Background:Electroacupuncture (EA), with varying stimulation intensities, has demonstrated therapeutic potentials in both animal and clinical studies for the treatment of chronic obstructive pulmonary disease (COPD). However, a comprehensive investigation of the intensity-related effects, particularly 1mA and 3mA of EA, and the underlying mechanisms remains lacking.Methods:A COPD rat model was established by prolonged exposure to cigarette smoke and intermittent intratracheal instillation of lipopolysaccharide. EA treatment was administered at acupoints BL13 (Feishu) and ST36 (Zusanli), 20 minutes daily for 2 weeks, with intensities of 1mA and 3mA. EA effectiveness was evaluated by pulmonary function, histopathological change, serum level of inflammatory cytokines, and level of oxidative stress markers in serum and lung tissues. Transcriptome profiling and weighted gene co-expression network analysis (WGCNA) were performed to reveal gene expression patterns and identify hub genes. Real-time quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect the mRNA and protein expression levels, respectively.Results:EA at both 1mA and 3mA exerted differing therapeutic effects by improving lung function and reducing inflammation and oxidative stress in COPD rats. Transcriptome analysis revealed distinct expression patterns between the two groups, functionally corresponding to shared and intensity-specific (1mA and 3mA) enriched pathways. Eight candidate genes were identified, including Aqp9, Trem1, Mrc1, and Gpnmb that were downregulated by EA and upregulated in COPD. Notably, Msr1 and Slc26a4 exclusively downregulated in EA-1mA, while Pde3a and Bmp6 upregulated solely in EA-3mA. WGCNA constructed 5 key modules and elucidated the module-trait relationship, with the aforementioned 8 genes being highlighted. Additionally, their mRNA and protein levels were validated by RT-qPCR and WB.Conclusion:Our results demonstrated that 1mA and 3mA intensities induce distinct gene expression patterns at the transcriptional level, associated with shared and 1mA vs 3mA-specific enriched pathways. Genes Mrc1, Gpnmb, Trem1, and Aqp9 emerge as promising targets, and further studies are needed to elucidate their functional consequences in COPD.

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

Excessive inflammatory response following ischemic stroke (IS) injury is a key factor affecting the functional recovery of patients. The efferocytic clearance of apoptotic cells within ischemic brain tissue is a critical mechanism for mitigating inflammation, presenting a promising avenue for the treatment of ischemic stroke. However, the cellular and molecular mechanisms underlying efferocytosis in the brain after IS and its impact on brain injury and recovery are poorly understood. This study explored the roles of inflammation and efferocytosis in IS with bioinformatics. Three Gene Expression Omnibus Series (GSE) (GSE137482-3 m, GSE137482-18 m, and GSE30655) were obtained from NCBI (National Center for Biotechnology Information) and GEO (Gene Expression Omnibus). Differentially expressed genes (DEGs) were processed for GSEA (Gene Set Enrichment Analysis), GO (Gene Ontology Functional Enrichment Analysis), and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses. Efferocytosis-related genes were identified from the existing literature, following which the relationship between Differentially Expressed Genes (DEGs) and efferocytosis-related genes was examined. The single-cell dataset GSE174574 was employed to investigate the distinct expression profiles of efferocytosis-related genes. The identified hub genes were verified using the dataset of human brain and peripheral blood sample datasets GSE56267 and GSE122709. The dataset GSE215212 was used to predict competing endogenous RNA (ceRNA) network, and GSE231431 was applied to verify the expression of differential miRNAs. At last, the middle cerebral artery (MCAO) model was established to validate the efferocytosis process and the expression of hub genes. DEGs in two datasets were significantly enriched in pathways involved in inflammatory response and immunoregulation. Based on the least absolute shrinkage and selection operator (LASSO) analyses, we identified hub efferocytosis-related genes (Abca1, C1qc, Ptx3, Irf5, and Pros1) and key transcription factors (Stat5). The scRNA-seq analysis showed that these hub genes were mainly expressed in microglia and macrophages which are the main cells with efferocytosis function in the brain. We then identified miR-125b-5p as a therapeutic target of IS based on the ceRNA network. Finally, we validated the phagocytosis and clearance of dead cells by efferocytosis and the expression of hub gene Abca1 in MCAO mice models.

