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Abstract Objective 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. Methods 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. Results WWI and ABSI were positively linked with sNfL (WWI: β = 0.05, 95% CI 0.01–0.09; ABSI: β = 1.65, 95% CI 3.53–13.72). There was no clear reliance on this association according to subgroup analysis and interaction tests. Smoothed curve fitting and saturation effects also demonstrated nonlinear associations between WWI and ABSI and sNfL, with inflection points of 10.38 and 0.38, respectively. Conclusion In the adult American population, while the WWI and ABSI are linearly positively correlated with serum neurofilament light protein (sNfL), the effect size is greater for the ABSI. This correlation provides fresh evidence connecting obesity to neurological conditions, deepening our comprehension of the extensive health impacts associated with obesity. Level of Evidence Level I, experimental studies.

Abstract Background The effectiveness and safety of acupuncture therapy to delay lung function decline in chronic obstructive pulmonary disease (COPD) remain unclear. This study aimed to determine whether acupuncture, as an adjunctive therapy to COPD-guided medication, could prevent lung function decline. Methods This randomised, two-centre study was conducted between February 2022 and July 2023. Men and women aged 40–80 years with COPD were recruited. Participants received active or sham acupuncture three times a week (36 sessions total). The primary outcome was the change in the percentage of forced expiratory volume for 1 s to the predicted value (FEV1%) between the baseline and after the intervention. Results Overall, 238 participants were screened, and 74 (58 men [78.4%]; mean [standard deviation] age, 69.6 [7.2] years) were randomised into the acupuncture and sham acupuncture groups (37 per group). After the intervention, the change in FEV1% was 1.35 (95% confidence interval [CI]: -0.47 to 3.17) and -2.44 (95% CI: -4.56 to -0.33) in the acupuncture and sham acupuncture groups, respectively. The difference was -3.97 (95% CI: -6.2 to -1.74), and the adjusted difference was -3.46 (95% CI: -5.69 to -1.24, P = 0.003) between the groups. A significantly less decline was found in forced expiratory volume for 1 s in the acupuncture group. All treatment-related adverse events (acupuncture = 11, sham = 2) were mild. Conclusions Compared with sham acupuncture, acupuncture plus medication may delay lung function decline. However, further studies with a larger sample size and longer-term follow-up are needed to clarify the effects.

Abstract Background ST-elevation myocardial infarction (STEMI) is a common acute ischemia heart disease that causes serious damage to human health worldwide. Even though morbidity and mortality have significantly decreased by percutaneous coronary intervention (PCI), an additional cardiac protection strategy is still required. Acupuncture therapy has presented a dominant cardiac protection in many studies lately. Thus, we aim to evaluate the effect and safety of acupuncture as an adjunctive therapy in STEMI patients after PCI through a randomized controlled trial. Methods/Design This study describes a protocol of multicenter, double-blinded, parallel-controlled, randomized controlled trial. Ninety-six patients with STEMI aged 18–85 years who undergoing PCI will be recruited from the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, The Affiliated Third Hospital of Chengdu Traditional Chinese Medicine University/Chengdu Pidu District Hospital of Traditional Chinese Medicine, and Zhaotong Municipal Hospital of Traditional Chinese Medicine. Participants will be randomly assigned (1:1 ratio) to the verum acupuncture plus basic therapy (i.e., treatment) group or the sham acupuncture plus basic therapy (i.e., control) group. These participants will be treated for 5 days and then will be followed up for 24 weeks. Any adverse events will be recorded throughout the study to evaluate safety. Discussion The present study aims to investigate the effect and safety of acupuncture for patients with STEMI after PCI and set up standardized treatment programs for acupuncture of these patients. Trial registration This study was registered in the Chinese Clinical Trial Registry (Registration ID: [ChiCTR2400081117]), on February 22, 2024.

Objectives: This meta-analysis aimed to explore the relationship between the dose of acupuncture sessions, acupuncture frequency, and acupuncture duration and its effects on migraine. Methods: Eight databases were searched for randomized controlled trials (RCTs) evaluating the efficacy of penetrating manual acupuncture for migraine published in English and Chinese from inception to June 20, 2024. The robust-error meta-regression (REMR) approach and non-linear meta-regression with restricted cubic spline (RCS) were used to investigate the dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and the frequency of migraine attacks. The potential nonlinear relationships was tested by restricting the regression coefficient to zero and a P value＜0.1. The statistical analysis was conducted using Stata 17.0. The risk of bias was independently assessed by two reviewers using the Cochrane tool. The reporting quality for acupuncture procedures was evaluated by STRICTA criteria. Results: Thirty-two RCTs involving 1562 participants were included, and the results showed a J-shaped dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. After 16 acupuncture sessions, the change in the frequency of migraine attacks was 3.95 (95 %CI: 3.13 to 4.77). Three sessions of acupuncture a week resulted in a significant decrease in the frequency of migraine attacks, reaching 4.04 (95 % CI: 2.49 to 5.58). After two months of acupuncture, the frequency of migraine attacks decreased significantly, showing a difference of 4.05 (95 % CI: 3.61 to 4.49). Subsequently, the improvement trend gradually flattened, yielding diminishing benefits to patients. The risk of bias showed that seven studies were rated as “low risk”, two were rated as “high risk”, and the others were rated as “unclear risk”. The reporting quality of RCTs of acupuncture for migraine remain suboptimal. Conclusions: A non-linear dose-response relationship was found between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. The results of our study recommend 16 sessions of acupuncture with a frequency of 3 sessions/week and a treatment duration of 1.5 to 2 months. Registration number: This meta-analysis has been registered on PROSPERO (CRD42023400493).

Objective: Disorders of glycolipid metabolism are important pathogenic factors leading to coronary artery disease, and there is no safe and effective comprehensive treatment, while acupuncture has a certain efficacy in heart disease and disorders of glycolipid metabolism. To assess the effects of acupuncture on glycolipid metabolism in patients with coronary heart disease, we conducted a systematic review and meta-analysis. Methods: From the time of library construction to August 18, 2023, Searches were conducted in eight databases, with no language restriction. Only RCTs that included acupuncture as a sole or secondary effect on glucose-lipid metabolism in coronary heart disease were included.Our primary outcome indicators were Low-density lipoprotein cholesterol(LDL-C), Hemoglobin A1c(HbA1c). Our analyses were conducted in strict accordance with the PRISMA statement, and the researchers used the Cochrane Handbook for literature screening and data extraction, the “Risk of Bias” tool (ROB.2) for assessing risk of bias, and RevMan (version 5.3) for meta-analysis of outcome metrics, and the GRADE criteria for assessing quality of evidence. Assessing the quality of acupuncture literature using the Standards for reporting interventions in clinical trials of acupuncture. Results: Our analysis included 18 eligible RCTs (N = 1346 participants). For the primary outcome metrics, acupuncture combined with standard treatment was effective in reducing LDL-C (SMD =-0.56; 95 % CI, −0.75 to −0.38; P < 0.00001), and HbA1c (MD = −1.15; 95 % CI, −1.73 to −0.58; P < 0.0001). For secondary outcome measures, combination therapy improved TC (SMD = −0.97; 95 % CI, −1.44 to −0.51; P < 0.0001), TG (MD = −0.39; 95 % CI, −0.58 to −0.20; P < 0.0001), hs-CRP (MD = −0.98; 95 % CI, −1.43 to −0.52; P

