Safety and effects of a home-based Tai Chi exercise rehabilitation program in patients with chronic heart failure: study protocol for a randomized controlled trial.

Introduction: Chronic heart failure (CHF), as the final stage of the progression of many cardiovascular disorders, is one of the main causes of hospitalization and death in the elderly and has a substantial impact on patients' quality of life (QOL). Exercise-based cardiac rehabilitation (CR) has been shown to considerably enhance QOL and prognosis. Given the barriers to center-based CR faced by most developing countries in the form of expensive instruments, the development of home-based CR is necessary. Tai Chi, as an instrument-free exercise, has been shown to be successful in treating elderly CHF individuals. Fu Yang, as one of the academic concept of Traditional Chinese Medicine (TCM), believes that the fundamental pathogenesis of CHF is the gradual decline of Yang, and emphasizes the restoration of Yang physiological function in the treatment process. Therefore, we develope a home-based Tai Chi exercise rehabilitation program called Fu Yang Tai Chi (FYTC) for elderly CHF patients by combining the Fu Yang Theory of TCM with the CR theory. The objective of this study is to evaluate the effectiveness, acceptability, and safety of the program. Methods and analysis: We suggest conducting a parallel randomized controlled clinical trial with open label. Eighty CHF elderly participants will be randomly assigned in a 1:1 ratio to the FYTC rehabilitation program group or the moderate-intensity aerobic walking control group. Eligible participants will engage in either three sessions weekly of FYTC or walking exercise for 12 weeks. The primary outcome is the relative change in 6 min walk distance (6MWD). The secondary outcomes are the plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), QOL, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), self-rating anxiety scale (SAS) and depression scale (SDS), exercise skills, and noninvasive hemodynamic monitoring. Throughout the trial, adverse events will be recorded for safety evaluation. Researchers who are blinded to the treatment allocation will analyze the data. Ethics and dissemination: This research was authorized by the Guang'anmen Hospital Ethics Committee of the Chinese Academy of Medical Sciences (2022-141-KY). Our findings will be shared online and in academic conferences as well as in peer-reviewed journals. Trial registration number: ChiCTR2200063511.

Identification and analysis of differential miRNA-mRNA interactions in coronary heart disease: an experimental screening approach.

Objective: This aim of this study is to screen the differential molecules of kidney deficiency and blood stasis (KDBS) syndrome in coronary heart disease by high-throughput sequencing. In addition, the study aims to verify the alterations in the expression levels of miR-4685-3p and its regulated downstream, namely, C1QC, C4, and C5, using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA), and to determine whether the complement and coagulation cascade pathway is the specific pathogenic pathway. Methods: Patients diagnosed with unstable angina pectoris with KDBS syndrome, patients with non-kidney deficiency blood stasis (NKDBS) syndrome, and a Normal group were recruited. The clinical symptoms of each group were further analyzed. Illumina's NextSeq 2000 sequencing platform and FastQC software were used for RNA sequencing and quality control. DESeq software was used for differential gene expression (DGE) analysis. qPCR and ELISA verification were performed on DGE analysis. Results: The DGE profiles of 77 miRNA and 331 mRNA were selected. The GO enrichment analysis comprised 43 biological processes, 49 cell components, and 42 molecular functions. The KEGG enrichment results included 40 KEGG pathways. The PCR results showed that, compared with the Normal group, the miR-4685-3p levels decreased in the CHD_KDBS group (P = 0.001), and were found to be lower than those observed in the CHD_NKDBS group. The downstream mRNA C1 regulated by miR-4685-3p showed an increasing trend in the CHD_KDBS group, which was higher than that in the Normal group (P = 0.0019). The mRNA C4 and C5 in the CHD_KDBS group showed an upward trend, but the difference was not statistically significant. ELISA was utilized for the detection of proteins associated with the complement and coagulation cascade pathway. It was found that the expression level of C1 was significantly upregulated in the CHD_KDBS group compared with the Normal group (P < 0.0001), which was seen to be higher than that in the CHD_NKDBS group (P < 0.0001). The expression levels of C4 and C5 in the CHD_KDBS group were significantly lower than the Normal group, and were lower than that in the CHD_NKDBS group (P < 0.0001). Conclusion: The occurrence of CHD_KDBS might be related to the activation of the complement and coagulation cascade pathway, which is demonstrated by the observed decrease in miR-4685-3p and the subsequent upregulation of its downstream C1QC. In addition, the expression levels of complement C4 and C5 were found to be decreased, which provided a research basis for the prevention and treatment of this disease.

