Acupuncture for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Pilot Randomized Clinical Trial.

Importance: Acupuncture is a promising therapy for irritable bowel syndrome (IBS), but the use of subjective scales as an assessment is accompanied by high placebo response rates. Objectives: To preliminarily test the feasibility of using US Food and Drug Administration (FDA)-recommended end points to evaluate the efficacy of acupuncture in the treatment of IBS. Design, Setting, and Participants: This pilot, multicenter randomized clinical trial was conducted in 4 tertiary hospitals in China from July 1, 2020, to March 31, 2021, and 14-week data collection was completed in March 2021. Individuals with a diagnosis of IBS with diarrhea (IBS-D) were randomized to 1 of 3 groups, including 2 acupuncture groups (specific acupoints [SA] and nonspecific acupoints [NSA]) and a sham acupuncture group (non-acupoints [NA]) with a 1:1:1 ratio. Interventions: Patients in all groups received twelve 30-minute sessions over 4 consecutive weeks at 3 sessions per week (ideally every other day). Main Outcomes and Measures: The primary outcome was the response rate at week 4, which was defined as the proportion of patients whose worst abdominal pain score (score range, 0-10, with 0 indicating no pain and 10 indicating unbearable severe pain) decreased by at least 30% and the number of type 6 or 7 stool days decreased by 50% or greater. Results: Ninety patients (54 male [60.0%]; mean [SD] age, 34.5 [11.3] years) were enrolled, with 30 patients in each group. There were substantial improvements in the primary outcomes for all groups (composite response rates of 46.7% [95% CI, 28.8%-65.4%] in the SA group, 46.7% [95% CI, 28.8%-65.4%] in the NSA group, and 26.7% [95% CI, 13.0%-46.2%] in the NA group), although the difference between them was not statistically significant (P = .18). The response rates of adequate relief at week 4 were 64.3% (95% CI, 44.1%-80.7%) in the SA group, 62.1% (95% CI, 42.4%-78.7%) in the NSA group, and 55.2% (95% CI, 36.0%-73.0%) in the NA group (P = .76). Adverse events were reported in 2 patients (6.7%) in the SA group and 3 patients (10%) in NSA or NA group. Conclusions and Relevance: In this pilot randomized clinical trial, acupuncture in both the SA and NSA groups showed clinically meaningful improvement in IBS-D symptoms, although there were no significant differences among the 3 groups. These findings suggest that acupuncture is feasible and safe; a larger, sufficiently powered trial is needed to accurately assess efficacy. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000030670.

[Research progress of acupuncture for peripheral inflammatory response].

Acupuncture can regulate peripheral inflammatory response mainly through somatosensory-vagal/sympathetic nerve-splenic/adrenal/local reflex pathway. Besides, acupuncture may also play an anti-inflammatory role through gut microbiota and neuro-endocrine pathway. The effects of acupuncture have acupoint specificity and time window effect, and are influenced by voltage, current and frequency of electroacupuncture. Future research should focus on the connection and interaction of multiple targets, pathways and mechanisms in the brain, and clarify the multi-target advantages of acupuncture anti-inflammatory.

The impact of expectancy on the efficacy of acupuncture treatment for postprandial distress syndrome: Secondary analysis of a randomized clinical trial.

BACKGROUND: Expectancy is an important source of the placebo effect. However, it is unclear whether this has an effect on the efficacy of acupuncture and sham acupuncture in the treatment of postprandial distress syndrome (PDS). AIM: To evaluate the effects of high expectancy (HE) and low expectancy (LE) on the efficacy of acupuncture and sham acupuncture in the treatment of PDS. METHODS: This post hoc secondary analysis used data from our previous randomized controlled trial. Patients were, respectively, enrolled in the HE group and LE group according to expectancy assessments. The composite primary outcomes were the response rate and the elimination rate after 4 weeks of treatment. Expectancy was considered a factor affecting the efficacy of acupuncture treatment only if both primary outcomes achieved significance. RESULTS: For the acupuncture group, the response rate was 84.5% in the HE group and 78.8% in the LE group (p = 0.458), and the elimination rate was 32.1% in the HE group and 21.2% in the LE group (p = 0.241). For the sham acupuncture group, the response rate at week 4 was 52.3% in the HE group and 53.1% in the LE group (p = 0.936), and the elimination rate at week 4 was 23.1% in the HE group and 10.6% in the LE group (p = 0.090). CONCLUSION: In this study, the response rate and elimination rate were higher in the high-expectancy group, but no conclusive evidence was found for an association between expectancy and the efficacy of acupuncture and sham acupuncture.

