Efficacy of Acupuncture in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Purpose: The effect of acupuncture as adjunctive therapy for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) was controversial. Thus, we aimed to evaluate the effects of acupuncture for treating AECOPD. Methods: Eight databases were searched from database inception to July 30, 2023. All RCTs compared acupuncture plus conventional western medicine with conventional western medicine alone were included. Outcomes were quality of life, lung function, blood oxygen condition, exercise capacity, daily symptoms, duration of hospitalization, and adverse events. The statistical analyses were conducted using Stata 17.0, and methodological quality was measured by the Cochrane bias risk assessment tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence. Results: Twelve studies including 915 patients were included. Compared with conventional western medicine alone, acupuncture combined with conventional western therapy significantly improved quality of life (CAT: MD: -3.25; 95% CI: -3.73 to -2.78, P<0.001) and arterial blood gas (PaCO2: MD: -1.85; 95% CI: -2.74 to -0.95, P<0.001; PaO2: MD: 5.15; 95% CI: 1.22 to 9.07, P = 0.01). And for lung function, statistical benefits were found in FEV1/FVC (MD: 4.66; 95% CI: 2.21 to 7.12, P<0.001), but no difference was seen for FEV1% (MD: 1.83; 95% CI: -0.17 to 3.83, P = 0.073). There was no significant improvement in exercise capacity (6MWD: MD: 96.69; 95% CI: -0.60 to 193.98, P = 0.051), hospitalization duration (MD: -5.70; 95% CI: -11.97 to 0.58, P = 0.075), and dyspnea (mMRC: MD: -0.19; 95% CI: -0.61 to 0.63, P = 0.376) between two groups. Overall bias for CAT and mMRC was in "high" risk, FEV1%, FEV1/FVC, PaCO2, and PaO2 was in "some concern" and 1 RCT assessing hospitalization duration was in "low" risk. And the overall assessments were either moderate, low or very low certainty. Seven trials performed safety assessment of acupuncture, and no serious adverse events were reported. Conclusion: Acupuncture might have auxiliary effects on AECOPD. However, the quality of the evidence is limited, and more high-quality RCTs are needed to be performed in the future.

Efficacy of acupuncture as an adjunctive treatment to patients with stable COPD: a multicenter, randomized, sham-controlled trial protocol.

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.

Modulatory effects of acupuncture on raphe nucleus-related brain circuits in patients with chronic neck pain: A randomized neuroimaging trial.

OBJECTIVE: Acupuncture has shown promise in treating neck pain. Clinical trials have shown mixed results, possibly due to heterogeneous methodologies and the lack of knowledge regarding underlying brain circuit mechanism of action. In this study, we investigated the specific contribution of the serotonergic system in treating neck pain, and the specific brain circuits involved. METHODS: A total of 99 patients with chronic neck pain (CNP) were randomized to receive true acupuncture (TA) or sham acupuncture (SA) 3 times weekly for 4 weeks. Patients with CNP in each group were assessed for primary outcomes by measuring the Visual Analog Scale (VAS) and the duration of each attack; secondary outcomes were measured using the Neck Disability Index (NDI), Northwick Park Neck Pain Questionnaire (NPQ), McGill Pain Questionnaire (MPQ), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and the 12-item Short Form Quality Life Scale (SF-12); levels of functional circuits connectivity were assessed using resting-state functional magnetic resonance imaging in the dorsal (DR) and median (MR) raphe nucleus, before and after undergoing acupuncture. RESULTS: Patients receiving TA showed more extensive symptom improvement compared with SA. Regarding the primary outcomes, changes observed in the TA group were as follows: VAS = 16.9 mm (p < 0.001) and the duration of each attack = 4.30 h (p < 0.001); changes in the SA group: VAS = 5.41 mm (p = 0.138) and the duration of each attack = 2.06 h (p = 0.058). Regarding the secondary outcomes, changes in the TA group: NDI = 7.99 (p < 0.001), NPQ = 10.82 (p < 0.001), MPQ = 4.23 (p < 0.001), SAS = 5.82 (p < 0.001), SDS = 3.67 (p = 0.003), and SF-12 = 3.04 (p < 0.001); changes in the SA group: NDI = 2.97 (p = 0.138), NPQ = 5.24 (p = 0.035) and MPQ = 2.90 (p = 0.039), SAS = 1.48 (p = 0.433), SDS = 2.39 (p = 0.244), and SF-12 = 2.19 (p = 0.038). The modulatory effect of TA exhibited increased functional connectivity (FC) between the DR and thalamus, between the MR and parahippocampal gyrus, amygdala, and insula, with decreased FC between the DR and lingual gyrus and middle frontal gyrus, between the MR and middle frontal gyrus. Furthermore, changes in the DR-related circuit were specifically associated with the intensity and duration of pain, and the MR-related circuit was correlated with the quality of life with CNP. CONCLUSION: These results demonstrated the effectiveness of TA in treating neck pain and suggested that it regulates CNP by reconfiguring the function of the raphe nucleus-related serotonergic system.

