Search

Na Zhang,1,2 Jian-Feng Tu,1 Ying Lin,1 Jin-Ling Li,1 Xuan Zou,1 Yu Wang,1 Hewen Li,1 Xiao-Ya Wei,1 Li-Qiong Wang,1 Guang-Xia Shi,1 Shi-Yan Yan,1 Cun-Zhi Liu1 1International Acupuncture and Moxibustion Innovation Institute, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Acupuncture-Moxibustion and Tuina, Shandong University of Chinese Medicine, Shandong, People’s Republic of ChinaCorrespondence: Guang-Xia Shi; Shi-Yan Yan Email shiguangxia2008@126.com; yanshiyan0927@sina.comBackground: Whether the clinical effect of acupuncture in chronic pain is effective has always been a hot topic of research, which has a great relationship with the overall reporting descriptions of acupuncture, especially the sham acupuncture intervention. To confirm the effectiveness of acupuncture, more clinical studies are often required. Therefore, it is necessary to report high-quality and complete descriptions of acupuncture in clinical trials. This study aims to assess the overall reporting quality of acupuncture for chronic pain in randomized controlled trials (RCTs).Methods: Three databases from inception to March 2020 were searched, to assess the quality of acupuncture reports included the RCTs based on the pain-specific supplement to Consolidated Standards for Reporting Trials (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) guidelines. The quality of sham acupuncture descriptions was evaluated based on the Template for Intervention Description and Replication (TIDieR)-placebo checklist. Descriptive statistics and analysis of the results were carried out according to the percentage of each item.Results: A total of 74 RCTs were included which met the inclusion criteria. Based on the pain-specific CONSORT, the reporting rates of “Statistical methods”, “Participant flow”, and “Blinding” were “ 52.70%”, “ 70.27%”, and “ 77.03%”, respectively. The weakest reported items in STRICTA were related to the depth of insertion (Item 2c, 54.05%) and the setting and context of treatment (Item 4b, 0.00%). Based on the TIDieR-placebo checklist, the reporting rates of “Item 12”, “Item 11”, “Item 13”, “Item 3”, and “Item 4” were “ 8.11%”, “ 10.81%”, “ 29.73%”, “ 44.59% ”, and “ 47.30%”, respectively.Conclusion: At present, the overall report quality of acupuncture treatment for chronic pain in English journals is acceptable, but the report rate in some aspects is still low. In the future, researchers should report RCTs of acupuncture following cleaner checklists and guidelines.Keywords: randomized controlled trials, overall reporting quality, sham acupuncture, chronic pain

Na Zhang,1,2 Li-Qiong Wang,1 Jin-Ling Li,1 Xin-Tong Su,1 Fang-Ting Yu,1 Guang-Xia Shi,1 Jing-Wen Yang,1 Cun-Zhi Liu1 1International Acupuncture and Moxibustion Innovation Institute, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Acupuncture-Moxibustion and Tuina, Shandong University of Chinese Medicine, Shandong, People’s Republic of ChinaCorrespondence: Cun-Zhi LiuSchool of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Chaoyang District, Beijing 100029, People’s Republic of ChinaEmail lcz_tg@126.comObjective: Acupuncture therapy is an effective non-drug therapy for sciatica, but it has not yet formed an effective treatment strategy and recommendations. Our objective was to establish an expert consensus on acupuncture treatment of sciatica for clinical guidance based on the improved Delphi survey.Methods: A group of 80 clinical specialists was invited to participate in two rounds of semi-open clinical issue investigation. At the same time, the PubMed, Embase, and Cochrane Library databases were searched for systematic reviews on acupuncture treatment of sciatica, and the quality of evidence was evaluated. Then the three-round Delphi survey was undertaken with 30 experts based on the clinical issue investigation and systematic reviews.Results: In round 1 of the Delphi survey, the experts evaluated 17 items identified from the results of the clinical investigation and literature review. The criterion for achieving consensus was a threshold of 80% agreement. After the three-round Delphi survey, 16 items (94.12%) achieved consensus, including 5 domains: the principle of acupuncture treatment for sciatica; the “dose” of acupuncture; the clinical effects of acupuncture; the adverse effects, and others.Conclusion: This Delphi survey achieved an expert consensus on key items in the management of sciatica for acupuncture, which provides the current opinions in China. We trust that these treatment recommendations may facilitate their implementation in the future.Keywords: acupuncture, sciatica, expert consensus, Delphi survey

Guang-Xia Shi,1 Jian-Feng Tu,2 Tian-Qi Wang,2 Jing-Wen Yang,2 Li-Qiong Wang,2 Lu-Lu Lin,2 Yu Wang,1 Yong-Ting Li,1 Cun-Zhi Liu2 1Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing, People’s Republic of China; 2School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Cun-Zhi Liu Email lcz_tg@126.comBackground: Inflammation plays a significant role in the pathogenesis of knee osteoarthritis (KOA). Although both electro-acupuncture (EA) and manual acupuncture (MA) are known to influence systemic inflammation, little is known about the potential changes in inflammation as a working mechanism of EA and MA in KOA.Methods: Data from the Acupuncture for Knee Osteoarthritis Trial (ATKOA) were used. Serum concentrations of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, IL-18, IL-4, IL-10, IL-13, IL-15, IL-17, monocyte chemotactic protein-1 (MCP-1), CC-chemokine ligand 5 (CCL5), and cartilage degradation biomarkers (matrix metalloproteinase-1 MMP-1, MMP-3, MMP-13 and cartilage oligomeric matrix protein COMP)) were measured at baseline and after 8 weeks of treatment. Clinical outcomes were valid and reliable self-reported pain and function measures for osteoarthritis using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analogue scale (VAS) at baseline and post-treatment.Results: Both 8-weeks EA and MA significantly reduced pro-inflammatory cytokines (TNFα, IL-1β), and cartilage degradation biomarkers (MMP-3, MMP-13) significantly increased the anti-inflammatory cytokine IL-13 compared with pre-treatment (p< 0.05). Further, the reduction of TNF-α was more significant in EA when compared to MA (p=0.046). While there was no significant difference between groups in cytokines IL-1β (p=0.102), MMP-3 (p=0.113), MMP-13 (p=0.623) or IL-13 (p=0.935). Moreover, in both EA and MA, the effect of acupuncture on the VAS and WOMAC function scale after 8 weeks is clinically important, although no significant differences were found between groups.Conclusion: Eight weeks of both EA and MA seem to provide improvement in pain relief and function among individuals with mild to moderate knee OA. This benefit is partly mediated by changes of major inflammatory factors TNF-α, IL-1β and IL-13.Trial Registration: Controlled-Trials.com Identifier: NCT03274713.Keywords: knee osteoarthritis, electro-acupuncture, manual acupuncture, inflammation

Guang-Xia Shi,1 Bao-Zhen Liu,2 Jun Wang,3 Qing-Nan Fu,1 San-Feng Sun,2 Rui-Li Liang,2 Jing Li,3 Jian-Feng Tu,1 Cheng Tan,3 Cun-Zhi Liu4 1Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing100010, China; 2Acupuncture and Moxibustion Department, Beijing Huairou District Hospital of Traditional Chinese Medicine, Beijing 101400, China; 3Department of Acupuncture and Moxibustion, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing100010, China; 4Department of Acupuncture and Moxibustion, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China Background: Strategies for preventing the persistence of pain and disability beyond the acute phase in shoulder pain patients are critically needed. Conventional acupuncture therapy (CAT) or motion style acupuncture therapy (MSAT) alone results in relative improvements in painful conditions in shoulder pain patients; combined interventions may have more global effects. The aim of this study is to evaluate the efficacy and safety of MSAT vs CAT for shoulder pain. Methods: A randomized controlled trial using a factorial design was conducted from January 2014 to December 2015. Patients with a primary complaint of one-sided shoulder pain participated at three study sites. Eligible individuals were randomly assigned to receive MSAT plus minimal CAT (mCAT), CAT plus minimal MSAT (mMSAT), MSAT plus CAT, or mMSAT plus mCAT for 6 weeks in a 1:1:1:1 ratio. The primary outcome was change in shoulder pain intensity (measured using visual analog scale). The secondary outcomes included change in function of the shoulder joint (Constant–Murley score) and the health-related quality of life (Short Form-36 Health Survey). Moreover, perceived credibility of acupuncture was measured using the Treatment Credibility Scale. The outcomes were assessed at baseline and at 6, 10, and 18 weeks after randomization. Analysis of covariance with the baseline score adjustment had been used to determine the primary end point. The between-group differences of MSAT vs mMSAT and CAT vs mCAT were estimated, respectively, after tests of interaction between the two-dimensional interventions. All main analyses followed the intention-to-treat principle. Results: A total of 164 patients completed the study. MSAT was superior to mMSAT in alleviating pain intensity at 10 weeks (P=0.024), and it was maintained for 18 weeks (P=0.013). Statistically significant differences were found when comparing MSAT with mMSAT for improvement in shoulder function (6 weeks, P=0.01; 10 weeks, P=0.006; and 18 weeks, P=0.01), physical health (10 weeks, P=0.023 and 18 weeks, P=0.015), and mental health (18 weeks, P=0.05). No significant differences were found in CAT when compared with mCAT. Conclusion: After 18 weeks of treatment, pain and joint functions are improved more with MSAT than with minimal motion style acupuncture or conventional acupuncture in patients with shoulder pain. Keywords: motion style acupuncture, shoulder pain, acupuncture therapy, randomized controlled trial