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

BACKGROUND:Long-term effects of individualized acupuncture in persons with chronic neck pain (CNP) remain unknown. OBJECTIVE:To evaluate the efficacy and safety of pressure pain, sensory-based individualized acupuncture for relieving CNP. DESIGN:A 24-week multicenter randomized controlled clinical trial. (ChiCTR1800016371). SETTING:Outpatient settings at 4 clinical centers in China from May 2018 to March 2020. PARTICIPANTS:716 participants with CNP. INTERVENTION:Participants were randomly assigned to a waiting list (WL) group or to 1 of 3 interventions, which consisted of 10 sessions over 4 weeks: higher sensitive acupoints (HSA), lower sensitive acupoints (LSA), and sham acupoints (SA) acupuncture groups. MEASUREMENTS:The primary outcome was the change in the visual analogue scale (VAS) score for neck pain (range, 0 to 100) from baseline to 4 weeks, with a difference of 10 points considered the minimum clinically important threshold. The VAS was also assessed every 4 weeks through 24 weeks. RESULTS:The modified intention-to-treat population included 683 participants. The mean baseline VAS was 50.36, 50.10, 49.24, and 49.16 for HSA, LSA, SA, and WL, respectively. Compared with a mean baseline to week 4 change of -12.16 in the HSA group, the mean changes were -10.19 in the LSA group (net difference [ND], -1.97 [95% CI, -5.03 to 1.09]), -6.11 in the SA group (ND, -6.05 [CI, -9.10 to -3.00]), and -2.24 in the WL group (ND, -9.93 [CI, -12.95 to -6.90]). The intervention effects persisted at 24-week follow-up. LIMITATION:Lack of complete blinding and limited generalizability. CONCLUSION:Individualized acupuncture interventions using high- or low-sensitivity acupuncture points were more effective in reducing CNP than SA and WL control groups sustained through 24 weeks, but the magnitude of relative improvement did not reach a minimal clinically important difference. PRIMARY FUNDING SOURCE:National Natural Science Foundation of China.

腧穴配伍作为针灸治疗的重要部分,也是精简处方的重要方法,然而目前在个体患者的处方中使用的腧穴数量与中医典籍记载中相比已增至数倍,腧穴配伍应用不足,用穴数量与疗效的关系仍有待广泛研究.笔者以阳陵泉穴为引,围绕痛证、痹证等针灸优势病种,论证针对单一病症,精简用穴也能达到相同的治疗效果.笔者随师侍诊总结老师经验,发现临床中结合患者体质、耐受度等因素应用不同学说拓展腧穴配伍;选用具备多重功能的腧穴等均有助于针灸处方的精简.本文倡导,在稳固临床疗效的同时,应进一步深入拓展腧穴配伍的研究,精简用穴,避免腧穴滥用.

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

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

Myocardial ischemia(Ml)is a common disease with high mortality and morbidity worldwide.Since the pathological process of Ml is very complicated,a comprehensive un-derstanding of its pathogenesis is the key to the treatment of MI.As chromatin plays a crucial role in regulating gene expression,and gene regulation is a fundamental process in developing and disease progression,combined analysis of the chromatin and gene can further reveal the pathological mechanism of MI.

目的:观察针刺对慢性偏头痛大鼠(CM)的足底机械痛阈、三叉神经脊束核尾侧亚核(Sp5 C)中趋化因子C-C配体2(CCL2)、C-X-C基序配体1(CXCL1)水平的影响,为临床运用针灸治疗偏头痛提供一定依据.方法:将28只大鼠随机分为对照组、模型组、针刺组、非经非穴组,每组7只.采用隔日颈背部皮下重复注射硝酸甘油(NTG)建立慢性偏头痛大鼠模型.每日对针刺组和非经非穴组进行针刺治疗,20 min/次.采用Von Frey仪器测定大鼠足底机械痛阈,采用酶联免疫吸附测定法检测各组Sp5 C中CCL2、CXCL1的水平.结果:与对照组比较,模型组大鼠足底机械痛阈明显降低(P<0.01);与模型组比较,针刺组大鼠足底机械痛阈明显升高(P<0.01).与对照组比较,模型组的Sp5 C中CCL2、CXCL1的水平升高(P<0.01);针刺组较模型组CCL2、CXCL1的水平降低(P<0.01).结论:针刺可以通过下调CCL2、CXCL1趋化因子的表达,从而减轻偏头痛的疼痛程度,发挥对偏头痛的治疗作用.

MicroRNA(miRNA),即非编码小RNA,是一种已知的调节动物和植物必需的生物过程.经筋病是指由于气血运行失常而导致经络循行部位出现的各种病理表现.目前已有大量研究发现,miRNA与经络病的关系密切,其异常表达可以导致病理现象的发生发展,同时调控miRNA的表达又可以起到延缓疾病发展以及治疗作用.根据文献资料,整理出不同经络病与miRNA的关系,以期对临床诊断疾病及治疗疾病有所帮助.

目的:采用随机森林算法构建膝骨关节炎(KOA)患者犊鼻穴穴位敏化判别模型,以期为穴位是否敏化的判别及病情评估提供参考.方法:以916例KOA患者和222名健康受试者为研究对象,采集犊鼻穴体表温度、机械痛阈以及压痛阈的数据,运用SPSS 24.0软件进行数据分析,采用Python软件随机森林算法对犊鼻穴穴位敏化数据构建穴位敏化判别模型.结果:与健康受试者比较,KOA患者犊鼻穴温度显著升高、机械痛阈和压痛阈显著降低(P＜0.01);穴位敏化判别模型能很好区分KOA患者与健康人(准确率77.85％),其中影像学3级(准确率82.76％)和临床3期(准确率88.37％)KOA患者区分效果最好.结论:穴位敏化判别模型可为穴位是否发生敏化的判别以及病情评估提供参考.