IntroductionIn vitro fertilization (IVF) is a technology that assists couples experiencing infertility to conceive children. However, unsuccessful attempts can lead to significant physical and financial strain. Some individuals opt for electro-acupuncture (EA) during IVF, even though there is limited evidence regarding the efficacy of this practice. Thus, this pilot study aims to explore the effectiveness and safety of EA during IVF on pregnancy outcomes.Methods and analysisThis clinical trial is a parallel, randomized, sham-controlled study. It aims to include a total of 118 infertile women who intend to undergo IVF. The participants will be randomly divided into three groups in a 1:1:1 ratio: the EA + IVF group, the placebo electro-acupuncture (pEA) +IVF group, and the IVF control group. All of the patients will be required to use ovarian stimulation drugs, while those in the EA + IVF and pEA + IVF groups will receive acupuncture treatment at three sessions per week (every other day) until trigger day with a minimum five session. The primary outcome of this trial will focus on the clinical pregnancy rate (CPR). CPR is defined as the rate of achieving clinical pregnancy from the first fresh/frozen embryo transfer cycle with an ultrasound-confirmed gestational sac in the uterine cavity. The secondary outcomes will assess embryology data, biochemical pregnancy rate, early miscarriage rate, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Fertile Quality of Life (FertiQoL), patient retention rate, treatment adherence, and safety outcomes.Ethics and disseminationEthics approval was obtained from the Ethics Committee of Sichuan Jinxin Xi’nan Women and Children Hospital (number 2021–007). The results will be disseminated through peer-reviewed publications. The participants gave informed consent to participate in the study before taking part in it.Clinical trial registrationhttps://www.chictr.org.cn, identifier ChiCTR2300074455.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose–effect relationship of acupuncture. Methods/design This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. Discussion This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. Trial registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a globally common chronic respiratory disease with a high morbidity and mortality rate. Acupuncture has been proven effective for COPD. A dose-response meta-analysis was conducted to assess the correlation between the acupuncture temporal parameters(session, frequency, and duration) and its effectiveness in patients with stable COPD. Methods: Acupuncture randomized controlled trials on COPD were searched in eight databases from their inception to June 2023. The ''doses'' were defined as the acupuncture session, frequency, and duration. The outcomes mainly included Forced Expiratory Volume in one-second rate (FEV1%) and Six-minute Walking Distance (6MWD). The assessment of bias risk and literature quality were conducted independently using the Cochrane risk of bias tool and the Standards for reporting interventions in clinical trials of acupuncture. The dose-response relationship was modeled using robust error element regression, and meta-analysis was operated by R 4.3.1 and Stata 15.0. The protocol was registered in PROSPERO with the registration number CRD42023401406. Result: Out of 1669 records, 17 RCTs with 1165 participants were finally included in the meta-analysis. There was notable heterogeneity among the studies, but sensitivity analysis demonstrated good robustness. The findings revealed a significant improvement in the following outcomes for stable COPD patients in the acupuncture group: FEV1% (MD=3.50, 95%CI: 2.05–4.95), 6MWD (MD=47.39, 95%CI: 29.29–65.50), St. George's respiratory questionnaire (SGRQ; MD=−8.25, 95%CI: −11.38 to −5.12); COPD assessment test (CAT; MD=−2.91, 95%CI: −3.99 to −1.83). The relationship between the acupuncture session, duration, and FEV1%, 6MWD followed a ''Λ'' curve pattern, while the relationship between acupuncture frequency and FEV1%, 6MWD exhibited logarithmic growth. Firstly, After 12 acupuncture sessions, FEV1% and 6MWD increased by 7.06% (95%CI: 4.56–9.55) and 36.28 m (95%CI: 20.37–52.20), respectively. The peak improvement in FEV1% and 6MWD was observed after 18 acupuncture sessions (MD=7.89, 95% CI: 5.33–10.45) and 45 sessions (MD=125.43, 95% CI: 72.80–178.07) each. Additionally, weekly acupuncture resulted in a 4.14% improvement in FEV1% (95% CI: 2.55–5.72) and a 42.49 m increase in 6MWD (95%CI: 17.16–67.81). Notably, the maximum effects on FEV1% and 6MWD improvement were achieved with different acupuncture frequencies, specifically three times a week (MD=6.00, 95% CI: 5.34–6.66) and once a day(MD=112.41, 95% CI: 77.27–147.56), respectively. Furthermore, after a 28-day duration of acupuncture treatment, FEV1% increased by 4.74% (95% CI: 3.73–5.75) and 6MWD increased by 47.34 m (95%CI: 22.01–72.67). During 60 days of acupuncture treatment, the FEV1% and 6MWD improvement reached their highest levels at 8.76% (95% CI: 7.05–10.47) and 88.06 m (95% CI: 45.96–130.16), respectively. Conclusion: Acupuncture was effective in improving FEV1%, 6MWD, SGRQ, and CAT in patients with stable COPD. There was a dose-response relationship between the time parameters of acupuncture (session, frequency, and duration) and the efficacy of COPD treatment (FEV1% and 6MWD). The minimal clinically important difference could be achieved after 12 acupuncture sessions. Acupuncture with a medium-frequency (2–3 times per week) over 60 days may result in the greatest improvement in FEV1%, while higher-frequency acupuncture (5–7 times per week) for 2 months may lead to the maximum improvements in 6MWD. It indicated that the optimal acupuncture duration for different indicators remains consistent, while the optimal frequencies may differ. To confirm these results, it is necessary to conduct multicenter, large-scale randomized controlled trials. Ethics and dissemination: Ethical approval is not required for literature-based studies. The results will be published in peer-reviewed journals or conferences.

This study aimed to investigate altered static and dynamic functional network connectivity (FNC) and its correlation with clinical symptoms in patients with knee osteoarthritis (KOA). One hundred and fifty-nine patients with KOA and 73 age- and gender-matched healthy subjects (HS) underwent resting-state functional magnetic resonance imaging (rs-fMRI) and clinical evaluations. Group independent component analysis (GICA) was applied, and seven resting-state networks were identified. Patients with KOA had decreased static FNC within the default mode network (DM), visual network (VS), and cerebellar network (CB) and increased static FNC between the subcortical network (SC) and VS (p < 0.05, FDR corrected). Four reoccurring FNC states were identified using k-means clustering analysis. Although abnormalities in dynamic FNCs of KOA patients have been found using the common window size (22 TR, 44 s), but the results of the clustering analysis were inconsistent when using different window sizes, suggesting dynamic FNCs might be an unstable method to compare brain function between KOA patients and HS. These recent findings illustrate that patients with KOA have a wide range of abnormalities in the static and dynamic FNCs, which provided a reference for the identification of potential central nervous therapeutic targets for KOA treatment and might shed light on the other musculoskeletal pain neuroimaging studies.

Abstract Numerous studies have reported that circulating cytokines (CCs) are linked to age-related neurodegenerative diseases (ANDDs); however, there is a lack of systematic investigation for the causal association. A two-sample bidirectional Mendelian Randomisation (MR) method was utilized to evaluate the causal effect. We applied genetic variants correlated with concentrations of CCs from a genome-wide association study meta-analysis (n = 8293) as instrumental variables. Summary data of three major ANDDs [Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic lateral sclerosis (ALS)] were identified from the IEU OpenGWAS platform (n = 627, 266). Inverse-variance weighted method is the main approach to analyse causal effect, and MR results are verified by several sensitivity and pleiotropy analyses. In directional MR, it suggested that several CCs were nominally correlated with the risk of ANDDs, with a causal odds ratio (OR) of Interleukin (IL)-5 of 0.909 for AD; OR of IL-2 of 1.169 for PD; and OR of Beta nerve growth factor of 1.142 for ALS). In reverse MR, there were some suggestively causal effects of ANDDs on CCs (AD on increased Basic fibroblast growth factor and IL-12 and decreased Stem cell growth factor beta; PD on decreased Monokine induced by interferon-gamma; ALS on decreased Basic fibroblast growth factor and IL-17). The findings were stable across sensitivity and pleiotropy analyses. However, after Bonferroni correction, there is no statistically significant association between CCs and ANDDs. Through the genetic epidemiological approach, our study assessed the role and presented possible causal associations between CCs and ANDDs. Further studies are warranted to verify the causal associations.

Abstract 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.

IntroductionMigraine is a common clinical disorder, ranks as the second most disabling disease worldwide, and often manifests with unilateral onset. Contralateral acupuncture (CAT), as a classical acupuncture method, has been proven to be effective in the treatment of migraine without aura (MWoA). However, its neural mechanisms have not been investigated using multimodal magnetic resonance imaging (MRI).Methods and analysisIn this multimodal neuroimaging randomized trial, a total of 96 female MWoA participants and 30 female healthy controls (HCs) will be recruited. The 96 female MWoA participants will be randomized into three groups: Group A (CAT group), Group B [ipsilateral acupuncture (IAT) group], and Group C (sham CAT group) in a 1:1:1 allocation ratio. Each group will receive 30 min of treatment every other day, three times a week, for 8 weeks, followed by an 8-week follow-up period. The primary outcome is the intensity of the migraine attack. Data will be collected at baseline (week 0), at the end of the 8-week treatment period (weeks 1–8), and during the 8-week follow-up (weeks 9–16). Adverse events will be recorded. Multimodal MRI scans will be conducted at baseline and after 8-week treatment.DiscussionThis study hypothesized that CAT may treat MWoA by restoring pathological alterations in brain neural activity, particularly by restoring cross-integrated functional connectivity with periaqueductal gray (PAG) as the core pathological brain region. The findings will provide scientific evidence for CAT in the treatment of MWoA.Ethics and disseminationThe Medical Ethics Committee of the Second Affiliated Hospital of Yunnan University of Chinese Medicine has given study approval (approval no. 2022-006). This trial has been registered with the Chinese Clinical Trials Registry (registration no. ChiCTR2300069456). Peer-reviewed papers will be used to publicize the trial’s findings.Clinical trial registrationhttps://clinicaltrials.gov/, identifier ChiCTR2300069456.

