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Both microRNAs (miRNAs) and purinergic signalling are widely and respectively expressed in various tissues of different organisms and play vital roles in a variety of physiological and pathological processes. Here, we reviewed the current publications contributed to the relationship of miRNAs and purinergic signalling in cardiovascular diseases, gastrointestinal diseases, neurological diseases, and ophthalmic diseases. We tried to decode the miRNAs-purinergic signalling network of purinergic signalling involved diseases. The evidence indicated that more than 30 miRNAs (miR-22, miR-30, miR-146, miR-150, miR-155, miR-187, etc.) directly or indirectly modulate P1 receptors (A1, A2A, A2B, A3), P2 receptors (P2X1, P2X3, P2X4, P2X7, P2Y2, P2Y6, P2Y12), and ecto-enzymes (CD39, CD73, ADA2); P2X7 and CD73 could be modulated by multiple miRNAs (P2X7: miR-21, miR-22, miR-30, miR-135a, miR-150, miR-186, miR-187, miR-216b; CD73: miR-141, miR-101, miR-193b, miR-340, miR-187, miR-30, miR-422a); miR-187 would be the common miRNA to modulate P2X7 and CD73.

Acupuncture point specificity has been recognized as a key scientific issue in traditional Chinese medicine (TCM), but there is limited clinical trial or animal study to verify the characteristics of PC6, BL15, and ST36 in the protection from myocardial injury. We aimed to compare the effects among these three acupoints on the acute myocardial infarction mice model and to explore possible mechanisms for the first time. We found that PC6 is the most appropriate acupoint to deliver efficacy and safety to treat acute MI in mice. BL15 stimulation improved the systolic function, but increased the risk of arrhythmia. ST36 only slightly attenuated systolic function and had no effect on arrhythmia during MI. RNA profiles of skin tissue in local acupoints demonstrated that the most altered DEGs and related pathways may partly support its best effects of PC6 treatment on MI injury, and support the observed phenomenon of the acupoint specificity. Graphical abstract

It is unclear how Toll-like receptor (TLR) 4 signaling affects protein succinylation in the brain after intracerebral hemorrhage (ICH). Here, we constructed a mouse ICH model to investigate the changes in ICH-associated brain protein succinylation, following a treatment with a TLR4 antagonist, TAK242, using a high-resolution mass spectrometry-based, quantitative succinyllysine proteomics approach. We characterized the prevalence of approximately 6700 succinylation events and quantified approximately 3500 sites, highlighting 139 succinyllysine site changes in 40 pathways. Further analysis showed that TAK242 treatment induced an increase of 29 succinyllysine sites on 28 succinylated proteins and a reduction of 24 succinyllysine sites on 23 succinylated proteins in the ICH brains. TAK242 treatment induced both protein hypersuccinylations and hyposuccinylations, which were mainly located in the mitochondria and cytoplasm. GO analysis showed that TAK242 treatment-induced changes in the ICH-associated succinylated proteins were mostly located in synapses, membranes and vesicles, and enriched in many cellular functions/compartments, such as metabolism, synapse, and myelin. KEGG analysis showed that TAK242-induced hyposuccinylation was mainly linked to fatty acid metabolism, including elongation and degradation. Moreover, a combined analysis of the succinylproteomic data with previously published transcriptome data revealed that most of the differentially succinylated proteins induced by TAK242 treatment were mainly distributed throughout neurons, astrocytes, and endothelial cells, and the mRNAs of seven and three succinylated proteins were highly expressed in neurons and astrocytes, respectively. In conclusion, we revealed that several TLR4 signaling pathways affect the succinylation processes and pathways in mouse ICH brains, providing new insights on the ICH pathophysiological processes. Data are available via ProteomeXchange with identifier PXD025622.

Purines and their derivatives, most notably adenosine and ATP, are the key molecules controlling intracellular energy homoeostasis and nucleotide synthesis. Besides, these purines support, as chemical messengers, purinergic transmission throughout tissues and species. Purines act as endogenous ligands that bind to and activate plasmalemmal purinoceptors, which mediate extracellular communication referred to as “purinergic signalling”. Purinergic signalling is cross-linked with other transmitter networks to coordinate numerous aspects of cell behaviour such as proliferation, differentiation, migration, apoptosis and other physiological processes critical for the proper function of organisms. Pathological deregulation of purinergic signalling contributes to various diseases including neurodegeneration, rheumatic immune diseases, inflammation, and cancer. Particularly, gout is one of the most prevalent purine-related disease caused by purine metabolism disorder and consequent hyperuricemia. Compelling evidence indicates that purinoceptors are potential therapeutic targets, with specific purinergic agonists and antagonists demonstrating prominent therapeutic potential. Furthermore, dietary and herbal interventions help to restore and balance purine metabolism, thus addressing the importance of a healthy lifestyle in the prevention and relief of human disorders. Profound understanding of molecular mechanisms of purinergic signalling provides new and exciting insights into the treatment of human diseases.

