Part I Application of Synchronized Transcutaneous Electroacupuncture in Patients with Gastroesophageal Reflux DiseaseBackground and aims Gastroesophageal reflux disease(GERD)represents a common esophageal disorder.The major manifestations are heartburn and/or regurgitation.Although proton pump inhibition(PPI)which suppresses acid secretion stands for the first-line drug therapy in the clinic,long maintenance use of PPI might be inevitable for some patients which may bring adverse drug reaction.Moreover,some GERD patients do not respond to PPI therapy.One reasonable explanation should be that PPI reduce gastric acidity production rather than radically prevent reflux event.Pathological reflux is concerned with multiple factors.Mechanical anti-reflux barrier incompetency,especially the reduced lower esophageal sphincters pressure(LESP)plays a key part in pathological reflux.Synchronized transcutaneous electro-acupuncture(STEA)has exhibited effective treating gastrointestinal motility dysfunction.Our goal was to explore the effects of STEA on esophageal motility in GERD patients and investigate the potential mechanism referring the autonomic pathway.Methods and Patients 1.A totality of sixty eligible GERD outpatients coming to Gastrointestinal Dynamics Clinic of Yinzhou People’s Hospital was included.All participants signed an informed consent form before the enrollment.The patients were randomly assigned to STEA(45 patients)and sham-TEA(15 patients)group based upon a computer-generated random digital table.2.The baseline clinical data were collected including Reflux Disease Questionnaire(RDQ)and GERD-Health Related Quality of Life(GERD-HRQL)rating score,as well as the severity of reflux esophagitis(RE)diagnosed with gastroscope based on the Los Angeles Classification,and PPI usage et al.Autonomic nerve function test(heart rate variability,HRV)and esophageal high resolution manometry test(HRM)were performed for each patient.3.In STEA group,the TEA therapy was administered via surface electrodes pasted on bilateral ST36(Zusanli).Importantly,the patient should breathe with frequency of the stimulation(12train/min).In sham-TEA group,electrical stimulation was given with the same parameters as STEA except that it was performed via sham points.The patients received thirty minutes’ treatment during which the HRV was re-evaluated.4.HRM test was retested to explore the therapeutic effect of STEA\sham-TEA on esophageal motility.Results 1.Clinical baseline data The mean disease duration of the enrolled patients(Male 33,Female 27;mean age: 54.4±13.6)was 12.61±11.28 months.A total of 37 patients are currently taking or have ever taken PPI drug.One patient had hiatal hernia(≤2cm),53 patients diagnosed with reflux esophagitis(19 with Grade A,28 with Grade B,6 with Grade C according to Los Angeles Classification).Eight patients(13.3%)had hypotensive LESP and eight patients(13.3%)had ineffective esophageal motility(IEM).2.Effects of STEA on LESP Seven patients(15.6%)in STEA group and one patient(6.67%)in sham-TEA group had hypotensive baseline LESP.After STEA treatment,the LESP increased from 21.9(16.1,31.7)to 31.9(22.2,38.7)mm Hg(p < 0.001).In sham-TEA group,no remarkable change in LESP was found.3.Correlation analysis of the increased percentage in LESP with the baseline LESP A significant negative correlation was exhibited between the increased percentage in LESP and the basal LESP(R =-0.471,p= 0.001).It was suggested that patients with reduced LESP(<13 mm Hg)achieved the largest increase in LESP from STEA treatment;whereas patients with normal or higher basal LESP showed minimal percentage increase in LESP following STEA treatment.4.Effects of STEA on esophageal motility Both STEA and sham-TEA decreased the contractile front velocity(CFV)(p<0.04 for both).In STEA group,the pooled number of ineffective esophageal contractions was significantly reduced(p=0.021).IEM was found in 13%(six patients)of patients in the STEA group and also 13%(two patients)in the sham-TEA group at baseline.In the STEA group,the IEM in 66.7%(4/6)patients was normalized following STEA;it was unchanged with sham-TEA.5.Compared to the basal data,the HF was remarkably enhanced(0.27±0.14 vs 0.36±0.18,p < 0.001)and the LF was significantly weakened(0.73±0.14 vs 0.64±0.18,p<0.001)after acute STEA.Conclusion Acute STEA enhanced LESP in GERD and the increased percentage in LESP was negatively related with baseline LESP.The therapeutic effect of STEA on LESP might be mediated via autonomic function.Part II Preventive Effects of Transcutaneous Electrical Acustimulation on Ischemic Stroke-induced Constipation Mediated via the Autonomic Pathway Background and aimsConstipation represents a common complication in ischemic stroke patients.It reduces the quality of life and brings the bad impact on the rehabilitation progress.The brain-gut axis dysregulation may play a crucial part in stroke-induced constipation.Especially,autonomic nerve dysfunction is prevalent among stroke population and predominance of sympathetic nerves activity may inhibit gastrointestinal peristalsis and decreased colonic propagating sequences which eventually resulted in constipation.The management of stroke-induced constipation is challenged and traditional therapy modality has shown limited effectiveness in treating secondary constipation in stroke population.Previous studies have confirmed that transcutaneous electrical acustimulation(TEA)might be served as an effective strategy in treating functional gastrointestinal motility disorders via re-regulate sympathetic-vagal imbalance.The purpose of our study was to investigate the preventive and therapeutic effect of TEA on secondary constipation and underlying mechanism via the autonomic nerve