Introduction: Atrial fibrillation (AF) is the prevalent cardiac arrhythmia and can significantly impair the quality of life (QoL). Although catheter ablation (CA) is an established treatment for AF,post-procedural complications or perceived inadequate control of AF may diminish the QoL for some patients, potentially even to levels lower than pre-procedure. Preliminary findings from our previous pilot trial indicate that acupuncture may positively influence QoL in AF patients post-CA. This study aims to increase the sample size to evaluate the efficacy of acupuncture as an adjunctive treatment to conventional medical therapy in improving QoL of patients with AF after CA., Methods and Design: This multicentre randomised clinical trial will be conducted in China. A total of 146 eligible patients will be randomly assigned in a 1:1 ratio to either the acupuncture group or the sham acupuncture group. All patients will receive standard postablation care and undergo 18 sessions of acupuncture/sham acupuncture within 12 weeks following CA, followed by a 9-month follow-up period. The primary outcome is the change in the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) summary score from baseline to months 6 after CA. Secondary outcomes include the changes in the AFEQT subscale scores at months 6, the AFEQT summary and subscale score at months 3 and 12, AF burden, AF recurrence, heart rate variability, number of cardioversions, repeat CA procedures, European Heart Rhythm Association score, number of arrhythmia-related hospitalisations, average heart rate, use of Six-Dimensional Health State Short Form to assess health status, costs incurred by disease treatment, Credibility/Expectancy Questionnaire and blinded assessments. Adverse events will also be meticulously recorded throughout the trial., Ethics and Dissemination: Ethics approval has been granted by the Ethics Committee of Beijing University of Traditional Chinese Medicine (approval no: 2020BZYLL0802) and seven other subcentres. The findings of the study results will be disseminated through presentations at scientific conferences or publications in peer-reviewed journals., Trial Registration Number: ChiCTR2100049323., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture- or sham acupuncture groups and received 10 sessions of treatment during 4 weeks. The visual analog scale for leg pain, oswestry disability index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression analyses were performed. Compared with sham acupuncture, acupuncture significantly improved symptoms, including visual analog scale for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus. Furthermore, the actual 4-week ODI values were positively correlated with the support vector regression-predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right postcentral gyrus may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. PERSPECTIVE: This clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Psoriasis is an inflammatory skin disease that relapses frequently. Keratinocyte apoptosis dysregulation plays a crucial role in the pathological mechanisms of psoriasis. PANoptosis is a process with intermolecular interaction among pyroptosis, apoptosis, and necroptosis. The mechanism of PANoptosis in the occurrence and development of psoriasis is still unclear. Here we present a novel approach by identifying PANoptosis-related signatures (PANoptosis-sig) from skin tissue of psoriasis patients and healthy controls on transcriptional and protein levels. Five PANoptosis-sig (TYMP, S100A8, S100A9, NAMPT, LCN2) were identified. Enrichment analysis showed they were mainly enriched in response to leukocyte aggregation, leukocyte migration, chronic inflammatory response and IL-17 signaling pathway. Single cell transcriptome analysis showed TYMP and NAMPT were expressed in almost all cell populations, while LCN2, S100A8 and S100A9 were significantly highly expressed in keratinocyte. We then constructed predictive and diagnostic models with the PANoptosis-sig and evaluated their performance. Finally, unsupervised consensus clustering analysis was conducted to ascertain psoriasis molecular subtypes by the PANoptosis-sig. The psoriasis cohort was divided into two distinct subtypes. Immune landscape showed that the stromal score of cluster 1 was significantly higher than cluster 2, while the immune and estimate scores of cluster 2 were expressively higher than cluster 1. Cluster 1 exhibited high expression of Plasma cells, Tregs and Mast cells resting, while cluster 2 showed high expression of T cells, Macrophages M1, Dendritic cells activated, and Neutrophils in immune infiltration analysis. And cluster 2 was more sensitive to immune checkpoints. In conclusion, our findings revealed potential biomarkers and therapeutic targets for the prevention, diagnosis, and treatment of psoriasis, enhancing our understanding of the molecular mechanisms underlying PANoptosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We aim to evaluate the prevalence of steatotic liver disease (SLD) in United States (US) adolescents and explore whether metabolic dysfunction-associated steatotic liver disease (MASLD) can identify individuals with clinically significant fibrosis (CSF) in this study. The prevalence of SLD and its categories, including MASLD, metabolic dysfunction and alcohol associated liver disease (MetALD), alcohol related liver disease (ALD) and other SLD were determined. Weighted multivariable logistic regression analysis was conducted to evaluate the association between MASLD and CSF in adolescents with SLD. Among the total 1,446 US adolescents, SLD was present in 291 (20.1%) of individuals, including 260 (17.9%) for MASLD, 9 (0.6%) for MetALD and 5 (0.3%) for ALD. Only 58 (4%) had CSF. Patients with SLD showed a higher prevalence of CSF (9.6% vs. 2.6%, p < 0.001). Among patients with SLD, 89.3% met the MASLD criteria. The risk of CSF in patients with MASLD was not significantly different (odds ratio [OR] = 1.07, 95% confidence interval [CI] = 0.30-3.83, p = 0.9180) compared with those without MASLD. MASLD was met by most of the US adolescents with SLD. Moreover, MASLD was not associated with higher prevalence of CSF among adolescents with SLD., (© 2024. The Author(s).)

Importance: Sciatica is commonly caused by herniated lumbar disc and contributes to severe pain and prolonged disability. Although acupuncture is widely used by patients with chronic sciatica, the evidence of its efficacy is scarce., Objective: To investigate the efficacy and safety of acupuncture compared with sham acupuncture in patients with chronic sciatica from herniated disk., Design, Settings, and Participants: This was a multicenter 2-arm randomized clinical trial conducted in 6 tertiary-level hospitals in China of patients with chronic sciatica from herniated disk. Participants were recruited from March 25, 2021, to September 23, 2021, with a final follow-up through September 22, 2022. Data analyses were performed from December 2022 to March 2023., Interventions: Participants were randomly assigned to receive 10 sessions of acupuncture (n = 110) or sham acupuncture (n = 110) over 4 weeks. Participants, outcome assessors, and statisticians were blinded., Main Outcomes and Measures: The 2 coprimary outcomes were changes in visual analog scale (VAS) for leg pain and Oswestry Disability Index (ODI) from baseline to week 4. Secondary outcomes were adverse events., Results: A total of 216 patients (mean [SD] age, 51.3 [15.2] years; 147 females [68.1%] and 69 males [31.9%]) were included in the analyses. The VAS for leg pain decreased 30.8 mm in the acupuncture group and 14.9 mm in the sham acupuncture group at week 4 (mean difference, -16.0; 95% CI, -21.3 to -10.6; P < .001). The ODI decreased 13.0 points in the acupuncture group and 4.9 points in the sham acupuncture group at week 4 (mean difference, -8.1; 95% CI, -11.1 to -5.1; P < .001). For both VAS and ODI, the between-group difference became apparent starting in week 2 (mean difference, -7.8; 95% CI, -13.0 to -2.5; P = .004 and -5.3; 95% CI, -8.4 to -2.3; P = .001, respectively) and persisted through week 52 (mean difference, -10.8; [95% CI, -16.3 to -5.2; P < .001; and -4.8; 95% CI, -7.8 to -1.7; P = .003, respectively). No serious adverse events occurred., Conclusions and Relevance: This randomized clinical trial found that in patients with chronic sciatica from herniated disk, acupuncture resulted in less pain and better function compared with sham acupuncture at week 4, and these benefits persisted through week 52. Acupuncture should be considered as a potential treatment option for patients with chronic sciatica from a herniated disk., Trial Registration: Chictr.org Identifier: ChiCTR2100044585.