Manganese chloride (MnCl2) has been shown to inhibit the Yes-associated protein (YAP) in high-fat diet-fed ApoE−/− mice. Although YAP has been implicated in atherogenesis, there are limited data on the effects of MnCl2 on cardiac remodeling. In this study, we discovered, by electrocardiography, that hyperlipidemia led to spontaneous supraventricular arrhythmia (SVA) in ApoE−/− (KO) mice, with 3 of 9 KO + MnCl2 mice (33%) exhibiting lower incidence of spontaneous SVA than KO mice (6 of 10 mice, 60%). Echocardiography revealed that reduced systolic function in KO mice was reversed by MnCl2 treatment. Oil Red O staining of the aortas and biochemical analysis of lipid levels showed that MnCl2 inhibited plaque formation in a lipid metabolism-independent manner. MnCl2 inhibited inflammatory cell infiltration and reduced fibrosis, as evidenced by hematoxylin and eosin, immunohistochemical and Masson's trichrome staining, respectively. Our findings demonstrate that spontaneous SVA and reduced systolic function were blocked by MnCl2. Our findings show that MnCl2 was useful in delaying cardiac remodeling and reducing susceptibility to spontaneous SVA in a mouse model of hyperlipidemia.

Ulcerative Colitis (UC) is a chronic inflammation disease, and the incidence of UC is increasing recently. Both clinical trials and animal experiments show that moxibustion is a complementary and alternative treatment for UC. Previous studies showed that moxibustion can improve UC by regulating the balance of Tregs and Th17 (Sun et al., 2017). Treg cells is one subset of CD4[Formula: see text] T cells that exert the immunosuppressive function. CD39 and CD73, expressed on the surface of Tregs, hydrolyze ATP to AMP and are further involved in the immunosuppressive function of Tregs. In this study, we investigated the effect of moxibustion on CD39[Formula: see text] Tregs and CD73[Formula: see text] Tregs in dextran sulfate sodium (DSS) induced UC mice. The A2a receptor (A2aR), one of the targets of adenosine, was also detected. The results showed that moxibustion could increase the expression of CD39, CD73, and A2aR in colonic tissue and improve the proportion of CD39[Formula: see text] Tregs and CD73[Formula: see text] Tregs in peripheral blood, inguinal draining lymph nodes and spleen in the UC model. Additionally, A2aR agonists enhanced the cell viability of colonic epithelial cells and inhibit the production of cytokines IL-6 and TNF-[Formula: see text] in vitro, which may further influence the pathway of ATP purine signal metabolism and alleviates the gut inflammation of UC mice. Taken together, this study provides supplemental evidence to reveal the immune related mechanism of moxibustion in the treatment of UC.

This review summarizes experimental evidence indicating that purinergic mechanisms are causally involved in acupuncture (AP)-induced analgesia. Electroacupuncture (EAP) and manual AP release at pain-relevant acupoints ATP which may activate purinergic P2X receptors (Rs) especially of the P2X3 type situated at local sensory nerve endings (peripheral terminals of dorsal root ganglion [DRG] neurons); the central processes of these neurons are thought to inhibit via collaterals of ascending dorsal horn spinal cord neurons, pain-relevant pathways projecting to higher centers of the brain. In addition, during AP/EAP non-neuronal P2X4 and/or P2X7Rs localized at microglial cells of the CNS become activated at the spinal or supraspinal levels. In consequence, these microglia secrete bioactive compounds such as growth factors, cytokines, chemokines, reactive oxygen, and nitrogen species, which modulate the ascending neuronal pathways conducting painful stimuli. Alternatively, ATP released at acupoints by AP/EAP may be enzymatically degraded to adenosine, stimulating in loco presynaptic A1Rs exerting an inhibitory influence on the primary afferent fibers (the above mentioned pain-sensing peripheral terminals of DRG neurons) which thereby fail to conduct action potentials to the spinal cord dorsal horn. The net effect of the stimulation of P2X3, P2X4, P2X7, and A1Rs by the AP/EAP-induced release of ATP/adenosine at certain acupoints will be analgesia.

Background Rheumatoid arthritis (RA) is a refractory autoimmune disease characterized by chronic synovitis. Moxibustion is a natural therapy that possesses anti-inflammatory bioactivity. However, the anti-inflammatory mechanism of moxibustion for the treatment of RA has not yet been clarified. Macrophage infiltration is a prominent characteristic in the pathological process of RA synovitis. Objective The aim of the present research is to investigate the effect of moxibustion on the polarization of macrophage. Methods The rats' right hind paws were injected with freundʼs complete adjuvant (FCA) to establish the model of RA. Seven days after the injection of FCA, moxibustion therapy was performed on the acupoints of Shenshu (BL23) and Zusanli (ST36) once a day for three weeks. The Immunofluorescence, Western bolt and Elisa were used to analyze the influence of moxibustion on the expression of STAT1/miR-155/SOCS1 signaling pathway and macrophage's marker. Results We observed that moxibustion decreased the thickness of foot pad and arthritis scores. Moxibustion up-regulated the exression of Tim-3, promoted the polarization of macrophages to M2 type and inhibited the polarization of macrophages to M1 type. Treatment with moxibustion decreased the level of interleukin (IL)-23 and increased the level of IL-4, IL-10 and Argininase (Arg)-1. Moreover, moxibustion blocked the activation of STAT1/miR-155/SOCS1 signaling pathway and promoted the polarization of macrophages to M2 type. Furthermore, when Tim-3 was knocked down, the anti-inflammatory effect of moxibustion was reduced and the effect of regulating macrophage polarization was inhibited. Conclusion moxibustion may regulate the expression of related molecules in the STAT1/miR-155/SOCS1 signaling pathway through Tim-3, promote the polarization of macrophages M2, and exhibit anti-inflammatory effects.

IntroductionIrritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder that presents with abdominal pain/discomfort and altered bowel patterns. IBS has multiple potential causes for which conventional medicines have had limited success, resulting in a significant number of patients who do not sensitively respond to pharmacotherapy for a period of 12 months and who develop a continuing symptom profile (described as refractory IBS) and seek help through (non)pharmacological treatments. The aim of this study is to investigate the efficacy and safety of acupuncture therapy for refractory IBS on the basis of conventional treatments.Methods and analysisA total of 170 eligible patients who meet the Rome IV criteria for refractory IBS will be randomly allocated to receive acupuncture or sham acupuncture. Each patient will receive 12 sessions of acupuncture over 4 weeks and a 4-week follow-up. The primary outcome will be the IBS Symptom Severity Score. Secondary outcomes will include the proportion of participants experiencing adequate relief of global IBS symptoms, the weekly frequency of defecation, the stool properties assessed by the Bristol Grading Scale, the Work and Social Adjustment Scale, the IBS-Quality of Life score, and the Self-Rating Depression Scale and Self-Rating Anxiety Scale anxiety and depression scores. Outcome measures will be collected at baseline, 2 and 4 weeks of the intervention, and 6 and 8 weeks after the intervention. Categorical variables will be compared with Fisher’s exact test or the Wilcoxon rank-sum test, and continuous variables will be compared using Student’s t-test or the Wilcoxon rank-sum test.Ethics and disseminationThe entire project has been approved by the ethics committees of Beijing University of Chinese Medicine (2020BZYLL0507) and Sichuan Province Regional Institution for Conducting Research on Traditional Chinese Medicine (2020KL-025). The outcomes of the trial will be disseminated through peer-reviewed publications.Trial registration numberNCT04276961.

Objectives. To study the influence of electroacupuncture (EA) and moxibustion on the hippocampus astrocyte and microglia activation in the ulcerative colitis model and to evaluate the mitochondria activity. Methods. 2.5% dextran sodium sulfate-induced colitis mice were treated by EA or moxibustion. Intestinal pathological structure was observed by hematoxylin and eosin (H&E) staining; the expression of GFAP or S100b (markers for astrocyte), Iba-1 (a marker for microglia), and Mitofilin (a marker for mitochondria) in hippocampus was detected by immunofluorescence staining or western blot. Results. The results demonstrated that both EA and moxibustion could improve the morphology of distal colonic mucosal epithelia in DSS-induced colitis mice. Expression of GFAP in the hippocampus was significantly increased after EA or moxibustion treatment. The effects were further supported by WB results. Meanwhile, expression of mitofilin in the hippocampus CA1 and CA3 regions showed the same trend as that of GFAP. Expression of Iba-1 in the hippocampus showed no significant difference after EA or moxibustion treatment, while the state of microglia changed from resting in control mice to activated state in colitis mice. Conclusion. EA and moxibustion were able to modulate the activation of astrocyte, microglial, and mitochondria in the hippocampus area in the colitis model.

As part of traditional Chinese medicine, acupoints are considered a dynamic functional area, which can reflect the internal condition of the body. When the body is suffering from disease or injury, corresponding acupoints are believed to be activated and manifest in several sensitized forms, including expansion of the receptive field, pain sensitization, and heat sensitization. Such phenomena are believed to gradually disappear concomitantly with recovery from the disease. Acupoint states are therefore changeable according to health status, a phenomenon known as acupoint sensitization. This review aims to provide an overview of acupoint sensitization based on existing research results and determine priorities for future research. Systematic literature retrieval was conducted in Medline, Embase, Cochrane Library, CINAHL, and AMED from inception to 18 July 2018. Current evidence from research findings to date indicate that acupoint sensitization is based on neurogenic inflammation and that stimulation of sensitized acupoints presents a potential trend of generating a better clinical effect when compared with stimulation of unsensitized points.