Effect of acupuncture for diarrhea-predominant irritable bowel syndrome: study protocol for a randomized clinical trial.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is the most common subtype of IBS. Acupuncture is commonly used to treat IBS-D, but its effect is uncertain because of the poor quality of prior studies. This trial aims to evaluate the efficacy and safety of acupuncture treatment for IBS-D through comparisons with sham acupuncture. METHODS/DESIGN: This is a large-scale, multi-center, randomized, two-arm interventional clinical trial. Participants will take part in a total of 20 weeks of study, which contained 3 phases: 2-week screening, 6-week treatment, and 12-week follow-up. Based on the composite response rate of the primary endpoint in our pilot study (a sham acupuncture response rate of 27% and a true acupuncture of approximately 45%), 280 randomly allocated participants were planned. Eligible participants will be randomly assigned to the true acupuncture group and sham acupuncture group according to a ratio of 1:1, and a total of 15 sessions of treatment overall 6-week treatment period will be brought. The primary endpoint is a composite response rate at week 6, and the responder is defined as who responses in both abdominal pain intensity and stool consistency. Furthermore, composite response rates at other weeks, IBS Symptom Severity Scale, IBS Quality of Life, Adequate Relief scale, and individual IBS symptoms (abdominal pain, bloating, stool frequency) are chosen as secondary endpoints. DISCUSSION: This trial may provide high-quality evidence for the efficacy and safety of acupuncture in the treatment of IBS-D. The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100044762. Registered on 26 March 2021.

Effects of Electroacupuncture at Different Acupoints on Functional Dyspepsia Rats.

Although, acupoint specificity is regarded as the core of scientific issues in electroacupuncture (EA), the difference of EA on treating functional dyspepsia (FD) at different acupoints is unclear. Therefore, this study aims to investigate the different therapeutic effects of EA at lower extremity or abdominal acupoints on the mucosal integrity and lower-inflammatory response in FD. The intragastric administration of iodoacetamide (IA) was performed in 48 rats to establish the FD model. These rats were randomly divided into the control group, the model group and the six EA groups receiving stimulation at the lower extremity (ST36, ST37, and ST39) or abdominal acupoints (ST25, CV4, and CV12) separately. The open-field test (OFT) was measured after 8 weeks of IA, and gastric emptying was evaluated after 10 days of the EA treatment. The local inflammation markers of CD45, eosinophil major basic protein (EMBP), and the tight junction proteins ZO1 and Claudin3 were assessed by immunofluorescence in all groups. Western blot analysis showed that the EMBP and Occludin1 levels in the duodenal. EA at lower extremity acupoint ST36 could improve the gastric emptying. EA at lower extremity acupoints reduced the immunoreactivity of EMBP, but the CD45 was reregulated by the ST37 and ST39 acupoints. The lower extremity acupoints also ameliorated FD-tight junction protein in the expression of Claudin3 and ZO1. However, only the ST36 suppressed the expression of EMBP and recovered the expression of Occludin1. Similarly, the effect of EA at abdominal acupoints was not obvious either in facilitating gastric motility or in improving inflammatory and mucosal injury. EA at lower extremity and abdominal acupoints with the same stimulation parameters had different therapeutic effects in gastric emptying, intestinal mucosal integrity, and inflammation response, thus proving the specificity of acupoints.

The Influence of Psychological Status on Acupuncture for Postprandial Distress Syndrome: A Subgroup Analysis of a Multicenter, Randomized Controlled Trial.

BACKGROUND: Postprandial distress syndrome (PDS) is accompanied by a high incidence of mood disorder. Acupuncture is an effective method in relieving dyspepsia symptoms; however, the impact of psychological status on acupuncture for PDS remains mysterious. METHODS: This secondary analysis of a multicenter, randomized controlled trial aims to evaluate the influence of anxiety and depression on acupuncture for PDS. 138 patients received the same acupuncture treatment and were followed up until week 16. The 2 primary outcomes were the response rate based on overall treatment effect and the elimination rate of all 3 cardinal symptoms after 4 weeks of treatment. RESULTS: Of 114 patients, 31 were anxiety patients and 83 were nonanxiety patients or 32 were depressive patients and 82 were nondepressive patients. The response rate and elimination rate at week 4 were 77.4% and 9.7% in anxiety patients versus 84.3% and 27.7% in nonanxiety patients, respectively (P = 0.388; P = 0.041). No significant difference was noted in the response rate (P = 0.552) and elimination rate (P = 0.254) at week 4 between nondepressive and depressive patients. There was no significant intergroup difference in the response rate and elimination rate between non-mood-disorder and mood disorder patients (P > 0.05) during the 12-week post-treatment follow-up, except for the response rate at week 8 (P < 0.05). CONCLUSION: The effect of acupuncture on response rate was similar for both non-mood-disorder and mood disorder patients. However, anxiety but not depression had a negative influence on the elimination rate, especially in postprandial fullness.