Background: Previous studies have reported alterations in brain structure in major depressive disorder (MDD) patients with suicide attempts. However, age-related changes in suicidal MDD patients remain unclear. Methods: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase, PubMed, and Web of Science were searched to identify relevant studies from inception to January 2023. All voxel-based and surface-based morphometry studies comparing suicidal MDD patients to MDD or healthy controls were included. Studies were then grouped by age range (old, middle-age, adolescent) and the commonalities and age-related structural brain alterations were summarized. The included studies were evaluated using the Newcastle-Ottawa Scale (NOS). Results: A total of 17 studies met the inclusion criteria, including 3 of late-life depression (LLD) patients, 11 of middle-aged depression (MAD) patients, and 3 of adolescent depression (AOD) patients. The majority of studies had moderate to high NOS scores, indicating good quality. Patients in all three age groups exhibited extensive alterations in the lateral, medial, and orbital regions of the frontal lobes. Furthermore, suicidal MAD patients showed a specific decrease in the gray matter volume of the dorsolateral prefrontal cortex compared to suicidal LLD patients. Cortical thickness and left angular gyrus volume were decreased in suicidal MAD and suicidal LLD patients, but increased in suicidal AOD patients. Conclusion: This systematic review summarizes structural brain changes in suicidal MDD patients at three age groups: elderly, middle-aged, and adolescent. These findings help elucidate the common circuitry of MDD related to suicide over the lifespan and highlight unique circuitry associated with different ages. These findings may help predict the risk of suicide in MDD patients at different ages.

Purpose. Two-sample Mendelian randomization (MR) was conducted to assess the causal relationship between angina pectoris and gout. Material and Methods. Based on genome-wide association studies, single nucleotide polymorphisms (SNPs) that were closely associated with gout were selected from the UK Biobank–Neale Lab (ukb-a-107) as genetic instrumental variables. Considering that gout is characterized by elevated blood uric acid levels, SNPs related to blood uric acid levels were screened from BioBank Japan (bbj-a-57) as auxiliary gene instrumental variables. SNPs closely associated with angina pectoris onset were screened from the FINN dataset (finn-b-I9_ANGINA) as outcome variables. Two-sample MR was conducted, with inverse variance weighting (IVW) of the random effects model as the primary result, along with the weighted median method (WME) and the MR-Egger regression method. To further confirm the causal relationship between angina and gout incidence, a meta-analysis was conducted on the IVW results of the ukb-a-107 and bbj-a-57. Results. The odds ratios and 95% confidence intervals of the IVW, WME, and MR-Egger results of ukb-a-107 were (OR = 33.72; 95% CI: 2.07∼550.38), (OR = 57.94; 95% CI: 2.75∼1219.82), and (OR = 96.38; 95% CI: 0.6∼15556.93), respectively. The P values of IVW and WME were 0.014 and 0.014 (both

Abstract Background The aberrance of gray matter morphology in migraineurs has been widely investigated. However, it remains largely unknown whether there are illness duration-related hierarchical changes in the gray matter structure. Methods A total of 86 migraine without aura (MwoA) patients and 73 healthy controls were included. The Voxel-Based Morphometry approach was utilized to compare the gray matter volume (GMV) differences between MwoA patients and healthy controls. The Structural Covariance Network analysis was conducted to quantify the cross-regional synchronous alterations of gray matter structure in MwoA patients. The Causal Structural Covariance Network analysis was performed to describe the progressive and hierarchical changes in the gray matter network of patients in the pathological progression of migraine. Results MwoA patients had duration-stage related GMV hypertrophy in the left parahippocampus, as well as synergistic GMV aberrance in the parahippocampus and the medial inferior temporal gyrus and cerebellum. Moreover, the GMV alteration of the parahippocampus, and the surrounding hippocampus, amygdala, and bilateral anterior cerebellum, preceded and causally influenced the morphological changes of lateral parietal-temporal-occipital gyrus, as well as the motor cortex and prefrontal gyrus with the increasing illness duration in MwoA patients. Conclusion The current study indicated that gray matter structural alterations in the medial inferior temporal gyrus, especially the parahippocampus, is a critical pathological characteristic in MwoA patients, which drives the gray matter structure alteration of other regions. These findings provide further evidence for understanding the progressive gray matter morphological changes in migraine and may facilitate the development of neuromodulation therapies targeting this procession.

BackgroundThe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common respiratory disease among older adults, which imposes a significant burden on individuals and society and poses a major challenge to the global public health system due to its high morbidity and mortality. Acupuncture is effective for AECOPD, but its efficacy has been questioned due to the limited methodological quality. Thus, we aim to investigate the efficacy of acupuncture as adjunctive therapy for AECOPD and determine whether the efficacy of acupuncture differs with the type of acupoint combinations.Methods and analysisThis study proposes a prospective, multicenter randomized controlled trial that will comprise four groups, including two acupuncture treatment groups, one sham acupuncture group, and one basic treatment group. The acupuncture treatment groups will be distinguished by their focus on different patterns of acupoint combination, namely the Xi-cleft and He-sea acupoint combination and the Eight Confluence points acupoint combination, which may vary in clinical efficacy based on traditional acupuncture theories. The study aims to randomize 556 patients in a 1:1:1:1 ratio across the four groups. Each patient in acupuncture group or sham acupuncture group will receive routine drug therapy and 7 sessions of acupuncture treatment over 1 week. Participants in the basic treatment group will only receive routine drug therapy. The trial will be conducted in seven hospitals located in China. The primary outcomes in this trial will include differences in the Breathlessness, Cough, and Sputum Scale (BCSS) before randomization, 7 days after randomization, 5 and 9 weeks after randomization.Ethics and disseminationEthical approval was obtained from the Sichuan Regional Ethics Review of Committee on Traditional Chinese Medicine (Approval ID: 2022KL-068). The results of this study will be distributed through peer-reviewed journals.Clinical Trial Registration: ClinicalTrials.gov, identifier ChiCTR2200064484.

Abstract Background Acupuncture effectively improves cognitive function in Alzheimer’s disease (AD). Many neuroimaging studies have found significant brain alterations after acupuncture treatment of AD, but the underlying central modulation mechanism is unclear. Objective This review aims to provide neuroimaging evidence to understand the central mechanisms of acupuncture in patients with AD. Methods Relevant neuroimaging studies about acupuncture for AD were retrieved from eight English and Chinese medicine databases (PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, WF, VIP) and other resources from inception of databases until June 1, 2022, and their methodological quality was assessed using RoB 2.0 and ROBINS - I. Brain neuroimaging information was extracted to investigate the potential neural mechanism of acupuncture for AD. Descriptive statistics were used for data analysis. Results Thirteen neuroimaging studies involving 275 participants were included in this review, and the overall methodological quality of included studies was moderate. The approaches applied included task-state functional magnetic resonance imaging (ts-fMRI; n = 9 studies) and rest-state functional magnetic resonance imaging (rs-fMRI; n = 4 studies). All studies focused on the instant effect of acupuncture on the brains of AD participants, including the cingulate gyrus, middle frontal gyrus, and cerebellum, indicating that acupuncture may regulate the default mode, central executive, and frontoparietal networks. Conclusion This study provides evidence of the neural mechanisms underlying the effect of acupuncture on AD involving cognitive- and motor-associated networks. However, this evidence is still in the preliminary investigation stage. Large-scale, well-designed, multimodal neuroimaging trials are still required to provide comprehensive insight into the central mechanism underlying the effect of acupuncture on AD. (Systematic review registration at PROSPERO, No. CRD42022331527).

Abstract The association between gut microbiome and chronic metabolic disease including polycystic ovary syndrome (PCOS), is well documented, however, the relationship between the gut microbiota and serum metabolites remains unknown. In this study, untargeted metabolomics together with a 16S rRNA gene sequencing tool was used to detect small molecule serum metabolites and the gut microbiome. We identified 15 differential metabolites between PCOS patients and the healthy control. Lysophosphatidylcholine (LPC) (18:2, 20:3, 18:1, P-16:0, 17:0, 15:0, 18:3, 20:4), phosphatidylcholine(PC), ganglioside GA2 (d18:1/16:0) and 1-linoleoylglycerophosphocholine were increased in the PCOS group, and the concentrations of phosphoniodidous acid, bilirubin, nicotinate beta-d-ribonucleotide and citric acid were decreased in the PCOS group, suggesting a lipid metabolism and energy metabolism disorder in the PCOS patients. The diversity of gut microbiota in PCOS group was lower than that in healthy controls. Escherichia/Shigella, Alistipes and an unnamed strain 0319_6G20 belonging to Proteobacteria were important distinguishing genera (LDA > 3.5) in PCOS. Prevotella_9 was positively correlated with phosphoniodidous acid, nicotinate beta-d-ribonucleotide and citric acid concentrations, and negatively correlated with the concentration of LPC (20:3) and 1-linoleoylglycerophosphocholine; Roseburia was negatively correlated with LPC concentration (20:4), while the characteristic genus 0319_6G20 of PCOS was positively correlated with LPC concentration (20:3) (COR > 0.45). SF-36 in the PCOS group was significantly lower than that in the healthy control (HC) group, which was associated with the presence of Escherichia-Shigella and Alistipes. Our finding demonstrated the correlation between the gut microbiota and serum metabolites in PCOS, and therefore characteristic gut microbiota and metabolites may play an important role in the insulin resistance and the mood changes of PCOS patients.