Acupuncture as adjunctive therapy for patients with AECOPD: study protocol for a multicenter, randomized controlled trial.

Background: The 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 analysis: This 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 dissemination: Ethical 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.

Dose-response relationship between acupuncture time parameters and the effects on chronic non-specific low back pain: a systematic review and Bayesian model-based network meta-analysis protocol.

INTRODUCTION: Low back pain (LBP) is a major global public health problem and the majority (nearly 90%) of patients with LBP suffer from non-specific LBP (NSLBP). Acupuncture has been widely used for relieving pain and is recommended as a first-line treatment in LBP guidelines. However, the guidelines do not recommend a specific acupuncture temporal dosage. A Bayesian model-based network meta-analysis (MBNMA) will be conducted to optimise the dosages of time parameters (session, frequency and duration). METHODS AND ANALYSIS: The following databases will be searched from their inception until 1 July 2023: MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, Cumulative Index to Nursing & Allied Health Literature (CINAHL), alternative health research database (Alt HealthWatch), China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database for Chinese Technical Periodicals, ClinicalTrials.gov, the WHO's International Clinical Trial and Chinese Clinical Registry. RCTs assessing the effects of acupuncture on chronic NSLBP will be selected. The primary outcome measure will be the improvement in pain intensity at different acupuncture time points. The MBNMA will be performed using R V.4.2.1 with related R packages. Risk of Bias V.2.0 and Confidence in Network Meta-Analysis will be used to assess the evidence quality. ETHICS AND DISSEMINATION: Ethical approval is not required for literature-based studies. The results will be published in peer-reviewed journals or conferences. PROSPERO REGISTRATION NUMBER: CRD42022336056.

Research trends of acupuncture therapy on postoperative nausea and vomiting from 2011 to 2023: A bibliometric analysis.

BACKGROUND: The utilization of acupuncture as a therapeutic intervention for the management of postoperative nausea and vomiting has experienced a notable increase in its popularity, and the purpose of this analysis is to provide a comprehensive understanding of the level of concern within the academic discipline and the main contributors and their partnership, as well as to identify research focal points and trends. METHODS: A comprehensive search was carried out to identify relevant articles on the topic of acupuncture therapy for PONV in the Web of Science and China National Knowledge Internet. The search spanned from January 1, 2011, to June 6, 2023. The annual publications were count to see the degree of scholarly attention devoted to the discipline and how it has changed over time. A statistical analysis of article distribution across various journals was conducted to serve a rough indicator for assessing the quality of articles. And a bibliometric analysis was conducted using the software CiteSpace to visually analyze various aspects of the literature. Analyze authors, institutions and countries to identify the main contributors and their collaborative relationship; and analyze keywords and references to explore research hotspots and trends. RESULTS: This study examined a comprehensive collection of 819 articles focused on acupuncture therapy for PONV, demonstrating a varying upward trend in the quantity of publications. Notably, the most productive author and institution were identified as Zheng Man and Guangzhou University of Traditional Chinese Medicine, respectively. While China had the highest number of publications, the United States held a greater prominence in this specific field. Collaboration among contributors was found to be weak. High-frequency keywords in the publications included "transcutaneous electrical acupoint stimulation," "electroacupuncture," "pain," and so forth. The literature with the highest citation count pertained to "Stimulation of the wrist acupuncture point PC6 for preventing postoperative nausea and vomiting," while the article with the highest centrality was "Consensus Guidelines for the Management of Postoperative Nausea and Vomiting." Several large clusters obtained from the references are also included "postoperative pain," "transcutaneous electrical acupoint stimulation". Nothing pertaining to mechanism study was found in the analysis results. CONCLUSION: The utilization of acupuncture for the treatment of postoperative nausea and vomiting has been gaining increasing recognition, although there remains room for improvement in the quality of research conducted in this area. Chinese authors and institutions have emerged as significant contributors to this field, while the United States has demonstrated greater proficiency in fostering collaborative efforts. It is imperative to enhance collaboration among these contributors. The current focal points of acupuncture for PONV encompass pain management, electroacupuncture, auricular acupuncture, and transcutaneous electrical acupoint stimulation. Additionally, TEA and enhanced recovery after surgery have been identified as the forefronts of research in this particular domain. In addition, there is still much room for research in the aspect of mechanism and insurance coverage. This study provides an in-depth perspective on acupuncture for PONV, which offers reference material for clinicians with rational choice of therapeutic scheme, educators with hot topics, and researchers with valuable research directions.

