Extracellular Vesicles Derived from Bone Mesenchymal Stem Cells Carrying circ_0000075 Relieves Cerebral Ischemic Injury by Competitively Inhibiting miR-218-5p and Up-regulating E3 Ubiquitin Ligase SMURF2.

Extracellular vesicle (EV)-encapsulated circRNAs have the potential role in affecting brain disorders. However, the role of circ_0000075 in cerebral ischemic injury remains unclear. Here, we tried to investigate the mechanism of bone marrow mesenchymal stem cell (BMSC)-derived EVs carrying circ_0000075 in the control of cerebral ischemic injury. Initially, a mouse model with cerebral ischemic injury was induced by middle cerebral artery occlusion (MCAO), followed by the determination of circ_0000075 expression. Then, neurons were isolated and subjected to oxygen-glucose deprivation/reperfusion. BMSCs were isolated for extraction of EVs. The correlation among circ_0000075, microRNA (miR)-218-5p, and Smad ubiquitination regulatory factor 2 (SMURF2) was detected with their roles in cerebral ischemic injury analyzed in vivo and in vitro. circ_0000075 was down-regulated in MCAO mice and engineered RVG-EVs were internalized by neurons to up-regulate circ_0000075 expression. Treatment of RVG-circ_0000075-EVs reduced brain tissue damage, increased neuronal count, and significantly curtailed apoptosis rate, suppressing cerebral ischemic injury in vitro and in vivo. miR-218-5p was targeted by circ_0000075 in neurons, which promoted SMURF2 expression. A negative correlation between SMURF2 and transcriptional regulator Yin Yang 1 (YY1) was identified. In vitro experiments further proved that circ_ 00,000 75 could down-regulate the expression of YY1 through SMURF2, and finally relieving cerebral ischemic injury. Collectively, engineered EVs delivered circ_0000075 into brain tissues and increased circ_0000075 expression, which down-regulated miR-218-5p and up-regulated SMURF2, thus alleviating cerebral ischemic injury.

Promoting the quality and transparency of health research in China.

BACKGROUND AND OBJECTIVES: To review the efforts and progress in promoting quality and transparency of health research in China and to discuss how to improve. METHODS: We focused on three different types of health research: clinical trials, systematic reviews, and clinical practice guidelines, and summarized China's progress from their registration, implementation, and reporting stages. RESULTS: In the last 3 decades, China's major works include the following: 1) For registration, the trials and CPGs registries have been set up, and released policies to mandate registration and submission of protocols for trials. 2) For implementation, multiple clinical research and EBM centers have been established. The ResMan platform for data management has been created and required researchers to share results data. 3) For reporting, the Chinese EQUATOR Center has been set up. Translations and extensions of the CONSORT, PRISMA, and RIGHT have been published. 4) For traditional Chinese medicine (TCM), specific guidelines for the registration and reporting of TCM research have been developed. CONCLUSION: China has made progress in promoting research quality and transparency, especially in research registration and reporting. Nevertheless, more can be done in data management and sharing for research implementation, and good publication practices in TCM.

Core Outcome Set for Clinical Trials on Coronavirus Disease 2019 (COS-COVID).

Since its outbreak in December 2019, a series of clinical trials on coronavirus disease 2019 (COVID-19) have been registered or carried out. However, the significant heterogeneity and less critical outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) Handbook: Version 1.0, a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine (TCM), evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (www.chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019 novel coronavirus (2019-nCoV) reverse transcription-polymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital stay, composite events, score of clinical symptoms, and time to 2019-nCoV RT-PCR negativity), five outcomes for the severe type (composite events, length of hospital stay, arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2), duration of mechanical ventilation, and time to 2019-nCoV RT-PCR negativity), one outcome for critical type (all-cause mortality), and one outcome for rehabilitation period (pulmonary function). The COS-COVID is currently the most valuable and practical clinical outcome set for the evaluation of intervention effect, and is useful for evidence assessment and decision-making. With a deepening understanding of COVID-19 and application feedback, the COS-COVID should be continuously updated.

