et al ldquoTai Chi training evokes sig-nificant changes in brain white matter network in olderwomenrdquo Healthcare vol 8 no 1 p 57 2020

[36] M Adcock M Fankhauser J Post et al ldquoEffects of an in-home multicomponent exergame training on physical func-tions cognition and brain volume of older adults a ran-domized controlled trialrdquo Frontiers in Medicine vol 6 p 3212019

[37] Z Zheng X Zhu S Yin et al ldquoCombined cognitive-psy-chological-physical intervention induces reorganization ofintrinsic functional brain architecture in older adultsrdquo NeuralPlasticity vol 2015 Article ID 713104 11 pages 2015

[38] M Equit J Niemczyk A Kluth C omas M Rubly andA von Gontard ldquoCentral nervous system processing ofemotions in children with fecal incontinence and con-stipationrdquo Zeitschrift fur Kinder- und Jugendpsychiatrie undPsychotherapie vol 47 no 1 pp 67ndash71 2019

[39] Q Zhu W Cai J Zheng et al ldquoDistinct resting-state brainactivity in patients with functional constipationrdquo Neurosci-ence Letters vol 632 pp 141ndash146 2016

[40] J Kong E Wolcott Z Wang et al ldquoAltered resting statefunctional connectivity of the cognitive control network infibromyalgia and the modulation effect of mind-body inter-ventionrdquo Brain Imaging and Behavior vol 13 no 2pp 482ndash492 2019

8 Evidence-Based Complementary and Alternative Medicine

[41] R Jalilianhasanpour E Beheshtian G Sherbaf S Sahraianand H I Sair ldquoFunctional connectivity in neurodegenerativedisorders Alzheimerrsquos disease and frontotemporal dementiardquoTopics in Magnetic Resonance Imaging vol 28 no 6pp 317ndash324 2019

Evidence-Based Complementary and Alternative Medicine 9

Page 9: TheSpecificandNonspecificEffectsofTaiChiandItsPossible ...the intervention. e metrics of HRV include standard deviation of NN intervals (SDNN), standard deviation of sequential 5-min

[41] R Jalilianhasanpour E Beheshtian G Sherbaf S Sahraianand H I Sair ldquoFunctional connectivity in neurodegenerativedisorders Alzheimerrsquos disease and frontotemporal dementiardquoTopics in Magnetic Resonance Imaging vol 28 no 6pp 317ndash324 2019

Evidence-Based Complementary and Alternative Medicine 9