The Analgesic Effect and Potential Mechanisms of Acupuncture for Migraine Rats: A Systematic Review and Meta-Analysis.

Purpose: To assess the inhibitory effect of acupuncture on pain symptoms in migraine models, and to further summarize the potential mechanisms of acupuncture in regulating hyperalgesia in the treatment of migraine. Materials and Methods: Literature search in databases such as China National Knowledge Infrastructure (CNKI), PubMed, and Web of Science (WOS) etc. The quality was evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) bias risk assessment tool and Collaborative Approach to Meta-analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. Meta-analyses were performed using Stata 17.0 software. Results: Twenty-one studies involving 489 animals were identified. The qualitative score ranged from 3 to 9 points. Facial mechanical withdrawal threshold (FMWT) and paw mechanical withdrawal threshold (PMWT) measured by Von Frey filaments were selected as major outcomes, and serum calcitonin gene-related peptide (CGRP) levels measured by ELISA were selected as secondary outcome. Meta-analysis results revealed that true acupuncture (TA) group significantly increased FMWT, PMWT and CGRP compared to model group. TA group showed superior effect in FMWT, PMWT relative to sham acupuncture (SA) group. Subgroup analysis results showed that high risk of bias scores may be responsible for the high heterogeneity of FMWT; additionally, CGRP analysis suggests that acupoint selection and blood collection sites may be sources of heterogeneity. In the treatment of migraine pain symptoms, the underlying mechanism of acupuncture treatment is either the regulation of hyperalgesia and neurotransmitters, or the reduction of inflammatory factors. Conclusion: The results indicate that TA treatment effectively increased the pain threshold and reduced hyperalgesia in migraine rats. In summary, our study highlights the potential of TA as an effective treatment for migraine, but further investigation is required to fully comprehend its mechanism of action and optimize its clinical application.

Clinical observation and mechanism of acupuncture on amnestic mild cognitive impairment based on the gut-brain axis: study protocol for a randomized controlled trial.

Background: Amnestic 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 design: This 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. Discussion: This 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 registration: http://www.chictr.org.cn, identifier ChiCTR2200062084.

Evaluation of a Clustering Approach to Define Distinct Subgroups of Patients With Migraine to Select Electroacupuncture Treatments.

BACKGROUND AND OBJECTIVES: The objective of this study was to propose a clustering approach to identify migraine subgroups and test the clinical usefulness of the approach by providing prognostic information for electroacupuncture treatment selection. METHODS: Participants with migraine without aura (MWoA) were asked to complete a daily headache diary, self-rating depression and anxiety, and quality-of-life questionnaires. Whole-brain functional connectivities (FCs) were assessed on resting-state functional MRI (fMRI). By integrating clinical measurements and fMRI data, partial least squares correlation and hierarchical clustering analysis were used to cluster participants with MWoA. Multivariate pattern analysis was applied to validate the proposed subgrouping strategy. Some participants had an 8-week electroacupuncture treatment, and the response rate was compared between different MWoA subgroups. RESULTS: In study 1, a total of 97 participants (age of 28.2 ± 1.0 years, 70 female participants) with MWoA and 77 healthy controls (HCs) (age of 26.8 ± 0.1 years, 61 female participants) were enrolled (dataset 1), and 2 MWoA subgroups were defined. The participants in subgroup 1 had a significantly lower headache frequency (times/month of 4.4 ± 1.1) and significantly higher self-ratings of depression (depression score of 49.5 ± 2.3) when compared with participants in subgroup 2 (times/month of 7.0 ± 0.6 and depression score of 43.4 ± 1.2). The between-group differences of FCs were predominantly related to the amygdala, thalamus, hippocampus, and parahippocampal area. In study 2, 33 participants with MWoA (age of 30.9 ± 2.0 years, 28 female participants) and 23 HCs (age of 29.8 ± 1.1 years, 13 female participants) were enrolled as an independent dataset (dataset 2). The classification analysis validated the effectiveness of the 2-cluster solution of participants with MWoA in datasets 1 and 2. In study 3, 58 participants with MWoA were willing to receive electroacupuncture treatment and were assigned to different subgroups. Participants in different subgroups exhibited different response rates (p = 0.03, OR CI 0.086-0.93) to electroacupuncture treatment (18% and 44% for subgroups 1 and 2, respectively). DISCUSSION: Our study proposed a novel clustering approach to define distinct MWoA subgroups, which could be useful for refining the diagnosis of participants with MWoA and guiding individualized strategies for pain prophylaxis and analgesia.

