Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress.

OBJECTIVE: To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill (WYP) on Parkinson's disease (PD) model mice. METHODS: Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal, PD, and PD+WYP groups, 12 mice in each group. One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the classical PD model in mice. Meanwhile, mice in the PD+WYP group were administrated with 16 g/kg WYP, twice daily by gavage. After 14 days of administration, gait test, open field test and pole test were measured to evaluate the movement function. Tyrosine hydroxylase (TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein (GRP78) in striatum and cortex were observed by immunohistochemistry. The levels of TH, GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1α, XBP1, ATF6, CHOP, ASK1, p-JNK, Caspase-12, -9 and -3 in brain were detected by Western blot. RESULTS: Compared with the PD group, WYP treatment ameliorated gait balance ability in PD mice (P<0.05). Similarly, WYP increased the total distance and average speed (P<0.05 or P<0.01), reduced rest time and pole time (P<0.05). Moreover, WYP significantly increased TH positive cells (P<0.01). Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex. Meanwhile, WYP treatment significantly decreased the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1 α, XBP1, CHOP, Caspase-12 and Caspase-9 (P<0.05 or P<0.01). CONCLUSIONS: WYP ameliorated motor symptoms and pathological lesion of PD mice, which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.

Acupuncture for emotional disorders in patients with inflammatory bowel disease: a systematic review protocol.

INTRODUCTION: Emotional disorders are often observed in inflammatory bowel disease (IBD). IBD with emotional disorders leads to poor quality of life. This systematic review aims to assess the effectiveness of acupuncture in patients with IBD with emotional disorders. METHODS AND ANALYSIS: Nine electronic databases, including Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Allied and Complementary Medicine Database, Cumulative Index to Nursing & Allied Health Literature, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database and Wanfang Database, will be searched from inception to October 2021 without language restriction. The grey literature containing conference proceedings, as well as systematic reviews listed in the reference of definite publications, will also be retrieved. Randomised controlled trials either in English or Chinese reporting acupuncture therapy for IBD with emotional disorders will be included. The primary outcome is changes of emotional functioning outcomes. The Colitis Activity Index, Crohn's Disease Activity Index, C reactive protein and adverse events will be assessed as the secondary outcomes. More than two assessors will conduct the study retrieval and selection, as well as the data extraction and evaluation of the risk of bias. Data synthesis will be performed using a random-effects model based on the results of heterogeneity. Data analysis will be performed using RevMan software (V.5.4). Moreover, the dichotomous data will be presented as risk ratios, and the continuous data will be calculated using weighted mean difference or standard mean difference. ETHICS AND DISSEMINATION: This systematic review contains no individual patient data; thus, ethical approval is not required. Moreover, this review will be disseminated in a peer-reviewed journal or relevant conference. PROSPERO REGISTRATION NUMBER: CRD42020176340.

Therapeutic effects and central mechanism of acupuncture and moxibustion for treating functional dyspepsia: study protocol for an fMRI-based randomized controlled trial.

BACKGROUND: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, with a high prevalence and significant influence on the quality of life (QoL). Either acupuncture or moxibustion is effective for dyspepsia, which is confirmed by both ancient documents and modern research. However, the therapeutic advantage and underlying mechanism between acupuncture and moxibustion for FD remain unclear. METHODS: This randomized controlled fMRI trial aims to (i) evaluate the therapeutic advantages of acupuncture and moxibustion treatment for FD, (ii) investigate the similarities and differences in cerebral activity elicited by acupuncture and moxibustion, and (iii) analyze the possible correlations between brain responses and clinical variables thus to explore the potential central mechanism of acupuncture and moxibustion for treating FD. Ninety-two FD patients will be randomly assigned to either the acupuncture group or the moxibustion group in a 1:1 ratio. Twenty sessions of acupuncture or moxibustion treatment over 4 weeks will be performed on each patient. The short form Leeds Dyspepsia Questionnaire, the Nepean Dyspepsia Index, etc., are used to evaluate the therapeutic effects. The heart rate variability will be analyzed to investigate the autonomic nerve function. Thirty-six FD patients in each group will be randomly selected for the fMRI scan to detect cerebral activity changes. DISCUSSION: We expect the results will deepen our knowledge on the clinical value and underlying mechanism of acupuncture and moxibustion and provide a reference for a better selection of interventions for treating FD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100049496. Registered on 2 August 2021.

