Objective:Pre-mRNA alternative splicing(AS)is an important post-transcriptional regulation mechanism.The abnormal splicing of genes can lead to cardiovascular diseases.Acupuncture has been shown to alleviate myocardial ischemia-reperfusion injury(MIRI),but most studies have focused on the regulation of gene expression by acupuncture.Previously,we reported that electroacupuncture(EA)can relieve angina by regulating the AS of GABARG2;however,the genome-wide regulation of AS by EA remains unknown. Methods:We explored the protective effects of EA on MIRI.We then studied the AS profiles retrieved from the previously submitted to Gene Expression Omnibus(GEO)database and analyzed the data using the replicate multivariate analysis of transcript splicing(rMATS)tool.Subsequently,we conducted validation experiments on splicing regulatory factors and their target genes modulated by EA,as identified through bioinformatics analysis. Results:The results showed that EA at PC6 point could effectively alleviate MIRI.More than 200 differential alternative splicing events(ASEs)changed following MIRI.The differential ASEs underwent protein-protein interaction(PPI)network analysis,gene ontology(GO)enrichment,and pathway analysis,and were shown to be involved in distinct biological functions,especially in the maintenance of synaptic structure.Enrichment analysis also identified several pathways that are potentially associated with the progression of MIRI.Importantly,we identified critical ASEs and pathways that could be completely rescued by EA treatment.In the validation experiments,we found that AS of the key gene CAMK2G,associated with synaptic function,is regulated by the expression level of the MBNL1 protein modulated by EA. Conclusions:Our results indicate that EA is not only an effective procedure to protect against MIRI by rescuing gene expression but also rescues abnormal ASEs.This study is a major contribution to a genome-wide comprehensive analysis of the regulation of AS by EA in MIRI.

This study explored how the weight-adjusted waist index (WWI) and a body shape index (ABSI) are related to serum neurofilament light chain (sNfL) levels among U.S. adults. We aimed to evaluate sNfL, which plays key roles in neuronal injury in neurological diseases, given its understudied connection to obesity. We used cross-sectional data from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) of people with complete information on the weight-adjusted waist index (WWI), a body shape index (ABSI), and serum neurofilament light chain (sNfL). Multiple linear regression analysis allowed us to investigate the separate connections among the WWI, ABSI, and sNfL. Moreover, interaction testing and subgroup analysis were performed to improve the general validity of our results. To assess any nonlinear correlations, we also performed threshold effect analysis and smoothed curve fitting. WWI and ABSI were positively linked with sNfL (WWI: β = 0.05, 95

Postprandial distress syndrome (PDS) is the most common functional dyspepsia (FD) subtype. Early satiety is one of the cardinal symptoms of the PDS subtype in FD patients. The heterogeneity of symptoms in FD patients hampered therapy for patients based on specific symptoms, necessitating a symptom-based understanding of the pathophysiology of FD. To investigate the correlation between reward circuit and symptom severity of PDS patients, seed (Nucleus accumbens, NAc, a key node in the reward circuit) based resting-state functional connectivity (FC) was applied in the neuroimaging data analysis. The results demonstrated that the patients with PDS manifested strengthened FC between NAc and the caudate, putamen, pallidum, amygdala, hippocampus, thalamus, anterior cingulate cortex (ACC), and insula. Moreover, the FC between NAc and ACC, insula, thalamus, and hippocampus exhibited significant positive associations with symptom severity. More importantly, the strengthened FC between NAc and the ACC, insula, amygdala, and hippocampus were found associated with the early satiety symptom of patients with PDS. This study indicated that the altered FC of reward circuit regions may play a role in the pathophysiology of patients with PDS, and some of the aberrant NAc-based FC within the reward circuit were more related to the early satiety of patients with PDS. These findings improve our symptom-based understanding of the central pathophysiology of FD, lay the groundwork for an objective diagnosis of FD, and shed light on the precise prescription for treating FD based on symptoms.