Corrigendum: Circulating exosomal microRNA profiles in migraine patients receiving acupuncture treatment: a placebo-controlled clinical trial.

[This corrects the article DOI: 10.3389/fnmol.2022.1098766.].

Acupuncture therapies for cancer-related fatigue: A Bayesian network meta-analysis and systematic review.

Background: Cancer-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. Methods: We 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. Results: In 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. Conclusion: This 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 registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022339769.

Traditional Chinese medicine in treating ischemic stroke by modulating mitochondria: A comprehensive overview of experimental studies.

Ischemic stroke has been a prominent focus of scientific investigation owing to its high prevalence, complex pathogenesis, and difficulties in treatment. Mitochondria play an important role in cellular energy homeostasis and are involved in neuronal death following ischemic stroke. Hence, maintaining mitochondrial function is critical for neuronal survival and neurological improvement in ischemic stroke, and mitochondria are key therapeutic targets in cerebral stroke research. With the benefits of high efficacy, low cost, and high safety, traditional Chinese medicine (TCM) has great advantages in preventing and treating ischemic stroke. Accumulating studies have explored the effect of TCM in preventing and treating ischemic stroke from the perspective of regulating mitochondrial structure and function. In this review, we discuss the molecular mechanisms by which mitochondria are involved in ischemic stroke. Furthermore, we summarized the current advances in TCM in preventing and treating ischemic stroke by modulating mitochondria. We aimed to provide a new perspective and enlightenment for TCM in the prevention and treatment of ischemic stroke by modulating mitochondria.

Acupuncture on mild cognitive impairment: A systematic review of neuroimaging studies.

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.

[Acupuncture relieves pain by inhibiting expression of Cx43 in astrocytes and release of interfe-ron-γ in neurons of trigeminal spinal nucleus in rats with migraine].

OBJECTIVE: To observe the effect of acupuncture on the expression of connexin 43 (Cx43), glial fibrillary acidic protein (GFAP), interferon-γ (IFN-γ) in the trigeminal spinal nucleus (TNC) of rats with migraine, so as to explore its mechanisms underlying amelioration of migraine. METHODS: A total of 44 SD rats were randomly divided into control, model, acu-puncture, and sham acupuncture groups (n=11 in each group). Acupuncture was applied to bilateral "Shuaigu"(GB8) and "Yanglingquan"(GB34) or non-acupoint Ⅰ (the spot about 10 mm superior to the iliac spine and 20 mm lateral to the post-median line) and non-acupoint Ⅱ (behind the iliac spine, the ending-spot of the posterior superior iliac spine at the muscles) on both sides for 20 min, once daily for 9 days. Paw withdrawal latency (mechanical pain threshold,PWMT) and thermal tail flick latency (TFL) were measured using a VonFrey detector and photothermal tail pain meter, respectively. The content of IFN-γ of TNC tissue was detected by ELISA. The expression levels of Cx43 and IFN-γ proteins of TNC tissue were detected by Western blot. The immunofluorescence dual labeling method was used to detect the positive expression of GFAP and Cx43, IFN-γR and NeuN in TNC tissue, for displaying the activity of Cx43 in astrocytes and IFN-γ in neurons, respectively. RESULTS: Compared with the control group, both PWMT and TFL at 3, 5, 7 and 9 days after modeling were significantly decreased (P<0.01), while the expression of Cx43 and IFN-γ proteins, the immunofluorescence intensity of GFAP, Cx43, IFN-γR, and the content of IFN-γ were considerably up-regulated in the model group (P<0.01). In comparison with the model group, both PWMT and TFL at 3, 5, 7 and 9 days after modeling were obviously increased (P<0.01), whereas the expression of Cx43 and IFN-γ proteins, the immunofluorescence intensity of GFAP, Cx43, IFN-γR, and the content of IFN-γ in the acupuncture group, as well as the protein expression of IFN-γR in the sham acupuncture group were also remarkably decreased (P<0.05, P<0.01). The effect of acupuncture was significantly superior to that of sham acupuncture in down-regulating the expression of Cx43 and IFN-γ proteins, and the immunofluorescence intensity of GFAP, Cx43, and IFN-γR (P<0.05, P<0.01). Immunofluorescence dual labeling outcomes showed that in the model group, a large number of GFAP and Cx43 co-expressed astrocytes were found, and the cell body and protrusion of GFAP-labelled astrocytes were evidently increased, and Cx43 was mainly expressed on the surface of astrocyte membrane and the protrusion site, and the proportion of IFN-γR and NeuN co-expressing neurons in the model group was significantly increased, suggesting an activation of astrocytes and neurons after modeling. Whereas in the acupuncture group, the bright green clustered particles on the cell membrane and protrusion of astrocytes, and the proportion of IFN-γR and NeuN co-expressing neurons were significantly reduced, suggesting a suppression of activities of Cx43, astrocytes and neurons and IFN-γ release from TNC after acupuncture intervention. CONCLUSION: Acupuncture can relieve the pain response in rats with migraine, which may be associa-ted with its functions in inhibiting the expression of Cx43 and activation of astrocytes and neurons, and reducing release of pro-inflammatory factor IFN-γ in TNC.