[Research progress on mechanism of acupuncture and moxibustion in treatment of irritable bowel syndrome].

The current clinical evidence and underlying mechanisms of acupuncture and moxibustion in the treatment of irritable bowel syndrome (IBS) were summarized, so as to better optimize clinical treatment. The relevant articles of acupuncture and moxibustion in the treatment of IBS in recent years were retrieved and summarized. We found that the clinical efficacy of acupuncture and moxibustion in the treatment of IBS was relatively reliable. However, the mutual relationships among various mechanisms of action such as abnormal gastrointestinal motility, high visceral sensitivity, intestinal microenvironment disorders, and abnormal intestinal-brain interactions need to be further explored. The authors believe that in-depth explorations of the bidirectional regulation of "gut-brain axis", the law of changes in the abundance and diversity of intestinal flora, and the establishment of a more ideal animal model of TCM syndrome differentiation are useful ideas for subsequent research.

Is acupuncture effective for knee osteoarthritis? A protocol for a systematic review and meta-analysis.

INTRODUCTION: Knee osteoarthritis (KOA) is one of the leading causes of disability. The effectiveness of acupuncture for treating KOA remains controversial. This protocol describes the method of a systematic review and meta-analysis evaluating the effectiveness and safety of acupuncture for treating KOA. METHODS AND ANALYSIS: Four English databases (PubMed, Embase, Cochrane Library databases and Web of Science) and four Chinese databases (China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, and Wanfang) will be searched from the database inception to 1 September 2021. All randomised controlled trials related to acupuncture for KOA will be included. Extracted data will include publication details, basic information, demographic data, intervention details and patient outcomes. The primary outcome will be pain intensity. Risk of bias will be assessed using the Cochrane Collaboration's tool for assessing risk of bias. Article selection, data extraction and risk of bias assessment will be performed in duplicate by two independent reviewers. If the meta-analysis is precluded, we will conduct a descriptive synthesis using a best-evidence synthesis approach. The strength of recommendations and quality of evidence will be assessed using the Grading of Recommendations Assessment Development and Evaluation working group methodology. ETHICS AND DISSEMINATION: Ethics approval is not required because individual patient data are not included. This protocol was registered in the international Prospective Register of Systematic Reviews on 25 February 2021. The systematic review and meta-analysis will be submitted for publication in a peer-reviewed journal. The findings will also be disseminated through conference presentations. TRIAL REGISTRATION NUMBER: CRD42021232177.

[Application of "patient and public involvement" in acupuncture clinical research].

In order to explore the application of "patient and public involvement" (PPI) in acupuncture clinical research, the connotation, reporting standards and research status of PPI at home and abroad are collated, and the key problems of PPI encountered in acupuncture clinical research are deeply considered and summarized. It is suggested that the short-form checklist of the Guidance for Reporting Involvement of Patients and the Public (GRIPP) of the 2nd edition should be applied to acupuncture clinical research. PPI provides a new perspective for acupuncture clinical research. It is beneficial for each stage of research, contributes to the improvement of acupuncture medical service mode and increases the success rate and cost-effectiveness of research so that the innovation and development of acupuncture science can be promoted.

[Optimization and implementation of clinical trial of acupuncture: reflection on the successful case of acupuncture for postprandial distress syndrome].

Taking the clinical trial of acupuncture in treatment of postprandial distress syndrome as an example, this paper proposes that the acupuncture clinical trial protocol should be optimized in view of acupuncture prescription, acupuncture frequency and outcomes. Besides, the data quality of acupuncture clinical trial should be improved in consideration of data sharing and electronic data capture so as to provide a reference for the majority of researchers to optimize and implement acupuncture clinical trial.

Electroacupuncture for postoperative ileus after laparoscopic surgery on colorectal cancer: study protocol for a randomized controlled trial.

