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Although electroacupuncture (EA) stimulation is a widely used therapy for chronic pain and comorbid psychiatric disorders, its long-term effects on chronic neuropathic pain-induced depression and the underlying mechanisms remain elusive. In the present study, we found that EA stimulation was able to restore adult neurogenesis in the ventral dentate gyrus (DG), by both increasing neuronal differentiation and restoring the normal morphology of newborn dendrites, in mice with spared nerve injury surgery. By ablating the Nestin+ neural stem cells (NSCs) via diphtheria toxin fragment A expression, we further proved that neurogenesis in the ventral DG was crucial to the long-term, but not the immediate antidepressant effect of EA, nor was it associated with nociception. Furthermore, we found that the restoration of neurogenesis was dependent on Tet1-mediated epigenetic modification upon EA treatment. Tet1 could bind to the promoter of the Prox1 gene, thus catalyzing its demethylation and facilitating its expression, which finally contributed to the restoration of neurogenesis and amelioration of depression-like behaviors induced by chronic neuropathic pain. Thus, we conclude that EA stimulation restores inhibited Tet1 expression in hippocampal NSCs of mice with chronic neuropathic pain, and increased Tet1 expression ameliorates hypermethylation of Prox1 and restores normal adult neurogenesis in the ventral DG, which contributes to the long-term antidepressant effect of EA., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The association between the body surface and viscera remains obscure, but a better understanding of the body surface-viscera correlation will maximize its diagnostic and therapeutic values in clinical practice. Therefore, this study aimed to investigate the specificity of body surface-viscera correlation in the pathological state. Methods: The study subjects included 40 participants with chronic obstructive pulmonary disease (COPD) in the COPD group and 40 age-matched healthy participants in the healthy control group. Laser Doppler flowmetry, infrared thermography, and functional near-infrared spectroscopy were respectively adopted to measure 1) the perfusion unit (PU), 2) temperature, and 3) regional oxygen saturation (rSO 2 ) of four specific sites distributed in the heart and lung meridians. These three outcome measures reflected the microcirculatory, thermal, and metabolic characteristics, respectively. Results: Regarding the microcirculatory and thermal characteristics of the body surface, the PU and temperature of specific sites on the body surface [i.e., Taiyuan (LU9) and Chize (LU5) in the lung meridian] in the COPD group were significantly increased compared with healthy controls ( p < 0.05), whereas PU and temperature of other sites in the heart meridian [i.e., Shenmen (HT7) and Shaohai (HT3)] did not change significantly ( p > 0.05). Regarding the metabolic characteristics, rSO 2 of specific sites in the lung meridian [i.e., Taiyuan (LU9) and Chize (LU5)] and Shaohai (HT3) of the heart meridian in the COPD group was significantly decreased compared with healthy controls ( p < 0.01), whereas rSO 2 of Shenmen (HT7) in the heart meridian did not change significantly ( p > 0.05). Conclusion: In the disease state of COPD, the microcirculatory, thermal, and metabolic characteristics of specific sites on the body surface in the lung meridian generally manifest more significant changes than those in the heart meridian, thereby supporting relative specificity for the body surface-viscera correlation in the pathological state., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Hu, He, Li, Zhang, Lou, Wu, Fang, Shao and Fang.)

Chronic pain is one of the most common clinical syndromes affecting patients' quality of life. Regulating the transition from acute to chronic pain is a novel therapeutic strategy for chronic pain that presents a major clinical challenge. However, the mechanism underlying pain transitions remains poorly understood. A rat hyperalgesic priming (HP) model, which mimics pain transition, was established decades ago. Here, this HP model and RNA sequencing (RNA-seq) were used to study the potential role of neuroinflammation in pain transition. In this study, HP model rats developed prolonged hyperalgesia in the hind paw after carrageenan (Car) and PGE2 injection, accompanied by obvious satellite glial cell (SGC) activation in the dorsal root ganglion (DRG), as indicated by upregulation of GFAP. RNA-Seq identified a total of differentially expressed genes in the ipsilateral DRG in HP model rats. The expression of several representative genes was confirmed by real-time quantitative PCR (qPCR). Functional analysis of the differentially expressed genes indicated that genes related to the inflammatory and neuroinflammatory response showed the most significant changes in expression. We further found that the expression of the chemokine CXCL1 was significantly upregulated in the rat DRG. Pharmacological blockade of CXCL1 reduced protein kinase C epsilon overproduction as well as hyperalgesia in HP rats but did not prevent the upregulation of GFAP in the DRG. These results reveal that neuroinflammatory responses are involved in pain transition and may be the source of chronic pain. The chemokine CXCL1 in the DRG is a pivotal contributor to chronic pain and pain transition in HP model rats. Thus, our study provides a putative novel target for the development of effective therapeutics to prevent pain transition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Du, Yi, Xi, Wang, Liu, Shao, Liang, He, Fang and Fang.)

Background: As a promising neuromodulation technique, vagus nerve stimulation (VNS) has been utilized to treat diverse diseases and the number of VNS studies has grown prosperously. Nonetheless, publication trends and research hotspots in this field remain unknown. This study aimed to perform a bibliometric analysis to systematically identify publication trends and research hotspots in VNS research within a 20-year panorama., Methods: The Web of Science Core Collection (WoSCC) database was retrieved to screen eligible VNS-related publications from 2002 to 2021. The online analytic tool of the WoSCC database was used to analyze various bibliometric parameters, such as the number of annual publications, the output of countries/regions, journals, total citations, citations per publication, and the Hirsch index. Bibliometrics (http://bibliometric.com/) and CiteSpace (version 5.6.R3) were used to identify research trends and hotspots., Results: A total of 7,283 publications were included for analysis. The annual number of publications increased stably but it increased significantly in recent years. The top five prolific countries were the United States, China, Germany, England, and France. The top five productive institutions were the University of California (Los Angeles), Harvard Medical School, Harvard University, University College London , and the University of Texas at Dallas . Notably, there was a geographical imbalance in countries and institutions. In addition, Epilepsy & Behavior, Epilepsia , and Plos One were the top three journals with the largest number of VNS publications. Michael P Kilgard was the most prolific author. Moreover, evolving research hotspots mainly included the effectiveness and mechanism of VNS on epilepsy, the role of VNS as an anti-inflammatory regulator, the application of VNS for psychiatric disorders, and the neuromodulation effect of VNS in headache management., Conclusion: This study has revealed the overall publication trends and evolving research trends at a global level over a 20-year panorama. The potential collaborators, institutions, hotspots, and future research trends are also identified in this field, which will help guide new research directions of VNS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Hu, Luo and Fang.)