Motherwort Injection for Preventing Postpartum Hemorrhage in Women with Vaginal Delivery: A Systematic Review and Meta-Analysis of Randomized Evidence.

BACKGROUND: Motherwort injection, a common traditional Chinese medicine, is widely used for the prevention of postpartum hemorrhage (PPH), which has been found to be potential benefit in clinical practice. OBJECTIVES: This study aimed to conduct a rigorous systematic review of randomized evidence to offer a comprehensive overview regarding the efficacy and safety of motherwort injection in maternal women with virginal delivery. METHODS: We included all randomized controlled trials involving pregnant women in vaginal delivery comparing motherwort injection or combination of motherwort injection and oxytocin with oxytocin alone for preventing postpartum hemorrhage. Paired reviewers independently screened citations, assessed risk of bias, and extracted data. Random-effects model by Mantel-Haenszal method was applied to pool the data. Predefined subgroup analyses and sensitivity analyses were conducted to explore the heterogeneity and robustness of results. The GRADE approach was used to rate the quality of evidence. MAIN RESULTS: 37 randomized controlled trials involving 7887 participants were included, all of which were at moderate to high risk of bias. Meta-analyses of eight trials showed no significant difference in blood loss and PPH events between oxytocin versus motherwort injection (very low quality). However, pooling of 29 trials suggested a reduced risk of blood loss (within 2 hours: MD -55.06mL, 95% CI -84.06 to -26.06; within 24 hours: MD -85.57 mL, 95% CI -94.26 to -76.88, very low quality), PPH events (RR 0.29, 95% CI 0.21 to 0.39, low quality), and adverse events (Peto OR 0.53, 95% CI 0.40 to 0.70, very low quality) in participants treated with motherwort injection and oxytocin versus oxytocin alone. CONCLUSIONS: The current evidence supports the suggestion that the additional use of motherwort injection on oxytocin had a preferable outcome. However, given that the evidence is not definitive with low quality, further careful designed and conducted randomized controlled trials in larger population are warranted to conform the effects.

Standard Protocol Items for Clinical Trials with Traditional Chinese Medicine 2018: Recommendations, Explanation and Elaboration (SPIRIT-TCM Extension 2018).

Traditional Chinese Medicine (TCM) is one of the oldest systems of medicine. More and more attention has been paid to TCM application, but the variable quality of clinical trials with TCM impedes its widespread acceptance. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement has established guidelines for designing clinical trials to ensure that the trial results are accurate and reliable. However, there are difficulties when applying SPIRIT 2013 Statement to trials with TCM, due to the unique theory and the characteristic of TCM intervention. An Extension to the original SPIRIT was developed to ensure the quality of trial design with TCM. As Chinese herbal formulae, acupuncture and moxibustion are common and representative interventions in TCM practice, the executive working group determined that the SPIRIT-TCM Extension focus on these three interventions. Extension was developed through initiation, 3 rounds of Delphi consensus survey, and finalizing expert meeting. Seven items from the SPIRIT 2013 Statement were modified, namely, "title", "background and rationale", "objectives", "eligibility criteria", "interventions", "outcomes", and "data collection methods". The Extension includes the introduction of the concept of TCM pattern and 3 major TCM interventions, with examples and explanations. The SPIRIT-TCM Extension 2018 provides suggestion for investigators in designing high quality TCM clinical trials. It is expected that wide dissemination and application of this extension ensure continuous improvement of TCM trial quality throughout the world.

The Effect of Acupuncture on the Quality of Life in Patients With Migraine: A Systematic Review and Meta-Analysis.