Effectiveness and safety of acupuncture for angina pectoris: An overview of systematic reviews.

Background: The number of systematic reviews meta-analyses (SRs/MAs) on the effectiveness of acupuncture for angina pectoris (AP) is increasing. Due to the inconsistent conclusions and unknown quality of these SRs/MAs, this overview aimed to systematically evaluate and synthesize the existing SRs/MAs, attempting to provide more reliable evidence for the effectiveness and safety of acupuncture in the treatment of AP. Methods: SRs/MAs were searched via eight databases from inception to March 14, 2022. The risk of bias was evaluated using the Risk of Bias in Systematic reviews (ROBIS) tool. The quality of the methodology, reporting, and evidence were assessed by the Assess Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Item for Systematic Review and Meta-analysis for Acupuncture (PRISMA-A), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, respectively. Results: Sixteen SRs/MAs were included and fifteen SRs/MAs were considered being of critically low quality according to AMSTAR-2. Only three SRs/MAs were rated at low risk of bias. No study reported all the items listed in the PRISMA-A checklist. No high-quality evidence with GRADE assessment was found. With the low-quality evidence, acupuncture combined with other interventions was superior to monotherapy (medications or Chinese medicine) in the angina symptom and electrocardiogram recovery. No adverse effects owing to acupuncture were reported. Conclusions: Owing to the lack of high-quality evidence provided by the current SRs/MAs, the effectiveness of acupuncture for AP still warrants further proof. Further researches with more critical design and methodology are needed for providing more convincing evidence. Registration: This review was registered at PROSPERO (www.crd.york.ac.uk/prospero/): CRD42021219367.

Effectiveness and safety of acupuncture therapy for inflammatory bowel disease: a protocol of systematic review and meta-analysis.

INTRODUCTION: Previous reviews have suggested that the effectiveness of acupuncture for inflammatory bowel disease (IBD) has not well been demonstrated due to the limited randomised controlled trials (RCTs). In recent years, the growing research on acupuncture for IBD make it possible to conduct a further systematic review and synthesise more sufficient clinical data to evaluate the effectiveness and safety of acupuncture for IBD. METHODS AND ANALYSIS: Nine electronic databases without language restriction will be retrieved from inception to March 2021, including the Cochrane Library, MEDLINE, EMBASE, Ovid, the Allied and Complementary Medicine Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, the Chongqing Chinese Science and Technology Periodical Database and Wanfang Database. The RCTs on acupuncture for IBD will be included. The data screening, data extraction and the assessment of risk bias will be performed respectively by two reviewers. The quality of evidence will be evaluated by using the Grading of recommendation Assessment, Development and Evaluation application. The meta-analysis will be performed if heterogeneity analysis conducted on the RevMan software (V.5.3) is insignificant. The primary outcome was symptoms alleviation after acupuncture treatment or even in the follow-up. ETHICS AND DISSEMINATION: Ethical approval will not be needed because data of this review are not involved in patient's information and privacy. The results will be published and diffused in a peer-reviewed journal or relative conferences. TRIAL REGISTRATION NUMBER: CRD42020157903.

The cerebral mechanism underlying the acupoints with specific effect for gallbladder stone disease: protocol for a randomized controlled task-fMRI trial.

BACKGROUND: As it has been recorded in ancient Chinese classics, Yanglingquan (GB34) and Dannangxue (EX-LE6) are two important acupoints that can regulate the function of the gallbladder. Acupuncture at these two acupoints is considered particularly effective for gallbladder disease treatment, especially for alleviating gallbladder stone disease (GSD) symptoms that can be aggravated after intaking high-fat food. However, the superior effect between the two acupoints still needs to be further explored, as well as the underlying central mechanism has never been investigated to date. METHODS AND DESIGN: Ninety participants diagnosed with GSD will be randomly divided into group A (acupuncture at GB34), group B (acupuncture at EX-LE6), and group C (acupuncture at non-acupoint) in a ratio of 1:1:1. All of them will receive a 30-min acupuncture treatment with fatty-food cues being presented before and after acupuncture. During the task, participants will be scanned by MRI and required to rate their desire for high-/low-fat food with an 11-point Likert scale. Additionally, the participants' pain/discomfort sensation will be evaluated using the Numeric Rating Scale (NRS) at four timepoints, including before the 1st task fMRI scan, before and after acupuncture, and after the 2nd task fMRI scan. For both behavior and fMRI data, the ANOVA analysis will be conducted among three groups to testify the immediate effect of GB34 and EX-LE6. The post hoc t-test will be employed to further explore the superiority between acupuncture with GB34 and EX-LE6. Furthermore, correlation analyses will be conducted to investigate a possible correlation between neural changes and clinical data. DISCUSSION: In comparison to the non-acupoint, the results will firstly explore the superior effect between acupuncture with GB34 and EX-LE6 on GSD patients by observing their behavioral and neural response change to fatty-food cue, and then to investigate the underlying central mechanism. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000034368 . Registered on 3 July 2020.