Previous studies have confirmed that acupuncture and moxibustion is an effective way for treating ulcerative colitis (UC). However, the exact mechanism is unclear yet. In this study, DSS-induced UC mice were treated by electroacupuncture and moxibustion, and the genome of intestinal flora was subsequently detected by high-throughput sequencing in order to explore the detailed mechanism in terms of intestinal flora. The results indicated that the alpha diversity indices and beta diversity of intestinal flora were improved by electroacupuncture and moxibustion treatments, especially by the moxibustion treatment. These treatments inhibited Streptococcus, Odoribacter, and Allobaculum whereas it facilitated Lactobacillus on genus level. Further correlation analysis showed that the alpha diversity indices were positively correlated with the percentage of Treg cells in CD4+ cells but negatively correlated with the percentage of Th17 in CD4+ cells. These data indicated that both electroacupuncture and moxibustion can promote the intestinal flora diversity, providing a new view to understand the relationship between host and microbiome when using some external therapies.

Objective. The aim of this study was to investigate the difference of efficacy between conventional moxibustion (CM) and smoke-free moxibustion (SM) for patients with osteoarthritis of the knee (KOA). Methods. This is a multicentre, randomized, single blinded, parallel-group clinical trial. Patients with KOA were randomly allocated to CM group (69) and SM group (69) in 7 hospitals of China. Moxibustion treatment in 12 sessions over 4 weeks was administrated at 3 acupuncture points (EX-LE4, ST35, and ST36). Patients completed standard questionnaires at baseline and after 2 weeks, 4 weeks, 8 weeks, and 12 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) from the baseline to 4 weeks. The secondary outcomes include Visual Analogue Scale (VAS) and Patient Global Assessment score (PGA). Results. Analyses showed that the WOMAC score improved in pain (95% CI,-0.1[-1.2 to 0.9], p=0.76), stiffness (95% CI,-0.1 [-0.5 to 0.3], p=0.71), and function (95% CI, 2.2 [-1.3 to 5.8], p=0.22) compared between the two groups at 4 weeks, as well as the VAS score (95% CI,0.1 [-0.3 to 0.6], p=0.60). Similar results presented at 8 and 12 weeks. No statistically significant difference was observed between CM and SM groups for outcome measurements. Conclusions. It suggested that smoke generated during moxibustion treatment does not affect the efficacy of moxibustion in the treatment of KOA, which should be taken into account to be removed for the sake of reducing environmental pollution or moxa smoke exposure of acupuncturists or patients. This trial is registered with Clinical Trials.gov, NCT02772055.

Background Research on acetylation modification and its modification sites will be of great significance for revealing the mechanism of disease and developing new targeted medicines. In this study, we aim to construct a complete atlas of acetylome in the DSS-induced ulcerative colitis mice model (UC model) Methods A high-resolution mass spectrometry-based quantitative approach was employed to identify lysine-acetylated proteins and acetylation sites. Bioinformatics analysis and in vitro experiments verified anti-inflammatory effects of HSP90B1-K142ac. Results 2597 acetylation events and 1914 sites were quantified, highlighting 140 acetylation site changes in the colitis colon tissue. 91 acetylation sites in 75 proteins were up-regulated, and 49 acetylation sites in 39 proteins were down-regulated in the UC models. The differentially acetylated proteins mainly consisted of non-histone proteins located in the cytoplasm and mitochondria. KEGG and protein-protein interaction networks analysis showed that the differentially acetylated proteins were enriched in the TCA cycle, fatty acid metabolism, and protein processing in the endoplasmic reticulum. 68% of the differentially metabolized enzymes have a down-regulated trend in acetylation levels. The acetylation level of lysine 142 in HSP90B1 was found to be obvious in the UC colon, and point mutation of HSP90B1-K142ac would result in the decreasing secretion of TNF-α and IL-2 in LPS-stimulated cultured cells. Conclusion Our work built a complete atlas of acetylome and revealed the potential role of metabolic enzymes and heat shock proteins in DSS-induced colitis.

A newly-developed "Mouse Forelimb Fixator" and two types of "Batch Mice Moxibustion Device" on the basis of our "Mouse Safe and Fast Fixation Board" (developed in 2012) were introduced in the present paper. The Forelimb Fixator inserted into the base part of the apparatus in tenon and mortise style is used to control the mouse's posture with the forelimbs' acupoints fully exposed, and can realize simultaneous fixation of several mice at the same time. By using the mobility of the base of the single-hole moxibustion frame and the magnet, the distance between the acupoint surface and the tip of the ignited moxa stick can be accurately controlled, and several acupoints of different meridians can be simultaneously stimulated at the same time. Utilizing the porous transparent moxibustion board, the Batch Mice Moxibustion Device can meet the requirement of moxibustion at multiple acupoints at the same time. In addition, these devices are convenient in operation, innovative in creativity, save manpower and material resources, and help improve experimental efficiency and research on moxibustion.设计一种新型的小鼠固定器及两种穴位批量艾灸装置。小鼠固定器添加前肢固定片，可使小鼠保持前肢穴位充分暴露姿势；固定器榫卯式插入底座，实现多只小鼠同时固定。运用单孔艾灸架底座和磁铁的可移动性，精准调控穴位与灸距，对小鼠不同经脉腧穴进行艾灸；运用多孔透明艾灸板，可满足多个穴位同时艾灸。此小鼠固定器和两种艾灸装置操作方便，创意新颖，节省人力物力，有助于提高实验效率，推动艾灸实验研究。.