Increasing evidence demonstrated that the ketogenic diet (KD) played a positive effect on cancer treatment. However, no systematic review and bibliometric analysis were conducted in this field. This study aimed to explore the current status, and reveal the potential trends and hotspots to provide a reference for future research. Publications were extracted from the Web of Science Core Collection. CiteSpace (5.6.R3) software and the website of bibliometrics were used for visual analysis. A total of 500 publications with 334 articles and 166 reviews were included, with the timespan of 2012 to 2021. The United States was the most productive country. Majority of the top 10 institutions were from the United States, and Harvard University was the top-contributing institution. The most prolific author and the co-cited author was Thomas N Seyfried from Boston College. The highest cited reference was published in PLoS ONE , authored by Abdelwahab Mohammed G, with 161 citations. Glioma and breast cancer were the most common types of cancer in this field, while hepatocellular carcinoma and pancreatic cancer were the new hotspots. The anti-tumor mechanism of KD mainly focused on regulating metabolism, decanoic acid, oxidative stress, fatty acid oxidation, and cell apoptosis. Additionally, the presence of "chemotherapy" and "radiotherapy" in the keywords indicated that KD combined with anti-tumor research was a topic, while "immunotherapy" has became a recent frontiers. Notably, as a metabolic therapy, KD was deserved more attention in the treatment of hepatocellular carcinoma and pancreatic cancer, and KD combined with immunotherapy was the new hotspot and frontier. Additionally, more molecular studies and high-quality uniformly, randomized, controlled clinical trials are urgently warranted to evaluate the effect of KD in multiple cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Huang, Ye, Wu, Luo, Lu, Fang and Wang.)

Competing Interests: The authors report no conflicts of interest in this communication.

Chronic pain, such as neuropathic pain, causes anxiety and other negative emotions, which aggravates the pain sensation and increases the risk of chronic pain over time. Dopamine receptor D1 (DRD1) and dopamine receptor D2 (DRD2) in the basolateral amygdala (BLA) have been implicated in mediating anxiety-related behaviors, but their potential roles in the BLA in neuropathic pain-induced anxiety have not been examined. Electroacupuncture (EA) is commonly used to treat chronic pain and emotional disorders, but it is still unclear whether EA plays a role in analgesia and anxiety relief through DRD1 and DRD2 in the BLA. Here, we used western blotting to examine the expression of DRD1 and DRD2 and pharmacological regulation combined with behavioral testing to detect anxiety-like behaviors. We observed that injection of the DRD1 antagonist SCH23390 or the DRD2 agonist quinpirole into the BLA contributed to anxiety-like behaviors in naive mice. EA also activated DRD1 or inhibited DRD2 in the BLA to alleviate anxiety-like behaviors. To further demonstrate the role of DRD1 and DRD2 in the BLA in spared nerve injury (SNI) model-induced anxiety-like behaviors, we injected the DRD1 agonist SKF38393 or the DRD2 antagonist sulpiride into the BLA. We found that both activation of DRD1 and inhibition of DRD2 could alleviate SNI-induced anxiety-like behaviors, and EA had a similar effect of alleviating anxiety. Additionally, neither DRD1 nor DRD2 in the BLA affected SNI-induced mechanical allodynia, but EA did. Overall, our work provides new insights into the mechanisms of neuropathic pain-induced anxiety and a possible explanation for the effect of EA treatment on anxiety caused by chronic pain., (© 2022. The Author(s).)

Background: Accumulate evidence indicated that moxibustion has a positive effect on pain treatment. However, the bibliometric analysis of moxibustion on pain remains uncertain. Herein, this study aimed to explore the current hotspots and the research trends over the past decade to bring a great panorama in this field., Methods: Publications were retrieved from the database Web of Science Core Collection (WoSCC) related to moxibustion therapy for pain treatment from January 1, 2012, to December 31, 2021. CiteSpace and Excel were applied to analyze the volume of publications, journals, cited journals, dual-map analysis, countries, institutes, authors, references, and keywords with citation bursts., Results: A total of 360 publications were retrieved from 2012 to 2021. The annual number of publications increased steadily with some fluctuations over the past 10 years. "The Evid Based Complement Alternat Med" and "the Gut" were the top-cited journals in frequency and centrality. China and Shanghai University of Traditional Chinese Medicine were the most prolific country and institutions, respectively. Among authors, Huangan Wu was the most active author with the highest cited frequency. Jun Xiong, Fanrong Liang and Guixing Xu held the articles with higher centrality. In the ranking of frequency and centrality in cited references, the top one was the article published by Shamseer L and Deng HY, respectively. "Acupuncture" was the keyword with the highest frequency. Pain disease (including rheumatoid arthritis, knee osteoarthritis, herpes zoster), research method (including randomized controlled trial), and risk (including quality of life, economic burden, physical and psychological problems) were the hotspots and frontier trends in this field., Conclusion: This bibliometric study reveals the current status and research trend in the treatment of pain with moxibustion. The formulation with bibliometric analysis further elicits hot spots and frontier issues in this field., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2022 Xia et al.)

Research shows that across life, the incidence of mental illness is highest in the young. In the context of the COVID-19 pandemic, mental health issues of the young in particular have received global attention. The rostral anterior cingulate cortex (rACC) plays an important role in psychiatric disorders and chronic pain-psychiatric comorbidities. However, it remains unknown whether or how the afferent and efferent circuits of the rACC change with aging. In this study, we microinjected a retrograde tracer virus and an anterograde trans-monosynaptic virus into the rACC of young and middle-aged mice (both male and female), and systematically and quantitatively analyzed the whole-brain afferent and efferent connections of rACC at different ages and sexes. Notably, in young and middle-aged mice, afferents of the rACC belong to four groups of brain structures arising mainly from the amygdala [mainly basolateral amygdaloid nucleus (BLA)] and cerebral cortex (mainly orbital cortex), with a small part originating from the basal forebrain and thalamus. In contrast, efferents of the rACC belong to four groups of brain structures mainly projecting to the thalamus (mainly ventral anterior-lateral/ventromedial thalamic nucleus (VAL/VM)], with a very small part projecting to the amygdala, basal forebrain, and cerebral cortex. Compared with young mice, the BLA-rACC circuit in middle-aged mice (male and female) did not change significantly, while the rACC-VAL/VM circuit in middle-aged mice (male and female) decreased significantly. In conclusion, this study comprehensively analyzed the input-output neural projections of rACC in mice of different ages and sexes and provided preliminary evidence for further targeted research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ma, Yu, Yao, Zhu, Dai, He, Liu, Xu, Shao, Fang and Shen.)

Background: Migraine without aura (MWoA) is a nervous system disease, which is closely related to autonomic nerves dysfunction. As a popular non-pharmacological alternative treatment for preventing migraine, it remains unclear whether the acupuncture can prevent MWoA. Thus, this trial aims to evaluate the preventive effect and safety of the acupuncture method of stimulating acupoints that regulate autonomic nerves in MWoA patients., Methods: This is a single-center, prospective, double-dummy, randomized controlled clinical trial. A total of ninety-six patients with MWoA are randomly allocated to acupuncture combined with the placebo group and sham acupuncture combined with the medication group in a 1:1 ratio. All subjects will receive intervention for 8 weeks and follow-up assessments three times (one month, three months, and six months in follow-up visiting). The frequency of acupuncture in both groups is three times a week for eight weeks. The primary outcome will be evaluated using a visual analog scale (VAS) and the number of migraine attacks per four weeks. The secondary outcome measures will include the migraine-specific quality of life (MSQOL) scale and headache needs assessment survey (HANA) questionnaire scale., Results: The acupoint selection of this clinical trial is based on the combination of traditional Chinese medicine theory with modern medicine, thereby evaluating the efficacy and safety of the acupuncture method of stimulating acupoints that regulate autonomic nerves in the prevention of MWoA. The results may provide evidence of the beneficial effects of acupuncture on the prevention of MWoA by regulating autonomic nerves dysfunction., Trial Registration: ClinicalTrials.gov NCT04766762., Competing Interests: The authors declare that they have no conflicts of interest in relation to this work., (© 2022 Zhou et al.)