Background: Acupuncture is frequently used as an efficient method to prevent and treat migraines. However, its effect on the quality of life remains controversial. Methods: Seven databases, such as PubMed and Cochrane Library were searched to retrieve reference lists of eligible trials and related reviews. Randomized controlled trials that were published in Chinese and English were included. Results: Acupuncture resulted in lower Visual Analog Scale scores than the medication group at 1 month after treatment (MD -1.22, 95%CI -1.57 to -0.87; low quality) and 1-3 months after treatment (MD -1.81, 95%CI -3.42 to -0.20; low quality). Compared with sham acupuncture, acupuncture resulted in lower Visual Analog Scale scores at 1 month after treatment (MD -1.56, 95%CI -2.21 to -0.92; low quality). Conclusion: Acupuncture exhibits certain efficacy both in the treatment and prevention of migraines, which is superior to no treatment, sham acupuncture and medication. Further, acupuncture enhanced the quality of life more than did medication.

Interventions for reducing inflammation in familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever, a hereditary auto-inflammatory disease, mainly affects ethnic groups living in the Mediterranean region. Early studies reported colchicine as a potential drug for preventing attacks of familial Mediterranean fever. For those people who are colchicine-resistant or intolerant, drugs such as rilonacept, anakinra, canakinumab, etanercept, infliximab, thalidomide and interferon-alpha might be beneficial. This is an updated version of the review. OBJECTIVES: To evaluate the efficacy and safety of interventions for reducing inflammation in people with familial Mediterranean fever. SEARCH METHODS: We used detailed search strategies to search the following databases: CENTRAL; MEDLINE; Embase; Chinese Biomedical Literature Database (CBM); China National Knowledge Infrastructure Database (CNKI); Wan Fang; and VIP. In addition, we also searched the clinical trials registries including ClinicalTrials.gov, the International Standard Randomized Controlled Trial Number Register, the WHO International Clinical Trials Registry Platform and the Chinese Clinical Trial Registry, as well as references listed in relevant reports.Date of last search: 21 August 2018. SELECTION CRITERIA: Randomized controlled studies (RCTs) of people diagnosed with familial Mediterranean fever, comparing active interventions (including colchicine, anakinra, rilonacept, canakinumab, etanercept, infliximab, thalidomide, interferon-alpha, ImmunoGuard™ (a herbal dietary supplement) and non-steroidal anti-inflammatory drugs) with placebo or no treatment, or comparing active drugs to each other. DATA COLLECTION AND ANALYSIS: The authors independently selected studies, extracted data and assessed risk of bias. We pooled data to present the risk ratio or mean difference with their 95% confidence intervals. We assessed overall evidence quality according to the GRADE approach. MAIN RESULTS: We included nine RCTs with a total of 249 participants (aged three to 53 years); five were of cross-over and four of parallel design. Six studies used oral colchicine, one used oral ImmunoGuard™ and the remaining two used rilonacept or anakinra as a subcutaneous injection. The duration of each study arm ranged from one to eight months.The three studies of ImmunoGuard™, rilonacept and anakinra were generally well-designed, except for an unclear risk of detection bias in one of these. However, some inadequacy existed in the four older studies on colchicine, which had an unclear risk of selection bias, detection bias and reporting bias, and also a high risk of attrition bias and other potential bias. Neither of the two studies comparing a single to a divided dose of colchicine were adequately blinded, furthermore one study had an unclear risk of selection bias and reporting bias, a high risk of attrition bias and other potential bias.We aimed to report on the number of participants experiencing an attack, the timing of attacks, the prevention of amyloid A amyloidosis, any adverse drug reactions and the response of a number of biochemical markers from the acute phase of an attack, but data were not available for all outcomes across all comparisons.One study (15 participants) reported a significant reduction in the number of people experiencing attacks at three months with 0.6 mg colchicine three times daily (14% versus 100%), risk ratio 0.21 (95% confidence interval 0.05 to 0.95) (low-quality evidence). A further study (22 participants) of 0.5 mg colchicine twice daily showed no significant reduction in the number of participants experiencing attacks at two months (low-quality evidence). A study of rilonacept in individuals who were colchicine-resistant or intolerant (14 participants) also showed no reduction at three months (moderate-quality evidence). Likewise, a study of anakinra given to colchicine-resistant people (25 participants) showed no reduction in the number of participants experiencing an attack at four months (moderate-quality evidence).Three studies reported no significant differences in duration of attacks: one comparing colchicine to placebo (15 participants) (very low-quality evidence); one comparing single-dose colchicine to divided-dose colchicine (90 participants) (moderate-quality evidence); and one comparing rilonacept to placebo (14 participants) (low-quality evidence). Three studies reported no significant differences in the number of days between attacks: two comparing colchicine to placebo (24 participants in total) (very low-quality evidence); and one comparing rilonacept to placebo (14 participants) (low-quality evidence).No study reported on the prevention of amyloid A amyloidosis.One study of colchicine reported loose stools and frequent bowel movements (very low-quality evidence) and a second reported diarrhoea (very low-quality evidence). The rilonacept study reported no significant differences in gastrointestinal symptoms, hypertension, headache, respiratory tract infections, injection site reactions and herpes, compared to placebo (low-quality evidence). The ImmunoGuard study observed no side effects (moderate-quality evidence). The anakinra study reported no significant differences between intervention and placebo, including injection site reaction, headache, presyncope, dyspnea and itching (moderate-quality evidence). When comparing single and divided doses of colchicine, one study reported no difference in adverse events (including anorexia, nausea, diarrhoea, abdominal pain, vomiting and elevated liver enzymes) between groups (moderate-quality evidence) and the second study reported no adverse effects were detected.The rilonacept study reported no significant reduction in acute phase response indicators after three months (low-quality evidence). In the ImmunoGuard™ study, these indicators were not reduced after one month of treatment (moderate-quality evidence). The anakinra study, reported that C-reactive protein was significantly reduced after four months (moderate-quality evidence). One of the single dose versus divided dose colchicine studies reported no significant reduction in acute phase response indicators after eight months (low-quality evidence), while the second study reported no significant reduction in serum amyloid A concentration after six months (moderate-quality evidence). AUTHORS' CONCLUSIONS: There were limited RCTs assessing interventions for people with familial Mediterranean fever. Based on the evidence, three times daily colchicine appears to reduce the number of people experiencing attacks, colchicine single dose and divided dose might not be different for children with familial Mediterranean fever and anakinra might reduce C-reactive protein in colchicine-resistant participants; however, only a few RCTs contributed data for analysis. Further RCTs examining active interventions, not only colchicine, are necessary before a comprehensive conclusion regarding the efficacy and safety of interventions for reducing inflammation in familial Mediterranean fever can be drawn.