Purinergic signalling adenosine and its A1 receptors have been demonstrated to get involved in the mechanism of acupuncture (needling therapy) analgesia. However, whether purinergic signalling would be responsible for the local analgesic effect of moxibustion therapy, the predominant member in acupuncture family procedures also could trigger analgesic effect on pain diseases, it still remains unclear. In this study, we applied moxibustion to generate analgesic effect on complete Freund’s adjuvant (CFA)-induced inflammatory pain rats and detected the purine released from moxibustioned-acupoint by high-performance liquid chromatography (HPLC) approach. Intramuscular injection of ARL67156 into the acupoint Zusanli (ST36) to inhibit the breakdown of ATP showed the analgesic effect of moxibustion was increased while intramuscular injection of ATPase to speed up ATP hydrolysis caused a reduced moxibustion-induced analgesia. These data implied that purinergic ATP at the location of ST36 acupoint is a potentially beneficial factor for moxibustion-induced analgesia.

Combining the current development of material science and acupunctology, we propose a new concept of "acupuncture-material science" as the new branch of acupunctology. We also hold that this new branch may be in the future the important direction of acupuncture-moxibustion instrument innovation. The future carding and development of the connotations and epita-xial contents of this discipline, the classification, applied range, research and development of the materials, as well as the related standard formulation, etc. should be paid more attention and improved in order to make greater contribution to the inheritance and innovation of acupunctology in the new era.结合材料学与针灸学自身的发展，提出针灸材料学分支学科概念。针灸材料学可能是未来针灸工具革新的重要方向，需加强学科内涵、外延的进一步梳理和发展，加强针灸材料的分类、应用范围、研发及标准建设等工作，以针灸材料学的发展促进新时代针灸学科的传承和创新。.

The details of Toll-like receptor (TLR) 4 signaling affects protein succinylation in intracerebral hemorrhage (ICH) brains remains completely unclear. In this study, we constructed mice ICH models to investigate the changes in ICH-associated brain protein succinylation with the treatment of TLR4 antagonist, TAK242, using a high-resolution mass spectrometry-based, quantitative succinyllysine proteomics approach. We characterized a concentration of approximately 6700 succinylation events and quantified approximately 3500 sites, highlighting 139 succinyllysine site changes in 40 pathways. Further analysis showed that TAK242 treatment induced an increase in 29 succinyllysine sites of 28 succinylated proteins and reduction of 24 succinyllysine sites on 23 succinylated proteins in ICH brains. Both the TAK242 treatment induced hypersuccinylated and hyposuccinylated proteins in ICH brains were mainly located in mitochondria and cytoplasm. GO analysis showed that TAK242 treatment induced changes in ICH-associated succinylated proteins were mostly located in synapse, membrane, vesicle, etc., and enriched in many processes, such as metabolism, synapse, myeline, etc.. KEGG analysis showed that TAK242 induced downregulation of succinylation was significantly linked to fatty acid metabolism and lysosome. Moreover, a combination analysis of our succinylproteomic data with previously published transcriptome data identified that most of the differentially succinylated proteins induced by TAK242 treatment were mainly distributed into neurons, astrocytes and endothelial cells; and 7 and 3 of these succinylated proteins significantly high express in neurons and astrocytes, respectively. In conclusion, our analyses uncover a number of TLR4 signaling affected succinylation processes and pathways in mouse ICH brains and provide new insights for understanding ICH pathophysiological processes. Data are available via ProteomeXchange with identifier PXD025622.

Background: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain, diarrhea or constipation, and changes in defecation patterns. No organic disease has been found to explain these symptoms by routine clinical examination. This study aims to investigate the efficacy and safety of acupuncture therapy for IBS patients based on conventional treatments. We also want to explore the optimal acupoint combination recommended for IBS and clarify the clinical advantage of "multi-acupoint co-effect and synergistic effect".Methods and analysis: A total of 204 eligible patients who meet the Rome IV criteria for IBS will be randomly allocated to receive different acupuncture. Each patient will receive 12 acupuncture treatments over four weeks and will be followed up for four weeks. The primary outcome is the IBS-symptom severity score (IBS-SSS). The secondary outcomes include the Bristol stool form scale(BSFS), the work and social adjustment score (WSAS), the IBS-quality of life (IBS-QOL), self-rating anxiety scale (SAS), and the self-rating depression scale (SDS). Both the primary outcome and the secondary outcomes measures are collected at baseline, 2 weeks, and 4 weeks of the intervention, 6 weeks, and 8 weeks after the intervention.Ethics and dissemination: The entire project has been approved by the ethics committee of Beijing University of Chinese Medicine ( 2020BZYLL0903 ) .Discussion: This is a multicenter randomized controlled trial for IBS in China. This may shed light on the efficacy of acupuncture as an alternative to IBS. The results of the trial will be disseminated in peer-reviewed publications. Trial registration: Chinese Clinical Trials Register, ID: ChiCTR2000041215.First registered on 12 December 2020. http://www.chictr.org.cn/.