function in patients immediately suffered from ischemic stroke.Methods and Patients 1.A totality of 90 eligible hospitalized patients diagnosed with first attack of acute ischemic stroke admitted in the Neurology Department of Yinzhou People’s Hospital,Ningbo was allocated into TEA group(45 patients)and sham-TEA group(45 patients)with randomization.All patients or the guardians should sign the written consent form before participating in the study.The following clinical baseline information of the patients were extracted: demographic data,smoking and drink,body mass index,stroke severity(NIHSS score),the performance in activities of daily living(BI),stroke recurrence risk stratification(ESRS),drug use,hemiplegia condition,gastric tube indwelling,bedpan use and laboratory biochemical parameters such as lipoprotein et al.Autonomic function test(HRV)was performed in each patient in the fasting state.2.Once recruited,TEA at ST36(zusanli)or sham-TEA was administered one hour,twice daily following breakfast and supper,respectively.The therapy in both groups lasted for 14 days.If a patient was discharged from the hospital before the study has finished,he or she was trained by a medical professional to use the stimulation device in advance and completed the treatment at home.3.Each patient was asked to filled out a bowel diary during the 2-week trial which contains the following: number of bowel movements(BMs);number of spontaneous bowel movements(SBMs);proportion of straining defecations;proportion of defecations with sense of incomplete emptying;use of laxative,enema,suppository and digital maneuver et al.The Bristol Stool Form Scale(BSFS)was recorded daily for all enrolled patients to standardize the stool consistency.4.When the study was over,autonomic nerve function test was conducted again.Stroke severity and daily performance ability were re-evaluated.Symptoms rating score including the Patient Assessment of Constipation Symptoms(PAC-SYM),The Patient Assessment of Constipation Quality of Life(PAC-QOL)were assessed.Results 1.Baseline characteristics of ischemic stroke patients A total of 86 patients(male 57,female 29;mean age 69.2±11.7,yrs)completed the study finally.There were no death occurred during the study period.The mean length of hospital stay was 11.7±4.0 days.The mean NIHSS score was 5.0±4.7 whereas the BI score was 62.1 ± 19.4,respectively.No significant difference was found between the demographic variables and baseline medical characteristics between two groups.2.Effects of TEA on stroke-induced constipation1)TEA reduced the cumulative incidence of stroke-induced constipation.At week 1,15 patients in TEA group and 19 patients in sham-TEA group had new-onset constipation(35.7% vs 43.2%,p=0.52).At week 2,3 patients in TEA and 11 patients in sham-TEA group had new-onset constipation(11.1% vs 44.0%,p=0.03).A remarkable difference in cumulative incidence of stroke-induced constipation during the 2-week period was noted between TEA group and sham-TEA group(42.9 vs.68.2%,p= 0.029).2)TEA improved the defecation frequency of ischemic stroke patients During the 2-week period,the number of BMs per week in TEA group was 5.5(5,6)and 4.5(3.5,5.5)in sham-TEA group,respectively(p<0.001).The number of SBMs per week in TEA group was 4.5(3,6)and 3(2.5,4)in sham-TEA group,respectively(p<0.003).TEA significantly increased the BMs by 20%(p=0.025)and SBMs by 25% from week 1 to week 2(p=0.004).3)TEA reduced laxative use and straining defecations in ischemic stroke patients.The proportion of straining defecations and laxative usage were remarkably reduced in TEA group compared to that in sham-TEA group during the second week(p<0.001 for both).TEA remarkably decreased the proportion of staining defecations(p<0.001)and reduced the laxative use from week 1 to week 2(p<0.008).4)TEA improved the stool consistency of ischemic stroke patients.The mean value of BSFS was 3.5±0.3 in TEA group and 2.8±0.6 in sham-TEA group,respectively(p<0.001).TEA substantially improved the stool consistency compared with sham-TEA treatment(F=27.69,p<0.001).5)TEA improved quality of life in patients with stroke-induced constipation.TEA significantly improved the quality of life in stroke patients with constipation (0.21 vs 0.30,p=0.026)which was mainly attributed to the alleviation in worriers and concerns subscale(0.17 vs.0.33,p<0.001).3.Mechanisms of stroke-induced constipation and TEA 1)Autonomic nerve system function was positively correlated with stroke severity.A remarkable positive correlation was exhibited between the sympathovagal balance(LF/HF ratio)and the NIHSS score prior to stimulation(R=0.473,p<0.001).2)The independent predictor factors for development of stroke-induced constipationMultivariate logistic regression analysis demonstrated that both the NIHSS score and the LF/HF ratio were independent risk factors for the development of stroke-induced constipation.The more serious stroke condition,the greater risk of stroke-induced constipation(odds ratio=1.44,p=0.004).It was also indicated that each unit increase in LF/HF ratio value was correlated with a 3.94-fold increase of risk for stroke-induced constipation(p<0.001).3)Autonomic mechanisms of TEAcompared with baseline data,the vagal tone was significantly increased from 0.29±0.13 to 0.36±0.13(p<0.001)and the sympathetic activity was significantly suppressed from 0.71±0.13 to 0.64±0.13(p<0.001)in TEA group.TEA remarkably decreased LF/HF ratio from 3.80±3.84 to 2.27±1.34(p=0.002).No statistical change was shown in sham-TEA group.Conclusion Autonomic function imbalance is prevalent in ischemic stroke population.The protective effect of TEA on stroke-induced constipation might be mediated via the regulation of the autonomic nerve function. |