[Outcome indicators in randomized controlled trials on traditional Chinese medicine intervention of sepsis-induced myocardial injury in recent five years].

This study aims to analyze the outcome indicators of randomized controlled trial(RCT) on traditional Chinese medicine(TCM) intervention of sepsis-induced myocardial injury(SIMI) in recent five years, which is expected to lay a basis for the construction of core outcome set(COS) for this disease treated by TCM. To be specific, RCT on the treatment of SIMI with TCM was retrieved from 4 Chinese databases, 3 English databases, and 2 clinical trial protocol registries. The quality of the included studies was evaluated with Cochrane risk-of-bias(ROB) tool, and the outcome indicators were analyzed. Finally, 42 RCTs were included, of which 2 were clinical trial registration schemes. The study found that 42 RCTs had a high risk of bias, and reported a total of 86 indicators in "clinical effective rate, disease severity, TCM syndrome score, inflammation, myocardium, cardiac structure and hemodynamics, electrocardiogram, immunology, metabolism and liver and kidney function, and safety". Outcome indicators on myocardium had the highest emergence frequency, followed by indicators on the cardiac structure and hemodynamics. A total of 8 RCTs reported TCM syndrome scores. Further analysis suggested the following problems in the selection of outcome indicators in the RCTs on TCM intervention of SIMI: no classification of primary and secondary indicators, disregard of endpoint indicators, irrational selection of alternative indicators, neglection of TCM characteristics, no assessment of patients' immune status, and no emphasis on economic indicators and safety indicators. Therefore, according to the recommendations of the core outcome measures in effectiveness trials(COMET) working group, a COS for TCM intervention of TCM for SIMI should be developed, so as to facilitate clinical researchers to select appropriate outcome indicators, the combination of conclusions of similar clinical studies, and the promotion of TCM interventions.

Comparative efficacy of five Chinese medicine injections for treating dilated cardiomyopathy with heart failure: A Bayesian network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese medicine injections (CMIs) are widely used by clinicians in China as an adjuvant treatment in dilated cardiomyopathy with heart failure (DCM-HF). However, comprehensive and systematic evidence supporting the beneficial effects of CMIs combined with Western medicine (WM) against DCM-HF was lacking. OBJECTIVE: This network meta-analysis aimed to assess the effectiveness of five different CMIs in the treatment of DCM-HF. METHODS: The Cochrane Library, Embase, PubMed, China National Knowledge Infrastructure (CNKI), Allied and Alternative Medieine Database (AMED), Chinese Biological Medicine Database (CBM), Wanfang Database, and Chinese Scientific Journal Database (VIP) were comprehensively searched from their inception to March 10, 2020, for randomized controlled trials (RCTs) focusing on the use of CMIs combined with WM to treat DCM-HF. The quality of the included RCTs was assessed using the Cochrane Handbook 5.1.0. Bayesian network meta-analysis were designed to access the effectiveness of different CMIs. RESULTS: A total of 38 eligible RCTs involving 3247 patients were enrolled. The study showed that Huangqi injection, Shengmai injection, Shenfu injection, Shenmai injection, and Xinmailong injection combined with WM significantly improved performance compared with WM alone in treating DCM-HF. Xinmailong injection + WM had the highest likelihood of being the best treatment in terms of the improvement in the clinical effectiveness rate, left ventricular end-diastolic dimension, and 6-min walking distance. Huangqi injection + WM had the highest probability of being the best treatment on account of the enhancement of left ventricular ejection fraction. Shenmai injection + WM had the highest likelihood of being the best treatment considering the improvement in cardiac output and the reduction in brain natriuretic peptide. CONCLUSIONS: The combination between CMIs and WM exerted a more positive effect in DCM-HF treatment. Xinmailong injection + WM had the best performance in treating DCM-HF, followed by Shenmai injection and Huangqi injection. However, due to the low qualities of the original studies, more high-quality studies are needed to support the findings.

Efficacy and Safety of TCMI in Patients With Combined Coronary Heart Disease and Heart Failure: A Systematic Review and Network Meta-Analysis.

Objective: To compare the efficacy and safety of conventional treatments (CTs) to those that included traditional Chinese medicine injections (TCMIs) in patients with combined coronary heart disease and heart failure (CHD-HF). Methods: Eight electronic literature databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure Database, Chinese Scientific Journal Database, Wanfang Database, Chinese Biomedical Database) were searched from their inceptions to May 18, 2021, to identify relevant randomised controlled trials (RCTs). The primary outcomes analyzed included the total effectiveness rate and adverse events (ADRs). The secondary outcomes analyzed included the left ventricular ejection fraction (LVEF), N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP), and 6-min walk test (6MWT). Cochrane risk-of-bias tool was used to assess quality of the analyzed RCTs. Stata and OpenBUGS software were used to prior to the systematic review and network meta-analysis. Results: Sixty-one eligible trials involved 5,567 patients and one of the following 15 TCMIs: Shuxuetong, Shenmai, Shenfu, Shengmai, Danshenduofenyansuan, Danhong, Dazhuhongjingtian, Xinmailong, Dengzhanxixin, Gualoupi, Shuxuening, Xuesaitong, Yiqi Fumai, Shenqi Fuzheng, Huangqi. Network meta-analysis revealed that Shuxuetong injection + CT group was superior to CT only in improving the total effectiveness rate [odds ratio (OR): 7.8, 95% confidence interval (CI): 1.17-27.41]. Shenmai injection + CT was superior to CT only for LVEF (OR: 8.97, CI: 4.67-13.18), Xinmailong injection + CT was superior to CT only for NT-proBNP (OR: -317.70, CI: -331.10-303.10), Shenqi Fuzheng injection + CT was superior to CT only for BNP (OR: -257.30, CI: -308.40-242.80); and Danhong injection + CT was superior to CT only for 6MWT (OR: 84.40, CI: 62.62-106.20). Different TCMIs had different toxicity spectrums. Conclusion: TCMIs combined with CT are better than CT alone in treating CHD-HF. Different TCMIs improve different outcomes. Additional properly designed RCTs are needed to conduce a more refined comparison of various TCMIs. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021258263].