OBJECTIVE:To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion.METHODS:In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint.RESULTS:Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients.CONCLUSION:It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.

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

Background: The number of systematic reviews or meta-analyses (SRs/MAs) on the effectiveness of acupuncture for angina pectoris (AP) is increasing. Due to the inconsistent conclusions and unknown quality of these SRs/MAs, this overview aimed to systematically evaluate and synthesize the existing SRs/MAs, attempting to provide more reliable evidence for the effectiveness and safety of acupuncture in the treatment of AP. Methods: SRs/MAs were searched via eight databases from inception to March 14, 2022. The risk of bias was evaluated using the Risk of Bias in Systematic reviews (ROBIS) tool. The quality of the methodology, reporting, and evidence were assessed by the Assess Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Item for Systematic Review and Meta-analysis for Acupuncture (PRISMA-A), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, respectively. Results: Sixteen SRs/MAs were included and fifteen SRs/MAs were considered being of critically low quality according to AMSTAR-2. Only three SRs/MAs were rated at low risk of bias. No study reported all the items listed in the PRISMA-A checklist. No high-quality evidence with GRADE assessment was found. With the low-quality evidence, acupuncture combined with other interventions was superior to monotherapy (medications or Chinese medicine) in the angina symptom and electrocardiogram recovery. No adverse effects owing to acupuncture were reported. Conclusions: Owing to the lack of high-quality evidence provided by the current SRs/MAs, the effectiveness of acupuncture for AP still warrants further proof. Further researches with more critical design and methodology are needed for providing more convincing evidence. Registration: This review was registered at PROSPERO (www.crd.york.ac.uk/prospero/): CRD42021219367.

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

检索近5年来艾灸治疗腰椎间盘突出症的报道。艾灸治疗腰椎间盘突出症的方法众多，报道中多单纯采用艾灸温和灸和热敏灸，艾灸也常结合其他治疗方式。分析发现艾灸治疗腰椎间盘突出症的证型中以寒湿型和血瘀型为多。通过总结最新研究进展，寻求最佳治疗方式或结合治疗方式。

慢性偏头痛是世界上最普遍和最易致残的神经源性炎症性病症之一,严重影响患者生命质量,但其机制至今仍未十分明确.最新研究提示在中枢炎症疾病中存在"星形胶质细胞-小胶质细胞"串扰,是阐释发病和治疗机制的新靶点.前期机制研究初步发现了针刺治疗慢性偏头痛与其调控星形胶质细胞与小胶质细胞关系密切.现从最新的神经炎症性疾病研究前沿"星形胶质细胞-小胶质细胞"串扰出发,探讨将其引入针刺治疗慢性偏头痛机制研究中的可能性,以期为针刺慢性偏头痛提供新的科学思路.

Review question / Objective: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease characterized by persistent respiratory symptoms and progressive airflow obstruction documented on spirometry. Acupuncture, as a safe and economical non-pharmacology therapy, has pronounced therapeutic effects in COPD patients. Several systematic reviews draw the conclusion that acupuncture could improve patients’ quality of life, exercise capacity and dyspnoea, however, the results about lung function were inconclusive. Recently, increasing number of animal studies has been published to illustrate the effects of acupuncture in improving lung function in COPD animal model. However, the efficacy of acupuncture for experimentally induced COPD have not been systematically investigated yet. A systematic review of animal experiments can benefit future experimental designs, promote the conduct and report of basic researches and provide some guidance to translate the achievements of basic researches to clinical application in acupuncture for COPD. Therefore, we will conduct this systematic review and meta-analysis to evaluate effects of acupuncture on COPD animal model.

Background The pathological process of myocardial ischemia (MI) is very complicated. Acupuncture at PC6 has been proved to be effective against MI injury, but the mechanism remains unclear. This study investigated the mechanism that underlies the effect of acupuncture on MI through full-length transcriptome. Methods Adult male C57/BL6 mice were randomly divided into control, MI, and PC6 groups. Mice in MI and PC6 group generated MI model by ligating the left anterior descending (LAD) coronary artery. The samples were collected 5 days after acupuncture treatment. Results The results showed that treatment by acupuncture improved cardiac function, decreased myocardial infraction area, and reduced the levels of cTnT and cTnI. Based on full-length transcriptome sequencing, 5083 differential expression genes (DEGs) and 324 DEGs were identified in the MI group and PC6 group, respectively. These genes regulated by acupuncture were mainly enriched in the inflammatory response pathway. Alternative splicing (AS) is a post-transcriptional action that contributes to the diversity of protein. In all samples, 8237 AS events associated with 1994 genes were found. Some differential AS-involved genes were enriched in the pathway related to heart disease. We also identified 602 new genes, 4 of which may the novel targets of acupuncture in MI. Conclusions Our findings suggest that the effect of acupuncture on MI may be based on the multi-level regulation of the transcriptome.