Functional compounds of ginseng and ginseng-containing medicine for treating cardiovascular diseases.

Ginseng (Panax ginseng C.A.Mey.) is the dry root and rhizome of the Araliaceae ginseng plant. It has always been used as a tonic in China for strengthening the body. Cardiovascular disease is still the main cause of death in the world. Some studies have shown that the functional components of ginseng can regulate the pathological process of various cardiovascular diseases through different mechanisms, and its formulation also plays an irreplaceable role in the clinical treatment of cardiovascular diseases. Therefore, this paper elaborates the current pharmacological effects of ginseng functional components in treating cardiovascular diseases, summarizes the adverse reactions of ginseng, and sorts out the Chinese patent medicines containing ginseng formula which can treat cardiovascular diseases.

Exploring the "gene-protein-metabolite" network of coronary heart disease with phlegm and blood stasis syndrome by integrated multi-omics strategy.

Background: According to the theory of traditional Chinese medicine, phlegm and blood stasis (PBS) is the pathological basis for coronary heart disease (CHD). This study aimed to explore the biological basis of PBS syndrome in CHD. Methods: Using a strategy that integrated RNA-seq, DIA-based proteomics, and untargeted metabolomics on 90 clinic samples, we constructed a "gene-protein-metabolite" network for CHD-PBS syndrome. We expanded the sample size and validated the differential genes and metabolites in the network through enzyme-linked immunosorbent assay. Results: Our findings revealed that the "gene-protein-metabolite" network of CHD-PBS syndrome included 33 mRNAs, four proteins, and 25 metabolites. JNK1, FOS, CCL2, CXCL8, PTGS2, and CSF1 were all poorly expressed in the PBS group during the sequencing stage, whereas arachidonic acid (AA) was highly expressed. During the validation stage, JNK1, AP-1, CCL2, and CXCL8 were poorly expressed, whereas PTGS2, CSF1, and AA were highly expressed. The area under the receiver operating curve was as follows: CSF1 [0.9635, 95%CI (0.9295, 0.9976)] >JNK1 [0.9361, 95% CI (0.8749, 0.9972)] >CXCL8 [0.8953, 95% CI (0.8222, 0.9684)] > CCL2 [0.8458, 95% CI (0.7676, 0.9241)] >AP-1 [0.7884, 95%CI (0.6869, 0.8899)]. The logistic regression model composed of CSF1 and JNK1 showed the greatest diagnostic value and significance for PBS syndrome. Conclusion: PBS syndrome is characterized by low levels of FOS, AP-1, CCL2, CXCL8, and JNK1 and elevated levels of PTGS2 and CSF1, implying that the AA metabolism is abnormal and that the JNK/AP-1 pathway is inhibited. PBS syndromes, as a subtype of CHD, may have unique molecular changes. Background. Globally, coronary heart disease (CHD) is the leading cause of death, and this would likely continue until 2030 (Mirzaei et al., 2009, 95, 740-746). According to the disease course, CHD can be classified as chronic stable CHD (or chronic coronary syndrome) and acute coronary syndrome (ACS) (Katus et al., 2017; Knuuti, 2019). Although stable CHD is not as lethal as ACS, it has a varied incidence range and patients with CHD have prolonged angina. Some symptoms of stable angina are alleviated with pharmacological therapy, but it cannot eliminate recurrent angina (Rousan et al., 2017). The clinical outcomes were not significantly improved in patients who underwent revascularization compared with those who received optimal pharmacological therapy (Shaw et al., 2008; Antman and Braunwald, 2020). A bottleneck appears to exist in CHD treatment, and traditional Chinese medicine (TCM) can act as a favorable complement. Because of its individualized treatment approach, TCM is widely practiced in eastern civilizations (Teng et al., 2016). TCM has become a principal complement in western countries (Wieland et al., 2013). Like "disease" is used in western medicine, "syndrome" is