[Review on characteristics of acupuncture-activated network regulatory effect based on brain connectomics].

The network analysis method based on brain connectomics is an important entry point to explore the working mechanism of brain and is also the current trend of researches on acupuncture stimulation-induced changes of neuroimages. We, in the present review, summarized the common network analysis methods for exploring the underlying mechanisms of brain network-mediated regulatory effects of acupuncture interventions. Moreover, combining the current research development and our team's previous research findings, we extracted the characteristics of targeting, conditionity and dynamic of regulatory effects of acupuncture-activated brain network, and put forward our prospects about the future research from the aspects of new scanning modes (for instance, multimodal data acquisition of magnetic resonance, electroencephalogram, near infrared spectrum, etc.), network analysis (such as Granger causality analysis, complex network measures, whole-brain connectivity dynamics tracking, high-order resting-state functional connectivity analysis, etc.) and experimental research paradigms (for example, introduce of transcranial magnetic stimulation induced transient changes of brain functional activity, machine learning approach, etc.).

Efficacy of Acupuncture Treatment of Migraine Delivered by Senior or Junior Acupuncturists: Study Protocol for a Randomized Controlled Trial.

INTRODUCTION: Acupuncture is an efficacious and safe treatment choice for migraine prevention. Results from clinical trials have shown that non-specific effects play an important role in acupuncture's efficacy. To date, however, there is no evidence available quantitatively evaluating the effect of non-specific effects, such as patients' expectations and beliefs for acupuncturists, on acupuncture efficacy, necessitating further exploration. METHODS: A total of 156 patients with migraine without aura (MwoA) will be randomized to either junior or senior acupuncturist group, at a ratio of 1:1. The study will last 24 weeks, for each patient, comprising baseline, treatment, and follow-up phases lasting 4, 8, and 12 weeks, respectively. All patients will undergo 12 sections of acupuncture treatment delivered by either a junior or senior acupuncturist following the same acupuncture prescription and manipulation. The primary outcomes will be changes in the number of migraine days and frequency of attacks per 4 weeks cycle, relative to the baseline. Secondary outcomes will include severity of headache pain, quality of life, anxiety/depression levels, and use of non-steroidal anti-inflammatory drugs (NSAIDs) per 4 weeks cycle, compared to the baseline, as well as adverse events and rate of positive response to treatment. Prior to randomization of patients into junior or senior acupuncturist groups, the Acupuncture Expectations Evaluation Scale (AES) will be used to evaluate their expectations and belief with regards to acupuncture efficacy delivered by senior or junior acupuncturists. DISCUSSION: Results from this clinical randomized controlled trial will help to quantitatively evaluate the extent of the effect of acupuncture treatment delivered by a senior or junior acupuncturist (high relative to low expectations) in migraine patients. ETHICS AND DISSEMINATION: This trial has been approved by the Institutional Review Boards and Ethics Committees of Hospital of Chengdu University of Traditional Chinese Medicine (Approval No. 2020KL-058).

[Acupuncture combined with opioid drugs on moderate and severe cancer pain: a randomized controlled trial].