Objective: Converging evidence indicates that subjective cognitive decline (SCD) could be an early indicator of dementia. The hippocampus is the earliest affected region during the progression of cognitive impairment. However, little is known about whether and how acupuncture change the hippocampal structure and function of SCD individuals., Methods: Here, we used multi-modal MRI to reveal the mechanism of acupuncture in treating SCD. Seventy-two older participants were randomized into acupuncture or sham acupuncture group and treated for 12 weeks., Results: At the end of the intervention, compared to sham acupuncture, participants with acupuncture treatment showed improvement in composite Z score from multi-domain neuropsychological tests, as well as increased hippocampal volume and functional connectivity. Moreover, the greater white matter integrity of the fornix, which is the major output tract of the hippocampus, was shown in the acupuncture group., Conclusion: These findings suggest that acupuncture may improve the cognitive function of SCD individuals, and increase hippocampal volume on the regional level and enhance the structural and functional connectivity of hippocampus on the connective level., Competing Interests: DISCLOSURES The authors report no conflicts with any product mentioned or concept discussed in this article., (Copyright © 2024 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Purpose: Knee osteoarthritis (KOA) is a common disorder among middle and older individuals. Electroacupuncture and exercise are present as two popular physical therapies for the management of KOA, and both were demonstrated to produce considerable results. However, the clinical decision-making process between these therapeutic interventions remains challenging due to the limited evidence of distinctions in their respective effects. This study aims to evaluate the clinical effect and cost effectiveness of electroacupuncture versus exercise in patients with KOA., Study Design and Methods: This is a randomized controlled trial in which 196 symptomatic KOA patients will be randomly assigned 1:1 either to the electroacupuncture group (n = 98) and the exercise group (n = 98). Patients in the electroacupuncture group will receive acupuncture with electric stimulation 3 times a week for 8 weeks, whereas patients in the exercise group will receive neuromuscular training twice a week for 8 weeks. Education concerning KOA management will be provided in both therapies. Co-primary outcomes include changes in numerical rating scale (NRS) and Knee injury and Osteoarthritis Outcome Score (KOOS) Activities of Daily Living (ADL) subscale from baseline at week 8. Secondary outcomes include KOOS Pain subscale, KOOS knee-related Quality of Life (QOL) subscale, Short Form 6 Dimensions (SF-6D), five-level EuroQol five-dimensional questionnaire (EQ-5D-5L), Credibility/ Expectancy Questionnaire, Patient's global assessment (PGA), 30-second Chair Stand Test (30s-CST), 40m (4*10m) Fast Paced Walk Test (40m FPWT), and Daily Physical Activity level (DPA)., Discussion: The results of this study will provide evidence regarding differences between these 2 physical therapies in multiple aspects and will provide specific guidance for the development of treatments based on the needs of individual patients., Trial Registration: ChiCTR2300070376., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS) are the most common systemic autoimmune diseases, and they are increasingly being recognized as occurring in the same patient population. These two diseases share several clinical features and laboratory parameters, but the exact mechanism of their co-pathogenesis remains unclear. The intention of this study was to investigate the common molecular mechanisms involved in RA and pSS using integrated bioinformatic analysis. RNA-seq data for RA and pSS were picked up from the Gene Expression Omnibus (GEO) database. Co-expression genes linked with RA and pSS were recognized using weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. Then, we screened two public disease-gene interaction databases (GeneCards and Comparative Toxicogenomics Database) for common targets associated with RA and pSS. The DGIdb database was used to predict therapeutic drugs for RA and pSS. The Human microRNA Disease Database (HMDD) was used to screen out the common microRNAs associated with RA and pSS. Finally, a common miRNA-gene network was created using Cytoscape. Four hub genes (CXCL10, GZMA, ITGA4, and PSMB9) were obtained from the intersection of common genes from WGCNA, differential gene analysis and public databases. Twenty-four drugs corresponding to hub gene targets were predicted in the DGIdb database. Among the 24 drugs, five drugs had already been reported for the treatment of RA and pSS. Other drugs, such as bortezomib, carfilzomib, oprozomib, cyclosporine and zidovudine, may be ideal drugs for the future treatment of RA patients with pSS. According to the miRNA-gene network, hsa-mir-21 may play a significant role in the mechanisms shared by RA and pSS. In conclusion, we identified commom targets as potential biomarkers in RA and pSS from publicly available databases and predicted potential drugs based on the targets. A new understanding of the molecular mechanisms associated with RA and pSS is provided according to the miRNA-gene network., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Osteoporosis is a metabolic condition distinguished by the degradation of bone microstructure and mechanical characteristics. Traditional Chinese medicine (TCM) has been employed in China for the treatment of various illnesses. Naringin, an ingredient found in Drynariae TCM, is known to have a significant impact on bone metabolism. For this research, we studied the precise potential effect of Drynaria Naringin on protecting against bone loss caused by stress deficiency. In this study, a tail-suspension (TS) test was performed to establish a mouse model with hind leg bone loss. Some mice received subcutaneous injections of Drynaria Naringin for 30 d. Trabecular bone microarchitecture was evaluated using micro-computed tomography analysis and bone histological analysis. Bone formation and resorption markers were quantified in blood samples from mice or in the supernatant of MC3T3-E1 cells by ELISA analysis, Western blotting, and PCR. Immunofluorescence was utilized to visualize the location of β-catenin. Additionally, siRNA was employed to knockdown-specific genes in the cells. Our findings highlight the efficacy of Drynaria Naringin in protecting against the deterioration of bone loss and promoting bone formation and Rspo1 expression in a mouse model following the TS test. Specifically, in vitro experiments also indicated that Drynaria Naringin may promote osteogenesis through the Wnt/β-catenin signalling pathway. Moreover, our results suggest that Drynaria Naringin upregulates the expression of Rspo1/Lgr4, leading to the promotion of osteogenesis via the Wnt/β-catenin signalling pathway. Therefore, Drynaria Naringin holds potential as a therapeutic medication for osteoporosis. Drynaria Naringin alleviates bone loss deterioration caused by mechanical stress deficiency through the Rspo1/Lgr4-mediated Wnt/β-catenin signalling pathway., (© 2023. The Society for In Vitro Biology.)

Abstract: Chronic pain has been one of the leading causes of disability. Acupuncture is globally used in chronic pain management. However, the efficacy of acupuncture treatment varies across patients. Identifying individual factors and developing approaches that predict medical benefits may promise important scientific and clinical applications. Here, we investigated the psychological and neurological factors collected before treatment that would determine acupuncture efficacy in knee osteoarthritis. In this neuroimaging-based randomized controlled trial, 52 patients completed a baseline assessment, 4-week acupuncture or sham-acupuncture treatment, and an assessment after treatment. The patients, magnetic resonance imaging operators, and outcome evaluators were blinded to treatment group assignment. First, we found that patients receiving acupuncture treatment showed larger pain intensity improvements compared with patients in the sham-acupuncture arm. Second, positive expectation, extraversion, and emotional attention were correlated with the magnitude of clinical improvements in the acupuncture group. Third, the identified neurological metrics encompassed striatal volumes, posterior cingulate cortex (PCC) cortical thickness, PCC/precuneus fractional amplitude of low-frequency fluctuation (fALFF), striatal fALFF, and graph-based small-worldness of the default mode network and striatum. Specifically, functional metrics predisposing patients to acupuncture improvement changed as a consequence of acupuncture treatment, whereas structural metrics remained stable. Furthermore, support vector machine models applied to the questionnaire and brain features could jointly predict acupuncture improvement with an accuracy of 81.48%. Besides, the correlations and models were not significant in the sham-acupuncture group. These results demonstrate the specific psychological, brain functional, and structural predictors of acupuncture improvement and may offer opportunities to aid clinical practices., (Copyright © 2023 International Association for the Study of Pain.)