Objective: The efficacy of conventional treatments for treating bladder pain syndrome (BPS) remains unsatisfactory. Electro-acupuncture (EA) is one of the complementary treatments with great analgesic effect and minimal side effect, but evidence of the efficacy of EA on BPS is limited. Thus, this study aims to investigate the efficacy and safety of EA for treating BPS and study on central mechanism of patients with BPS., Methods/design: The study is a randomized controlled and assessor-blinded design trial. A total of 84 participants will be randomly assigned to medication group (n=21), EA group (n=42) and sham electro-acupuncture (SA) group (n=21) in a 1:2:1 allocation ratio. This trial will include baseline period, 4-week treatment period and 4-week follow-up period. Participants in medication group will undergo treatment of amitriptyline for a period of 4 weeks. Participants in EA and SA groups will receive a 30 min EA or SA treatment for a total of 12 sessions over 4 weeks. The primary outcome is the Visual Analog Scale (VAS). The secondary outcomes include the O'Leary-Sant questionnaire, 24-hour voiding diary, Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and functional magnetic resonance imaging (fMRI). The VAS will be collected at baseline, week 2, week 4, and week 8 after randomization. The O'Leary-Sant questionnaire, HAMA and HAMD will be assessed at baseline, week 4 and week 8 after randomization. The 24-hour voiding diary will be assessed every single day. The fMRI data will be collected at baseline and week 4., Discussion: The results will provide evidence on the efficacy and safety of EA in the management of BPS and investigate the central mechanism of EA in treating patients with BPS., Trial Registration: ClinicalTrials.gov identifier: NCT05279963. Registered on 15 March 2022., Competing Interests: The authors declare that they have no competing interests., (© 2022 Xu et al.)

Introduction: This multicenter, randomized, noninferiority trial compared electroacupuncture with prucalopride for the treatment of severe chronic constipation (SCC)., Methods: Participants with SCC (≤ 2 mean weekly complete spontaneous bowel movements [CSBMs]) were randomly assigned to receive either 28-session electroacupuncture over 8 weeks with follow-up without treatment over 24 weeks or prucalopride (2 mg/d before breakfast) over 32 weeks. The primary outcome was the proportion of participants with ≥3 mean weekly CSBMs over weeks 3-8, based on the modified intention-to-treat population, with -10% as the noninferior margin., Results: Five hundred sixty participants were randomized, 280 in each group. Electroacupuncture was noninferior to prucalopride for the primary outcome (36.2% vs 37.8%, with a difference of -1.6% [95% confidence interval, -8% to 4.7%], P < 0.001 for noninferiority); almost the same results were found in the per-protocol population. The proportions of overall CSBM responders through weeks 1-8 were similar in the electroacupuncture and prucalopride groups (24.91% vs 25.54%, with a difference of -0.63% [95% confidence interval, -7.86% to 6.60%, P = 0.864]). Except during the first 2-week treatment, no between-group differences were found in outcomes of excessive straining, stool consistency, and quality of life. Adverse events occurred in 49 (17.69%) participants in the electroacupuncture group and 123 (44.24%) in the prucalopride group. One non-treatment-related serious adverse event was recorded in the electroacupuncture group., Discussion: Electroacupuncture was noninferior to prucalopride in relieving SCC with a good safety profile. The effects of 8-week electroacupuncture could sustain for 24 weeks after treatment. Electroacupuncture is a promising noninferior alternative for SCC (see Visual Abstract, http://links.lww.com/AJG/B776)., (Copyright © 2020 by The American College of Gastroenterology.)

Background: Stable angina pectoris (SAP) is a global health challenge. Multiple previous systematic reviews (SRs) have been conducted to assess the effectiveness of acupuncture and related therapies on SAP. We will carry out a comprehensive overview to map, synthesize, and assess the all the available evidence of acupuncture and related therapies on SAP., Methods: We will search 7 databases, including China National Knowledge Infrastructure (CNKI) and Chinese Biomedical Literature Database (CBM), WanFang Database, the Cochrane Library, PubMed, EMbase, MEDLINE. SRs and meta-analyses (MAs) of acupuncture and related therapies on SAP will be screened for eligibility. Systematic reviews, qualification evaluation, data extraction, methodological quality, and evidence quality evaluation will be conducted in pairs. The outcomes of interest include: frequency of angina attack, changes in nitroglycerin use, intensity of anginal pain, depression assessment, changes of the electrocardiogramme (ECG), anxiety assessment, results of the Six-Minute Walk Test (6-MWT), overall effectiveness, the Seattle Angina Questionnaire (SAQ), and adverse events. Where appropriate, the evidence will be synthesized based on the outcomes and patient subgroups., Results: This overview will be published in a peer-reviewed journal., Conclusion: This overview is expected to provide a reliable and valuable evidence of acupuncture for treating SAP., Ethics and Communication: Given that this is an overview of published research, patient consent and ethical approval are not needed. The findings of this study will be disseminated through conference presentations and publication in peer-reviewed journals., Prospero Registration Number: CRD42020164466., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Musculoskeletal injuries (MSDs) have become a major public health problem worldwide. Current diagnosis techniques for MSDs are often associated with radiation exposure, expensive cost, or contraindication. Infrared thermography (IRT) is becoming a proposed tool to assist in diagnosing MSDs, but current evidence is inconclusive. Thus, herein we aimed to evaluate the diagnostic accuracy of IRT for MSDs., Methods: We will search EMBASE, MEDLINE, EBSCO, Cochrane Library, SCOPUS, Web of Science, CNKI, SinoMed, and Wangfang. Two researchers will independently screen eligible studies. Study quality will be evaluated based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Data synthesis will be completed using STATA 14.0 software. A bivariate random-effects analysis will be utilized to estimate the pooled estimation of the diagnostic odds ratio (DOR) and the summary receiver operating characteristics (SROC) curve. Subgroup analyses will be performed to determine heterogeneity sources., Results: This systematic review and meta-analysis will provide reliable evidence about the diagnostic accuracy of IRT for MSDs., Conclusion: The conclusion of this study will be published in a peer-reviewed journal., Ethics and Communication: Given that this is a systematic review of published research, patient consent and ethical approval are not relevant. The findings of this study will be disseminated through conference presentations and publication in peer-reviewed journals., Prospero Registration Number: CRD42020184867.

Diabetic neuropathic pain (DNP) is a troublesome diabetes complication all over the world. P2X3 receptor (P2X3R), a purinergic receptor from dorsal root ganglion (DRG), has important roles in neuropathic pain pathology and nociceptive sensations. Here, we investigated the involvement of DRG P2X3R and the effect of 2 Hz electroacupuncture (EA) on DNP. We monitored the rats' body weight, fasting blood glucose level, paw withdrawal thresholds, and paw withdrawal latency, and evaluated P2X3R expression in DRG. We found that P2X3R expression is upregulated on DNP, while 2 Hz EA is analgesic against DNP and suppresses P2X3R expression in DRG. To evaluate P2X3R involvement in pain modulation, we then treated the animals with A317491, a P2X3R specific antagonist, or α β-me ATP, a P2X3R agonist. We found that A317491 alleviates hyperalgesia, while α β-me ATP blocks EA's analgesic effects. Our findings indicated that 2 Hz EA alleviates DNP, possibly by suppressing P2X3R upregulation in DRG.