OBJECTIVE: To explore the clinical therapeutic effect of acupuncture combined with opioid drugs on moderate and severe cancer pain. METHODS: A total of 60 patients with cancer were randomized into an observation group and a control group, 30 cases in each group. Oxycodonehydrochloride prolonged-release tablet was taken orally in the control group. On the basis of the control group, acupuncture was applied at Hegu (LI 4), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6), etc. Corresponding back-shu points, xi-cleft points and ashi points were selected additionally according to primary viscera and pain sites in the observation group. The treatment was given once a day for 2 weeks. Symptomatic and supportive treatment were implanted, and no other antalgic measures were given during the trial. The daily dosage of opioid drug and the adverse reactions were recorded in both groups. Karnofsky performance status (KPS) and quality of life (QOL) scale scores were compared before and after treatment. Numerical rating scale (NRS) score was calculated to evaluate the clinical therapeutic effect. RESULTS: Compared before treatment, the daily dosage of opioid drugs after treatment was obviously reduced in the observation group (P<0.01), and was obviously increased in the control group (P<0.05). The dosage of opioid drugs after treatment in the observation group was much less than the control group (P<0.01). After treatment, the KPS and QOL scores were increased in both groups (P<0.01), and the scores in the observation group were superior to the control group (P<0.01, P<0.05). The analgesic effective rate was 90.0% (27/30) in the observation group, which was superior to 76.7% (23/30) in the control group (P<0.05). The adverse reactions rate in the observation group was lower than the control group (P<0.01). CONCLUSION: Acupuncture combined with opioid drugs can effectively relieve the cancer pain, improve the performance status and quality of life in cancer patients, reduce the dosage of opioid drugs and adverse reactions rate.

Acupuncture for emotional disorders in patients with migraine: a systematic review protocol.

INTRODUCTION: Migraine is the second-leading cause of years lived with disability worldwide. The high prevalence of migraine-related emotional disorders is often overlooked. Acupuncture is often used to treat both migraine and emotional disorders. This systematic review protocol aims to analyse whether acupuncture is effective for treating emotional disorders in patients with migraine. METHODS AND ANALYSIS: Nine databases will be searched from inception to may 2019: cochrane central register of controlled trials, medline, embase, allied and complementary medicine database, cinahl, china national knowledge infrastructure, chinese biomedical literature database, vip database and wanfang database. Randomised controlled trials (rcts) of acupuncture therapy for migraine with emotional functioning outcomes, which were reported in chinese or english, will be included. The primary outcome is the change in emotional functioning. Study selection, data extraction and assessment of the risk of bias will be performed independently by two or more reviewers. Revman software (v.5.3) will be used to perform the assessment of the risk of bias and data synthesis. ETHICS AND DISSEMINATION: Ethics approval is not be needed because the data will not contain individual patient data, and there are no concerns about privacy. The results of this meta-analysis will be disseminated through publication in a peer-reviewed journal or relevant conference. TRIAL REGISTRATION NUMBER: CRD42019139433.

[Progress and prospect of machine learning in research of acupuncture and moxibustion].

The application progress of machine learning in research of acupuncture and moxibustion was reviewed from three aspects: mining of acupuncture and moxibustion prescription and indications, acupuncture efficacy prediction and its influencing factors, acupoint specificity and acupuncture manipulation research, and the existing problems in current research and future research trends were discussed. It is believed that the appropriate machine learning algorithm should be selected to build the model according to the research purpose and data characteristics in the future research; attention should be paid to feature design, feature selection and feature cleaning; sample data collection should be a priority, and data sharing platform and standardized data collection should be developed to improve the data quality.

Cerebral mechanism of puncturing at He-Mu point combination for functional dyspepsia: study protocol for a randomized controlled parallel trial.

Acupuncture is widely used to treat functional dyspepsia with satisfactory outcomes. Combination of the He and Mu acupoints is commonly used and has a synergistic effect on functional dyspepsia; however, its underlying mechanisms remain unclear. Therefore, a randomized controlled parallel clinical trial is currently underway at Chengdu University of Traditional Chinese Medicine, China. This trial is designed to explore the efficacy of and central responses to the He-Mu point combination in patients with functional dyspepsia using functional magnetic resonance imaging. A total of 105 patients with functional dyspepsia will be allocated into 3 groups: the low-He point group (puncturing at Zusanli (ST36)), Mu point group (puncturing at Zhongwan (CV12)), and He-Mu point combination group (puncturing at ST36 and CV12). Every participant will receive 20 sessions of manual acupuncture for 4 weeks. The needles will be inserted perpendicularly to a depth of 1 to 2 cun. The angle of rotation and twisting will range from 90 to 180 degrees, while lifting and thrusting will range from 0.3 to 0.5 cm. The various manipulations will be performed 60 to 90 times per minute. The needles will remain in place for 30 minutes, during which manipulation will be applied every 10 minutes. Magnetic resonance imaging will be performed before and after 20 sessions of acupuncture. The primary outcome is symptom improvement according to the Chinese version of the Nepean Dyspepsia Index. Secondary outcomes include the Leeds dyspepsia questionnaire, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Beck Anxiety Inventory, Beck Depression Inventory, and visual analogue scale scores before and after 10 and 20 sessions of acupuncture. Needle sensation and adverse events will be used to assess the therapeutic effects. This study will promote more widespread awareness of the benefits of acupoint combination in the clinical setting and provide a further explanation of the neuromechanism by which acupuncture at the He-Mu point combination for functional dyspepsia. Registration: Chinese Clinical Trial Registry, ChiCTR-IOR-15006402.