used in TCM to comprehend anomalous human conditions on the basis of patients' symptoms, tongue, and pulse (Li et al., 2012). On the basis of disease-syndrome diagnose, a TCM doctor can subclassify CHD patients into various categories, such as phlegm and blood stasis (PBS) syndrome, cold congealing and Qi stagnation syndrome, and Qi stagnation and blood stasis syndrome. PBS syndrome has recently emerged as a hot research topic in the TCM field. Objective diagnosis, expert consultations, and efficacy evaluation scales have been developed for PBS syndrome (Ren et al., 2020; Liu et al., 2021; Zheng et al., 2022). The concept of "omics" originates from the genome. It refers to the vocabulary generated by biological molecules at different levels to describe high-sequence molecular biological data resources (Dai and Shen, 2022). RNA, protein, and metabolites decipher the essence of complex etiologies, and the integration of transcriptomics, proteomics, and metabolomics are becoming a promising research mode (Pan et al., 2022). Multi-omics studies have revealed the biological characteristics of APOE transgenic mice, bronchopulmonary dysplasia, and plant tolerant to heavy metals (Singh et al., 2016; Lal et al., 2018; Mohler et al., 2020). Over the past few years, many academic achievements related to CHD-PBS syndrome have been accrued in the single-omic area. For example, Zhou identified the differential metabolites between PBS syndrome and Qi and Yin deficiency syndrome by using the urine samples of 1072 volunteers. Some of the specific metabolites of PBS syndrome are pyroglutamic acid, glutaric acid, glucose, mannitol, and xanthine (Zhou et al., 2019). Li's metabolomic study suggested that valine, leucine, isoleucine, and glycerol phospholipid metabolism could represent PBS syndrome (Zheng et al., 2022). Although some progress has been made in the understanding of PBS syndrome in CHD through the studies conducted, some issues still exist, such as a single-omics level, a lack of in-depth research, an inability to verify each other's research results, and a lack of validation of research conclusions. Overall, a systematic description of the biological foundation of PBS syndrome is lacking. Thus, the present study utilizes system biology methodologies and constructs a multi-omics network by integrating differential genes, proteins, and metabolites to systematically and comprehensively reveal the biological basis of CHD-PBS syndrome. The current study explored 1) the characteristics of the transcriptome, proteome, and metabolome for CHD-PBS syndrome; 2) the "gene-protein-metabolite" network based on differential genes (DGs), differential proteins (DPs), and differential metabolites (DMs); 3) the key biological process and metabolic pathway most related to PBS syndrome; and 4) quantitative results and the diagnostic potential of biomarkers for PSB syndrome. Materials and methods. Multi-omics sequencing, bioinformatics analysis, and clinical validation research strategy. We collected the blood samples from healthy subjects as well as CHD patients with PBS and non-phlegm and blood stasis (NPBS) syndrome to compare the differences between them by subjecting the samples to the transcriptome, proteome, and metabolomics analyses. Bioinformatics analysis identified differential molecules as well as related biological processes and pathways. Next, the "gene-protein-metabolite" network was constructed using the MetaboAnalyst database, String database, and Cytoscape software. We selected molecules with strong centrality and biological association as potential PBS syndrome biomarkers and recruited more volunteers for further validation by enzyme-linked immunosorbent assay (ELISA). Finally, the ROC curve was utilized to assess the level and diagnostic efficacy of various molecules (Figure 1).

Knowledge Mapping of Multicriteria Decision Analysis in Healthcare: A Bibliometric Analysis.