BackgroundAmnestic mild cognitive impairment (aMCI) is a pre-dementia condition associated with declined cognitive function dominated by memory impairment. The occurrence of aMCI is associated with the gut-brain axis. Previous studies have shown cognitive improvements in MCI after acupuncture treatment. This study evaluates whether acupuncture can produce a therapeutic effect in patients with aMCI by modulating the gut-brain axis.Methods and designThis is a prospective, parallel, multicenter randomized controlled trial. A total of 40 patients with aMCI will be randomly assigned to an acupuncture group (AG) or a waiting-list group (WG), participants in both groups will receive health education on improving cognitive function at each visit, and acupuncture will be conducted twice a week for 12 weeks in the AG. Another 20 matched healthy volunteers will be enrolled as normal control. The primary outcome will be the change in Alzheimer’s Disease Assessment Scale-cognitive scale score before and after treatment. Additionally, functional magnetic resonance imaging data, faeces, and blood will be collected from each participant to characterize the brain function, gut microbiota, and inflammatory cytokines, respectively. The differences between patients with aMCI and healthy participants, and the changes in the AG and WG groups before and after treatment will be observed. Ultimately, the correlation among brain function, gut microbiota, inflammatory cytokines, and clinical efficacy evaluation in patients with aMCI will be analyzed.DiscussionThis study will identify the efficacy and provide preliminary data on the possible mechanism of acupuncture in treating aMCI. Furthermore, it will also identify biomarkers of the gut microbiota, inflammatory cytokines, and brain function correlated with therapeutic effects. The results of this study will be published in peer-reviewed journals.Clinical trial registrationhttp://www.chictr.org.cn, identifier ChiCTR2200062084.

Abstract Background The acupoint selections impact the effects of acupuncture, and preliminary evidence showed potential connection between pain threshold (PT) and acupuncture response. This study examined whether acupuncture at acupoints with lower PT versus higher PT would yield different effects in patients with knee osteoarthritis (KOA). Methods In this multicenter randomized clinical trial, patients were randomly assigned (1:1:1) to receive acupuncture at acupoints with lower PT (LPT group), acupuncture at acupoints with higher PT (HPT group), and no acupuncture (waiting-list group). PT was measured with electronic von Frey detector. The primary outcome was the change in WOMAC total score from baseline to 16 weeks, and the secondary outcomes were SF-12 score, and active knee range of motion (ROM). Intention-to-treat analysis was conducted with linear mixed-effect model. Results Among 666 randomized patients, 625 (93.84%) completed the study. From baseline to 16 weeks, patients in the LPT group versus HPT group had similar effects in reducing WOMAC total score (adjusted mean difference (MD) 2.21, 95% confidence interval (CI) −2.51 to 6.92, P = 0.36), while a greater reduction in WOMAC total score was observed in LPT group (−9.77, 95% CI −14.47 to −5.07, P

Abstract Background Myocardial fibrosis changes the structure of myocardium, leads to cardiac dysfunction and induces arrhythmia and cardiac ischemia, threatening patients’ lives. Electroacupuncture at PC6 (Neiguan) was previously found to inhibit myocardial fibrosis. Long non-coding RNAs (lncRNAs) play a variety of regulatory functions in myocardial fibrosis, but whether electroacupuncture can inhibit myocardial fibrosis by regulating lncRNA has rarely been reported. Methods In this study, we constructed myocardial fibrosis rat models using isoproterenol (ISO) and treated rats with electroacupuncture at PC6 point and non-point as control. Hematoxylin–eosin, Masson and Sirius Red staining were performed to assess the pathological changes and collagen deposition. The expression of fibrosis-related markers in rat myocardial tissue were detected by RT-qPCR and Western blot. Miat, an important long non-coding RNA, was selected to study the regulation of myocardial fibrosis by electroacupuncture at the transcriptional and post-transcriptional levels. In post-transcriptional level, we explored the myocardial fibrosis regulation effect of Miat on the sponge effect of miR-133a-3p. At the transcriptional level, we studied the formation of heterodimer PPARG–RXRA complex and promotion of the TGF-β1 transcription. Results Miat was overexpressed by ISO injection in rats. We found that Miat can play a dual regulatory role in myocardial fibrosis. Miat can sponge miR-133a-3p in an Ago2-dependent manner, reduce the binding of miR-133a-3p target to the 3ʹUTR region of CTGF mRNA and improve the protein expression level of CTGF. In addition, it can also directly bind with PPARG protein, inhibit the formation of heterodimer PPARG–RXRA complex and then promote the transcription of TGF-β1. Electroacupuncture at PC6 point, but not at non-points, can reduce the expression of Miat, thus inhibiting the expression of CTGF and TGF-β1 and inhibiting myocardial fibrosis. Conclusion We revealed that electroacupuncture at PC6 point can inhibit the process of myocardial fibrosis by reducing the expression of lncRNA Miat, which is a potential therapeutic method for myocardial fibrosis.

Abstract Background This study aims to develop an evidence-based clinical practice guideline of acupuncture in the treatment of patients with moderate and severe cancer pain. Methods The development of this guideline was triggered by a systematic review published in JAMA Oncology in 2020. We searched databases and websites for evidence on patient preferences and values, and other resources of using acupuncture for treatment of cancer pain. Recommendations were developed through a Delphi consensus of an international multidisciplinary panel including 13 western medicine oncologists, Chinese medicine/acupuncture clinical practitioners, and two patient representatives. The certainty of evidence, patient preferences and values, resources, and other factors were fully considered in formulating the recommendations. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to rate the certainty of evidence and the strength of recommendations. Results The guideline proposed three recommendations: (1) a strong recommendation for the treatment of acupuncture rather than no treatment to relieve pain in patients with moderate to severe cancer pain; (2) a weak recommendation for the combination treatments with acupuncture/acupressure to reduce pain intensity, decrease the opioid dose, and alleviate opioid-related side effects in moderate to severe cancer pain patients who are using analgesics; and (3) a strong recommendation for acupuncture in breast cancer patients to relieve their aromatase inhibitor-induced arthralgia. Conclusion This proposed guideline provides recommendations for the management of patients with cancer pain. The small sample sizes of evidence limit the strength of the recommendations and highlights the need for additional research.

BackgroundCancer-related fatigue (CRF) is one of the most commonly reported symptoms impacting cancer survivors. This study evaluated and compared the effectiveness and safety of acupuncture treatments for CRF.MethodsWe searched PubMed, Embase, Web of Science, Cochrane Library, China Biology Medicine China National Knowledge Infrastructure, China Science and Technology Journal Database, and WanFang Database from inception to November 2022 to identify eligible randomized controlled trials (RCTs) comparing acupuncture treatments with sham interventions, waitlist (WL), or usual care (UC) for CRF treatment. The outcomes included the Cancer Fatigue Scale (CFS) and Pittsburgh Sleep Quality Index (PSQI), and pair-wise and Bayesian network meta-analyses were performed using STATA v17.0.ResultsIn total, 34 randomized controlled trials featuring 2632 participants were included. In the network meta-analysis, the primary analysis using CFS illustrated that point application (PA) + UC (standardized mean difference [SMD] = −1.33, 95% CI = −2.02, −0.63) had the highest probability of improving CFS, followed by manual acupuncture (MA) + PA (SMD = −1.21, 95% CI = −2.05, −0.38) and MA + UC (SMD = −0.80, 95% CI = −1.50, −0.09). Moreover, the adverse events of these interventions were acceptable.ConclusionThis study demonstrated that acupuncture was effective and safe on CRF treatment. However, further studies are still warranted by incorporating more large-scale and high-quality RCTs.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42022339769.

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.