Recent trends in acupuncture for chronic pain: A bibliometric analysis and review of the literature.

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 pain studies, revealing pivotal points, research hotspots, and research trends. Valuable ideas are provided for future research activities.

Clinical Evidence for Association of Acupuncture with Improved Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Control Trials.

INTRODUCTION: Depression is the most significant contributor to non-fatal health reductions worldwide. Acupuncture is the most commonly used complementary alternative therapy to relieve major depressive disorder (MDD) effectively. Nevertheless, the effects of acupuncture for MDD are uncertain. This review aimed to determine the efficacy and safety of acupuncture for MDD. METHODS: Meta-analysis was performed for randomized controlled trials of acupuncture for MDD data from eight databases searched from inception until February 10, 2022. All RCTs with adult participants undergoing acupuncture treatment for MDD were included. The primary outcome measure was the Hamilton rating scale for depression (HAMD). We used random-effects meta-analysis to synthesize the results with a mean difference or odds ratio. Furthermore, the potential heterogeneity was tested through meta-regression/subgroup analyses/sensitive analysis. The quality of evidence for each outcome was assessed by the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Forty-three studies were included: 9 acupuncture versus sham acupuncture (n = 920), 26 acupuncture versus antidepressants (n = 2169), and 9 acupuncture plus antidepressants versus antidepressants (n = 667). Of the 43 high-quality articles, 24 and 8 were determined to have a low and moderate risk of bias, respectively. The pooled results for HAMD and SDS revealed the clinical benefits of acupuncture or acupuncture plus antidepressants compared to sham acupuncture or antidepressants, with high-quality evidence. Furthermore, high-quality evidence showed that acupuncture led to fewer adverse effects than antidepressants. CONCLUSIONS: Acupuncture or acupuncture plus antidepressants were significantly associated with reduced HAMD scores, with high-quality evidence. Also, more rigorous trials are needed to identify the optimal frequency of acupuncture for MDD and integrate such evidence into clinical care to reduce antidepressant use.

Effectiveness and Safety of Acupuncture-Related Therapies for Chronic Musculoskeletal Pain: A Protocol for Systematic Review and Network Meta-Analysis.

Introduction: Chronic pain is one of the major health problems worldwide in recent years, and acupuncture-related therapies have been reported to have definite analgesic effects. However, it is still unclear which treatment is the most effective. Our systematic review and network meta-analysis protocol aims to summarize the evidence and determine the most effective method to treat the chronic musculoskeletal pain. Methods and Analysis: Our literature search will be performed in five electronic databases-the Cochrane Library, EMBASE, and PubMed, AMED, CINAHL, until May 20, 2022. All randomized controlled trials of acupuncture-related therapies for chronic musculoskeletal pain will be included. The primary outcomes will be common pain-related scales, and the secondary outcomes will include quality of life and incidence of adverse events. Excel 2019 will be used for data extraction, RoB2 will be used for bias risk assessment. R 3.6.2 and WinBUGS V.1.4.3 software will be used for network data synthesis and to produce related plots. During the study, literature selection, data extraction, quality assessment and bias risk assessment will be independently completed by two reviewers, and differences will be judged by the third reviewer. Finally, the risk of bias and sources of heterogeneity in the study will be analyzed and explained in order to obtain reliable results. Results: Our study will evaluate the effectiveness and safety of acupuncture-related therapies for the treatment of chronic musculoskeletal pain, and we will rank all methods to recommend the best appropriate treatment option. Conclusion: This study will provide a good foundation for complementary and alternative medicine to treat chronic musculoskeletal pain. It will be also helpful to promote the clinical practice by providing evidence-based medical evidence.