Objective To clarify the key outcomes of acupuncture-moxibustion treatment of ulcerative colitis.Methods The clinical randomized controlled trials(RCTs)for ulcerative colitis treated with acupuncture and moxibustion were searched from CNKI,Wanfang,VIP,SinoMed,PubMed,EMbase,Cochrane Library,and Web of Science,from the inception of each database to March 20th,2023.The basic information of literature,intervention measures and outcome indexes were collected.The selection of primary and secondary outcomes,the use frequency of each index and the combination of them in utility were analyzed;and index domains of acupuncture and moxibustion for ulcerative colitis were summarized.Results A total of 215 RCTs were included and 54 outcomes were involved,classified into 6 categories,i.e.TCM syndromes,symptoms/physical signs,physical and chemical tests,quality of life,long-term prognosis and safety events.The top 3 outcomes with high use frequency were clinical effect evaluation,adverse reactions of acupuncture and moxibustion and the score of main symptoms.Only 3 articles clearly reported the primary outcome and the secondary ones,180 articles used two types of outcomes simultaneously,3 articles clearly described the time points of the observation indexes,and 126 articles determined the sources of the evaluation criteria of therapeutic effect,with 57 criteria involved.Conclusion At present,the outcomes have not been standardized in RCTs of acupuncture and moxibustion for ulcerative colitis.It needs to clarify the primary one and the secondary ones.The criteria have not been unified for the evaluation of therapeutic effects and there is less consideration on the quality of life in patients,the follow-up visit and safety events.The attention should be paid to develop the outcome set,in which,the endoscopic score is taken as the objective,and the improvements in the symptoms/physical signs and the biochemical examination as the supplementary.

ObjectiveTo summarize the general information and hotspots of functional near-infrared spectroscopy (fNIRS)-based clinical disease research over the past 10 years and provide some references for future research.MethodsThe related literature published between 1 January 2011 and 31 January 2022 was retrieved from the Web of Science core database (WoS). Bibliometric visualization analysis of countries/regions, institutions, authors, journals, keywords and references were conducted by using CiteSpace 6.1.R3.ResultsA total of 467 articles were included, and the annual number of articles published over nearly a decade showed an upward trend year-by-year. These articles mainly come from 39 countries/regions and 280 institutions. The representative country and institution were the USA and the University of Tubingen. We identified 266 authors, among which Andreas J Fallgatter and Ann-Christine Ehlis were the influential authors. Neuroimage was the most co-cited journal. The major topics in fNIRS disease research included activation, prefrontal cortex, working memory, cortex, and functional magnetic resonance imaging (fMRI). In recent years, the Frontier topics were executive function, functional connectivity, performance, diagnosis, Alzheimer’s disease, children, and adolescents. Based on the burst of co-cited references, gait research has received much attention.ConclusionThis study conducted a comprehensive, objective, and visual analysis of publications, and revealed the status of relevant studies, hot topics, and trends concerning fNIRS disease research from 2011 to 2022. It is hoped that this work would help researchers to identify new perspectives on potential collaborators, important topics, and research Frontiers.

BackgroundNeuroimaging studies have identified aberrant activity patterns in multiple brain regions in functional dyspepsia (FD) patients. However, due to the differences in study design, these previous findings are inconsistent, and the underlying neuropathological characteristics of FD remain unclear.MethodsEight databases were systematically searched for literature from inception to October 2022 with the keywords “Functional dyspepsia” and “Neuroimaging.” Thereafter, the anisotropic effect size signed the differential mapping (AES-SDM) approach that was applied to meta-analyze the aberrant brain activity pattern of FD patients.ResultsA total of 11 articles with 260 FD patients and 202 healthy controls (HCs) were included. The AES-SDM meta-analysis demonstrated that FD patients manifested increased activity in the bilateral insula, left anterior cingulate gyrus, bilateral thalamus, right precentral gyrus, left supplementary motor area, right putamen, and left rectus gyrus and decreased functional activity in the right cerebellum compared to the HCs. Sensitivity analysis showed that all these above regions were highly reproducible, and no significant publication bias was detected.ConclusionThe current study demonstrated that FD patients had significantly abnormal activity patterns in several brain regions involved in visceral sensation perception, pain modulation, and emotion regulation, which provided an integrated insight into the neuropathological characteristics of FD.