Background: Acupuncture has been increasingly used in patients with chronic pain, yet no bibliometric analysis of acupuncture studies for chronic pain exists. Objectives: To investigate the characteristics, hotspots and frontiers of global scientific output in acupuncture research for chronic pain over the past decade. Methods: We retrieved publications on acupuncture for chronic pain published from 2011 to 2022 from the Science Citation Index Expanded (SCI-expanded) of the Web of Science Core Collection (WoSCC). The co-occurrence relationships of journals/countries/institutions/authors/keywords were performed using VOSviewer V6.1.2, and CiteSpace V1.6.18 analyzed the clustering and burst analysis of keywords and co-cited references. Results: A total of 1616 articles were retrieved. The results showed that the number of annual publications on acupuncture for chronic pain has increased over time, with the main types of literature being original articles (1091 articles, 67.5 %) and review articles (351 articles, 21.7 %). China had the most publications (598 articles, 37 %), with Beijing University of Traditional Chinese Medicine (93 articles, 5.8 %) and Evidence-based Complementary and Alternative Medicine ranked first (169 articles, 10.45 %) as the most prolific affiliate and journal, respectively. Liang FR was the most productive author (43 articles), and the article published by Vickers Andrew J in 2012 had the highest number of citations (625 citations). Recently, ''acupuncture'' and ''pain'' appeared most frequently. The hot topics in acupuncture for chronic pain based on keywords clustering analysis were experimental design, hot diseases, interventions, and mechanism studies. According to burst analysis, the main research frontiers were functional connectivity (FC), depression, and risk. Conclusion: This study provides an in-depth perspective on acupuncture for chronic painstudies, revealing pivotal points, research hotspots, and research trends. Valuable ideas are provided for future research activities.

Mild cognitive impairment (MCI) is a multifactorial and complex central neurodegenerative disease. Acupuncture appears to be an effective method for cognitive function improvement in MCI patients. Neural plasticity remaining in the MCI brain implies that acupuncture-associated benefits may not be limited to the cognitive function. Instead, neurological alternations in the brain play a vital role in corresponding to the cognitive improvement. However, previous studies have mainly focused on the effects of cognitive function, leaving neurological findings relatively unclear. This systematic review summarized existing studies that used various brain imaging techniques to explore the neurological effect regarding acupuncture use for MCI treatment. Potential neuroimaging trials were searched, collected, and identified independently by two researchers. Four Chinese databases, four English databases, and additional sources were searched to identify studies reporting the use of acupuncture for MCI from the inception of databases until 1 June 2022. Methodological quality was appraised using the Cochrane risk-of-bias tool. In addition, general, methodological, and brain neuroimaging information was extracted and summarized to investigate the potential neural mechanisms by which acupuncture affects patients with MCI. In total, 22 studies involving 647 participants were included. The methodological quality of the included studies was moderate to high. The methods used included functional magnetic resonance imaging, diffusion tensor imaging, functional near-infrared spectroscopy, and magnetic resonance spectroscopy. Acupuncture-induced brain alterations observed in those patients with MCI tended to be observable in the cingulate cortex, prefrontal cortex, and hippocampus. The effect of acupuncture on MCI may play a role in regulating the default mode network, central executive network, and salience network. Based on these studies, researchers could extend the recent research focus from the cognitive domain to the neurological level. Future researches should develop additional relevant, well-designed, high-quality, and multimodal neuroimaging researches to detect the effects of acupuncture on the brains of MCI patients.

BackgroundThere is insufficient evidence to support the use of acupuncture for mild cognitive impairment (MCI), and there is no consensus on its efficacy. This review aimed to determine the acupuncture effect in patients with MCI.MethodsRelevant and potentially eligible randomized controlled trials (RCTs) of acupuncture for MCI were obtained from four Chinese databases, four English databases, and additional resources up to 1 August 2022. The primary outcome was the improvement in overall cognitive function (OCF). Secondary outcomes were improved memory function (MF) and activities of daily living (ADLs). The revised Cochrane collaboration risk of bias (ROB) assessment tool (ROB 2.0) was applied to evaluate their methodological quality. The Review Manager software v 5.4 was used for analyses. Trial sequential analysis (TSA) 0.9.5.10 β software was used to estimate the required sample size and test the reliability of the pooled outcome. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool.ResultsThis meta-analysis included 11 RCTs with a total of 602 patients. The methodological quality of all trials was moderate. Low-quality evidence showed that acupuncture significantly improved OCF (Mini-Mental State Examination (MMSE): mean difference (MD) = 1.22, 95% confidence interval (CI): 0.78–1.66; the Montreal Cognitive Assessment Scale (MoCA): MD = 1.22, 95% CI: 0.47–1.97). In subgroup analyses, it was revealed that acupuncture significantly increased OCF in patients with MCI when compared to conventional medicine (CM) and sham acupuncture (SA). TSA's findings indicated that the evidence of improving OCF with acupuncture for patients with MCI was conclusive. Meanwhile, there is no statistical difference in the improvement of MF and ADL between acupuncture and CM. TSA showed that the evidence of improving MF and ADL for patients who had MCI and received acupuncture was inconclusive. The shreds of evidence of improving MF and ADL were ranked from low to critically low.ConclusionAcupuncture appears to be an effective clinical application method for improving OCF in patients with MCI. However, due to low-quality evidence, more relevant and high-quality research is needed in this field.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021291284, PROSPERO, No. CRD42021291284.

Objective: To conduct an inductive analysis of neuroimaging studies following the global popularity surrounding the effects of acupuncture. Methods: The relevant works of literature on acupuncture effects-related neuroimaging studies were retrieved from the web of science core collection database from the date of its establishment to 2022. Bibexcel software was used to extract information, such as article numbers, countries, journals, agencies, funding sources and keywords. The VOSviewer software’s co-occurrence and clustering module was used for the co-occurrence and cluster analysis of collaborative networks and high frequency keywords, such as authors, institutions and countries. Results: Neuroimaging research on the effects of acupuncture began in the 1960 s and has since received the extensive attention of scholars. China, The United States and South Korea conduct more neuroimaging research on the effects of acupuncture than other countries. Academic journals such as Evidence-Based Complementary and Alternative Medicine, Journal of Alternative and Complementary Medicine, Neural Regeneration Research and Acupuncture in Medicine have published the highest number of acupuncture-related neuroimaging articles. Moreover, cluster analysis differentiates high-frequency keywords into six clusters. Furthermore, the use of the keyword ‘density atlas’ reveals that neuroimaging research on the effects of acupuncture surrounding pain and neurofunctional rehabilitation is currently the research focus. Conclusions: This bibliometric study identifies six important research hot spots: Static brain functional connectivity analysis of acupuncture analgesic effects, key theories on the scientific problems of acupuncture, acupuncture analgesic effect of the placebo effect, the neuroimaging of acupoint ST-36, the value of acupuncture in regulating the autonomic nerves and acupuncture therapy as complementary medicine.

IntroductionAcupuncture is an effective and safe therapy for patients with migraine without aura (MwoA), but only 41–59% of patients show improvement with this treatment. Screening positive responders to acupuncture treatment for MwoA can ensure that healthcare resources can be appropriately targeted to specific patients who would most benefit. The objective of this study is to determine whether the structure and functional activity in certain brain regions can predict analgesia response in patients with MwoA who receive acupuncture treatment.Methods and analysisA total of 72 patients with MwoA and 72 healthy controls (HCs) will be enrolled in this study. Resting-state structural and functional magnetic resonance imaging (MRI) data will be collected from each participant at baseline. Patients with MwoA will undergo 12 sessions of acupuncture treatment for 8 weeks, twice per week in the first 4 weeks and once per week for the last 4 weeks. The follow-up will be 12 weeks. The number of days with migraine, frequency of migraine attacks, and average visual analog scale scores will be recorded in detail at weeks 0, 4, 8, 12, and 16 and at the end of follow-up (week 20). The positive response rate will be calculated as the proportion of patients with ≥50% reduction in the number of migraine days during follow-up compared with baseline. Machine learning methods will be applied to classify patients with MwoA and HCs and predict patients with response or non-response to acupuncture treatment based on multimodal MRI parameters, such as gray matter volume, regional homogeneity, amplitude of low-frequency fluctuation, fractional anisotropy, and mean diffusivity.DiscussionThis study aims to establish brain structural and functional characteristics that can identify patients with MwoA who will derive analgesia benefits from acupuncture treatment.Trial registration numberhttp://www.chictr.org.cn/showproj.aspx?proj=65443, identifier: ChiCTR2100042915.