Background: Postherpetic neuralgia (PHN) is the most common complication and sequela of herpes zoster (HZ) that greatly affects the life and emotional experience of patients. Acupuncture therapy has been confirmed as an effective and safe treatment for PHN. Several systematic reviews (SRs) and meta-analysis (MAs) have reported the evidence of acupuncture therapy for treating PHN. However, the evidence has not been systematically synthesized. This overview aims to synthesize and assess the reliability of evidence generated from these SRs and MAs of acupuncture therapy for PHN., Methods: We will conduct a systematic search of the China Biology Medicine (CBM), VIP database, Wangfang database, China National Knowledge Infrastructure (CNKI), Pubmed, Cochrane Library, Excerpt Medical Database (Embase), and Web of Science to identify eligible SRs and MAs, from their inception to October 31, 2020. We will use Assessment of Multiple Systematic Reviews-2 (AMSTAR2) for methodological quality assessment, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for report quality assessment, Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) for the quality of evidence assessment, and ROBIS for the bias assessment. Our reviewers will conduct systematic reviews, qualification evaluation, data extraction, methodological quality, and evidence quality screening in pairs. The outcomes include pain intensity, Quality of life (QoL), Hamilton Anxiety Scale (HAMA), Global impression, and adverse events. All the extracted data will be provided in tabular form to summarize characteristics of each review. The evidence will be a narrative synthesis of the type and content of the intervention and the results reported., Results: The results of this study will be published in a peer-reviewed journal., Conclusions: This overview will provide comprehensive evidence of acupuncture therapy for patients with PHN., Ethics and Dissemination: This review will not involve private information of participants, so the ethical approval will not be required. The results will be disseminated in a peer-reviewed journal or conference presentation. Important protocol modifications will be updated on PROSPERO., Prospero Registration Number: CRD42020178738.

Background: There are numerous studies worldwide on the use of acupuncture as complementary therapy for chronic stable angina pectoris (CSAP). However, the high morbidity of CSAP-associated anxiety and depression is often overlooked. This protocol of systematic review and meta-analysis aims to assess whether acupuncture is effective as a complementary therapy for anxiety and depression in patients with CSAP., Methods: The following 8 databases will be searched from inception to February 2020 with no language restrictions: PubMed, Excerpt Medical Database, Web of Science, the Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database. Eligible randomized controlled trials and controlled clinical trials will be included. Study selection, data extraction, and risk of bias assessment will be performed independently by 2 reviewers, differences will be resolved by the third reviewer. The primary outcomes include the level of anxiety or depression measured by qualified scales, angina attack frequency, and angina pain intensity. Revman 5.3 software will be used to perform the assessment of the risk of bias and data synthesis. The review will grade the quality of the evidence based on the Grading of Recommendation, Assessment, Development, and Evaluation system., Results: This systematic review and meta-analysis will provide reliable evidence about the effect and safety of acupuncture as a complementary therapy for CSAP-associated anxiety and depression., Conclusion: The conclusion of this study will be published in a peer-reviewed journal., Ethics and Dissemination: This review will not involve private information of participants, so the ethical approval will not be required. The results will be disseminated in a peer-reviewed journal or conference presentation. Important protocol modifications will be updated on PROSPERO., Prospero Registration Number: CRD42020165492.

Introduction: By detecting the metabolic difference of the Heart and Lung meridians, the present study aims to investigate the specificity of different meridians and verify whether functional near infrared spectroscopy is validated as an add-on technique to assist diagnosis of chronic obstructive pulmonary disease (COPD)., Methods and Analysis: The Lung and Heart meridians are chosen as the target for comparison; accordingly, 120 eligible participants will be included and divided into the COPD group, healthy control group, and healthy intervention group. Functional near infrared spectroscopy will be adopted to measure the metabolic characteristics of the Heart and Lung meridians. On one hand, the specificity of the meridian-visceral association will be investigated by comparing the metabolic difference in the Heart and Lung meridians between the healthy control group and COPD group. On the other hand, the specificity of site-to-site association will be determined by comparing the metabolic change between the 2 meridians that induced by moxibustion in the Heart meridian and Lung meridian, respectively, in the healthy control group. The primary outcome will be regional oxygen saturation of corresponding regions along the Heart and Lung meridians., Trial Registration: ClinicalTrials.gov NCT04046666.

Introduction: The aim of the present study is to compare the microcirculatory difference of different meridians by using laser doppler flowmetry and investigate the specificity for the meridian-visceral association and site-to-site association between 2 specific meridians., Methods and Analysis: The Lung and Heart meridians are chosen as 2 specific studied meridians. 120 participants will be enrolled and divided into the healthy control group, chronic stable angina pectoris group and healthy intervention group. Laser doppler flowmetry will be used to assess the blood perfusion of the Heart and Lung meridians. The specificity for the meridian-visceral association will be investigated by comparing the microcirculatory difference between the Heart and Lung meridians in the healthy control group and chronic stable angina pectoris group. Besides, participants in the healthy intervention group will receive 2 sessions of moxibustion in the Heart meridian and Lung meridian, respectively, to explore the specificity for the site-to-site association on the body surface. Primary outcomes will be blood flow curve and blood perfusion units of relevant sites along the Heart and Lung meridians. Statistical analysis will be conducted by third party statisticians., Ethics and Dissemination: Ethics approval (approval No: ZSLL-KY-2019-001A-01) has been obtained from the Ethics Committee of the Third Affiliated Hospital of Zhejiang Chinese Medical University. The study findings will be disseminated through presentation at peer-reviewed medical journals., Trial Registration: ClinicalTrials.gov NCT04244812.

Introduction: Classical trigeminal neuralgia (CTN) is a kind of trigeminal neuralgia which is due to neurovascular compression. The common neurological treatment CTN drug called carbamazepine is the main measure, although it usually has side effects and a high-rate of relapse. As a critical alternative therapy, electroacupuncture (EA) has been shown to benefit for neuropathic pain. The aims of this study are to observe the therapeutic effect and safety of EA for CTN, to evaluate whether EA has the advantage over carbamazepine in the analgesia of CTN. Furthermore, we would to establish a standardized, effective, and convenient therapy program of EA., Methods and Analysis: One hundred twenty patients diagnosed with CTN will be randomized for a 4-week intervention. The interventions will be different according to the four groups (EA + carbamazepine group, sham EA + carbamazepine group, EA + placebo group and sham EA + placebo group). EA therapy will be performed in specific acupoints with a dilute wave (2/100 Hz) for 60 minutes. Carbamazepine tablets will be taken orally with 0.1 g each time, thrice daily. Sham EA and placebo intervention will not receive EA and drug treatment. The main outcomes are the change from baseline intensity of pain at 6 months (pain evaluation by visual analogue score) and the change from baseline brief introduction of 2-week pain to evaluate pain comprehensively. The data management and statistical analysis will be conducted by third party statisticians. Incidence of adverse events will be investigated., Ethics and Dissemination: Ethics approval was obtained from the Clinical Trial Ethics Committee of The Third Affiliated Hospital of Zhejiang Chinese Medical University (NO. ZSLL-KY-2017-033) and Jiaxing Hospital of Traditional Chinese Medicine (NO. 2018-JZLK-002). The results will be disseminated by presentation at peer-reviewed journals.