Whilst acupuncture has been shown to be an effective treatment for functional dyspepsia (FD), its efficacy varies significantly among patients. Knowing beforehand how each patient responds to acupuncture treatment will facilitate the ability to produce personalized prescriptions, therefore, improving acupuncture efficacy. The objective of this study was to construct the prediction model, based on the clinical-neuroimaging signature, to forecast the individual symptom improvement of FD patients following a 4-week acupuncture treatment and to identify the critical predictive features that could potentially serve as biomarkers for predicting the efficacy of acupuncture for FD. Clinical-functional brain connectivity signatures were extracted from samples in the training-test set (100 FD patients) and independent validation set (60 FD patients). Based on these signatures and support vector machine algorithms, prediction models were developed in the training test set, followed by model performance evaluation and predictive features extraction. Subsequently, the external robustness of the extracted predictive features in predicting acupuncture efficacy was evaluated by the independent validation set. The developed prediction models possessed an accuracy of 88% in predicting acupuncture responders, as well as an R2 of 0.453 in forecasting symptom relief. Factors that contributed significantly to stronger responsiveness of patients to acupuncture therapy included higher resting-state functional connectivity associated with the orbitofrontal gyrus, caudate, hippocampus, and anterior insula, as well as higher baseline scores of the Symptom Index of Dyspepsia and shorter durations of the condition. Furthermore, the robustness of these features in predicting the efficacy of acupuncture for FD was verified through various machine learning algorithms and independent samples and remained stable in univariate and multivariate analyses. These findings suggest that it is both feasible and reliable to predict the efficacy of acupuncture for FD based on the pre-treatment clinical-neuroimaging signature. The established prediction framework will promote the identification of suitable candidates for acupuncture treatment, thereby improving the efficacy and reducing the cost of acupuncture for FD.

BACKGROUND:The analgesic effect of acupuncture is widely recognized, but the mechanical characteristics of acupuncture for pain relief, compared to non-steroidal anti-inflammatory (NSAIDs) and placebo medication, remain unknown.AIMS:To compare the modulation effects of acupuncture treatment with NSAIDs and placebo medication on descending pain modulation system (DPMS) in knee osteoarthritis (KOA) patients.METHODS:This study recruited 180 KOA patients with knee pain and 41 healthy controls (HCs). Individuals with KOA knee pain were divided randomly into groups of verum acupuncture (VA), sham acupuncture (SA), celecoxib (SC), placebo (PB), and waiting list (WT), with 36 patients in each group. VA and SA groups included ten sessions of puncturing acupoints or puncturing non-acupoints acupuncture treatment for two successive weeks. Celecoxib capsules were continuously given orally to patients in the SC group at a dosage of 200 mg daily for 2 weeks. In the PB group, patients received a placebo capsule once a day for 2 weeks at the same dosage as celecoxib capsules. In the WL group, patients did not receive any treatment. Patients underwent a resting-state BOLD-fMRI scan pre- and post-receiving the therapy, whereas HCs only underwent a baseline scan. Seed (ventrolateral periaqueductal gray, vlPAG, a key node in DPMS) based resting-state functional connectivity (rs-FC) was applied in the data analysis.RESULTS:All groups demonstrated improved knee pain scores relative to the initial state. There was no statistical difference between the VA and SA groups in all clinical outcomes, and vlPAG rs-FC alterations. KOA knee pain individuals reported higher vlPAG rs-FC in the bilateral thalamus than HCs. KOA knee pain patients in the acupuncture group (verum + sham, AG) exhibited increased vlPAG rs-FC with the right dorsolateral prefrontal cortex (DLPFC) and the right angular, which is associated with knee pain improvement. In contrast with the SC and PB group, the AG exhibited significantly increased vlPAG rs-FC with the right DLPFC and angular. Contrary to the WT group, the AG showed greater vlPAG rs-FC with the right DLPFC and precuneus.CONCLUSIONS:Acupuncture treatment, celecoxib, and placebo medication have different modulation effects on vlPAG DPMS in KOA knee pain patients. Acupuncture could modulate vlPAG rs-FC with brain regions associated with cognitive control, attention, and reappraisal for knee pain relief in KOA patients, compared with celecoxib and placebo medication.