BACKGROUND: Postoperative ileus (POI) occurs in almost all patients after abdominal laparoscopic surgery, resulting in complications and increasing the length of hospitalization. Electroacupuncture has been used as an alternative therapy for gastrointestinal dysfunction, but its efficacy for POI is inconclusive. The study is designed to determine whether electroacupuncture can accelerate recovery from POI. METHODS/DESIGN: This study is a three-arm, randomized controlled trial. A total of 105 patients will be randomized into a group receiving electroacupuncture at Tianshu (ST25), a group receiving electroacupuncture at Zusanli (ST36), or a control group in a 1:1:1 ratio. Patients in the electroacupuncture groups will receive electroacupuncture treatment for 4 days from the first day after surgery. The primary outcome consists of the time to first flatus and the time to first defecation. Secondary outcomes include the time to first tolerance of liquid and semiliquid food; the length of the hospital stay; postoperative pain, nausea, and vomiting; abdominal distension; the time to first get out of bed; and postoperative complications. The outcomes will be assessed by the patients themselves every day during hospitalization. Surgeons, nurses, assessors, and statisticians will be blinded to the group assignments. Patients in the two electroacupuncture groups, but not in the control group, will be blinded to the group assignments. The acupuncturists will not be blinded. DISCUSSION: The aim of this trial is to provide a nonpharmacological therapy for POI and may provide evidence of the effect of electroacupuncture at ST25 or ST36 on POI. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027466 . Registered on 14 November 2019.

Standardizing and optimizing acupuncture treatment for irritable bowel syndrome: A Delphi expert consensus study.

BACKGROUND: Acupuncture has been widely utilized for irritable bowel syndrome (IBS). However, heterogeneity is large among therapeutic strategies and protocols. The aim of this study was to propose some down-to-earth recommendations and establish an optimized protocol for acupuncture practice in IBS. METHODS: A panel of 74 traditional Chinese medicine (TCM) acupuncturists participated in clinical issue investigation. Subsequently, systematic reviews concerning acupuncture for IBS were screened within 3 databases. An initial consensus questionnaire was formed from the results of clinical issue investigation and literature review. Ultimately, a Delphi vote was carried out to determine these issues. 30 authoritative experts with extensive experience were requested to respond with agreement, neutrality, or disagreement for the items. Consensus achievement on a given item was defined as greater than 80% agreement. RESULTS: Following a 2-round Delphi survey, there were 19 items reaching consensus; of which 5 items (26.32%) achieved thorough consensus, and significant agreement was reached for the other 14 items. These items can be classified into the 3 major domains: 1) clinical outcomes that acupuncture can bring for favorable intervention population (5 items), 2) suitable therapeutic principles and parameters of acupuncture (13 items), 3) possible adverse events in the treatment (1 item). CONCLUSION: Without any ready-made guidelines and lacking of homogeneity in the published literatures, such expert consensus could be valuable for TCM acupuncturists in daily practice and patients with IBS to obtain appropriate and standardized acupuncture treatment. In addition, it also points out the clinical focus which need to be further explored in future trials.

[Improvement in dyspepsia related symptoms treated with acupuncture in 278 patients with postprandial distress syndrome: a secondary analysis of a multi-center randomized controlled trial].

OBJECTIVE: To evaluate the clinical effect of acupuncture for the improvements in various dyspeptic symptoms of postprandial distress syndrome. METHODS: The secondary analysis on the data of a multi-center randomized controlled trial (RCT) was conducted. 278 patients with postprandial distress syndrome were randomized into an acupuncture group (138 cases) and a sham-acupuncture group (140 cases). In the acupuncture group, acupuncture was applied to Baihui (GV 20), Danzhong (CV 17), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), Zusanli (ST 36), etc. In the sham-acupuncture group, 6 sites, neither located on meridians nor belonged to meridian acupoints, were selected and punctured shallowly. The duration of treatment was 20 min each time, 3 times a week, for 4 weeks totally in the two groups. The follow-up visit lasted for 12 weeks. The scores of dyspeptic symptoms were compared between the two groups before treatment, during treatment (in week 1, 2, 3 and 4) and during follow-up (in week 8, 12 and 16) separately. RESULTS: Besides the scores of early satiety and vomiting in the sham-acupuncture group in week 1, the scores of the other dyspepsia symptoms during treatment and follow-up were all reduced in the two groups as compared with those before treatment (P<0.05). In week 2 and 3, the score of early satiety in the acupuncture group was lower than that in the sham-acupuncture group (P<0.05). In week 3, the scores of postprandial fullness, upper abdominal bloating and belching in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05). In week 4 and during follow-up, the scores of postprandial fullness, early satiety, upper abdominal bloating and belching in the acupuncture group were all lower than those in the sham-acupuncture group (P<0.05). CONCLUSION: Acupuncture remarkably relieves postprandial fullness, early satiety, upper abdominal bloating and belching in patients with postprandial distress syndrome.