Introduction: Knee osteoarthritis (KOA) is a chronic disease with symptoms of persistent pain or resting pain, joint stiffness, numbness, limitation of activity and even disability, with significant associated costs and effects on individuals' life quality. The use of acupuncture for the management of chronic pain is receiving increasing recognition from both the public and professionals. The aim of this study is to identify the effects of three commonly used acupuncture treatments for KOA., Methods/analysis: In a prospective trial involving six hospitals in Zhejiang Province (China), 360 patients with KOA will be included. Eligible patients will be randomized into six groups: Acupuncture, Electro-acupuncture, Mild moxibustion, Warm-needling, Sham acupuncture and Celebrex treatment. Twelve treatment sessions will be performed over a 4-week period. The primary outcome will be the visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function scores (the average of the past 3 days) at weeks 2 and 4 and at 3-month and 6-month follow-up. Secondary outcome measures will be as follows: the WOMAC pain score and WOMAC stiffness score (the average of the past 3 days); the Physical Activity Scale of the Elderly (PASE); knee joint swelling measurement; the WHO Quality Of Life-BREF (WHOQOL-BREF) life quality scale; and the incidence of adverse events., Trial Registration: ClinicalTrials.gov, NCT03563690. Registered on 2rd July 2018.

Background and Purpose: Acupuncture is increasingly used by patients with primary trigeminal neuralgia (PTN). We aimed to evaluate the efficacy and safety of acupuncture for PTN., Methods: Seven databases were searched. Risk of bias was assessed and meta-analyses were conducted. The evidence level was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE)., Results: Thirty-three RCTs were included. Meta-analysis results demonstrated that the effect of both manual acupuncture (MA) and electro-acupuncture (EA) for improving response rate and recurrence rate was more significant than carbamazepine. Besides, MA achieved more significant effect on alleviating pain intensity. Moreover, acupuncture combined with carbamazepine had a more positive effect on response rate than carbamazepine alone., Conclusions: Acupuncture might have some positive effects for PTN. Nevertheless, the level of all evidence was low or very low. We could not yet draw a firm conclusion on the efficacy of acupuncture for PTN., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Professor FANG Jianqiao ' s clinical experience in the treatment of primary cervical dystonia based on the syndrome differentiation of TCM was explored preliminarily. Based on the disease identification of western medicine and the syndrome differentiation of TCM, in combination with the differentiations of meridians and collaterals of acupuncture, Professor FANG proposes the three-dimensional system of diagnosis and treatment of acupuncture, named "disease differentiation, TCM syndrome differentiation and meridian differentiation". Regarding the diagnosis and treatment of primary cervical dystonia, the physical examination of nerve system, TCM syndrome differentiation and meridian differentiation are equally important. It is pointed out that the key pathogenesis of the disease is qi and blood obstruction and the malnutrition in the muscle regions of meridians. Hence, the treating principle is proposed as eliminating the exogenous pathogens, regulating qi and blood and unblocking the muscle regions of meridians. Professor FANG also stresses that the affected sites and the factors of dystonia should be considered in acupuncture treatment. The local points are mainly those adjacent to the responsible muscles with the motor disturbance in the neck region. "Xinshe" point (Extra) is taken as the empirical point. The distal points are selected in accordance with the three-dimensional system of diagnosis and treatment. At the same time, the percutaneous acupoint electric stimulation is applied to the starting and ending points or the conjunctive points of the affected muscles, acting on regulating qi , nourishing blood and promoting the circulation in meridians and collaterals.

Objective: To observe the effects of electroacupuncture (EA) on pain behavior in rats with bone cancer pain and morphine tolerance, and to explore partial action mechanism., Methods: Forty-two SD healthy female rats were randomly divided into a sham operation group (7 rats), a bone cancer pain group (8 rats), a morphine tolerance group (9 rats), an EA group (9 rats) and a sham EA group (9 rats). The rats in the sham operation group were treated with injection of phosphate buffer saline at medullary cavity of left-side tibia, and the rats in the remaining groups were injected with MRMT-1 breast cancer cells. After operation, no treatment was given to rats in the sham operation group and bone cancer pain group. 11 days after operation, rats in the morphine tole-rance group, EA group and sham EA group were treated with intraperitoneal injection of morphine hydrochloride, once every 12 hours, for 11 days to establish the model of bone cancer pain and morphine tolerance. One day after the establishment of this bone cancer pain model, the rats in the morphine tolerance group were injected with morphine, once every 12 hours (9:00 a.m. and 9:00 p.m.) for 7 days; the rats in the EA group and sham EA group were injected with morphine at 9:00 a.m., and treated with EA (2 Hz/100 Hz) and sham EA (only injected into the subcutaneous tissue) at bilateral "Zusanli" (ST 36) and "Kunlun" (BL 60), 30 min per treatment, once a day for 7 days. One day before cancer cell injection, 6 days, 8 days, 10 days after operation, after 30 min on 1 days, 5 days, 9 days, 11 days of morphine injection, and after 30 min on 1 days, 3 days, 5 days, 7 days of EA treatment, the paw withdrawal threshold (PWT) was measured in each group. On 11 day of morphine injection, HE staining was applied to observe the morphology and structure change of tibia in the sham operation group, bone cancer pain group and morphine tolerance group, random 2 rats in each group. On 7 days of EA treatment, fluorescent immunohistochemical method was applied to observe the expression of μ-opioid receptor positive cells in nucleus ceruleus in each group, random 4 rats in each one., Results: After 10 days of the cancer cells injection, the PWT of 28 rats of bone cancer pain model (8 rats in the bone cancer pain group, 8 rats in the morphine tolerance group, 6 rats in the EA group and 6 rats in the sham EA group) was significantly lower than that of 7 rats in the sham operation group ( P <0.01). After one day of morphine injection, the PWT of the morphine tolerance group, EA group and sham EA group was higher than that of the bone cancer pain group (all P <0.01); on 11 d of morphine injection, the PWT of the morphine tolerance group, EA group and sham EA group was not significantly different from that of the bone cancer pain group (all P >0.05). On 11 d of morphine injection, the tumor induced by cancer cells was observed in upper 1/3 tibia in the bone cancer pain group and morphine tolerance group, and the marrow cavity was filled with MRMT-1 cancer cells; no abnormal change was observed in the sham operation group. On 1 d, 3 d, 5 d and 7 d of EA treatment, the PWT of the cancer pain group, morphine tolerance group and sham EA group was lower than that of the EA group (all P <0.01). On 7 d of EA treatment, the positive expression of MOR in nucleus ceruleus in the cancer pain group, morphine tolerance group, EA group and sham EA group was lower than that in the sham operation group ( P <0.01, P <0.05), and that in the cancer pain group, morphine tolerance group and sham EA group was lower than that in the EA group (all P <0.01)., Conclusions: EA can improve mechanical pain threshold in rats with bone cancer pain-morphine tolerance, and improve the abnormal pain, which is likely to be involved with improvement of the MOR positive cells expression in nucleus ceruleus by EA.