Background Biliary colic (BC) is a frequent hepatobiliary disorder encountered in emergency departments. Acupuncture may be effective as an alternative and complementary medicine for BC. Nonetheless, rigorous trials investigating its efficacy are lacking. Therefore, the aim of this study protocol is to determine whether acupuncture provides immediate relief of pain and associated symptoms in BC patients. Method Eighty-six participants who aged from 18 to 60 years with BC will be recruited in the First People's Hospital of Longquanyi District, Chengdu (West China Longquan Hospital Sichuan University). All participants will be allocated into two treatment groups including acupuncture group and sham acupuncture group using a 1:1 ratio. Each group will only receive a single 30-min needle treatment while waiting for their test results after completing the routine examination for BC. The primary outcome of the study is to assess the change in pain intensity after the 30-min acupuncture treatment. The secondary outcomes of the study include the change in pain intensity at various time points, the degree of gastrointestinal symptoms at different time points, the level of anxiety experienced during pain episodes at different time points, the score of Pain Anxiety Symptoms Scale-20 (PASS-20), the score of Fear of Pain Questionnaire-III (FPQ-III), and the score of Pain Catastrophizing Scale (PCS), among others. Discussion The results of this research will provide substantial evidence regarding the efficacy of acupuncture in alleviating symptoms associated with BC. Trial registration ClinicalTrials.gov, ChiCTR2300070661. Registered on 19 April 2023.

Acupuncture is effective in treating functional dyspepsia (FD), while its efficacy varies significantly from different patients. Predicting the responsiveness of different patients to acupuncture treatment based on the objective biomarkers would assist physicians to identify the candidates for acupuncture therapy. One hundred FD patients were enrolled, and their clinical characteristics and functional brain MRI data were collected before and after treatment. Taking the pre-treatment functional brain network as features, we constructed the support vector machine models to predict the responsiveness of FD patients to acupuncture treatment. These features contributing critically to the accurate prediction were identified, and the longitudinal analyses of these features were performed on acupuncture responders and non-responders. Results demonstrated that prediction models achieved an accuracy of 0.76 ± 0.03 in predicting acupuncture responders and non-responders, and a R2 of 0.24 ± 0.02 in predicting dyspeptic symptoms relief. Thirty-eight functional brain network features associated with the orbitofrontal cortex, caudate, hippocampus, and anterior insula were identified as the critical predictive features. Changes in these predictive features were more pronounced in responders than in non-responders. In conclusion, this study provided a promising approach to predicting acupuncture efficacy for FD patients and is expected to facilitate the optimization of personalized acupuncture treatment plans for FD.

IntroductionEmotional 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 analysisNine 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 disseminationThis 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 numberCRD42020176340.

Functional dyspepsia (FD) is a disorder of gut-brain interaction. Previous studies have demonstrated a wide range of abnormalities in functional brain activity and connectivity patterns in FD. However, the connectivity pattern of the subcortical network (SCN), which is a hub of visceral information transmission and processing, remains unclear in FD patients. The study compared the resting-state functional connectivity (rsFC) and the global and nodal topological properties of SCN between 109 FD patients and 98 healthy controls, and then explored the correlations between the connectivity metrics and clinical symptoms in FD patients. The results demonstrated that FD patients manifested the increased rsFC in seventeen edges among the SCN, decreased small-worldness and local efficiency in SCN, as well as increased nodal efficiency and nodal degree centrality in the anterior thalamus than healthy controls (p < 0.05, false discovery rate corrected). Moreover, the rsFC of the right anterior thalamus-left nucleus accumbens edge was significantly correlated with the NDSI scores (r = 0.255, p = 0.008, uncorrected) and NDLQI scores (r = -0.241, p = 0.013, uncorrected), the nodal efficiency of right anterior thalamus was significantly correlated with NDLQI scores (r = 0.204, p = 0.036, uncorrected) in FD patients. This study indicated the abnormal rsFC pattern, as well as global and nodal topological properties of the SCN, especially the bilateral anterior thalamus in FD patients, which enhanced our understanding of the central pathophysiology of FD and will lay the foundation for the objective diagnosis of FD and the development of new therapies.