Objective: Multicriteria decision analysis (MCDA) is a useful tool in complex decision-making situations, and has been used in medical fields to evaluate treatment options and drug selection. This study aims to provide valuable insights into MCDA in healthcare through examining the research focus of existing studies, major fields, major applications, most productive authors and countries, and most common journals in the domain. Methods: A bibliometric analysis was conducted on the publication related to MCDA in healthcare from the Web of Science Core Collection (WoSCC) database on 14 July 2021. Three bibliometric software (VOSviewer, R-bibliometrix, and CiteSpace) were used to conduct the analysis including years, countries, institutes, authors, journals, co-citation references, and keywords. Results: A total of 410 publications were identified with an average yearly growth rate of 32% (1999-2021), from 196 academic journals with 23,637 co-citation references by 871 institutions from 70 countries/regions. The United States was the most productive country (n = 80). Universiti Pendidikan Sultan Idris (n = 16), Université de Montréal (n = 13), and Syreon Research Institute (n = 12) were the top productive institutions. A A Zaidan, Mireille Goetghebeur and Zoltan Kalo were the biggest nodes in every cluster of authors' networks. The top journals in terms of the number of articles (n = 17) and citations (n = 1,673) were Value in Health and Journal of Medical Systems, respectively. The extant literature has focused on four aspects, including the analytic hierarchy process (AHP), decision-making, health technology assessment, and healthcare waste management. COVID-19 and fuzzy TOPSIS received careful attention from MCDA applications recently. MCDA in big data, telemedicine, TOPSIS, and fuzzy AHP is well-developed and an important theme, which may be the trend in future research. Conclusion: This study uncovers a holistic picture of the performance of MCDA-related literature published in healthcare. MCDA has a broad application on different topics and would be helpful for practitioners, researchers, and decision-makers working in healthcare to advance the wheel of medical complex decision-making. It can be argued that the door is still open for improving the role of MCDA in healthcare, whether in its methodology (e.g., fuzzy TOPSIS) or application (e.g., telemedicine).

Efficacy and Safety of Traditional Chinese Medicine in Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis.

Introduction: Until now, there is no clinically approved specific medicine to treat COVID-19. Prior systematic reviews (SRs) have shown that traditional Chinese medicine (TCM) reduces the number of patients with severe disease and time to fever clearance, promotes clinical effectiveness, and improves chest images and the negativity rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test. Few SRs arrived at a definitive conclusion, and more randomized controlled trials (RCTs) were published. We conducted this study to summarize the latest evidence of TCM in COVID-19. Methods: Eight online databases were searched from December 2019 to July 2020, updated to March 2021. Only RCTs evaluating the clinical efficacy and safety of TCM in the treatment of COVID-19 were included. Primary outcomes were clinical cure and the negativity of the SARS-CoV-2 nucleic acid test. Secondary outcomes included clinical deterioration, ARDS, mechanical ventilation, death, time to fever clearance, duration of hospitalization, and chest imaging improvement. Safety outcomes included adverse events and serious adverse events during treatment. Two reviewers selected the included articles, assessed the risk of bias, and extracted data independently and in duplicate. Results: A total of 25 RCTs involving 2222 participants were selected in the systematic review, and seven RCTs were included in the meta-analysis. The results showed that TCM plus routine treatment was significantly better than routine treatment alone in clinical cure (risk ratio [RR] = 1.20, 95% confidence interval (CI) [1.04, 1.38], P = 0.01) and chest image improvement (RR = 1.22, 95% CI [1.07, 1.39], P = 0.01) and could reduce clinical deterioration (RR = 0.39, 95% CI [0.18, 0.86], P = 0.02), ARDS (RR = 0.28, 95% CI [0.11, 0.69], P = 0.01), mechanical ventilation (RR = 0.30, 95% CI [0.12, 0.77], P = 0.01), or death rate (RR = 0.28, 95% CI [0.09, 0.84], P = 0.02). No significant difference between TCM and routine treatment in the negativity of SARS-CoV-2 nucleic acid test (RR = 1.08, 95% CI [0.94, 1.23], P = 0.29) was observed. Finally, there was no overall significant difference in the incidence of adverse events between the two groups. The summary of evidence showed moderate confidence of a benefit of 11.8% in clinical cure and 14.0% in chest image improvement and a reduction of 5.9% in clinical deterioration, 25.4% in ARDS, 18.3% in mechanical ventilation, and 4.5% in death with TCM plus routine treatment compared to routine treatment alone in patients with COVID-19. A low confidence of a benefit of 5.4% in the negativity of SARS-CoV-2 nucleic acid test was also observed. Conclusions: Synethized evidence of 21 outcomes in 8 RCTs showed moderate certainty that TCM treatment plus routine treatment may promote a clinical cure and chest image improvement compared to routine treatment alone while reducing clinical deterioration, development of ARDS, use of mechanical ventilation, and death in patients with COVID-19. TCM treatment plus routine treatment may not promote the negativity of the SARS-CoV-2 nucleic acid test compared to routine treatment alone. TCM treatment was found to be safe for patients with COVID-19.