The clinical manifestation and clinical diagnosis and treatment of acupuncture for persistent somatoform pain disorder (PSPD) were observed to explore its etiology. It is found that the causative factor of PSPD is probably relevant with pain memory induced by the negative emotions during the first attack of pain, which is in the category of "depression" in TCM. In clinical diagnosis, the medical history should be explored to discover the potential etiology and determine the diagnosis. In treatment, the root cause should be considered, focusing on mind and qi regulation and associating with analgesia. It is different from the common treatment for analgesia in other pain disorders. For PSPD, the root cause is considerable, with "mind regulation" in priority. The acupoints relevant with mind on the head[such as Baihui (GV 20) and Sishencong (EX-HN1)], the acupoints for warming and tonifying the primary qi [such as Qihai (CV 6), Guanyuan (CV 4) and Zusanli (ST 36)] and the auricular points (such as xin (CO 15 ), gan (CO 12 ), shenmen (TF 4 ), neifenmi (CO 18 )) are selected to regulate qi activity and calm down the mind. Additionally, the therapy for reliving pain specifically is applied with transcutaneous electric stimulation, 2 Hz/100 Hz, disperse-dense wave at bilateral Zusanli (ST 36) and Sanyinjiao (SP 6) to erase pain memory trace. Ultimately, the therapeutic effects are achieved for mind regulation and pain easing.

Objective: To observe the intervention effect of electroacupuncture (EA) on small intestinal motility in the rats of postoperative ileus (POI) at perioperative stage and explore the mechanism on the regulation of interstitial cells of Cajal (ICC) in the treatment of POI., Methods: Sixty heathy male SD rats were randomized into a sham-operation group, a model group, an EA group and a sham-EA group, 15 rats in each one. Except the sham-operation group, POI modeling was done in the rest groups. In the EA group, separately, 48 h, 24 h and 0.5 h before modeling, during modeling and 6 h, 12 h and 24 h after modeling, EA was given bilaterally to "Zusanli" (ST 36), 5 Hz, 1-2 mA, for 30 min. The sham-EA stimulation was given in the sham-EA group at the same time points. The same fixation was the only intervention in the model group. No intervention was applied in the sham-operation group. Five rats were selected randomly from each group 6 h, 12 h and 24 h after modeling for the determination of small intestine motility and they were sacrificed. Afterwards, the small intestinal muscular layer was collected for the determination of c-kit and P2X7 mRNA. In 24 h of modeling, the immunofluorescence test was done for c-kit determination., Results: In 6 h, 12 h and 24 h of modeling, in the model group, the EA groupand the sham-EA group, the small intestine motility was apparently lower than that in the sham-operation group at the same time points (all P <0.01). In 6 h and 12 h of modeling, the small intestine motility in the EA group was not different significantly as compared with that in the model group (both P >0.05). In 24 h of modeling, the small intestine motility in the EA group was better than that in the model group and the sham-EA group at the same time points (both P <0.05). The difference was not significant between the sham-EA group and the model group ( P >0.05). In 6 h, 12 h and 24 h of modeling, c-kit mRNA expression of small intestine muscular layer was reduced apparently in the model group (all P <0.01) and P2X7 mRNA expression did not change apparently (all P >0.05). In 24 h of modeling, as compared with the model group and the sham-EA group, c-kit mRNA expression and positive cell area in the small intestine muscular layer were increased in the EA group (all P <0.01)., Conclusions: EA effectively increases the small intestinal motility in POI rats, shortens the recovery time, which is probably closely relevant with the increase of ICC count in small intestinal muscular layer.

Poison ivy-induced allergic contact dermatitis (ACD) is the most common environmental allergic condition in the United States. Case numbers of poison ivy ACD are increasing due to growing biomass and geographical expansion of poison ivy and increasing content of the allergen, urushiol, likely attributable to rising atmospheric CO 2 Severe and treatment-resistant itch is the major complaint of affected patients. However, because of limited clinical data and poorly characterized models, the pruritic mechanisms in poison ivy ACD remain unknown. Here, we aim to identify the mechanisms of itch in a mouse model of poison ivy ACD by transcriptomics, neuronal imaging, and behavioral analysis. Using transcriptome microarray analysis, we identified IL-33 as a key cytokine up-regulated in the inflamed skin of urushiol-challenged mice. We further found that the IL-33 receptor, ST2, is expressed in small to medium-sized dorsal root ganglion (DRG) neurons, including neurons that innervate the skin. IL-33 induces Ca 2+ influx into a subset of DRG neurons through neuronal ST2. Neutralizing antibodies against IL-33 or ST2 reduced scratching behavior and skin inflammation in urushiol-challenged mice. Injection of IL-33 into urushiol-challenged skin rapidly exacerbated itch-related scratching via ST2, in a histamine-independent manner. Targeted silencing of neuronal ST2 expression by intrathecal ST2 siRNA delivery significantly attenuated pruritic responses caused by urushiol-induced ACD. These results indicate that IL-33/ST2 signaling is functionally present in primary sensory neurons and contributes to pruritus in poison ivy ACD. Blocking IL-33/ST2 signaling may represent a therapeutic approach to ameliorate itch and skin inflammation related to poison ivy ACD., Competing Interests: The authors declare no conflict of interest.

Objective: To compare the efficacy between the multi-directional stimulation technique and routine needling technique in the range of motion (ROM) of the lower limbs in patients of post-stroke spasmodic paralysis., Methods: Sixty patients were randomized into a multi-directional stimulation technique group and a routine needling technique group, 30 cases in each one. In the two groups, Biguan (ST 31), Fengshi (GB 31), Yang-lingquan (GB 34), Xiyangguan (GB 33), Zhongfeng (LR 4), Jiexi (ST 41), Qiuxu (GB 40), Kunlun (BL 60) and Xuanzhong (GB 39) on the affected side, scalp acupuncture sites and the acupoints on the upper limb of the affected side were selected. The even needling technique was used in the routine needling technique group and the multi-directional stimulation technique was used in the multi-directional stimulation technique group. The treatment was given once daily, 5 days a week, for 4 weeks totally. Before and after treatment, Fugl-Meyer function and Berg balance were scored. The three-dimensional gait analysis was adopted to analyze ROM of hip, knee and ankle joints., Results: Fugl-Meyer function score and Berg balance score were improved significantly after treatment as compared with those before treatment in the two groups (all P <0.01). The scores in the multi-directional stimulation technique group were all higher than those in the routine needling technique group ( P <0.01, P <0.05). The abduction and adduction of hip joints and flexion-extension ROM were all improved after treatment as comparedwith those before treatment in the two groups (all P <0.05). The maximum flexibility and flexion extension ROM of knee joint were improved after treatment as compared with those before treatment in the two groups (all P <0.05), and the changes in extension of knee joint were not apparent (both P >0.05). After treatment, the maximal flexion and the flexion-extension ROM of knee joint in the multi-directional stimulation technique group were improved significantly as compared with those in the routine needling technique group (both P <0.05). The maximal dorsal flexion of ankle joint in the multi-directional stimulation technique group after treatment was increased as compared with that before treatment ( P <0.05), and the change was better than that in the routine needling technique group ( P <0.05)., Conclusions: Acupuncture effectively increases the maximal adduction angle and flexion-extension ROM of hip joint, and reduces abduction of hip joint. The multi-directional stimulation technique contributes to the flexion of knee joint and dorsal flexion of ankle joint and the maintenance of limb balance. The efficacy of it is better than that of routine acupuncture stimulation technique.