Motherwort injection for preventing postpartum hemorrhage in pregnant women with cesarean section: A systematic review and meta-analysis.

OBJECTIVE: To assess the impact of motherwort injection alone or combined with oxytocin for preventing postpartum hemorrhage in pregnant women with caesarean section. METHODS: A systematic review and meta-analysis of randomized trials were performed. PubMed, EMbase, The Cochrane Central Register of Controlled Trials (CENTRAL), Chinese database Sino-Med, Chinese National Knowledge Infrastructure Database (CNKI), VIP Chinese Science and Technique Journals Database, WanFang, and ClinicalTrials.gov were searched. Randomized controlled trials (RCTs) that compared motherwort injection alone or motherwort injection combined with oxytocin in pregnant women receiving cesarean section were included. Paired reviewers independently screened abstracts and full texts for eligibility, assessed risk of bias, and extracted data. We performed random-effects meta-analyses of RCTs along with a limited number of prespecified subgroup hypotheses, and sensitivity analyses were carried out with other statistical approaches. RESULTS: Forty-six RCTs (n = 7359) proved eligible. Compared with oxytocin, both motherwort injection and motherwort injection combined with oxytocin had a significantly lower blood loss within 2 hours (MD = -21.81, 95% CI -37.05 to -6.58 and MD = -53.04, 95% CI -61.68 to -44.39); lower blood loss within 24 hours (MD = -25.44, 95% CI -39.38 to -11.51 and MD = -67.81, 95% CI -78.02 to -57.60); and lower the risk of adverse events (ORPeto 0.40, 95% CI 0.16 to 0.96 and ORPeto 0.50, 95% CI 0.35 to 0.71). Motherwort injection combined with oxytocin also decreased the risk of postpartum hemorrhage (OR 0.22, 95% CI 0.14 to 0.35.) CONCLUSIONS: In pregnant women with cesarean section, motherwort injection suggests an obvious benefit and less adverse event.