Background Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain, diarrhea or constipation, and changes in defecation patterns. No organic disease is found to explain these symptoms by routine clinical examination. This study aims to investigate the efficacy and safety of acupuncture therapy for IBS patients compared with those of conventional treatments. We also aim to identify the optimal acupoint combination recommended for IBS and to clarify the clinical advantage of the “multiacupoint co-effect and synergistic effect.” Methods and analysis A total of 204 eligible patients who meet the Rome IV criteria for IBS will be randomly stratified into acupuncture group A, acupuncture group B, or the control group in a 1:1:1 ratio with a central web-based randomization system. The prespecified acupoints used in the control group will include bilateral Tianshu (ST25), Shangjuxu (ST37), Neiguan (PC6), and Zusanli (ST36). The prespecified acupoints used in experimental group A will include bilateral Tianshu (ST25), Shangjuxu (ST37), and Neiguan (PC6). The prespecified acupoints used in experimental group B will include bilateral Tianshu (ST25), Shangjuxu (ST37), and Zusanli (ST36). Each patient will receive 12 acupuncture treatments over 4 weeks and will be followed up for 4 weeks. The primary outcome is the IBS-Symptom Severity Scale (IBS-SSS) score. The secondary outcomes include the Bristol Stool Form Scale (BSFS), Work and Social Adjustment Score (WSAS), IBS-Quality of Life (IBS-QOL), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) scores. Both the primary outcome and the secondary outcome measures will be collected at baseline, at 2 and 4 weeks during the intervention, and at 6 weeks and 8 weeks after the intervention. Ethics and dissemination The entire project has been approved by the ethics committee of the Beijing University of Chinese Medicine (2020BZYLL0903). Discussion This is a multicenter randomized controlled trial for IBS in China. The findings may shed light on the efficacy of acupuncture as an alternative to conventional IBS treatment. The results of the trial will be disseminated in peer-reviewed publications. Trial registration Chinese Clinical Trials Register ChiCTR2000041215. First registered on 12 December 2020. http://www.chictr.org.cn/.

Objective. Primary dysmenorrhea (PD) is a common and high incidence disease in gynecology, which seriously affects the quality of life in young women. Our previous study found that mild moxibustion could treat abdominal pain of PD patients, but the mechanism is still unclear. Therefore, this study aims to partly investigate the treatment mechanism of moxibustion for PD, especially on uterine microcirculation. Methods. Forty 3-month-old Sprague Dawley female rats were randomly divided into four groups, including group A (saline control group, n = 10), group B (control plus moxibustion group, n = 10), group C (PD model group, n = 10), group D (PD. model plus moxibustion group, n = 10). The PD rat model was established by injecting estradiol benzoate and oxytocin. Mild moxibustion on Sanyinjiao (SP6) and Guanyuan (CV4) acupoints was once a day, 20 minutes per time, for 10 consecutive days. A vaginal smear was used to test the estrous cycle of rats. Uterine microvascular thickness was observed by stereomicroscope. And we detected the content of prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2) in uterine tissue by enzyme-linked immunosorbent assay. Results. Mild moxibustion can enlarge the microvessels, improve the microcirculation disturbance, and relieve the swelling of the uterus in PD rats. During the mild moxibustion intervention, the contents of PGF2α and PGE2 in uterus issues were synchronous increases or decreases and the changes of PGE2 were more obvious, but the changes of uterine microvasculature and morphology caused by the decrease of PGF2α were greater than PGE2. Conclusion. Mild moxibustion at SP6 and CV4 acupoints may relax uterine microvascular obstacle by reducing the content of PGF2α in uterine tissue, improve the microcirculation disorder, and then alleviate the PD rat’s uterine swelling.

Tai Chi has been proven to be a safe and effective assistant therapy for healthcare and disease treatment. However, whether the adjuvant therapeutic effect of Tai Chi is general or disease-oriented remains uncertain. This trial focuses on exploring the specific and nonspecific effects of Tai Chi and its potential central responses. The results will deepen our understanding of the characteristics of Tai Chi exercise for adjuvant therapeutic effects and promote its application in the clinic. In this neuroimaging trial, 40 functional constipation (FC) patients and 40 healthy subjects (HS) will be recruited and will receive 10 weeks of Tai Chi exercise. The motor function, respiratory function, stool-related symptoms, quality of life, and emotional state of the participants will be evaluated at the baseline, the 5-week Tai Chi practice, and the end of practice. The potential changes in the heart rate variability and the cerebral function will be recorded by the 24 h dynamic electrocardiogram at the baseline and the functional magnetic resonance imaging at the end of practice. The possible correlations among the clinical variables, the heart rate variability, and the cerebral activity alterations in FC patients and HS will be analyzed. The healthcare and therapeutic effects of Tai Chi exercise might consist of the specific and nonspecific effects. This study provides not only a new perspective for understanding Tai Chi but also a new approach for investigating the mind-body exercise. This trial was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=33243) on 28 November 2018 (registration number: ChiCTR1800019781; protocol version number: V1.0). This trial is currently in the stage of recruiting patients. The first patient was included on 1 December 2018. To date, 18 FC patients and 20 HS have been included. Recruitment will be completed in December 2020.