Objective: To verify the clinical effect of the penetration acupuncture at the acupoints of governor vessel(GV) and bladder meridian on head for mild cognitive disorder after stroke., Methods: One hundred and ten patients were randomly divided into an observation group and a control group, 55 cases in each one. Penetration acupuncture was used at the acupoints of GV and bladder meridian on head in the observation group,namely Wuchu (BL 5) to Chengguang (BL 6) and Tongtian (BL 7) to Luoque (BL 8) bilaterally, and Shenting (GV 24) to Xinhui (GV 22), Qianding (GV 21) to Baihui (GV 20), Houding (GV 19) to Qiangjian (GV 18). Body acupuncture and conventional western medication were applied in the both two groups. Acupuncture was adopted once a day, five times a week and eight weeks totally. The changes of Montreal Cognitive Assessment (MoCA), Mini mental state examination scale(MMSE), self-rating depressive scale (SDS) and activities of daily living scale (Barthel index) were compared between the two groups before treatment, in the middle of treatment(at the forth week) after treatment(at the eighth week) and in three weeks after treatment(follow-up)., Results: After treatment of four and eight weeks and at the time of follow-up, the results of MoCA, MMSE, SDS and Barthel index were apparently im proved compared with those before treatment in the two groups (all P < 0.01). After treatment of eight weeks and at the time of follow-up, the scores of MoCA and SDS were obviously improved in the observation group compared with those in the control group (P < 0.01, P < 0.05). The improvements of MMSE in the observation group were more marked than those in the control group at all times (P < 0.01, P < 0.05). But there was no statistical significance about the change of Barthel index between the two groups (all P > 0.05)., Conclusion: Penetration acupuncture at the acupoints of GV and bladder meridian on head can remarkablely improve the cognitive function of the patients with mild cognitive disorder after stroke,and have some efficacy of relieving the bad mood such as depression.

Trigerninal neuralgia is a common refractory disease in clinic. Professor FANG Jianqiao has rich experience through diagnosing and treating the disease for many years. In the first diagnosis, professor FANG underlines the position of damaged neuron and syndrome differentiation. He considers acupuncture should be implemented by stages,namely according to whether the patients are in the period of pain attack, different acupuocture prescriptions are made. Acupuncture manipulation and needle-retention time should be adjusted according to the condition of disease. And the appropriate application of electroacupuncture and transcutaneous electrical acupoint stimulation can strengthen the effect.

Pain is often comorbid with emotional disorders such as anxiety and depression. Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission. This review primarily aims to outline the main circuitry (including the input and output connectivity) of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons; it also describes the neurotransmitters/neuromodulators affecting these neurons, their intercommunication with other neurons, and their importance in mental comorbidities associated with chronic pain disorders. Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions. However, the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive. It is also unclear as to whether the mechanisms are presynaptic or postsynaptic. Further exploration of the complexities of this system may reveal new pathways for research and drug development., (Copyright © 2025 Neural Regeneration Research.)

Objective: To study whether the dose of controlling antihypertensive drug is reduced by transcutaneous electrical acupoint stimulation (TEAS) and the anesthetics, as well as the control of blood pressure (BP) and heart rate (HR) in endoscopic endonasal surgery with general anesthesia., Methods: Sixty patients for selective endoscopic endonasal surgery with general anesthetics and controlling antihypertension involved were selected and randomized into a TEAS group, a sham-TEAS group, 30 cases in each one. The electric pads were attached to bilateral Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6) and Quchi (LI 11), stimulated with Hans-200 apparatus, 3 to 5 mA, 2 Hz/100 Hz in the TEAS group based on the patients' response to comfort. No electric stimulation was applied to the sham-TEAS group. The general anesthesia started after 30 min intervention and lasted till the end of surgery. The BP and HR were observed and recorded at the end of monitoring in operation room, 10 min after tranquilization (T0), 30 min after intervention (Tj, after induction~of general anestiesa (T2), 30 min after surgery start (T3), 60 min after surgery start (T4) and 30 min after extubation (T5). The doses of vecuronium bromide, propofol and nitroglycerin were recorded statistically in surgery, as well as the operative bleeding volume, the operative time, the resuscitation time and the visual analogue scale (VAS) score after resuscitation., Results: Compared with that at T0, the mean arterial pressure (MAP) at T2, T3, T4 and T5 in the TEAS group and at T3 and T4 in the sham-TEAS group was all reduced, indicating the significant difference (all P < 0.01). MAP at T2 and T5 in the TEAS group was lower than that in the sham-TEAS group (both P < 0.01). Compared, with that at T5, except at T2 in the TEAS group (P<0. 05), HR was not different significantly at the rest time points (all P > 0.05). HR was different at T2 to Ts in the sham-TEAS group statistically (all P < 0.01). The doses of vecuronium bromide, propofol and nitroglycerin, the operative bleeding volume, the operative time, the resuscitation time and VAS after resuscitation were not different significantly between the two groups (all P > 0.05)., Conclusion: The general anesthesia with TEAS and anesthetics involved for controlling antihypertension contributes to the control of BP and HR in the patients in endoscopic endonasal surgery. The impacts are not obvious on the doses of antihypertensive drug, the general anesthetics, the operative bleeding volume, the time of resuscitation and the postoperative analgesia.

Objective: To verify the clinical efficacy of acupuncture for mild cognitive impairment of stroke at subacute stage., Methods: One hundred patients at subacute stage of cerebral infarction or cerebral hemorrhage with scores of Montreal cognitive assessment (MoCA) less than 26 were randomly divided into an observation group and a control group,50 cases in each one. Based on the regulation of blood pressure and blood sugar and anticoagulation,cognitive rehabilitation training was adopted in the control group. On the basis of treatment in the control group,acupuncture was applied in the observation group. The acupoints were Baihui(GV 20), Sishencong (EX-HN 1), Shenting (GV 24), Yintang(GV 29), Hegu (LI 4) and Taichong(LR 3). Sishencong(EX-HN 1), Shenting (GV 24) and Yintang (GV 29) were connected to electroacupuncture apparatus. The treatment was given once a day,5 times a week, and 8-week treatment was acquired in the two groups. In the 4th week and the 8th week,limbs motor function, daily life ability and cognitive function were evaluated by Fugl-Meyer assessment (FMA) scale,Bathel index and MoCA scale., Results: In 4 weeks and 8 weeks, the scores of FMA, Bathel index and MoCA in the two groups were improved compared with those before treatment (all P < 0.05). After 8-week treatment, the scores of Bathel index and MoCA in the observation group were better than those in the control group (both P < 0.05)., Conclusion: Based on the cognitive rehabilitation training and the conventional treatment, acupuncture can improve the cognitive function and daily life ability of stroke patients at subacute stage with mild cognitive impairment.