Panax Notoginseng Saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NF κ B Pathway.

OBJECTIVE: To explore whether Panax notoginseng saponins (PNS) exhibits heart protective effect in myocardial infarction (MI) rats and to identify the potential signaling pathways involved. METHODS: MI rats induced by ligating the left anterior descending (LAD) coronary artery were assigned to sham coronary artery ligation or coronary artery ligation. Totally 36 Sprague-Dawley rats were randomly divided into sham group (distilled water, n=9), MI group (distilled water, n=9), PNS group (PNS, 40 mg/kg daily, n=9) and fosinopril group (FIP, 1.2 mg/kg daily, n=9) according to a random number table. The left ventricular morphology and function were conducted by echocardiography. Histological alterations were evaluated by the stainings of HE and Masson. The serum levels of C reactive protein (CRP), tumor necrosis factor α (TNF-α), growth differentiation factor-15 (GDF-15) and the ratio of metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-9 (TIMP-1) were determined by ELISA. The levels of activating transcription factor 3 (ATF3), mitogen-activated protein kinase kinase 3 (MAP2K3), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylation of p38 MAPK (p-p38 MAPK), transforming growth factor-ß (TGF-ß1), collagen I, nuclear factor kappa B p65 (NFκB p65), phosphorylation of NFκB p65 (p-NFκB p65), and phosphorylation of inhibitory kappa Bα (p-Iκ Bα) in hearts were measured by Western blot and immunohistochemical staining, respectively. RESULTS: PNS improved cardiac function and fibrosis in MI rats (P<0.05). The serum levels of CRP, TNF-α, GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats. The expressions of TGF-ß1, collagen I, MAP2K3, p38 MAPK, p-p38 MAPK, NFκB p65, p-NFκB p65, and p-IκBα were down-regulated, while ATF3 increased with the treatment of PNS (P<0.05). CONCLUSIONS: PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2K3/p38 MAPK and NFκB signaling pathways. These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.

Effects of Danlou tablet for the treatment of stable angina pectoris: A study protocol of a randomized, double-blind, and placebo-controlled clinical trial.

INTRODUCTION: Stable angina pectoris has a high prevalence and causes serious harm. Revascularization therapy can relieve angina pectoris to some extent, but it is not widely accepted in China due to the cost and secondary events. The Chinese proprietary medicine Danlou tablet has been widely used to treat angina pectoris, but previous trials had inadequate methodologies. In this study, we aim to conduct a randomized controlled trial to evaluate its efficacy and safety on stable angina. METHODS AND ANALYSIS: This study is a WeChat-based randomized, double-blind, and placebo-controlled clinical trial in China. Eligible participants are adults (aged 30-75 years) with CT-confirmed stable angina and traditional Chinese medicine-diagnosed intermingled phlegm and blood stasis syndrome. A total of 76 participants will be randomly allocated in a 1:1 ratio to the oral Danlou tablet group (1.5 mg a time, 3 times daily for 28 days) or the placebo group. Patients are permitted concomitant use of routine medications during these 28 days. The primary outcome is angina frequency per week. The secondary outcomes include angina severity, angina duration, traditional Chinese medicine efficacy, the withdrawal rate of emergency medications, blood lipids, and electrocardiograph efficacy. The WeChat app will be used to remind patients to take their medicines and fill out the forms. All data will be recorded in case report forms and analyzed by Statistical Analysis System software. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (No. 2019-225-KY). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, ID: ChiCTR1900028068.

A randomized controlled trial for gualou danshen granules in the treatment of unstable angina pectoris patients with phlegm-blood stasis syndrome.