Integrated Pharmacogenetics Analysis of the Three Fangjis Decoctions for Treating Arrhythmias Based on Molecular Network Patterns.

Aim: To explore the diverse target distribution and variable mechanisms of different fangjis prescriptions when treating arrhythmias based on the systems pharmacology. Methods: The active ingredients and their corresponding targets were acquired from the three fangjis [Zhigancao Tang (ZT), Guizhigancao Longgumuli Tang (GLT), and Huanglian E'jiao Tang (HET)] and the arrhythmia-related genes were identified based on comprehensive database screening. Networks were constructed between the fangjis and arrhythmia and used to define arrhythmia modules. Common and differential gene targets were identified within the arrhythmia network modules and the cover rate (CR) matrix was applied to compare the contributions of the fangjis to the network and modules. Comparative pharmacogenetics analyses were then conducted to define the arrhythmia-related signaling pathways regulated by the fangjis prescriptions. Finally, the divergence and convergence points of the arrhythmia pathways were deciphered based on databases and the published literature. Results: A total of 187, 105, and 68 active ingredients and 1,139, 1,195, and 811 corresponding gene targets of the three fangjis were obtained and 102 arrhythmia-related genes were acquired. An arrhythmia network was constructed and subdivided into 4 modules. For the target distribution analysis, 65.4% of genes were regulated by the three fangjis within the arrhythmia network. ZT and GLT were more similar to each other, mainly regulated by module two, whereas HET was divided among all the modules. From the perspective of signal transduction, calcium-related pathways [calcium, cyclic guanosine 3',5'-monophosphate (cGMP)-PKG, and cyclic adenosine 3',5'-monophosphate (cAMP)] and endocrine system-related pathways (oxytocin signaling pathway and renin secretion pathways) were associated with all the three fangjis prescriptions. Nevertheless, heterogeneity existed between the biological processes and pathway distribution among the three prescriptions. GLT and HET were particularly inclined toward the conditions involving abnormal hormone secretion, whereas ZT tended toward renin-angiotensin-aldosterone system (RAAS) disorders. However, calcium signaling-related pathways prominently feature in the pharmacological activities of the decoctions. Experimental validation indicated that ZT, GLT, and HET significantly shortened the duration of ventricular arrhythmia (VA) and downregulated the expression of CALM2 and interleukin-6 (IL-6) messenger RNAs (mRNAs); GLT and HET downregulated the expression of CALM1 and NOS3 mRNAs; HET downregulated the expression of CRP mRNA. Conclusion: Comparing the various distributions of the three fangjis, pathways provide evidence with respect to precise applications toward individualized arrhythmia treatments.

A clinical study to assess the influence of acupuncture at "Wang's Jiaji" acupoints on limb spasticity in patients in convalescent stage of ischemic stroke: study protocol for a randomized controlled trial.

BACKGROUND: Stroke is characterized by high morbidity, high mortality, and high disability. Spasticity, one of the most common complications after stroke, may reduce the potential success of rehabilitation and has a detrimental effect on stroke patients' daily function and quality of life. Moreover, the long-term management of spasticity is a financial burden to patients and increases societal costs. The current treatments, mainly including physical therapy, oral drugs, drug injection therapy, and surgical interventions, have been used to reduce spasticity. However, every conventional approach has its limitations. Acupuncture at the "Wang's Jiaji" acupoints, based on the experience of the famous old doctor of traditional Chinese medicine (TCM) Le Ting Wang in treating post-stroke limb spasm, has been widely practiced in our department. This intervention has effectively avoided the controversy around acupuncture at local acupoints on the limbs, and is easy to apply without side effects. Our previous studies had found that acupuncture at the "Wang's Jiaji-points" can reduce the occurrence and severity of spasticity occurring after stroke in the early stage (the first 21 days). In this study, we chose patients in the convalescent stage, 1-6 months after stroke, so as to study the efficacy and the specific intervention time of "Wang's jiaji" in the convalescent stage after stroke. METHODS: This is a randomized, controlled, and single-blind study. Patients in the convalescent stage within 1-6 months of ischemic stroke will be selected as subjects. A total of 100 subjects will be randomly assigned to two groups. The acupuncture group will be given acupuncture treatment five times a week; the medicine group will be given 10mg baclofen three times a day. These two groups will continue to receive current usual care for the prevention and treatment of cerebrovascular diseases, but drugs that affect muscle tone will not be allowed. The treatment will last for 2 weeks. The primary outcome measurement is the simplified Fugl-Meyer Assessment. The secondary outcome measurements are the Modified Ashworth Scale, Modified Barthel Scale, and the H-reflex, F response, and H/M ratios of electromyography. All outcome measurements are assessed at baseline, 2 weeks, 4 weeks, and 12 weeks after first treatment except the electromyography, which is assessed at baseline and 2 weeks after first acupuncture. DISCUSSION: This trial aims to evaluate the effects and the specific intervention time of "Wang's Jiaji" acupoints on spasticity after stroke. TRIAL REGISTRATION: ISRCTN registry, ISRCTN31511176 . Registered on 29 August 2017. Version number of protocol 2016-2-1161 Version date of protocol: 2016-1.