BackgroundWith high morbidity and mortality, cardiopathy is a major component of cardiovascular disease, causing a huge burden of disease to public health worldwide. In recent years, research on acupuncture treatment of cardiopathies has been increasing. However, no bibliometric analysis has been conducted to systematically describe the research progress and hotspots in this field. Therefore, this study aimed to conduct a bibliometric analysis of the relevant literature to explore the current status and future development of acupuncture for cardiopathies.MethodsThe Web of Science (WoS) Core Collection Database was searched for literature related to acupuncture therapies for cardiopathies from 2011 to 2021. Using CiteSpace 5.8 R3, cooperation network diagrams of authors, institutions, countries and journals, keyword co-occurrences, and clustering were performed and analyzed.ResultsA total of 321 studies were included. Overall, the number of annual publications increased yearly. These publications came from 31 countries or regions, of which China and the United States made the greatest contributions. In total, 333 authors from 258 institutions participated in this field, and Beijing University of Chinese Medicine and Professor Fanrong Liang were the most published institution and author, respectively. Evidence-based Complementary and Alternative Medicine published the largest number of articles, and CIRCULATION was the most commonly cited journal. Based on co-occurrences and cluster analysis of 257 keywords, three research frontiers and hotspots were identified: acupuncture for blood pressure regulation, acupuncture for coronary heart disease, and acupuncture for regulation of heart rate. In these three research frontiers, the rostral ventrolateral medulla (RVLM) and autonomic nervous system (ANS) are the most popular mechanisms.ConclusionA stable development trend has formed in this field. Further research should focus on the role of acupuncture therapies in the treatment of hypertension or hypertensive heart disease, coronary heart disease, and arrhythmia based on the mechanisms related to the RVLM and ANS.

BackgroundElectroacupuncture (EA) has been commonly used for the management of neck pain caused by cervical spondylosis (NPCS); however, current electrical instruments have limitations on intelligence, digitalization, and visualization. The intelligent electronic stimulator (CX-DZ-II) is a digital device with an evidence-based diagnosis and treatment system. This study aimed to investigate the efficacy and safety of the CX-DZ-II intelligent EA instrument for NPCS.Materials and MethodsA total of 164 patients with NPCS [mean age (SD), 49.48 (13.47) years] were randomly assigned to receive 8 sessions (over 2 weeks) EA of the intelligent electronic stimulator (CX-DZ-II) or the regular electronic stimulator (SDZ-II). The primary outcome was the change of the visual analog scale (VAS) from baseline to 2 weeks of treatment. Secondary outcomes included mean scores of the VAS after each treatment in 1 week, responder rate, drug-usage rate of non-steroidal antipyretic analgesics (NSAAs), the occurrence rate of adverse events (AEs), proportions of apparatus with defect during treatment, and excellent rate of apparatus.ResultsThe intelligent electronic stimulator (CX-DZ-II) was non-inferior to the regular electronic stimulator (SDZ-II) for changes from baseline in the VAS [3.36 vs. 3.23, with a difference of 0.17 (95% CI, −0.36 to 0.69), P < 0.025 for non-inferiority]. No between-group differences were found in outcomes of VAS in 1 week, overall responders, and drug-usage rate of NSAAs. The defect rate and excellent rate of the instrument were similar in the CX-DZ-II and SDZ-II groups. Adverse events occurred in 9 (10.84%) patients in the CX-DZ-II group and 4 (5.00%) patients in the SDZ-II group.ConclusionThe intelligent electronic stimulator (CX-DZ-II) was non-inferior to the regular electronic stimulator (SDZ-II) in relieving neck pain. The intelligent electronic stimulator (CX-DZ-II) is a promising non-inferior alternative instrument for NPCS.Clinical Trial Registration[https://clinicaltrials.gov/], identifier [NCT030 05301].

Essential hypertension is a polygenic cardiovascular disease that is associated with maladaptive metabolic changes. Acupuncture as a non-pharmacologic intervention is used to lower blood pressure and improve metabolic dysfunction. However, such effects have not been clinically characterized. We will conduct a randomized clinical trial to evaluate the antihypertensive effect of acupuncture among patients with essential hypertension and determine the associated metabolic improvements. This study is a phase II, two-arm, randomized, sham-controlled trial (Trial registration: ChiCTR2100043737), in which biospecimens will be collected for metabolic profiling. A total of 64 patients with a clinical diagnosis of essential hypertension will be randomly assigned to either the acupuncture or the sham acupuncture group in a 1:1 ratio. All participants will receive 10 treatments over 4 weeks, with three sessions per week for the first 2 weeks and two sessions per week for the remaining weeks. The primary outcome is the change of the systolic and diastolic blood pressure measured by the 24-h ambulatory blood pressure monitoring from baseline to 4 weeks. Secondary outcomes include the circadian rhythm of blood pressure, sleep quality measured by the Insomnia Severity Index, cognitive function measured by the Montreal Cognitive Assessment, and others. Fasting blood serum and urine samples will be collected at baseline and 4 weeks for targeted and untargeted metabolomics analysis. We will use the mixed-effects model and other related bioinformatics approaches to analyze the clinical and metabolome data. This metabolomic-based trial will provide important clinical data regarding the efficacy of acupuncture for essential hypertension to better inform evidence-based care delivery for hypertension patients. Moreover, the findings will offer important insights into the mechanism of action of acupuncture for hypertension by revealing its effect on metabolism. The results of this study will be used to inform the design of a statistically powered, multicenter, randomized trial. We will publish the study findings in peer-reviewed journals. The ethical approval of this study has been reviewed and approved by the Sichuan Regional Ethics Review Committee on Traditional Chinese Medicine (ID: 2021KL-006). The outcomes of the trial will be disseminated through peer-reviewed publications.

ObjectiveAcupuncture has been shown to be effective in the treatment of chronic pain. However, their neural mechanism underlying the effective acupuncture response to chronic pain is still unclear. We investigated whether metabolic patterns in the pain matrix network might predict acupuncture therapy responses in patients with primary dysmenorrhea (PDM) using a machine-learning-based multivariate pattern analysis (MVPA) on positron emission tomography data (PET).MethodsForty-two patients with PDM were selected and randomized into two groups: real acupuncture and sham acupuncture (three menstrual cycles). Brain metabolic data from the three special brain networks (the sensorimotor network (SMN), default mode network (DMN), and salience network (SN)) were extracted at the individual level by using PETSurfer in fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) data. MVPA analysis based on metabolic network features was employed to predict the pain relief after treatment in the pooled group and real acupuncture treatment, separately.ResultsPaired t-tests revealed significant alterations in pain intensity after real but not sham acupuncture treatment. Traditional mass-univariate correlations between brain metabolic and alterations in pain intensity were not significant. The MVPA results showed that the brain metabolic pattern in the DMN and SMN did predict the pain relief in the pooled group of patients with PDM (R2 = 0.25, p = 0.005). In addition, the metabolic pattern in the DMN could predict the pain relief after treatment in the real acupuncture treatment group (R2 = 0.40, p = 0.01).ConclusionThis study indicates that the individual-level metabolic patterns in DMN is associated with real acupuncture treatment response in chronic pain. The present findings advanced the knowledge of the brain mechanism of the acupuncture treatment in chronic pain.

BackgroundAcupuncture 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.MethodsThirty-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.ResultsChronic 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.ConclusionRegulating 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.

Abstract Objectives To explore the possible concurrent brain functional and structural alterations in patients with migraine without aura (MwoA) patients compared to healthy subjects (HS). Methods Seventy-two MwoA patients and forty-six HS were recruited. 3D-T1 and resting state fMRI data were collected during the interictal period for MwoA and HS. Voxel-based morphometry (VBM) for structure analysis and regional homogeneity (Reho) for fMRI analysis were applied. The VBM and Reho maps were overlapped to determine a possible brain region with concurrent functional and structural alteration in MwoA patients. Further analysis of resting state functional connectivity (FC) alteration was applied with this brain region as the seed. Results Compared with HS, MwoA patients showed decreased volume in the bilateral superior and inferior colliculus, periaqueductal gray matter (PAG), locus ceruleus, median raphe nuclei (MRN) and dorsal pons medulla junction. MwoA patients showed decreased Reho values in the middle occipital gyrus and inferior occipital gyrus, and increased Reho values in the MRN. Only a region in the MRN showed both structural and functional alteration in MwoA patients. Pearson correlation analysis showed that there was no association between volume or Reho values of the MRN and headache frequency, headache intensity, disease duration, self-rating anxiety scale or self-rating depression scale in MwoA patients. Resting state functional connectivity (FC) with the MRN as the seed showed that MwoA patients had increased FC between the MRN and PAG. Conclusions MRN are involved in the pathophysiology of migraine during the interictal period. This study may help to better understand the migraine symptoms. Trial registration NCT01152632 . Registered 27 June 2010.