[Evidence-based Chinese medicine：theory and practice].

The introduction and popularization of evidence-based medicine has opened up a new research field of clinical efficacy evaluation of traditional Chinese medicine(TCM), produced new research ideas and methods, and promoted the progress of clinical research of TCM. After about 20 years assiduous study and earnest practice, the evidence based evaluation method and technique, which conforms to the characteristics of TCM theory and practice, has been developing continuously. Evidence-based Chinese medicine (EBCM) has gradually formed and become an important branch of evidence-based medicine. The basic concept of evidence-based Chinese medicine: EBCM is an applied discipline, following the theory and methodology of evidence-based medicine, to collect, evaluate, produce, transform the evidence of effectiveness, safety and economy of TCM, to reveal the feature and regular pattern of TCM taking effect, and to guide the development of clinical guidelines, clinical pathways and health decisions. The effects and achievements of EBCM development: secondary studies mainly based on systematic review/Meta-analysis were extensively carried out; clinical efficacy studies mainly relying on randomized controlled trials grew rapidly; clinical safety evaluations based on real world study have been conducted; methodological researches mainly focused on study quality control deepened gradually; internationalization researches mainly on report specifications have got some breakthroughs; standardization researches based on treatment specification were strengthened gradually; the research team and talents with the characteristics of inter-disciplinary have been steadily increased. A number of high-quality research findings have been published at international well-known journals; the clinical efficacy and safety evidence of TCM has been increased; the level of clinical rational use of TCM has been improved; a large number of Chinese patent medicines with big market have been cultured. The future missions of EBCM mainly consist of four categories (scientific research, methodology and standard, platform construction and personnel training) with nine tasks. ①Carry out systematic reviews to systematically collect clinical trial reports of TCM and establish database of clinical evidence of TCM; ②Carry out evidence transformation research to lay the foundation for the development of clinical diagnosis and treatment guidelines, clinical pathways of TCM, and for the screening of basic drug list and medical insurance list, and for the policy-making relevant to TCM; ③Conduct researches to evaluate the advantages and effective regular patterns of TCM and form the evidence chain of TCM efficacy; ④Carry out researches for the safety evaluation of TCM, and provide evidence supporting the rational and safe use of TCM in clinical practice; ⑤Conduct researches on methodology of EBCM and provide method for developing high quality evidence; ⑥Carry out researches to develop standards and norms of TCM, and to form methods, standards, specifications and technical systems; ⑦Establish data management platform for evidence-based evaluation of TCM, and promote data sharing; ⑧Build international academic exchange platform to promote international cooperation and mutual recognition of EBCM research; ⑨Carry out education and popularization activities of evidence-based evaluation methods, and train undergraduate students, graduate students, clinical healthcare providers and practitioners of TCM. The development of EBCM, as it was, not only promoted the transformation of clinical research and decision-making mode of TCM, contributed to the modernization and internationalization of TCM, but also enriched the connotation of Evidence-based Medicine.

Celastrol mediates Th17 and Treg cell generation via metabolic signaling.