Purpose: Acupuncture has been widely used in the treatment of knee osteoarthritis (KOA), but the selection of acupoints is indeterminate and lacks biological basis. The skin temperature of acupoints can reflect the state of local tissue and may be a potential factor for guiding acupoint selection. This study aims to compare the skin temperature of acupoints between KOA patients and the healthy population., Study Design and Methods: This is a protocol for a cross-sectional case-control study with 170 KOA patients and 170 age- and gender-matched healthy individuals. Diagnosed patients aged 45 to 70 will be recruited in the KOA group. Participants in the healthy group will be matched with the KOA group based on mean age and gender distribution. Skin temperature of 11 acupoints (ST35, EX-LE5, GB33, GB34, EX-LE2, ST34, ST36, GB39, BL40, SP9, SP10) will be extracted from infrared thermography (IRT) images of the lower limbs. Other measurements will include demographic data (gender, age, ethnicity, education, height, weight, BMI) and disease-related data (numerical rating scale, pain sites, duration of pain, pain descriptors, pain activities)., Discussion: The results of this study will provide biological evidence for acupoint selection. This study is a precondition for follow-up studies, in which the value of optimized acupoint selection will be verified., Trial Registration: ChiCTR2200058867., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chromatin immunoprecipitation (ChIP) is an antibody-based approach that is frequently utilized in chromatin biology and epigenetics. The challenge in experimental variability by unpredictable nature of usable input amounts from samples and undefined antibody titer in ChIP reaction still remains to be addressed. Here, we introduce a simple and quick method to quantify chromatin inputs and demonstrate its utility for normalizing antibody amounts to the optimal titer in individual ChIP reactions. For a proof of concept, we utilized ChIP-seq validated antibodies against the key enhancer mark, acetylation of histone H3 on lysine 27 (H3K27ac), in the experiments. The results indicate that the titration-based normalization of antibody amounts improves assay outcomes including the consistency among samples both within and across experiments for a broad range of input amounts., (© 2023. The Author(s).)

Understanding the function of non-coding genomic sequence variants represents a challenge for biomedicine. Many diseases are products of gene-by-environment interactions with complex mechanisms. This study addresses these themes by mechanistic characterization of non-coding variants that influence gene expression only after drug or hormone exposure. Using glucocorticoid signaling as a model system, we integrated genomic, transcriptomic, and epigenomic approaches to unravel mechanisms by which variant function could be revealed by hormones or drugs. Specifically, we identified cis-regulatory elements and 3D interactions underlying ligand-dependent associations between variants and gene expression. One-quarter of the glucocorticoid-modulated variants that we identified had already been associated with clinical phenotypes. However, their affected genes were 'unmasked' only after glucocorticoid exposure and often with function relevant to the disease phenotypes. These diseases involved glucocorticoids as risk factors or therapeutic agents and included autoimmunity, metabolic and mood disorders, osteoporosis and cancer. For example, we identified a novel breast cancer risk gene, MAST4, with expression that was repressed by glucocorticoids in cells carrying the risk genotype, repression that correlated with MAST4 expression in breast cancer and treatment outcomes. These observations provide a mechanistic framework for understanding non-coding genetic variant-chemical environment interactions and their role in disease risk and drug response., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: Activation of muscarinic receptors located in bladder sensory pathways is generally considered to be the primary contributor for driving the pathogenesis of neurogenic detrusor overactivity following spinal cord injury. The present study is undertaken to examine whether moxibustion improves neurogenic detrusor overactivity via modulating the abnormal muscarinic receptor pathway., Materials and Methods: Female Sprague-Dawley rats were subjected to spinal cord injury with T9-10 spinal cord transection. Fourteen days later, animals were received moxibustion treatment for one week. Urodynamic parameters and pelvic afferents discharge were measured. Adenosine triphosphate (ATP) content in the voided cystometry fluid was determined. Expressions of M2, M3, and P2X3 receptors in the bladder mucosa were evaluated., Results: Moxibustion treatment prevented the development of detrusor overactivity in spinal cord injury rats, with an increase in the intercontraction interval and micturition pressure threshold and a decrease in afferent activity during filling. The expression of M2 was markedly suppressed by moxibustion, accompanied by a reduction in the levels of ATP and P2X3. M2 receptor antagonist methoctramine hemihydrate had similar effects to moxibustion on bladder function and afferent activity, while the M2-preferential agonist oxotremorine methiodide abolished the beneficial effects of moxibustion., Conclusion: Moxibustion is a potential candidate for treating neurogenic bladder overactivity in a rat model of spinal cord injury, possibly through inhibiting the M2/ATP/P2X3 pathway., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The authors investigated the effectiveness of home-based transcutaneous electrical acupoint stimulation (TEAS) combined with lifestyle modification on blood pressure (BP) control and explored the feasibility of the trial design in this prospective, randomized controlled trial. The authors recruited individuals with high-normal BP who had a systolic blood pressure (SBP) of 120-139 mm Hg and a diastolic blood pressure (DBP) of 80-89 mm Hg, or both. Participants were randomly assigned to receive either lifestyle modification combined with TEAS four times weekly for 12 weeks at home (intervention group) or solely lifestyle modification (control group). The primary outcome was the change in mean SBP at week 12 from the baseline measurement. A total of 60 participants were randomized in a 1:1 ratio, and an intention-to-treat analysis was performed on all of the outcomes. The mean difference in the change in SBP for the intervention group (compared to the control) at week 12 was -3.85 mm Hg (95% CI: -7.58 to -.12; p = .043); for the DBP, the change was -2.27 mm Hg (95% CI: -5.76 to 1.23; p = .199). There was no difference in the proportion of progression to hypertension, quality of life, body mass index (BMI) or waist circumference. In addition, two participants reported TEAS-related adverse events. The authors found a reduction in SBP control in the pragmatic, home-based intervention by using TEAS combined with lifestyle modification in adults with high-normal BP. Trial Registration: The study was registered in the Chinese Clinical Trial Registry (ChiCTR 1900024982) on August 6, 2019., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Importance: Renal colic is described as one of the worst types of pain, and effective analgesia in the shortest possible time is of paramount importance., Objectives: To examine whether acupuncture, as an adjunctive therapy to analgesics, could accelerate pain relief in patients with acute renal colic., Design, Setting, and Participants: This single-center, sham-controlled, randomized clinical trial was conducted in an emergency department in China between March 2020 and September 2020. Participants with acute renal colic (visual analog scale [VAS] score ≥4) due to urolithiasis were recruited. Data were analyzed from October 2020 to January 2022., Interventions: After diagnosis and randomization, all patients received 50 mg/2 mL of diclofenac sodium intramuscular injection immediately followed by 30-minute acupuncture or sham acupuncture., Main Outcomes and Measures: The primary outcome was the response rate at 10 minutes after needle manipulation, which was defined as the proportion of participants whose VAS score decreased by at least 50% from baseline. Secondary outcomes included response rates at 0, 5, 15, 20, 30, 45, and 60 minutes, rescue analgesia, and adverse events., Results: A total of 115 participants were screened and 80 participants (66 men [82.5%]; mean [SD] age, 45.8 [13.8] years) were enrolled, consisting of 40 per group. The response rates at 10 minutes were 77.5% (31 of 40) and 10.0% (4 of 40) in the acupuncture and sham acupuncture groups, respectively. The between-group differences were 67.5% (95% CI, 51.5% to 83.4%; P < .001). The response rates of acupuncture were also significantly higher than sham acupuncture at 0, 5, 15, 20 and 30 minutes, whereas no significant difference was detected at 45 and 60 minutes. However, there was no difference between the 2 groups in rescue analgesia rate (difference 2.5%; 95% CI -8.8% to 13.2%; P > .99). No adverse events occurred during the trial., Conclusions and Relevance: These findings suggest that acupuncture plus intramuscular injection of diclofenac is safe and provides fast and substantial pain relief for patients with renal colic compared with sham acupuncture in the emergency setting. However, no difference in rescue analgesia was found, possibly because of the ceiling effect caused by subsequent but robust analgesia of diclofenac. Acupuncture can be considered an optional adjunctive therapy in relieving acute renal colic., Trial Registration: Chinese Clinical Trial Registry: ChiCTR1900025202.