Abstract Background Allergic rhinitis (AR) is a common symptomatic, inflammatory, and immunological disorder of nasal mucosa. Multiple clinical trials and systematic reviews have implicated acupuncture methods as potentially effective treatment strategies for AR, however, considering the great burden of AR, it is crucial to explore the most recent clinical evidence supporting acupuncture in AR. Besides, the methodologies reported in previous studies as well as those commonly applied during clinical practices greatly vary. Herein, we conducted network meta-analysis to compare the effectiveness of diverse acupuncture methods for AR treatment. Methods We conducted a literature search for relevant reports published from inception to 1 July 2020 in several scientific databases, including PubMed, Embase, Cochrane library, Web of Science, CNKI, WF, VIP, CBM, AMED as well as related registration platforms. Primary outcomes as reported in the identified studies were assessed using nasal symptoms. All Meta-analyses were performed with RevMan, ADDIS, and STATA software. To ensure consistency among our reviewers, the intra-class correlation coefficient was used. Results Exactly 39 studies with 3433 participants were covered in this meta-analysis. The meta-analysis demonstrated that all acupuncture types were superior to sham acupuncture in terms of total nasal symptom score and rhinoconjunctivitis quality of life questionnaire. Moxibustion was recommended as the most effective intervention as it reduced nasal symptoms in 6 treatments. On the other hand, manual acupuncture plus conventional medicine was recommended as the most effective intervention in improving the quality of life in 9 treatments. Notably, moxibustion was recommended as the most effective intervention that changed the content of IgE in 9 treatments. Moreover, adverse events of these interventions were acceptable. Conclusion Our findings revealed that all acupuncture methods are effective and safe for AR. Moreover, either moxibustion or manual acupuncture plus conventional medicine are potentially the most effective treatment strategies for AR. Based on these findings, it is evident that acupuncture therapy is not inferior to pharmacologic therapy. Therefore, for AR patients who are either unresponsive to conventional medicine or are intolerant to adverse events, acupuncture therapy should be administered. However, the quality of these included trials was mainly ranked as moderate quality, we recommend additional well-designed RCTs with larger sample sizes to validate these findings.

Abstract Background Although previous clinical studies suggest possible benefits of acupuncture for knee osteoarthritis (KOA), the value of acupuncture at sensitized points is uncertain. We aimed to preliminarily assess the feasibility of performing a definitive randomized controlled trial to explore the effectiveness of acupuncture for KOA with highly sensitized acupoints. Methods In this randomized, single-blind, parallel, pilot trial, 36 participants with KOA were randomly assigned to receive acupuncture at highly sensitized acupoints (high-sensitization group) or at low/non-sensitized points (low/non-sensitization group) by a computer-generated random sequence. Both groups received three treatment sessions per week for four consecutive weeks (12 sessions in total). Assessments were performed at screening and at 4, 8, 12, and 16 weeks after randomization. Primary feasibility outcomes were patient recruitment, retention rate, and adherence to group treatment. Secondary outcomes included the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score from baseline to 16 weeks, the change of Short Form (SF)-12 health survey score, and safety outcomes. Results Patient recruitment of 36 patients took 2 months, achieving the recruitment target. Retention rates were similar between the treatment groups, 14 (77.8%) patients in the high-sensitization group completed the 16-week follow-up and compared to 14 (77.8%) patients in low/non-sensitization group, but the result was lower than expected. All patients received at least ten treatment sessions in total. The WOMAC total score and the pain, stiffness, and physical function score in the high-sensitization group were lower or very close to those in the control group at each assessment point. Similar results were observed on quality of life. No adverse events occurred. Conclusion This trial has presented preliminary data on the feasibility of conducting a large trial to test the effectiveness of acupuncture at sensitized points in KOA patients. Trial registration ClinicalTrials.gov, NCT03008668 . Registered on 26 December 2016—retrospectively registered.

BackgroundFunctional and structural alterations in the gray matter have been observed in patients with knee osteoarthritis (KOA). However, little is known about white matter changes in KOA. Here, we evaluated fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) to investigate potential alterations in the white matter of patients with KOA.MethodsA total of 166 patients with KOA, along with 88 age- and sex-matched healthy controls were recruited and underwent brain magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) data were collected and analyzed using tract-based spatial statistics (TBSS). Statistical significances were determined at p < 0.05 and were corrected by the threshold-free cluster enhancement (TFCE) method. Then, we evaluated potential correlations between FA, MD, AD, RD values and disease duration, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and visual analog scale (VAS) scores.ResultsFA values for the body of corpus callosum, splenium of corpus callosum, bilateral superior longitudinal fasciculus, cingulum, bilateral superior corona radiata, and right posterior corona radiata were significantly higher in patients with KOA than in healthy controls (p < 0.05, TFCE corrected). Compared with healthy controls, patients with KOA also had significantly lower MD, AD, and RD values of the genu of corpus callosum, body of corpus callosum, splenium of corpus callosum, corona radiata, right posterior thalamic radiation, superior longitudinal fasciculus, and middle cerebellar peduncle (p < 0.05, TFCE corrected). Negative correlations were detected between WOMAC scores and AD values for the body of the corpus callosum and the splenium of the corpus callosum (p < 0.05, FDR corrected).ConclusionPatients with KOA exhibited extensive white matter alterations in sensorimotor and pain-related regions. Longitudinal observation studies on the causation between abnormalities in the white matter tracts and KOA is needed in the future.

Introduction Breathlessness in advanced cancer, a frequent multicomponent and debilitating disorder, severely reduces function and quality of patients’ life. Multiple studies have shown that non-pharmacological therapies can effectively palliate breathlessness in advanced cancer. However, no systematic review has investigated the application of acupuncture, as a non-pharmacological treatment, for breathlessness in advanced cancer. A systematic review will be conducted to summarise evidence supporting the efficacy and safety of acupuncture as a therapeutic option for breathlessness in advanced cancer based on existing randomised controlled trials (RCTs).Methods RCTs will be retrieved from nine scientific databases, including the MEDLINE via PubMed, Web of Science via the Web of Knowledge, Embase via Ovid, the Cochrane Central Register of Controlled Trials via the Cochrane Library, and Allied and Complementary Medicine Database via EBSCO, China National Knowledge Infrastructure, Wanfang Database, VIP Database, Chinese Biomedical Literature Database; three clinical registry platforms, including the WHO International Clinical Trials Registry Platform, NIH Clinical trials.gov and Chinese Clinical Trial Registry, as well as from other sources. Studies published since inception of these databases to 1 August 2021 will be retrieved. Search terms will include breathlessness, cancer, acupuncture and RCT. Two investigators will independently select and extract data from RCTs and assess the risk of bias. The primary outcome, which is alleviation of breathlessness, will be assessed. Meta-analysis will be performed using RevMan V.5.4 and STATA V.15.0. The TSA 0.9.5.10 β software will be used to conduct trial sequential analysis. Finally, the quality of evidence from RCTs will be assessed using the Grading of Recommendations Assessment, Development and Evaluation System tool.Ethics and dissemination Results will be disseminated through peer-reviewed journals or conference reports. Since this study involves acquisition of secondary data, ethical approval requirements will be waived.PROSPERO registration number CRD42021240085.

Migraine is a pervasive neurologic disease closely related to neurogenic inflammation. The astrocytes and microglia in the central nervous system are vital in inducing neurogenic inflammation in migraine. Recently, it has been found that there may be a crosstalk phenomenon between microglia and astrocytes, which plays a crucial part in the pathology and treatment of Alzheimer's disease and other central nervous system diseases closely related to inflammation, thus becoming a novel hotspot in neuroimmune research. However, the role of the crosstalk between microglia and astrocytes in the pathogenesis and treatment of migraine is yet to be discussed. Based on the preliminary literature reports, we have reviewed relevant evidence of the crosstalk between microglia and astrocytes in the pathogenesis of migraine and summarized the crosstalk pathways, thereby hoping to provide novel ideas for future research and treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Acupuncture is safe and effective for reducing the symptoms of knee osteoarthritis (KOA), but the underlying mechanisms of acupuncture for treating KOA are not fully understood. Methods/design In total, 108 participants diagnosed with KOA will be recruited. They will be blinded to group assignment and randomized to either verum acupuncture, sham acupuncture or waiting-list groups with 36 patients in each group. Each patient in the acupuncture group will receive five treatments per week for 2 weeks. This study will focus on detecting the cerebral functional connectivity changes elicited by acupuncture treatment. The Visual Analog Scale and the short form of the McGill Pain Questionnaire, the Western Ontario and McMaster Universities Osteoarthritis Index, the Attention Test Scale, the Pain Assessment of Sphygmomanometer and the 12-Item Short Form Health Survey will be used to evaluate the symptoms and quality of life improvement at the baseline and the end of treatment. The Self-rating Anxiety Scale and the Self-rating Depression Scale will be used at the baseline and the end of treatment to investigate the influence of emotional state on brain activity and clinical variable. To ensure the consistency of acupuncture manipulation, the deqi scale will be performed after each acupuncture treatment. During the procedure of outcome evaluation and data analysis, the evaluators and statisticians will be blinded to the group allocation. The repeated measures analysis of variance (3 groups × 2 time points ANOVA) will be employed to analyze numerical variables of the clinical and neuroimaging data generated in the study, then the t test will be used in the post-hoc analysis. Discussion The results of this randomized, sham- and waiting-list-controlled functional magnetic resonance imaging (fMRI) study will help to investigate the influence of verum acupuncture treatment on the brain activities of patients with KOA, which might provide evidence for the clinical application of verum acupuncture for KOA management. Trial registration Chinese Clinical Trial Registry, ID: ChiCT-IOR-17012364. Registered on 14 August 2017.