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(Plt;0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(Plt;0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.

Manganese chloride (MnCl

To explore the clinical therapeutic effect of light and heat of moxibustion for knee osteoarthritis (KOA).A total of 216 patients with KOA were randomized into a traditional moxibustion group (72 cases, 8 cases dropped off), a moxibustion light group (72 cases, 9 cases dropped off) and a moxibustion heat group (72 cases, 10 cases dropped off).The special light-heat separation moxibustion cup was applied, the patients in the traditional moxibustion group received the treatment of moxibustion, the patients in the moxibustion light group received the treatment of moxibustion light and the patients in the moxibustion heat group received the treatment of moxibustion heat. The acupoint selection of the three groups was Neixiyan (EX-LE 4), Dubi (ST 35) and Zusanli (ST 36), the treatment was given 20 min each time, 3 times a week, 4 weeks were required totally, and the follow-up surveys were made 4 and 8 weeks after treatment. The scores of Western Ontario and McMaster University osteoarthritis index (WOMAC) and visual analogue scale (VAS) were observed before treatment, after 2 and 4 weeks of treatment, 4 and 8 weeks after treatment. The therapeutic effects were evaluated according to the criterion of patient global assessment (PGA) after 4 weeks of treatment and 8 weeks after treatment.Compared with before treatment, the pain scores, stiffness scores, physical function scores and total scores of WOMAC were reduced after 2, 4 weeks of treatment and 4 weeks after treatment in the three groups (The light and heat of moxibustion have therapeutic effect for KOA, and the therapeutic effect of moxibustion heat is superior to moxibustion light.

Background and Aims. Psychological disorders are prevalent in patients with inflammatory bowel disease, but the underlying mechanisms remain unknown. The aim of this study was to study whether electroacupuncture (EA) and moxibustion (MB) can improve anxiety behavior in DSS-induced colitis mice and to investigate whether this effect is related to hypothalamic-pituitary-adrenocortical (HPA) axis. Methods. The colitis model was established by drinking 2.5% dextran sodium sulfate (DSS). DSS-induced colitis mice were treated by EA or MB. Disease activity index (DAI) was scored; intestinal morphological and pathological structure was observed; anxiety behavior was tested by the elevated plus maze and open field. The concentration of corticotropin-releasing hormone (CRH) and cortisol (CORT) in serum was measured by enzyme-linked immunosorbent assay (ELISA). The protein expression of CRH in the colon and hypothalamus was detected by Western blot (WB). Results. Both EA and MB treatments can improvethe morphology of their distal colonic mucosal epithelia, as well as the disease activity index. Meanwhile, anxiety behavior in colitis mice was improved slightly after EA and MB treatment. In addition, the levels of CRH and CORT in the serum were slightly improved after EA and MB treatment. These effects are further supported by WB results. The expression of CRH in the colon and hypothalamus was increased significantly after treatment, compared with the model group. Conclusion. EA and MB were able to regulate the concentration of CRH in serum and protein expression in the peripheral and central at different levels and promote the recovery of the HPA axis that may be the basis for EA and MB to improve colonic pathology and alleviate anxiety behavior in DSS-induced colitis.

The aim of this study was to investigate whether contralateral moxibustion would generate a similar analgesic effect with ipsilateral moxibustion. Contra- and ipsilateral moxibustion were separately applied to Zusanli (ST36) acupoints of inflammatory pain mice. The analgesic effect was evaluated, respectively, by licking/biting time (LBT) of formalin-induced inflammatory pain and thermal withdrawal latency (TWL) of complete Freund’s adjuvant- (CFA-) induced inflammatory pain. For formalin-induced pain, compared with formalin group, the total LBT of ipsi- and contralateral moxibustion reduced in both phase I and phase II, but there was no significant difference between ipsi- and contralateral moxibustion. For CFA-induced inflammatory pain, compared with CFA group, TWL of ipsi- and contra-Moxi groups increased immediately after moxibustion intervention; however there was no obvious difference between ipsi- and contralateral moxibustion at any timepoint. It indicated that contralateral moxibustion had a similar analgesic effect with ipsilateral moxibustion in both formalin- and CFA-induced pain. These results suggest that both ipsi- and contralateral moxibustion could be applied for pain relief.