Acupuncture for the treatment of diarrheal-predominant irritable bowel syndrome: study protocol for a pilot randomized controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal diseases. Although acupuncture has become a common alternative therapy for IBS, there is insufficient evidence for its effectiveness. This study was designed to assess the efficacy and feasibility of acupuncture in the treatment of IBS. METHODS/DESIGN: This is a multicenter randomized controlled clinical trial. According to the ratio of 1:1:1, 90 patients with irritable bowel syndrome will be randomly divided into specific acupoints (SA) group, non-specific acupoints (NSA) group, and non-acupoints (NA) group. All patients will be treated with acupuncture 12 times within 4 weeks and followed up for 8 weeks. The primary outcome is the response rate, the percentage of patients whose average value of worst abdominal pain is 30% better and the days of loose stool is 50% less than the baseline, at week 4 after randomization. The secondary outcomes include the response rates at other time points, IBS Symptom Severity Scale (IBS-SSS), Patient Health Questionnaire-9 depression scale (PHQ-9), IBS-Quality of Life scale (IBS-QOL), IBS Adequate Relief (IBS-AR), Abdominal Pain Score, Abdominal Bloating Score, Bristol Stool Score (BBS), blinding assessment, and credibility evaluation. Adverse events will be monitored and recorded during the trial. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2000030670. Registered on 9 March 2020.

Electroacupuncture ameliorates intestinal inflammation by activating α7nAChR-mediated JAK2/STAT3 signaling pathway in postoperative ileus.

Inflammatory cytokines produced by muscularis macrophages largely contribute to the pathological signs of postoperative ileus (POI). Electroacupuncture (EA) can suppress inflammation, mainly or partly via activation of vagal efferent. The goal of this study was to investigate the mechanisms by which EA stimulation at an hindlimb region ameliorates inflammation in POI. Methods: Intestinal motility and inflammation were examined after 24 h after intestinal manipulation (IM)-induced POI in mice. Local immune response in the intestinal muscularis, expression of macrophages, α7 nicotinic acetylcholine receptor (α7nAChR), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were determined by flow cytometry, Western Blot, qPCR and immunofluorescence. The effects of α7nAChR antagonists (methyllycaconitine and α-bungarotoxin) and JAK2/STAT3 inhibitors (AG490 and WP1066) were also administered in a subset of mice prior to EA. In the parasympathetic pathways, intestinal motility and inflammation were determined after cervical vagotomy and sub-diaphragmatic vagotomy. The expression of gamma absorptiometry aminobutyric acid (GABAA) receptor in dorsal motor nucleus of vagal (DMV) cholinergic neurons was assessed by immunofluorescence and the response to DMV microinjection of bicuculine (antagonist of GABAA receptor) or muscimol (agonist of GABAA receptor) were assessed. Results: EA suppressed intestinal inflammation and promoted gastrointestinal motility. Mechanistically, EA activated the α7nAChR-mediated JAK2/STAT3 signaling pathway in macrophages which reduced the production of inflammatory cytokines. Furthermore, we also demonstrated that hindlimb region stimulation drove vagal efferent output by inhibiting the expression of GABAA receptor in DMV to ameliorate inflammation. Conclusions: The present study revealed that EA of hindlimb regions inhibited the expression of GABAA receptor in DMV neurons, whose excited vagal nerve, in turn suppressed IM-induced inflammation via activation of α7nAChR-mediated JAK2/STAT3 signaling pathway.

Potential Mechanisms of Acupuncture for Functional Dyspepsia Based on Pathophysiology.

Functional dyspepsia (FD), a common disorder of gastrointestinal function, originated from the gastroduodenum. Although the therapeutic effect of acupuncture has been investigated by various high-quality randomized controlled trials, the potential mechanisms showed obvious heterogeneity. This review summarized the potential mechanisms of acupuncture on FD in order to guide for future laboratory and clinical studies. Here, we argued that the primary cause of FD was gastroduodenal low-grade inflammation and acid exposure, which impaired mucosal integrity, caused brain-gut axis dysfunction, and impaired brain network connectivity, all of which generated various symptom patterns. Overall the clinical studies indicated that acupuncture was a promising treatment to alleviate symptoms in FD patients, whose efficacy was influenced by acupoints and individual variance. Mechanistically, studies with animal models of FD and patients have shown that acupuncture, a non-invasive strategy for nerve stimulation, may have the potential to control intestinal inflammation and suppress acid-secretion via different somatic autonomic reflex pathways, regulate the brain-gut axis through intestinal microbiota, and has the potential to ameliorate FD-symptoms. The cumulative evidence demonstrated that acupuncture is a promising treatment to alleviate symptoms of FD patients.