Abstract Background Celecoxib is frequently prescribed to treat knee osteoarthritis (KOA), but how celecoxib influences the activity of the central nervous system to alleviate chronic pain remains unclear. Methods One hundred eight patients with KOA will be enrolled in this study. Patients will be allocated randomly to three groups: the celecoxib group, the placebo group, and the waiting list group. The patients in the celecoxib group will orally take celecoxib 200 mg once daily and the patients in placebo group with placebo 200 mg every day for 2 weeks. Functional magnetic resonance imaging scan will be performed on all patients at baseline and the end of interventions to detect the cerebral activity changes. The short form of McGill pain questionnaire and the Visual Analog Scale will be used as the primary endpoints to evaluate the improvement of knee pain. The secondary endpoints include the Western Ontario and McMaster osteoarthritis index (WOMAC), the Attention Test Scale, the Pain Assessment of Sphygmomanometer, the Self-rating Anxiety Scale, the Self-rating Depression Scale, and 12-Item Short Form Health Survey (SF-12). Discussion The results will investigate the influence of celecoxib treatment on cerebral activity of patients with KOA and the possible relationship between the cerebral activity changes and improvement of clinical variables so as to explore the central mechanism of celecoxib in treating knee pain. Trial registration ChiCTR-IOR-17012365. Registered on August 14, 2017.

Background: Migraine is a chronic neurological disorder characterized by attacks of moderate or severe headache and various neurological symptoms. Migraine is typically treated by pharmacological or non-pharmacological therapies to relieve pain or prevent migraine attacks. Pharmacological therapies show limited efficacy in relieving headache and are often accompanied by adverse effects, while the benefits of acupuncture, a non-pharmacological therapy, have been well-documented in both the treatment and prevention of acute migraine attacks. However, the underlying mechanism of the effect of acupuncture on relieving migraine remains unclear. Recent advances in neuroimaging technology have offered new opportunities to explore the underlying neural mechanism of acupuncture in treating migraine. To pave the way for future research, this review provides an overview neuroimaging studies on the use of acupuncture for migraine in the last 10 years.Methods: Using search terms about acupuncture, neuroimaging and migraine, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure from January 2009 to June 2020 for neuroimaging studies that examined the effect of acupuncture in migraine. All published randomized and non-randomized controlled neuroimaging studies were included. We summarized the proposed neural mechanism underlying acupuncture analgesia in acute migraine, and the proposed neural mechanism underlying the sustained effect of acupuncture in migraine prophylaxis.Results: A total of 619 articles were retrieved. After removing reviews, meta-analyses, animal studies and etc., 15 articles were eligible and included in this review. The methods used were positron emission computed tomography (PET-CT; n = 2 studies), magnetic resonance spectroscopy (n = 1), and functional magnetic resonance imaging (fMRI; n = 12). The analyses used included the regional homogeneity (ReHo) method (n = 3), amplitude of low frequency (ALFF) method (n = 2), independent component analysis (ICA; n = 3), seed-based analysis (SBA; n = 1), both ICA and SBA (n = 1), Pearson's correlation to calculate functional connectivity (FC) between brain regions (n = 1), and a machine learning method (n = 1). Five studies focused on the instant effect of acupuncture, and the research objects were those with acute migraine (n = 2) and migraine in the interictal phase (n = 3). Ten studies focused on the lasting effect of acupuncture, and all the studies selected migraine patients in the interictal phase. This review included five task-based studies and 10 resting-state studies. None of the studies conducted a correlation analysis between functional brain changes and instant clinical efficacy. For studies that performed a correlation analysis between functional brain changes and sustained clinical efficacy, the prophylactic effect of acupuncture on migraine might be through regulation of the visual network, default mode network (DMN), sensory motor network, frontoparietal network (FPN), limbic system, and/or descending pain modulatory system (DPMS).Conclusion: The neural mechanism underlying the immediate effect of acupuncture analgesia remains unclear, and the neural mechanism of sustained acupuncture treatment for migraine might be related to the regulation of pain-related brain networks. The experimental design of neuroimaging studies that examined the effect of acupuncture in migraine also have some shortcomings, and it is necessary to standardize and optimize the experimental design. Multi-center neuroimaging studies are needed to provide a better insight into the neural mechanism underlying the effect of acupuncture on migraine. Multi-modality neuroimaging studies that integrate multiple data analysis methods are required for cross-validation of the neuroimaging results. In addition, applying machine learning methods in neuroimaging studies can help to predict acupuncture efficacy and screen for migraineurs for whom acupuncture treatment would be suitable.

Primary dysmenorrhea (PDM) is a common gynecological disease characterized by lower abdominal pain. Acupuncture is considered a good alternative therapy for PDM. However, the central mechanism of the analgesic effect of acupuncture is largely unknown. In this study, eligible patients were randomized into the real and sham acupuncture groups using a computer-generated, permuted block randomization method. The study cohort comprised 34 patients: 19 in the real acupuncture group and 15 in the sham acupuncture group. The clinical characteristics of the patients during their menstrual period were collected, and imaging scans were performed during the first 3 days of the patients’ menstrual period. We analyzed task and resting functional magnetic resonance imaging (fMRI) data to investigate the potential central mechanism of the immediate effect of acupuncture intervention on the intensity of PDM pain. The task fMRI study found that the rostral anterior cingulate cortex (rACC) and right supplemental motor area were activated during real acupuncture. Using the resting-state functional connectivity (FC) method, we found a post- versus pre-treatment change in the FC of the rACC and left precentral gyrus in the comparison of real acupuncture versus sham acupuncture. In addition, the FC of the rACC–left precentral gyrus at baseline was negatively correlated with short-term analgesia, while the change in the FC of the rACC–left precentral gyrus was positively correlated with short-term analgesia after acupuncture treatment. These findings support the importance of rACC–left precentral gyrus resting-state FC in the modulation of the intensity of PDM pain through acupuncture, which may shed light on the central mechanism of acupuncture in the treatment of PDM.

IntroductionMigraine without aura (MwoA) is a primary type of migraine, a common disabling disorder, and a disabling neurological condition. The headache is a complex experience, a common form of pain, in which multiple sensory information dimensions are combined to provide a unified conscious event. Migraine ictal have unique neuroimage biomarkers, but the brain is also affected during the inter-ictal phase. According to the current studies, a hypothesis was constructed that the altered integration of pain spatial and intensity information impacts headache intensity in the inter-ictal period.MethodsIn this study, we applied theory-based region-to-region functional connectivity (FC) analyses to compare the differences in resting-state FC between MwoA participants and healthy controls with the pain integration hypothesis. After the correlation matrices between FC edges and clinical symptoms were constructed, the moderating effect and simple slope tests were investigated to explain whether and how the dysfunction of pain features discrimination affects the clinical symptoms.ResultsFunctional connectivity analyses showed significantly decreased FC edges between the left dorsolateral superior frontal gyrus (SFGdor) and left insula, and an increased FC edge between the left SFGdor and bilateral angular gyrus. The correlation matrix showed no significant correlation between significantly altered FC edge and headache duration, frequency, Zung self-rating anxiety scale, and Zung self-rating depression scale. Only one significantly altered edge in the MwoA condition was significantly correlated with headache intensity. Moderating Module 1 and 2 manifested the moderator variable (altered rs-FC edge) moderated the link between the normal edges and headache intensity.ConclusionThe pain features integration processes in migraineurs vary from HCs, related to the clinical symptoms during a migraine attack. Moreover, the clinical symptoms will be affected by one or more discrimination modules. And the spatial or intensity discrimination modules have a higher impact when combined with another module on clinical symptoms than the single module.

Introduction Biliary colic (BC) is a severe pain associated with nausea and vomiting, which is the most common symptom among the gallstone population. This protocol proposes a methodology for conducting a systematic review and meta-analysis that aims to assess the benefits and safety of acupuncture in patients with BC.Methods and analysis Clinical trials will be identified through nine databases from inception to December 2020, using Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Allied and Complementary Medicine Database (AMED), CINAHL, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Database and Wanfang Database. Search words will be used for the BC and acupuncture. The analysis would include randomised, controlled, clinical trials of adults with BC that were published in either Chinese or English. The primary outcome is to measure pain relief. Two or three reviewers should be in charge of study selection, data extraction and evaluating the risk of bias. RevMan software (V.5.4) will be used to perform the assessment of the risk of bias and data synthesis.Ethics and dissemination Ethics approval will not be required for this review, as it will only involve the collection of literature previously published. The results of this meta-analysis will be disseminated in a peer-reviewed journal or relevant conference, through publication.Trial registration number CRD42020167510.