Introduction: Hypertension is a common risk factor for cardiovascular disease. Transcutaneous electrical acupoint stimulation (TEAS) may be effective for hypertension, but the evidence remains limited. The aim of this study is to evaluate the effectiveness and safety of the smart phone-based TEAS as adjunctive therapy for hypertension., Methods and Analysis: This study is a 52-week cluster randomised controlled trial with 1600 hypertension patients in 32 community health service centres. Patients who meet the inclusion criteria will be randomised into usual care group or TEAS group in a 1:1 ratio. All patients will be provided with usual care as recommended by the guidelines. In addition to this, patients in the TEAS group will receive non-invasive acupoint electrical stimulation for 30 min at home, 4 times weekly for 12 weeks. The primary outcome will be the mean difference in the changes in office systolic blood pressure from baseline to 12 weeks between TEAS and usual care groups. Secondary outcomes will include the change of mean diastolic blood pressure, proportion of patients with controlled blood pressure (blood pressure <140/90 mm Hg), proportion of patients taking antihypertensive drugs, change in number of antihypertensive drugs and changes in 12-item Short-Form. Tertiary outcomes will include change in body mass index, change in waist circumference, physical activity and medication adherence. Safety outcomes will be any serious adverse events and clinical events., Ethics and Dissemination: This study has been approved by ethics committee of Beijing University of Chinese Medicine (No. 2020BZHYLL0104). Written informed consent will be obtained from all patients before randomisation. Trial results will be disseminated in peer-reviewed publications., Trial Registration Number: ChiCTR2000039400., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Postoperative ileus after colorectal surgery is a frequent problem that significantly delays recovery, increases perioperative costs, and negatively impacts on daily life, physical and psychosocial functioning, and wellbeing. We investigated the effect of acupuncture at different single acupoint combined with standard care on postoperative ileus., Methods: In this single-centre, three-arm, prospective, randomised trial, we enrolled patients with primary colorectal cancer undergoing elective colorectal resection at Cancer Hospital Chinese Academy of Medical Science in Beijing, China. Patients were randomly assigned (1:1:1) to receive either electroacupuncture (EA) at ST36 or ST25 combined with standard care (two EA groups) once daily from post-operative days 1-4, or standard care alone (standard care group). The co-primary outcomes were time to first flatus and time to defecation assessed in the intention-to-treat population. This study is registered with Chictr.org.cn, ChiCTR1900027466., Finding: Between Nov 15, 2019, and Sep 30, 2020, 129 patients were assessed for eligibility, 105 patients (35 patients per group) were enrolled and included in the intention-to-treat analysis. After receiving EA at ST36, the time to first flatus and defecation were shorter (between-group difference -10.98 [97.5% CI -21.41 to -0.56], p  = 0·02 for flatus; -25.41 [-47.89 to -2.93], p  = 0·02 for defecation). However, we did not observe a significant difference in time to first flatus and defecation between the EA at ST25 group and standard care group (between-group difference -5.54 [97.5% CI -15.78 to 4.70], p  = 0·26 for flatus; -17.69 [-40.33 to 4.95], p  = 0·08 for defecation). There were no serious adverse events., Interpretation: Compared with standard care alone, standard care combined with EA at ST36, but not ST25, significantly enhances bowel function recovery in a postoperative setting to patients with colorectal cancer with laparoscopic elective colorectal resection., Funding: The National Key R&D Program of China (No: 2019YFC1712100) and the National Science Fund for Distinguished Young Scholars (No:81825024)., Competing Interests: We declare no competing interests., (© 2022 Published by Elsevier Ltd.)

Background: Chronic Sciatica is a disabling condition causing considerable medical, social and financial implications. Currently, there is no recognised long-term effective treatment to alleviate sciatica. Acupuncture has been widely used for treating chronic pains with persistent analgesic effects. We aim to evaluate the efficacy and safety of acupuncture for chronic sciatica with follow-up in 52 weeks., Methods and Analysis: This is a multicenter randomised sham-controlled trial. A total of 216 patients with chronic sciatica will be enrolled and randomly assigned to the acupuncture or sham acupuncture group. There will be 10 treatment sessions applied in 4 weeks with frequency decreased over time. Patients will complete follow-ups during 52 weeks. The primary outcomes are changes in leg pain intensity and disability from baseline to week 4. Secondary outcomes include back pain intensity, frequency and bothersomeness, quality of life, and global perceived effect. Adverse events will be recorded in detail., Ethics and Dissemination: Ethical approval of this trial was granted from the ethics committee of Beijing University of Chinese Medicine and all study centres (No. 2020BZYLL0803). Written informed consent will be obtained from enrolled patients. Trial results will be disseminated in peer-reviewed publications., Trial Registration Number: ChiCTR2100044585 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 24 March 2021); preresults., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Metabolic syndrome (MS) is a clinical syndrome with multiple metabolic disorders. As the diagnostic criteria for MS still lacking of imaging laboratory method, this study aimed to explore the differences between healthy people and MS patients through infrared thermography (IRT). However, the observation region of the IRT image is uncertain, and the research tried to solve this problem with the help of knowledge mining technology. 43 MS participants were randomly included through a cross-sectional method, and 43 healthy participants were recruited through number matching. The IRT image of each participant was segmented into the region of interest (ROI) through the preprocessing method proposed in this research, and then the ROI features were granulated by the K-means algorithm to generate the formal background, and finally, the two formal background were separately built into a knowledge graph through the knowledge mining method based on the attribute partial order structure. The baseline data shows that there is no difference in age, gender, and height between the two groups (P > 0.05). The image preprocessing method can segment the IRT image into 18 ROI. Through the K-means method, each group of data can be separately established with a 43 × 36 formal background and generated a knowledge graph. It can be found through knowledge mining and independent-samples T test that the average temperature and maximum temperature difference between the chest and face of the two groups are statistically different (P < 0.01). IRT could reflect the difference between healthy people and MS people. The measurement regions were found by the method of knowledge mining on the premise of unknown. The method proposed in this paper may add a new imaging method for MS laboratory examinations, and at the same time, through knowledge mining, it can also expand a new idea for clinical research of IRT., (© 2022. The Author(s).)

The process of intervertebral disc degeneration (IVDD) is complex, and its mechanism is considered multifactorial. Apoptosis of oxidative stressed nucleus pulposus cells (NPCs) should be a fundamental element in the pathogenesis of IVDD. In our pilot study, we found that the expression of MAT2A decreased, and METTL16 increased in the degenerative nucleus pulposus tissues. Previous studies have shown that the balance of splicing, maturation, and degradation of MAT2A pre-mRNA is regulated by METTL16 m 6 A modification. In the current study, we aimed to figure out whether this mechanism was involved in the aberrant apoptosis of NPCs and IVDD. Human NPCs were isolated and cultured under oxidative stress. An IVDD animal model was established. It showed that significantly higher METTL16 expression and lower MAT2A expression were seen in either the NPCs under oxidative stress or the degenerative discs of the animal model. MAT2A was inhibited with siRNA in vitro or cycloleucine in vivo . METTL16 was overexpressed with lentivirus in vitro or in vivo . Downregulation of MAT2A or upregulation of METTL16 aggravated nucleus pulposus cell apoptosis and disc disorganization. The balance of splicing, maturation, and degradation of MAT2A pre-mRNA was significantly inclined to degradation in the NPCs with the overexpression of METTL16. Increased apoptosis of NPCs under oxidative stress could be rescued by reducing the expression of METTL16 using siRNA with more maturation of MAT2A pre-mRNA. Collectively, oxidative stress aggravates apoptosis of NPCs through disrupting the balance of splicing, maturation, and degradation of MAT2A pre-mRNA, which is m 6 A modified by METTL16., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Peng-Bo Chen et al.)

Background: Constipation is known as a common adverse effect of antipsychotics. Advice for its management remains inadequate. This study is designed to investigate the efficacy and safety of electro-acupuncture (EA) for antipsychotic-related constipation., Methods: This is a single-centric, parallel-group, randomized controlled trial with blinded participants, outcome assessor, and statistician. One hundred twelve participants will be randomly assigned into the EA group or sham acupuncture (SA) group in a 1:1 ratio. The study will last for 22 weeks for each participant, including a 2-week baseline assessment period, an 8-week treatment period, and a follow-up for 12 weeks. The primary outcome is the change of mean weekly complete spontaneous bowel movements (CSBMs) during weeks 1 to 8 from baseline. Secondary outcomes include the change from baseline of mean weekly CSBMs during the follow-up period, mean weekly spontaneous bowel movements (SBMs), overall CSBM response rate, scores on Bristol Stool Form Scale (BSFS), straining level, Patient Assessment of Constipation Symptoms (PAC-SYM), Patient Assessment of Constipation Quality of life questionnaire (PAC-QOL), and Brief Psychiatric Rating Scale (BPRS). Adverse events and medicine use will be recorded as well., Discussion: The study is designed based on a rigorous methodology to evaluate the efficacy and safety of EA for antipsychotic-related constipation. The finding will be published in peer-reviewed journals as reliable evidence., Trial Registration: ClinicalTrials.gov ChiCTR2000032582. Registered May 3, 2020, with the Chinese Clinical Trial Registry., (© 2021. The Author(s).)