Objective: To observe the analgesic effect of electroacupuncture (EA) on collagen-induced arthritis (CIA) rats and its regulating effect on inflammation reaction and the endogenous opioid system of synovial tissues. Methods A total of 30 healthy male Wistar rats were randomly divided into a control group, a model group and an EA group, 10 rats in each one. The chronic pain model of CIA rats was made by cattle type-II collagen in the model group and EA group. Rats in the EA group were treated with EA at "Zusanli" (ST 36) and "Kunlun" (BL 60) for 30 min from 16th day after model establishment, once a day for consecutive 10 days. Rats in the control group did not receive any treatment. Rats in the model group were treated with fixation as the EA group. Threshold of pain, arthritis index, paw swelling were measured before model establishment and 16 d, 20 d, 23 d and 25 d after model establishment. The levels of beta-endorphin (β-END), met-enkephalin (met-ENK), dynorphin A (Dyn A) were measured by radioimmunoassay; the mRNA expressions of mu opioid receptor (MOR), kappa opioid receptor (KOR) and delta opioid receptor (DOR) in synovial tissues of CIA rats were detected by I quantitative polymerase chain reaction (qPCR)., Results: Compared with the control group, threshold of pain was reduced (all P<0. 01), arthritis index was increased (all P<0. 01) and paw swelling was increased (all P<0. 01) in the model group on the 16th day, 20th day, 23rd day, 25th day after model establishment. Compared with the model group, the threshold of pain was increased in the EA group (all P<0. 01), arthritis index and paw swelling were reduced (all P<0. 01) on the 23rd day and 25th day after model establishment. Compared with the control group, the level of Dyn A in synovial tissues of CIA rats was increased in the model group (P<0. 01); the mRNA expressions of MOR, KOR and DOR were down-regulated lower than 0. 5 fold of normal level. Compared with the model group, the level of β-END in synovial tissues of the knee joint was increased in the EA group (P<0. 05), and the mRNA expressions of MOR, KOR and DOR in synovial tissues of CIA rats were up-regulated more than 2 folds of normal level., Conclusion: The intervention of EA on chronic pain of CIA rats is superior, which is likely to be related with effects of EA on anti-inflammation and up-regulation of synovial tissue β-END and MOR, KOR, DOR.

Introduction: Multiple interventions are effective for migraine prophylaxis. However, the comparative effectiveness of these interventions is still not clear. Therefore, the aim of this study is to summarise the direct and indirect evidence for pharmacological and non-pharmacological interventions to prevent migraine attack., Methods and Analysis: We will perform an umbrella systematic review to identify eligible randomised controlled trials (RCTs) for the recommended interventions for migraine prophylaxis according to the guidelines. A comprehensive literature search will be conducted in MEDLINE, EMBASE and the Cochrane library for systematic reviews, which will be screened for RCTs. We will describe the general information of the RCTs for participants, interventions, outcome measurements, comparisons and the primary findings. Additionally, a network meta-analysis will be conducted to determine the comparative effectiveness of the treatments with a random-effects model. The absolute and relative effectiveness of the treatments will be provided. The heterogeneity and inconsistency between trials will be assessed by the I(2) statistical test and Cochrane's Q test. Risk of bias will be assessed and the overall strength of the evidence will be summarised., Discussion: The result of this network meta-analysis will provide direct and indirect evidence of treatments for migraine prophylaxis, and it may provide a ranking of the treatments for patients and clinicians to help them select the best option., Trial Registration Number: PROSPERO CRD42015015297., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

There are many eminent acupuncture masters in modern times in the regions of Zhejiang province, which has developed the acupuncture schools of numerous characteristics and induces the important impacts at home and abroad. Through the literature collection on the acupuncture schools in Zhejiang and the interviews to the parties involved, it has been discovered that the acupuncture manipulation techniques of acupuncture masters in modern times are specifically featured. Those techniques are developed on the basis of Neijing (Internal Classic), Jinzhenfu (Ode to Gold Needle) and Zhenjiu Dacheng (Great Compendium of Acupuncture and Moxibustion). No matter to obey the old maxim or study by himself, every master lays the emphasis on the research and interpretation of classical theories and integrates the traditional with the modern. In the paper, the acupuncture manipulation techniques of Zhejiang acupuncture masters in modern times are stated from four aspects, named needling techniques in Internal Classic, feijingzouqi needling technique, penetrating needling technique and innovation of acupuncture manipulation.

Objective: To observe the intervention of electroacupuncture (EA) with different current frequencies and treatment frequencies on pain thresholt in rats with bone-cancer pain, so as to optimize treatment parameters of EA against bone cancer pain; and by measuring gene expression of opioid receptor and precursor in different tissues to preliminarily explore the possible mechanism of EA against bone cancer pain., Methods: Ninety healthy female SD rats were randomly divided into a control group, a model group, EA groups (6 subgroups according to different frequencies) and a sham EA group, ten rats in each one. Rats in the control group were injected with 10 µL of amicrobic phosphate buffer solution (PBS) into tibial cavity; rats in the remaining groups were injected with Walker 256 cancer cells to establish model of bone-cancer pain. No treatment was given to rats in the control group and model group; rats in the EA groups were treated with EA at bilateral "Housanli" (ST 36) and "Genduan" with 3 different current frequencies (2 Hz, 100 Hz and 2 Hz/100 Hz), once a day and once every other day, 30 min per treatment (1mA for 15 min, 2 mA for 15 min); rats in the sham EA group were treated with identical acupoints as the EA group, but the acupoints were needled subcutaneously and EA was connected with power off. All the treatment was given for 14 days. Dynamic plantar aesthesiometer was applied to measure the paw withdrawal thresholds (PWTs) of the affected side before the model establishment, 6d, 8d, 10d, 12d, 14d, 16d, 18d, and 20d after model establishment. The mRNA expressions of µ-opioid receptor (MOR), κ-opioid receptor (KOR), δ-opioid receptor (DOR), proopiomelanocortin (POMC) and prodynorphin (PDYN) in dorsal root ganglion (DRG) and lumbar spinal cord dorsal horn (SCDH) of L4-L6 of the affected side were detected by PCR method., Results: There were no differences in PWTs among all groups before model establishment (P>0. 05). Each time point after model establishment, PWTs in model group were obviously lower than those in the control group (all P<0. 01). Compared with the model group, PWTs in each EA subgroup were all increased (all P<0.05), but the differences at different time points were not significant among EA subgroups (P>0.05). The mRNA expressions of MOR, KOR, POMC, and PDYN in L4-L6 DRG in the 2 Hz/100 Hz II group were significantly higher than those in model group (P<0. 05, P<0. 01), while the mRNA expressions of MOR, KOR, DOR, POMC and PDYN in SCDH were not different compared with the model group (P>0. 05)., Conclusion: EA treatment has obvious analgesic effect on bone-cancer pain, however, its effect is not related with current frequency and treating frequency. EA against bone-cancer pain may be related with increasing the mRNA expression of some peripheral opioid receptors and precursor.

Introduction: The aim of this review is to assess the effectiveness, efficacy and safety of non-pharmacological therapies for patients with functional constipation., Methods and Analysis: We will electronically search OVID MEDLINE, EMBASE, Cochrane library, CINAHL, AMED and ISI web of knowledge without any language restrictions. We will also try to obtain literatures from other sources, such as a hand search of library journals or conference abstracts. After searching and screening of the studies, we will run a meta-analysis of the included randomised-controlled trials. We will summarise the results as risk ratio for dichotomous data and standardised or weighted mean difference for continuous data., Dissemination: This systematic review will summarise current evidence for using non-pharmacological therapies to treat functional constipation, and will be disseminated through peer-review publications or conference presentations., Trial Registration Number: PROSPERO 2014: CRD42014006686., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)