Background Acupuncture is an effective adjunctive therapy for chronic stable angina pectoris (CSAP), while the underlying mechanism is unclear. This study aimed to investigate the central pathophysiology of CSAP and explore the mechanism of different acupoint prescriptions for CSAP from the perspective of brain-heart interaction. Methods Thirty-seven CSAP patients and sixty-five healthy subjects (HS) were enrolled, and thirty CSAP patients were divided into two acupoint prescriptions groups (Group A: acupoints on the meridian directly related to the Heart; Group B: acupoints on the meridian indirectly related to the Heart). The Magnetic Resonance Imaging data and clinical data were collected at baseline and after treatment. The comparisons of brain spontaneous activity patterns were performed between CSAP patients and HS, as well as between baseline and after treatment in CSAP patients. Then, the changes in resting-state functional connectivity before and after treatment were compared between the two acupoint prescriptions. Results Chronic stable angina pectoris patients manifested higher spontaneous activity on the bilateral calcarine, left middle occipital gyrus, right superior temporal gyrus, and right postcentral gyrus. After acupuncture treatment, the spontaneous activity of the left calcarine, left cuneus, and right orbitofrontal gyrus was decreased. The left calcarine was identified as region-of-interest for functional connectivity analysis. Compared with group B, CSAP patients in group A had significantly increased functional connectivity between left calcarine and the left inferior temporal gyrus/cerebellum crus 1, left hippocampus, left thalamus, and left middle cingulate cortex after treatment. Thresholds for all comparisons were p < 0.05, Gaussian Random Field corrected. Conclusion Regulating the aberrant spontaneous activity of the calcarine might be an underlying mechanism of acupuncture for CSAP. The multi-threaded modulation of functional connectivity between calcarine and multiple pain-related brain regions might be a potential mechanism for better efficacy of acupuncture at points on the meridian directly related to the Heart.

Background Acupuncture is safe and effective for functional dyspepsia (FD), while its efficacy varies among individuals. Predicting the response of different FD patients to acupuncture treatment in advance and therefore administering the tailored treatment to the individual is consistent with the principle of predictive, preventive, and personalized medicine (PPPM/3PM). In the current study, the individual efficacy prediction models were developed based on the support vector machine (SVM) algorithm and routine clinical features, aiming to predict the efficacy of acupuncture in treating FD and identify the FD patients who were appropriate to acupuncture treatment. Methods A total of 745 FD patients were collected from two clinical trials. All the patients received a 4-week acupuncture treatment. Based on the demographic and baseline clinical features of 80% of patients in trial 1, the SVM models were established to predict the acupuncture response and improvements of symptoms and quality of life (QoL) at the end of treatment. Then, the left 20% of patients in trial 1 and 193 patients in trial 2 were respectively applied to evaluate the internal and external generalizations of these models. Results These models could predict the efficacy of acupuncture successfully. In the internal test set, models achieved an accuracy of 0.773 in predicting acupuncture response and an R-2 of 0.446 and 0.413 in the prediction of QoL and symptoms improvements, respectively. Additionally, these models had well generalization in the independent validation set and could also predict, to a certain extent, the long-term efficacy of acupuncture at the 12-week follow-up. The gender, subtype of disease, and education level were finally identified as the critical predicting features. Conclusion Based on the SVM algorithm and routine clinical features, this study established the models to predict acupuncture efficacy for FD patients. The prediction models developed accordingly are promising to assist doctors in judging patients' responses to acupuncture in advance, so that they could tailor and adjust acupuncture treatment plans for different patients in a prospective rather than the reactive manner, which could greatly improve the clinical efficacy of acupuncture treatment for FD and save medical expenditures.

Background and objective Acupuncture is a promising non-pharmacological therapy for patients with prolonged disorder of consciousness (PDOC); however, its underlying mechanism remains uncertain. This study aimed to reveal the modulatory effects of acupuncture on the cerebral cortex activity among patients with PDOC. Materials and methods Twenty-eight PDOC patients were randomly assigned to the treatment (n = 14) or control (n = 14) group. The treatment group received one session of acupuncture, while the control group received one session of sham acupuncture. All patients underwent evaluation of the functional connectivity and activation response of the dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), and primary somatosensory cortex (S1) via functional near-infrared spectroscopy. We further explored the potential correlation of the consciousness level and activation response/functional connectivity with acupuncture. Results Compared to the control group, a single session of acupuncture significantly tended to enhance resting-state functional connectivity (rsFC) in DLPFC-M1, DLPFC-M1, and S1-S1. And the activation level of the DLPFC (both sides) in the acupuncture group is significantly higher than those in sham acupuncture group. However, no significant correlation was found between the consciousness level and activation response/functional connectivity. Conclusion One session of acupuncture has a significant modulation of rsFC and activation in the DLPFC, M1, and S1 with PDOC patients. Acupuncture-evoked effect may have some functional significance in PDOC patients. This is an important step toward exploring the acupuncture effects on PDOC patients.