A T helper 17 (Th17) cell/regulatory T (Treg) cell imbalance is involved in many immune disorders and diseases. Celastrol, a Chinese herbal compound that has anti-inflammatory and immunosuppressive properties, has been indicated to suppress T cell proliferation and Th17 cell induction, while facilitating Forkhead box P3 (Foxp3) expression and Treg cell generation. In this study, we explored the impact and mechanism of celastrol on Th17 cell/induced Treg (iTreg) cell induction. CD4+CD25- T cells were purified, stimulated with anti-CD3 and anti-CD28 antibodies, and polarized in vitro to generate Th17 or iTreg cells in the presence or absence of celastrol. Initially, we determined that Interleukin (IL)-17 expression by celastrol-treated Th17 was significantly decreased compared with untreated cells; however, the frequency of Foxp3+ cells was increased in celastrol-treated cells. We verified that celastrol inhibited phospho-STAT3 expression in cultured Th17 cells and up-regulated phospho-STAT5 expression in iTreg cells. Furthermore, T cells treated with celastrol were more likely to participate in FAO metabolism instead of glycolysis. Celastrol suppressed the expression of glucose transporter, Glut1, and the rate-limiting enzyme, HK2, in addition to mTOR, HIF-1α, c-Myc and Akt expression in Th17 cells. Conversely, celastrol promoted FAO of lipids by up-regulating CPT1A and AMPKα expression in iTreg cells. Our results suggest that celastrol suppresses Th17 cell induction, while promoting the generation of iTreg cells. We found that celastrol inhibits glycolysis in Th17 cells and promotes FAO by iTreg cells, suggesting that celastrol could mediate the metabolism of Th17 and iTreg cells.

Toward Evidence-Based Chinese Medicine: Status Quo, Opportunities and Challenges.

How to test the treatments of Chinese medicine (CM) and make them more widely accepted by practitioners of Western medicine and the international healthcare community is a major concern for practitioners and researchers of CM. For centuries, various approaches have been used to identify and measure the efficacy and safety of CM. However, the high-quality evidence related to CM that produced in China is still rare. Over the recent years, evidence-based medicine (EBM) has been increasingly applied to CM, strengthening its theoretical basis. This paper reviews the past and present state of CM, analyzes the status quo, challenges and opportunities of basic research, clinical trials, systematic reviews, clinical practice guidelines and clinical pathways and evidence-based education developed or conducted in China, pointing out how EBM can help to make CM more widely used and recognized worldwide.

Systematic Reviews/Meta-Analyses of Integrative Medicine in Chinese Need Regulation and Monitoring Urgently and Some Suggestions for Its Solutions.

With the introduction and development of evidence-based medicine in China, it has been spread rapidly in the area of integrative medicine (IM) and has become a new unique discipline. During almost 20 years, as one of the most important parts of evidence-based IM, systematic review (SR)/meta-analysis (MA) of IM have shown a good development momentum in the aspects of quantity, depth, breadth and influence, but also face the harsh situation of the uncontrolled quantity and quality, especially for SRs in Chinese. Therefore, how to supervise and standardize this area effectively becomes a problem to be solved. Based on the experience both at home and abroad, the authors put forward several kinds of solutions for laying the foundation for further development such as promoting the registration system of SR/MA of IM, effectively setting up the regulatory platform of quality and quantity, launching professional training for SR/MA reviewers, forming qualification registration, developing the data transfer and sharing platform to realize the transparency of evidence process.

CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration (Simplified Chinese Version).

Editors' Note: This article is the simplified Chinese version of the CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration. (Cheng C, Wu T, Shang H, Li, Y, Altman D, Moher D; CONSORT-CHM Formulas 2017 Group. CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration. Ann Intern Med. 2017;167:112-21. [Epub 27 June 2017]. doi:10.7326/M16-2977).

CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration.

Chinese herbal medicine (CHM) formulas are the major components of traditional Chinese medicine (TCM) interventions. The general reporting quality of randomized controlled trials (RCTs) of CHM formulas is disappointing, although CONSORT (Consolidated Standards of Reporting Trials) Statement extensions for herbal medicinal interventions and acupuncture interventions are available. A group of TCM clinical experts, methodologists, epidemiologists, and editors has developed this CONSORT Extension for CHM Formulas (CONSORT-CHM Formulas 2017) through a comprehensive process, including publication of the draft version, solicitation of comments, revision, and finalization. The CONSORT 2010 Statement was extended by introducing the idea of TCM Pattern and the features of CHM formulas. One new checklist subitem, keywords, was added to facilitate indexing and data searching. Seven of the 25 CONSORT checklist items, namely title and abstract, background and objectives, participants, interventions, outcomes, generalizability, and interpretation, are now elaborated, and the explanation of harms specific to CHM formulas is revised. Illustrative examples and explanations are also provided. The group hopes that CONSORT-CHM Formulas 2017 can improve the reporting quality of RCTs of CHM formulas.

CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration (Traditional Chinese Version).

Editors' Note: This article is the traditional Chinese version of the CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration. (Cheng C, Wu T, Shang H, Li, Y, Altman D, Moher D; CONSORT-CHM Formulas 2017 Group. CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration. Ann Intern Med. 2017;167:112-21. [Epub 27 June 2017]. doi:10.7326/M16-2977).

Electroacupuncture Treatment Alleviates Central Poststroke Pain by Inhibiting Brain Neuronal Apoptosis and Aberrant Astrocyte Activation.

Electroacupuncture (EA) is reported to effectively relieve the central poststroke pain (CPSP). However, the underlying mechanism remains unclear. The present study investigated the detailed mechanisms of action of EA treatment at different frequencies for CPSP. A CPSP model was established with a single collagenase injection to the left ventral posterolateral nucleus of the thalamus. The EA-treated groups then received EA treatment at frequency of 2, 2/15, or 15 Hz for 30 min daily for five days. The pain-related behavioral responses, neuronal apoptosis, glial activation, and the expression of pain signal transmission-related factors (ß-catenin, COX-2, and NK-1R) were assessed using behavioral tests, Nissl staining, TUNEL staining, and immunohistochemical staining, respectively. The low-frequency EA treatment significantly (1) reduced brain tissue damage and hematoma sizes and (2) inhibited neuronal apoptosis, thereby exerting abirritative effects. Meanwhile, the high-frequency EA treatment induced a greater inhibition of the aberrant astrocyte activation, accompanied by the downregulation of the expressions of COX-2, ß-catenin, and subsequently NK-1R, thereby alleviating inflammation and producing strong analgesic effects. Together, these findings suggest that CPSP is closely related to pathological changes of the neocortex and hippocampus. EA treatments at different frequencies may exert abirritative effects by inhibiting brain neuronal apoptosis and aberrant astrocyte activation in the brain.

Effectiveness of moxibustion for exercise-induced fatigue--a systematic review for randomized controlled trials.

OBJECTIVE: To review and assess the effect of single moxibustion for exercise-induced fatigue: (EIF). METHODS: Computer-search for 8 medical databases and 5 clinical trail registries were conducted for: randomized controlled trials (RCTs), added with hand-search for 10 Chinese acupuncture-moxibustion journals and additional references. Data from included RCTs were pooled by RevMan5.1. Methodology quality of RCTs was judged by Cochrane Collaboration assessment tool while quality of primary outcomes was evaluated by GRADE3.2. RESULTS: Five RCTs were finally included, all reported in small sample size with high risk of: bias. Comparisons on single moxibustion and rest relief (without treatment) were studied. Six outcomes were reported, all favored moxibustion to rest relief for EIF. Primary outcomes showed as rating of perceived exertion (RPE) with mean difference (MD)=-0.49, 95% confidence interval (CI) [-0.80, -0.19], 800-m race performance with MD=-2.21, 95% CI [-3.57, -0.85], and Harvard Step Index (HSI) with MD=14.75, 95% CI [8.35, 21.15]. Moreover, all primary outcomes as RPE, 800-m race performance and HSI were rated low quality. CONCLUSIONS: Single moxibustion might be considered effective for EIF. However, due to small samples of included RCTs, high risk of bias among studies and poor quality of primary outcomes and subjects restricted to Chinese athletes only, these results present limitation, and should be taken with caution for practice. More large-size studies with rigorous design are warranted to further test effectiveness of moxibustion for EIF.