A close relationship between knee osteoarthritis (KOA) and gut microbiota has recently been described. Herein, we aim to investigate the effect of electroacupuncture (EA) on gut microbiota in participants with KOA. We conducted a study of 60 participants with KOA and 30 matched healthy controls (HCs). Sixty participants were allocated to either EA group (n=30) or sham acupuncture (SA) group (n=30). Five obligatory acupoints and three adjunct acupoints were punctured in the EA group. Eight non-acupoints that were separated from conventional acupoints or meridians were used for the SA group. Participants in both groups received 24 sessions within eight weeks. Fecal microbial analyses by 16S ribosomal RNA gene sequencing were carried out after collecting stools at T 0 and T 8 weeks (Four samples with changed defecation habits were excluded). The results showed that both Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score ( P= 0.043) and NRS score ( P= 0.002) decreased more in EA group than those in SA group. Moreover, EA could reverse more KOA-related bacteria including Bacteroides , [Eubacterium]&#95;hallii&#95;group , Agathobacte r and Streptococcus . The number of significantly different genera between KOA patients and HCs were less after EA treatment than that after SA treatment. This meant that EA modified the composition of the gut microbiome, making it closer to healthy people, while not significantly affecting the microbial diversity. Two genera including Agathobacter ( P =0.0163), Lachnoclostridium ( P =0.0144) were statistically increased than baseline in EA group (paired Wilcoxon rank sum test). After EA treatment, Bacteroides ( P= 0.0394) was more abundant and Streptococcus ( P= 0.0306) was significantly reduced in patients who demonstrated adequate response than in those with inadequate response (Wilcoxon rank-sum test). Spearman correlation test between gut microbe and KOA clinical outcomes indicated that Bacteroides and Agathobacter was negatively correlated with NRS score, WOMAC total score, and WOMAC pain, stiffness and pain scores ( P <0.001 or 0.05 or 0.01), while Streptococcus was positively correlated with them ( P <0.05 or 0.01). Our study suggests that EA contributes to the improvement of KOA and gut microbiota could be a potential therapeutic target., 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 © 2021 Wang, Li, Tan, Yang, Shi, Wang, Hu, Liu, Wang, Wang, Yuan, Jia, Li, Wang, Wu, Tu and Liu.)

Background: Current evidence suggests that acupuncture is an effective adjunctive therapy that can bring potential benefits to patients with cardiac arrhythmias. However, there are relevant gaps in the optimal therapeutic strategy, which may cause uncertainties on the best practice of acupuncture treatment for arrhythmia. We aim to develop consensus-based recommendations for clinical guidance on acupuncture treatment of cardiac arrhythmias., Methods: A multidisciplinary panel of specialists was invited to participate in a two-round semi-open clinical issue investigation. Meanwhile, relevant literature reviews were searched in 3 databases to provide evidence. Subsequently, an initial consensus voting list on acupuncture as an adjunctive therapy for cardiac arrhythmias was derived from the clinical investigation and literature review. Finally, 30 authoritative experts reached a consensus on the key issues of the voting list by a three-round modified Delphi survey. Consensus was defined when >80% agreement was achieved., Results: Following the three-round Delphi survey, there were 32 items (91.43%) finally reaching consensus, including the following 5 domains: (I) the benefits of acupuncture for the appropriate population; (II) the general therapeutic principle; (III) the acupuncture strategy; (IV) the relevant adverse events; (V) others., Conclusions: Consensus was achieved on some key elements. Given the lack of guidelines and the substantial heterogeneity of previous studies, these recommendations are of value in providing guidance for clinical practice of acupuncturists and in assisting patients with arrhythmia to obtain standardized acupuncture treatment. It also pointed out some problems that need to be carefully explored in future studies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/cdt-21-201). The authors have no conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

The aim of this trial was to evaluate the feasibility and effect of home-based transcutaneous electrical acupoint stimulation (TEAS) in patients with hypertension. In this randomized pilot trial, patients with hypertension were randomly assigned to the TEAS group or the usual care group. Participants in the usual care group were instructed to continue taking their antihypertensive drugs and received education on lifestyle modifications. In addition, participants in the TEAS group received 4 weekly sessions of noninvasive acupoint stimulation for 12 weeks at home. The primary outcome was the change in office systolic blood pressure at week 12 from baseline. Withdrawal from the study and adverse events associated with TEAS were also recorded. Sixty patients were randomized, with 30 patients in the TEAS group, of whom 1 was lost at week 36, and 30 patients in the usual care group, of whom 3 were lost by week 12. The reduction in systolic blood pressure at week 12 was greater in the TEAS group (-8.53 mm Hg; 95% CI [-13.37, -3.70 mm Hg]) than in the usual care group (-1.70 mm Hg; 95% CI [-4.29, -0.89 mm Hg]), with a between-group difference of -6.83 mm Hg (95% CI, [-12.23, -1.43 mm Hg]; P = 0.014). No TEAS-related adverse events occurred. In conclusion, home-based TEAS added to usual care for patients with hypertension was acceptable and safe and may be a potential treatment option. A larger randomized controlled trial of this intervention is warranted., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Acute renal colic caused by urinary calculi (ARCUC) has a considerable impact on the quality of life. Acupuncture might be a potential treatment option. However, the evidence is limited. We will conduct this trial to evaluate the efficacy and safety of acupuncture as adjunctive treatment to diclofenac for ARCUC., Methods/design: A total of 80 eligible patients who are diagnosed with urinary stone renal colic will be randomly allocated to the acupuncture group or the sham acupuncture group. Each patient will receive 1 session of acupuncture or sham acupuncture. The primary outcome will be the response rate of patients achieving a reduction of > 50% on visual analog score (VAS) from baseline to 10 min after treatment. Secondary outcomes will include the VAS, remedial analgesia, re-visit and admission rate, blinding assessment, credibility and expectancy, and adverse event. All patients who receive randomization will be included in the intent-to-treat analysis., Discussion: The finding of this trial will provide evidence on the efficacy and safety of acupuncture for the treatment of ARCUC. The results of this study will be published in peer-reviewed journals., Trial Registration: ClinicalTrials.gov ChiCTR 1900025202 . Registered on August 16, 2019., (© 2021. The Author(s).)

Backgrounds: Diabetic nephropathy (DN) is one of the most important clinical complications of diabetes mellitus (DM) and is the most common cause of end-stage renal disease. Currently, there is no highly effective medicine that can prevent, halt, or reverse the progressive course of DN. Initial clinical data showed that Tripterygium glycosides (TGs), a traditional Chinese medicine, can decrease proteinuria in patients with DN., Objectives: The objective of the present study is to investigate the efficacy and safety of TGs for the treatment of DN through meta-analysis of randomized controlled trials (RCTs)., Methods: All RCTs of TGs for DN were collected from The China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, Wanfang Data, Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP) by setting the study inclusion and elimination standards. Two reviewers evaluated the quality of the trials and extracted the data independently. RevMan 5.4 software was used for meta-analyses. The primary outcome was a change in 24-hours urinary total protein (24 h TUP)., Results: 26 RCTs with 1824 participants were identified. Studies were assessed using the Cochrane risk of bias tool. The overall effects showed that TGs was compared with the controls, TGs showed significant effects in reducing 24 h TUP [WMD = -0.84, 95 % CI (-1.09, -0.59)], elevating serum albumin [WMD = 2.88, 95 % CI (1.87, 3.90)], and the total efficiency [OR = 4.08, 95 % CI (2.37, 7.04)]. This effect was consistent across the subgroups of period of intervention., Conclusions: The present research showed that TGs was significantly associated with improvement of renal function in patients with DN. TGs offers a novel approach to the treatment of DN, more high-quality RCTs are needed for a better understanding of the role of TGs in DN therapy., (© 2021. The Author(s).)

Background: Acupuncture has been widely utilized for irritable bowel syndrome (IBS). However, heterogeneity is large among therapeutic strategies and protocols. The aim of this study was to propose some down-to-earth recommendations and establish an optimized protocol for acupuncture practice in IBS., Methods: A panel of 74 traditional Chinese medicine (TCM) acupuncturists participated in clinical issue investigation. Subsequently, systematic reviews concerning acupuncture for IBS were screened within 3 databases. An initial consensus questionnaire was formed from the results of clinical issue investigation and literature review. Ultimately, a Delphi vote was carried out to determine these issues. 30 authoritative experts with extensive experience were requested to respond with agreement, neutrality, or disagreement for the items. Consensus achievement on a given item was defined as greater than 80% agreement., Results: Following a 2-round Delphi survey, there were 19 items reaching consensus; of which 5 items (26.32%) achieved thorough consensus, and significant agreement was reached for the other 14 items. These items can be classified into the 3 major domains: 1) clinical outcomes that acupuncture can bring for favorable intervention population (5 items), 2) suitable therapeutic principles and parameters of acupuncture (13 items), 3) possible adverse events in the treatment (1 item)., Conclusion: Without any ready-made guidelines and lacking of homogeneity in the published literatures, such expert consensus could be valuable for TCM acupuncturists in daily practice and patients with IBS to obtain appropriate and standardized acupuncture treatment. In addition, it also points out the clinical focus which need to be further explored in future trials., (© 2021 Published by Elsevier B.V. on behalf of Korea Institute of Oriental Medicine.)