Background: The number of systematic reviews or 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.

The diagnosis of functional dyspepsia (FD) presently relies on the self-reported symptoms. This study aimed to determine the potential of functional brain network features as biomarkers for the identification of FD patients. Firstly, the functional brain Magnetic Resonance Imaging data were collected from 100 FD patients and 100 healthy subjects, and the functional brain network features were extracted by the independent component analysis. Then, a support vector machine classifier was established based on these functional brain network features to discriminate FD patients from healthy subjects. Features that contributed substantially to the classification were finally identified as the classifying features. The results demonstrated that the classifier performed pretty well in discriminating FD patients. Namely, the accuracy of classification was 0.84 ± 0.03 in cross-validation set and 0.80 ± 0.07 in independent test set, respectively. A total of 15 connections between the subcortical nucleus (the thalamus and caudate) and sensorimotor cortex, parahippocampus, orbitofrontal cortex were finally determined as the classifying features. Furthermore, the results of cross-brain atlas validation showed that these classifying features were quite robust in the identification of FD patients. In summary, the current findings suggested the potential of using machine learning method and functional brain network biomarkers to identify FD patients.

Introduction As the main manifestation of gallstone disease, biliary colic (BC) is an episodic attack that brings patients severe pain in the right upper abdominal quadrant. Although acupuncture has been documented with significance to lead to pain relief, the immediate analgesia of acupuncture for BC still needs to be verified, and the underlying mechanism has yet to be covered. Therefore, this trial aims first to verify the immediate pain-alleviation characteristic of acupuncture for BC, then to explore its influence on the peripheral sensitised acupoint and central brain activity. Methods and analysis This is a randomised controlled, paralleled clinical trial, with patients and outcome assessors blinded. Seventy-two patients with gallbladder stone disease presenting with BC will be randomised into a verum acupuncture group and the sham acupuncture group. Both groups will receive one session of immediate acupuncture treatment. Improvements in patients' BC will be evaluated by the Numeric Rating Scale, and the pain threshold of acupoints will also be detected before and after treatment. During treatment, brain neural activity will be monitored with functional near-infrared spectroscopy (fNIRS), and the needle sensation will be rated. Clinical and fNIRS data will be analysed, respectively, to validate the acupuncture effect, and correlation analysis will be conducted to investigate the relationship between pain relief and peripheral-cerebral functional changes. Ethics and dissemination This trial has been approved by the institutional review boards and ethics committees of the First Teaching Hospital of Chengdu University of Traditional Chinese Medicine, with the ethical approval identifier 2019 KL-029, and the institutional review boards and ethics committees of the First People's Hospital of Longquanyi District, with the ethical approval identifier AF-KY-2020071. The results of this trial will be disseminated through peer-reviewed publications and conference abstracts or posters.

IntroductionAcupuncture 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.MethodsA 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.DiscussionResults 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 DisseminationThis 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).

In 2012, a lacquer figure was unearthed from the Han dynasty tomb (188 BC-87 BC) at Chengdu Laoguanshan. The lines intaglioed on the Laoguanshan lacquer figure were similar to the meridians. Objective: To investigate the relationship between the lines on this Laoguanshan lacquer figure and the regular meridians so as to explore the development of meridian system in ancient China. Methods: Based on collecting the photos of the Laoguanshan lacquer figure and the representative acupuncture classics, the double evidence method (combining the unearthed relics / literature and extant literature) was performed to investigate the relationship between the lines on this Laoguanshan lacquer figure and the regular meridians. Furthermore, the development of regular meridians theory was analyzed from the number, distribution, direction and branches. Results: The routes of the 28 longitudinal white lines on the Laoguanshan lacquer figure are similar to the regular meridians in the ancient literature including HuangdiNeijing (Yellow Emperor's Inner Classic). The number, distribution and branches of the meridians intaglioed on the Laoguanshan lacquer figure suggested the evolution of the regular-meridian system from the eleven-meridian system to the twelve-meridian system. Conclusions: The meridian system of Laoguanshan lacquer figure was a link connecting the preceding and the following. The Laoguanshan lacquer figure played an important role in the development of the early meridian theory. (C) 2021 Published by Elsevier B.V. on behalf of World Journal of Acupuncture Moxibustion House.