ObjectiveThe purpose of this study was to evaluate the difference of efficacy between moxibustion (experimental group) and local diclofenac sodium gel (control group) in the treatment of knee osteoarthritis (KOA).MethodsA multicenter, double-blinded, double-placebo, randomized controlled clinical trial was conducted in this research. 144 participants with knee osteoarthritis were randomly divided into two groups according to 1:1 ratio. The participants in the experimental group were treated with active Moxibustion plus placebo gel, whereas the control group was given diclofenac sodium gel plus placebo moxibustion. Moxibustion treatment was administrated at 3 acupoints (EX-LE4, ST35, ST36) for 4 weeks in 12 sessions. The entire trial cycle lasted 13 weeks, including 1 week at baseline, 4 weeks at treatment and 8 weeks at follow-up. Diclofenac sodium gel or placebo gel at a dose of 4 g per knee were applied three times per day for 4 weeks. The primary outcome measures were the changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures included changes in other subscales of WOMAC (pain, stiffness and function), visual analogue scale (VAS) and participant overall assessment (PGA).ResultsThe analysis showed that both the experimental group and the control group at 2 weeks, 4weeks, 8weeks and 12 weeks were statistically significant compared with baseline (P 0.05). At 8 weeks, WOMAC total score (95% CI, 4.3 [0.5 to 8.1], P=0.03), pain score (95% CI, 1.0 [0.2 to 1.9], P=0.02) and functional score (95% CI, 3.0 [0.1 to 5.8], P=0.04) the control group are better than the experimental group (P < 0.05). At 12 weeks, there were no significant difference between the two groups (P > 0.05). ConclusionsDuring the treatment, moxibustion has the same therapeutic effect as local diclofenac sodium gel, which can alleviate the pain of KOA participants to different degrees, rigidity and dysfunction. The therapeutic effect of it can basically maintained until 2 months after treatment. Local diclofenac sodium gel was superior to moxibustion in relieving knee pain and knee dysfunction at 8 weeks.Trial registration number Clinical Trials.gov, NCT02769572.Date of trial registration May 2016＃These authors contributed equally to this work.

The immunological responses are a key pathological factor in Alzheimer's disease (AD). We hypothesized that microglial polarization alters microglia-astrocyte immune interactions in AD. M1 and M2 microglia were isolated from primary rat microglia and were confirmed to secrete pro-inflammatory and anti-inflammatory factors, respectively. Primary rat astrocytes were co-cultured with M1 or M2 microglial medium. M1 microglial medium increased astrocyte production of pro-inflammatory factors (interleukin [IL]-1β, tumor necrosis factor α and IL-6), while M2 microglial medium enhanced astrocyte production of anti-inflammatory factors (IL-4 and IL-10). To analyze the crosstalk between microglia and astrocytes after microglial polarization specifically in AD, we co-cultured astrocytes with medium from microglia treated with amyloid-β (Aβ) alone or in combination with other inflammatory substances. Aβ alone and Aβ combined with lipopolysaccharide/interferon-γ induced pro-inflammatory activity in M1 microglia and astrocytes, whereas IL-4/IL-13 inhibited Aβ-induced pro-inflammatory activity. Nuclear factor κB p65 was upregulated in M1 microglia and pro-inflammatory astrocytes, while Stat6 was upregulated in M2 microglia and anti-inflammatory astrocytes. These results provide direct evidence that microglial polarization governs communication between microglia and astrocytes, and that AD debris alters this crosstalk.

OBJECTIVE To investigate the effects of long-term exposure to moxa smoke on acupuncturists and to consider the association between physical symptoms and gender, age, secondhand smoke (SHS) exposure, and the duration of exposure. METHODS A self-report, web-based questionnaire was used to evaluate the effects of moxa smoke on acupuncturists. Logistic regression was used to analyze the relationship between physical symptoms and possible correlative factors. RESULTS A total of 858 questionnaires were analyzed. The data showed that 42.42% of acupuncturists had been exposed to moxa smoke for 5-10 years. The most frequent symptom was tearing (32.98%) and the least frequent symptom was asthma (5.24%). Logistic regression analysis showed that female acupuncturists were slightly more susceptible to cough and tearing than males (cough: OR: 1.583, 95% CI: 1.079, 2.321, P = 0.019; tearing: OR: 1.519, 95% CI: 1.094,2.108, P = 0.013). Acupuncturists aged over 25 years reported a slightly lower incidence of eye itchiness than those aged under 25 years (26-40 years: OR: 0.604, 95% CI: 0.379, 0.965, P = 0.035; over 40 years: OR: 0.330, 95% CI: 0.114, 0.958, P = 0.042). Ophthalmodynia occurred less in acupuncturists aged 26-40 years (OR: 0.591, 95% CI: 0.359,0.970, P = 0.038) than in those younger than 25 years. The only association between prevalence of symptoms and tobacco use and SHS exposure was that smokers had a lower occurrence of phlegm in the throat (OR: 0.579, 95% CI: 0.392, 0.856, P = 0.006). Shortness of breath was less frequent in participants exposed to moxa smoke for more than 5 years (5-10 years: OR: 0.400, 95% CI: 0.204, 0.785, P = 0.008; 11-20 years: OR: 0.392, 95% CI: 0.178, 0.864, P = 0.02), but a slightly higher incidence of eye itchiness was found in those with over 20 years of moxa exposure (OR: 4.200, 95% CI: 1.344, 3.128, P = 0.014). CONCLUSION The most frequent symptom of moxa smoke exposure in acupuncturists was tearing. The association of symptoms with age and duration of exposure to moxa smoke were rather complicated; hence, care should be taken in drawing conclusions about the safety of moxa smoke based solely on its potentially harmful ingredients.