[Effect of Moxibustion Stimulation of "Feishu" (BL 13) and "Xinshu" (BL 15) on Expression of Myocardial MyD 88 Protein and Caspase 3 mRNA in Chronic Heart Failure Rats].

OBJECTIVE: To observe the effect of moxibustion stimulation of "Feishu" (BL 13) and "Xinshu" (BL 15) on pathological changes of myocardium and the expression of myocardial myeloid differentiation factor 88 (MyD 88) protein and Caspase 3 mRNA in chronic heart failure (CHF) rats, so as to explore its mechanism underlying improvement of CHF. METHODS: SD male rats were randomly divided into normal (n=9), model (n=8), moxibustion (n=8), medication (n=8) and moxibustion + medication (n=8) groups. In addition, the other 6 rats (3/normal and 3/model groups) were used for measuring cardiac ventricle weight and H.E. stain. The CHF model was made by intraperitoneal injection of Adriamycin (ADR, from 1 to 4 mg/kg, once every other day for 15 days). Mild moxibustion was applied to bilateral BL13 and BL15 for 15 min, once daily for 3 weeks. Rats of the medication group were treated by Captopril (gavage) for 3 weeks. The expression of myocardial Caspase 3 mRNA and MyD 88 protein of the left ventricle was determined by quantitative real time-PCR and Western blot, respectively. RESULTS: In comparison with the normal group, the myocardial damage (cell swelling, cytoplasma vaculation, and disordered arrangement, rupture and lysis of some cardiac muscle fibers), and the expression levels of myocardial MyD 88 protein and Caspase 3 mRNA were obviously increased in the model group(P<0.01). After the interventions, the myocardial damage was relatively milder, and the expression of myocardial MyD 88 protein and Caspase 3 mRNA were significantly down-regulated in the moxibustion, me-dication and moxibustion+medication groups in comparison with the model group(P<0.05). No significant differences were found among the 3 treatment groups in the expression levels of MyD 88 protein and Caspase 3 mRNA(P>0.05). CONCLUSIONS: Moxibustion intervention can suppress CHF induced up-regulation of expression of myocardial MyD 88 protein and Caspase 3 mRNA in rats, which may contribute to its effect in relieving myocardial injury.

[Current Status of Researches on Brain-imaging Responses of Acupuncture Stimulation Based on Functional Magnetic Resonance Imaging].

Using functional magnetic resonance imaging (fMRI) to investigate the underlying mechanisms of acupuncture therapy attracts an increasing attention nowadays. In the present article, the authors make a brief analysis on the progresses of researches about the intra-brain responses of acupuncture stimulation following collecting original research papers with key words of "acupuncture","fMRI" and "magnetic resonance imaging" in PubMed and CNKI databases from January 2003 to December 2014. As a result, a total of 253 original research articles were collected. We found that:1) in the past 10 years, the amount of fMRI studies on acupuncture is growing; 2) most of these studies (183) are conducted in healthy subjects, and fewer studies (44) conducted in patients with problems of neurology, psychonosology, gastroenterology, circulation system, pediatrics, myopia and dermatology, or with pain; 3)a larger population of studies are designed to reveal the specificity of responses of acupuncture point stimulation, and fewer focus on analyzing the regularities of acupuncture points combination. The authors suggest that the coming acupuncture-neuroimaging studies need to expand the research ranges or contents, and improve experimental designs, data analysis and quality control (for example, reducing differences of baseline data, age span, psychological state, etc., and increasing sample size, etc).