Effectiveness and Safety of Electroacupuncture for Depression: A Systematic Review and Meta-Analysis.

Purpose: The purpose of this systematic review and meta-analysis was to comprehensively evaluate the efficacy and safety of electroacupuncture as an effective adjunctive therapy for patients with depression. Methods: Randomized controlled trials (RCTs) about the treatment of depression by electroacupuncture therapy from inception to September 2021 were searched and collected in eight databases. HAMD, SDS, and Adverse Reactions were used as outcome indicators. The quality of relevant articles was evaluated using the Cochrane Collaboration's risk of bias tool. The quality of evidence for each outcome was assessed through the Grading of Recommendations Assessment and the Development and Evaluation approach. Stata 15.0 software was used for data analysis. Results: A total of 16 depression-related RCTs were included in this meta-analysis. For the main outcome, electroacupuncture significantly reduced HAMD scores (I2:0.0%, SMD: -2.28% (95% CI-3.16 to -1.39)), and the quality of evidence was moderate. The improvement effect of electroacupuncture plus antidepressants was better than that of western drugs in patients with depression (I2:26.2%, SMD: -1.18% (95% CI-1.42 to -0.94)), and the quality of evidence was moderate. Electroacupuncture significantly reduced HAMD scores without significant heterogeneity (I2:0.0%, SMD: -3.76% (95%CI-5.78-1.73)). Studies with very low quality of evidence found that electroacupuncture was as effective as antidepressants in reducing SDS scores (I2:36.4%, WMD: -1.15% (95%CI-2.93-0.63)), and electroacupuncture was found to be more effective than sham electroacupuncture stimulation as well. Moderate quality evidence showed no statistical difference between electroacupuncture plus antidepressants/electroacupuncture and antidepressants (I2:0%, RR:1.05% (95%CI 0.73 to 1.53)). Conclusions: Our meta-analysis shows that electroacupuncture reduces HAMD scores. It is suggested to use electroacupuncture plus antidepressants to improve the curative effect and effectively reduce drug side effects.

Effect of Acupuncture on Blood Pressure and Metabolic Profile Among Patients With Essential Hypertension: Protocol of a Randomized Clinical Trial.

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.

Manual acupuncture as prophylaxis for migraine without aura: study protocol for a multi-center, randomized, single-blinded trial.

BACKGROUND: Migraine is a highly prevalent neurological disorder. It is the third most prevalent disorder and the seventh highest cause of disability worldwide. Acupuncture may be a viable prophylactic treatment option for frequent or uncontrolled migraine. Clinical studies comparing acupuncture and placebo acupuncture have not reached a consistent conclusion in confirming whether acupuncture is effective in migraine prophylaxis. The effect of acupuncture mainly depends on acupoints and needles operation. We found that the design of the placebo acupuncture in previous studies included shallow needling at sham acupoints, non-penetrating needling at sham acupoints, and needling at inactive acupuncture points to achieve the inert effect of control group, but the non-penetrating needling at true acupoints was ignored. This randomized controlled trial aims to use true acupoints for non-penetrating acupuncture as control to evaluate the efficacy of manual acupuncture for the prophylaxis of migraine without aura (MWoA). METHODS/DESIGN: This is a single-blinded, randomized, controlled, prospective, multi-center trial with two parallel treatment groups. A total of 198 eligible patients with MWoA will be randomly divided into two groups (1:1 allocation ratio). The intervention group will receive manual acupuncture and the control group will receive placebo acupuncture (non-penetrating). Patients will receive three acupuncture treatment sessions per week for 4 consecutive weeks. All patients will then receive a 12-week follow-up. DISCUSSION: In this study, we are evaluating the efficacy and safety of manual acupuncture in the prophylaxis of MWoA. The placebo control is using non-penetrating needling verum acupoints. It is essential to determine an appropriate control method to ensure the methodological quality of a randomized controlled trial. TRIAL REGISTRATION: The trial has been registered in the Chinese Clinical Trial Registry (approval no. ChiCTR2000032308 ) in April 2020.