Background: Sympathetic activation leads to elevated blood pressure. Neuronal nitric oxide synthase (nNOS) inhibits sympathetic nervous system activity, thereby decreasing blood pressure (BP). nNOS is highly expressed in the arcuate nucleus (ARC) and ventrolateral periaqueductal gray (vlPAG), which play essential roles in the regulation of the cardiovascular and sympathetic nervous systems., Objective: This study was designed to verify the hypothesis that acupuncture exerts an antihypertensive effect via increasing the expression of nNOS in ARC and vlPAG of spontaneously hypertensive (SHR) rats., Methods: Rats without anesthesia were subject to daily acupuncture for 2 weeks. BP was monitored by the tail-cuff method. nNOS expressions in the ARC and vlPAG were detected by western blot and immunofluorescence. BP was measured after 7-Nitroindazole (7-NI), a specific nNOS inhibitor, was microinjected into ARC or vlPAG in SHR rats treated with acupuncture., Results: Acupuncture for 14 days significantly attenuated BP, and the Taichong (LR3) acupoint was superior to Zusanli (ST36) and Fengchi (GB20) in lowering BP. In addition, acupuncture at Taichong (LR3) induced an increase of nNOS expression in ARC and vlPAG, whereas microinjection of 7-NI into ARC or vlPAG reversed the antihypertensive effect of acupuncture., Conclusions: This study indicates that acupuncture at Taichong (LR3) induces a better antihypertensive effect than at Zusanli (ST36) or at Fengchi (GB20) in SHR rats, and enhancement of nNOS in ARC and vlPAG probably contributes to the antihypertensive effect of acupuncture., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Lu Wang et al.)

Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal diseases. Although acupuncture has become a common alternative therapy for IBS, there is insufficient evidence for its effectiveness. This study was designed to assess the efficacy and feasibility of acupuncture in the treatment of IBS., Methods/design: This is a multicenter randomized controlled clinical trial. According to the ratio of 1:1:1, 90 patients with irritable bowel syndrome will be randomly divided into specific acupoints (SA) group, non-specific acupoints (NSA) group, and non-acupoints (NA) group. All patients will be treated with acupuncture 12 times within 4 weeks and followed up for 8 weeks. The primary outcome is the response rate, the percentage of patients whose average value of worst abdominal pain is 30% better and the days of loose stool is 50% less than the baseline, at week 4 after randomization. The secondary outcomes include the response rates at other time points, IBS Symptom Severity Scale (IBS-SSS), Patient Health Questionnaire-9 depression scale (PHQ-9), IBS-Quality of Life scale (IBS-QOL), IBS Adequate Relief (IBS-AR), Abdominal Pain Score, Abdominal Bloating Score, Bristol Stool Score (BBS), blinding assessment, and credibility evaluation. Adverse events will be monitored and recorded during the trial., Trial Registration: Chictr.org.cn ChiCTR2000030670. Registered on 9 March 2020.

Objective: To assess the efficacy of intensive acupuncture (3 times weekly for 8 weeks) versus sham acupuncture for knee osteoarthritis (OA)., Methods: In this multicenter, randomized, sham-controlled trial, patients with knee OA were randomly assigned to receive electroacupuncture (EA), manual acupuncture (MA), or sham acupuncture (SA) 3 times weekly for 8 weeks. Participants, outcome assessors, and statisticians were blinded with regard to treatment group assignment. The primary outcome measure was response rate, which is the proportion of participants who simultaneously achieved minimal clinically important improvement in pain and function by week 8. The primary analysis was conducted using a Z test for proportions in the modified intent-to-treat population, which included all randomized participants who had ≥1 post-baseline measurement., Results: Of the 480 participants recruited in the trial, 442 were evaluated for efficacy. The response rates at week 8 were 60.3% (91 of 151), 58.6% (85 of 145), and 47.3% (69 of 146) in the EA, MA, and SA groups, respectively. The between-group differences were 13.0% (97.5% confidence interval [97.5% CI] 0.2%, 25.9%; P = 0.0234) for EA versus SA and 11.3% (97.5% CI -1.6%, 24.4%; P = 0.0507) for MA versus SA. The response rates in the EA and MA groups were both significantly higher than those in the SA group at weeks 16 and 26., Conclusion: Among patients with knee OA, intensive EA resulted in less pain and better function at week 8, compared with SA, and these effects persisted though week 26. Intensive MA had no benefit for knee OA at week 8, although it showed benefits during follow-up., (© 2020, American College of Rheumatology.)

Inflammatory cytokines produced by muscularis macrophages largely contribute to the pathological signs of postoperative ileus (POI). Electroacupuncture (EA) can suppress inflammation, mainly or partly via activation of vagal efferent. The goal of this study was to investigate the mechanisms by which EA stimulation at an hindlimb region ameliorates inflammation in POI. Methods: Intestinal motility and inflammation were examined after 24 h after intestinal manipulation (IM)-induced POI in mice. Local immune response in the intestinal muscularis, expression of macrophages, α7 nicotinic acetylcholine receptor (α7nAChR), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were determined by flow cytometry, Western Blot, qPCR and immunofluorescence. The effects of α7nAChR antagonists (methyllycaconitine and α-bungarotoxin) and JAK2/STAT3 inhibitors (AG490 and WP1066) were also administered in a subset of mice prior to EA. In the parasympathetic pathways, intestinal motility and inflammation were determined after cervical vagotomy and sub-diaphragmatic vagotomy. The expression of gamma absorptiometry aminobutyric acid (GABA A ) receptor in dorsal motor nucleus of vagal (DMV) cholinergic neurons was assessed by immunofluorescence and the response to DMV microinjection of bicuculine (antagonist of GABA A receptor) or muscimol (agonist of GABA A receptor) were assessed. Results: EA suppressed intestinal inflammation and promoted gastrointestinal motility. Mechanistically, EA activated the α7nAChR-mediated JAK2/STAT3 signaling pathway in macrophages which reduced the production of inflammatory cytokines. Furthermore, we also demonstrated that hindlimb region stimulation drove vagal efferent output by inhibiting the expression of GABA A receptor in DMV to ameliorate inflammation. Conclusions: The present study revealed that EA of hindlimb regions inhibited the expression of GABA A receptor in DMV neurons, whose excited vagal nerve, in turn suppressed IM-induced inflammation via activation of α7nAChR-mediated JAK2/STAT3 signaling pathway., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: High-normal blood pressure (BP) is associated with increased all-cause, cardiovascular mortality and frequently progresses to hypertension. Transcutaneous electrical acupoint stimulation (TEAS) might be a non-pharmaceutical therapy option to control BP. This trial aims to determine the effectiveness and safety of TEAS combined with lifestyle modification for high-normal BP., Methods/design: This prospective, randomized, and parallel clinical trial will be conducted in a community service center in China. Sixty participants with high-normal BP will be randomly allocated to receive TEAS plus lifestyle modification (intervention group) or lifestyle modification alone (control group) in a 1:1 ratio. In addition to lifestyle modification, the intervention group will receive TEAS at four acupoints for 30 min, 4 times weekly for 12 weeks for a total of 48 sessions at home. The control group will receive same lifestyle modification but no TEAS. The primary outcome will be the change in mean systolic blood pressure at 12 weeks from the baseline measurement. Secondary outcomes include the change of mean diastolic blood pressure, proportion of subjects with progression to hypertension, quality of life, body mass index, and waist circumference. Adverse events during the trial will be monitored., Discussion: This trial will explore the feasibility and provide potential evidence for the effectiveness and safety of TEAS plus lifestyle modification for high-normal BP. Furthermore, this pilot trial is being undertaken to determine the feasibility of a full scale definitive randomized controlled trial. The results of this study will be published in a peer-reviewed journal., Trial Registration: Chinese Clinical Trial Registry, ChiCTR 1900024982 . Registered on August 6, 2019.

Abstract: This study conducts a correlation exploration of CYP2C19 gene polymorphism and clopidogrel resistance in Han Chinese patients with cerebral infarction in Guizhou Region.A total of 270 Han Chinese patients with cerebral infarction, who were hospitalized in our hospital from January 2016 to January 2018, are selected. These patients were divided into 2 groups, clopidogrel resistance group (n = 60) and clopidogrel sensitive group (n = 210). According to the TEG results, the CYP2C19 gene polymorphism detection was carried out by using the PCR-RFLP method, while IL-6 level in the patient's blood was measured by using the ELISA method.The resistance group occupies 22.22%. The platelet inhibition ratio of the resistance group was 23 ± 7%, which was significantly lower than that of the sensitive group (65 ± 13%), and the difference was statistically significant (P < .05). The Logisitic regression analysis revealed that the history of diabetes, history of high blood pressure, increase in low density lipoprotein and CYP2C19 mutant gene were independent risk factors of clopidogrel resistance. After treatment, the serum IL-6 level of patients in the resistance group was 17.21 ± 0.98 ng/L, which was significant higher than that of patients in the sensitive group (11.21 ± 0.68 ng/L), and the difference was statistically significant (P < .05).Patients with cerebral infarction in Guizhou region have a higher occurrence rate of clopidogrel resistance. Clopidogrel resistance not only will weaken the anti-inflammatory action of the drug, but also correlates with the patient's CYP2C19 mutant gene and blood lipid level., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Accumulating evidence supports an association between chronic pain and psychological disorders, a connection that seems to be bidirectional. Treating both the pain and psychological conditions together is essential for effective treatment outcomes. Acupuncture is a somatosensory-guided mind-body therapy that can tackle the multidimensional nature of pain with fewer or no serious adverse effects. In this review, we discuss the use of acupuncture in some conditions with a high incidence of psychological disorders caused by chronic pain: headache, musculoskeletal pain, low back pain, and cancer pain, focusing on the effect and potential mechanisms of acupuncture. Overall clinical studies indicated that acupuncture might effectively contribute to management of psychological disorders caused by chronic pain. Mechanistic studies showed that acupuncture significantly alleviated such psychological disorders by regulating the activity of amygdala and insula, and regulating functional connectivity of insular and limbic regions/medial prefrontal cortex in humans and the corresponding animal models. In addition, 5-HT in the dorsal raphe nucleus, opioid receptors in the cingulate cortex, and plasma met-enkephalin are involved in acupuncture relief of pain and psychological symptoms. Substantial evidences from animal and human research support a beneficial effect of acupuncture in psychological disorders caused by chronic pain., 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 © 2021 Lin, Li, Yang, Hao, Yan, Wang, Yu, Shi and Liu.)

Background: Atrial fibrillation (AF) is a common arrhythmia, which is closely related to cardiovascular morbidity and mortality. Although acupuncture is used in the treatment of AF, the evidence is insufficient. The objective of this pilot trial is to evaluate the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after catheter ablation (CA)., Methods and Design: This will be a multi-center, 3-arm, pilot randomized controlled trial in China. Sixty patients in total will be randomly assigned to the specific acupoints group, the non-specific acupoints group, or the non-acupoints group in a 1:1:1 ratio. The whole study period is 6 months, including a 3-month treatment period and a 3-month follow-up period. All patients will receive 18 sessions of acupuncture over 12 weeks after CA and appropriate post-ablation routine treatment. The primary outcome is AF burden at 6 months after CA measured by electrocardiography patch that can carry out a 7-day continuous ambulatory electrocardiographic monitoring. The secondary outcomes include AF burden at 3  months after CA, recurrence of AF, quality of life, etc. The adverse events will also be recorded., Discussion: This pilot study will contribute to evaluating the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after CA. The results will be used for the sample size calculation of a subsequent large-scale trial., Trial Registration: Chinese Clinical Trial Registry ChiCTR2000030576 . Registered on 7 March 2020.

Background: Acupuncture is widely used for pain diseases while evidence of its efficacy for sciatica is insufficient. We aim to explore the feasibility and efficacy of acupuncture with different acupoint selecting strategies for sciatica induced by lumbar disc herniation., Methods: This is a multicenter, three-arm, patient-assessor-blinded randomized controlled pilot trial. Ninety patients will be assigned randomly into 3 groups including disease-affected meridians (DAM) group, non-affected meridians (NAM) group, and sham acupuncture (SA) group in a 1:1:1 ratio. The trial involves a 4-week treatment along with follow-up for 22 weeks. The primary outcome is the change of leg pain intensity measured by the visual analogue scale (VAS) from baseline to week 4 after randomization. Secondary outcomes include functional status, back pain intensity, and quality of life. Adverse events will also be recorded., Discussion: The results will inspire the optimal acupuncture strategy for sciatica and help establish a better design as well as power calculation for a full-scale study., Trial Registration: ChiCTR2000030680 (Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 9 March 2020).

Background: Current research evidence challenges clinical decision-making when acupuncture is taken into consideration in the treatment of cognitive impairment (CI). Aiming to provide some viable recommendations for acupuncture practitioners in dealing with actual clinic issues, an expert consensus study was conducted., Methods: A clinical question investigation among 47 acupuncturists yielded 24 initial items. Subsequently, systematic reviews on acupuncture for CI were searched within three online databases. A panel of 30 authoritative experts were requested to respond with agreement, neutrality, or disagreement for each item. Consensus establishment was defined as the percentage of agreement on a given item >80%., Results: Following a 2-round Delphi survey, there were 21 items reaching consensus and three items resulting in no consensus; of which 10 items reached 90∼100% agreement, and 80∼90% expert agreement was achieved for 11 items. These items could be roughly categorized into six domains: (1) therapeutic effects of acupuncture, (2) therapeutic principles, (3) acupoint selection and combination, (4) acupuncture parameters, (5) considerable combined therapies, and (6) possible adverse events., Conclusion: Without ready-made guidelines, this expert consensus may be conducive to guide acupuncturists in implementing clinical acupuncture practice for CI. Moreover, given the lack of high-quality research evidence and plenty of unresolved clinical issues in this field, it is of necessity to carry out more studies to better clarify the treatment algorithm., 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 © 2020 Su, Wang, Li, Zhang, Wang, Shi, Yang and Liu.)

This 16-week randomised controlled trial (8-week treatment followed by 8-week follow-up) evaluated the symptomatic improvement in patients with knee osteoarthritis on 3 sessions per week of acupuncture (TSWA) compared to 1 session per week of acupuncture (OSWA). Sixty participants were randomised to either the TSWA or the OSWA group in a 1:1 ratio. The primary outcome was response rate, defined as the percentage of participants achieving ≥2 points decrease on the numerical rating scale (NRS) and ≥6 points decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Additional outcomes included response rates at weeks 4 and 16, NRS, WOMAC, Patient Global Assessment, 12-item Short Form Health Survey (SF-12), and treatment credibility and expectancy. No significant difference was seen in response rate between TSWA and OSWA groups at week 8 (64.7% vs 50.0%; difference, 14.7 percentage points [95% CI, -10.1 to 39.4 percentage points], P = 0.435). At weeks 4 and 16, the TSWA group had higher response rates than the OSWA group (week-4: difference, 44.7 percentage points [95% CI, 23.2-66.1 percentage points], P = 0.001; week-16: difference, 46.0 percentage points [95% CI, 24.4-67.6 percentage points], P < 0.001). Participants in the TSWA group experienced significantly greater improvements in NRS, WOMAC function, and Patient Global Assessment than those in the OSWA group. There were no significant between-group differences in WOMAC stiffness and SF-12. In summary, TSWA immediately improved knee pain and dysfunction compared with OSWA. In addition, the benefit of TSWA persists throughout follow-up.

Background: Evidence for treating postprandial distress syndrome with acupuncture is limited., Aim: We aimed to evaluate the feasibility of verum acupuncture versus sham acupuncture in patients with postprandial distress syndrome., Methods: A total of 42 eligible patients were randomly allocated to either verum acupuncture or sham acupuncture groups in a 1:1 ratio. Each patient received 12 sessions over 4 weeks. The primary outcome was the response rate based on the overall treatment effect (OTE) 4 weeks after randomization. Secondary outcomes included dyspepsia symptom severity and adverse events., Results: In each group, 19 patients (91.5%) completed the study. Thirteen patients receiving verum acupuncture and seven patients receiving sham acupuncture were classified as responders according to OTE (61.9% vs 33.3%; rate difference 28.6%; p  = 0.06). Dyspepsia symptom severity at the end of treatment also differed significantly between verum acupuncture and sham acupuncture groups (5.9 units vs 3.7 units; between-group difference 2.2 (95% CI, 0.2-4.2); p  = 0.04). No serious adverse events occurred., Conclusion: Four weeks of acupuncture may represent a potential treatment for postprandial distress syndrome. The treatment protocol and outcome measures used in this trial were feasible. Since this was a pilot study, the efficacy of acupuncture still needs to be determined by a larger, adequately powered trial.