INTRODUCTION: Unstable angina pectoris is an acute exacerbation secondary to coronary artery occlusion. In routine clinical treatment, patients with unstable angina pectoris are prone to recurrence or aggravation of symptoms. Based on the traditional Chinese medicine (TCM) theory, phlegm, and blood stasis are one of the main pathological factors of unstable angina pectoris. The treatment of unstable angina pectoris with phlegm-blood stasis syndrome by Gualou Danshen granules (GLDS) has been the focus of many clinical trials. However, there is no evidence to prove the safety or clinical efficacy of GLDS. METHODS AND ANALYSIS: In this study, we will conduct a 4-week randomized, controlled feasibility study, with participants recruited from Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine. Sixty subjects are to be diagnosed as having phlegm-blood stasis syndrome and randomly divided into a treatment group (GLDS) and placebo group in a 1:1 ratio. Result measurements will include therapeutic indicators (Clinical Symptom Rating Scale, Phlegm-Blood Stasis Syndrome Scale, and Seattle Angina Questionnaire) and safety indicators (blood routine, urine routine, electrocardiogram, liver function, and kidney function). The clinical data management system (http://www.tcmcec.net/) will be used to collect and manage data. Quality control will be implemented according to good clinical practice. DISCUSSION: Previous TCM clinical trials have investigated if adding GLDS to standard routine treatment can improve the therapeutic effect in patients with unstable angina pectoris. This study focuses on the safety and efficacy of GLDS on unstable angina pectoris of phlegm-blood stasis type, in order to obtain relevant clinical evidence. TRIAL REGISTRATION: This study is approved by the Ethics Committee of Guang'anmen Hospital of the China Academy of Chinese Medical Sciences (no. 2019-187-KY-02) and is registered with chictr.org (registration number ChiCTR2000031780).

Effectiveness and safety of Suxiao Jiuxin pill in treating acute coronary syndrome: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness and safety of Suxiao Jiuxin pill (SX) in acute coronary syndrome (ACS) treatment. METHODS: An extensive search of four English databases (Medline/PubMed, Cochrane Library, Embase, and World Health Organization International Clinical Trials Registration Platform) and four Chinese databases (Chinese National Knowledge Infrastructure, Wanfang, China Science and Technology Journal, and Chinese Biomedical Literature Service System) was performed. Randomized, controlled trials (RCTs) involving SX combined with conventional therapy versus conventional therapy were included. The extracted data included populations, interventions, outcomes, and risk of bias. The cardiovascular events served as the primary outcome. Review Manager 5.3 software was used for data analysis. Relative risks (RRs) with 95% confidence intervals (CIs) were the effect measure. RESULTS: A total of eight RCTs with 979 patients were included. There were 559 patients with unstable angina (UA) in six RCTs and 420 patients with acute myocardial infarction (AMI) in two RCTs. Our review showed that SX plus conventional therapy might reduce the incidence of the total endpoint (RR: 0.34, 95% CI: 0.17, 0.68, P = 0.002), with no obvious adverse events (RR: 1.29, 95% CI: 0.60, 2.77, P = 0.52) compared with conventional therapy for patients with UA. Additionally, SX plus conventional therapy also reduced the incidence of the total endpoint (RR: 0.35, 95% CI: 0.18, 0.68, P = 0.002) compared with conventional therapy in patients with AMI. SX plus conventional therapy also reduced the incidence of ventricular fibrillation (RR: 0.23, 95% CI: 0.10, 0.57, P = 0.001) compared with conventional therapy in patients with AMI. CONCLUSION: Our results suggest that SX is beneficial for treating patients with UA or AMI. However, our findings should be treated with caution because of the poor methodological quality of the included trials. Therefore, more multicenter, large-sample, high-quality RCTs are required to provide high-quality evidence.

Qidong Yixin Oral Liquid for Viral Myocarditis: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of Qidong Yixin (QY) oral liquid in the treatment of viral myocarditis (VMC). METHODS: We searched seven databases for randomized clinical trials on QY for treating VMC. The retrieval period was from database establishment to December 31, 2019. Cochrane risk of bias tool in the Cochrane Handbook was used to assess the methodological quality. Review Manager (RevMan) 5.3 was used to analyze the results. RESULTS: We included 19 studies comprising 2,608 patients, albeit with low methodological quality. Our meta-analysis revealed that combination therapy with QY and western medicine was more effective than western medicine alone (QY vs other Chinese patent medicines: RR = 1.37, 95% Cl: 1.23∼1.52, P < 0.00001; QY + coenzyme Q10 + routine treatment vs coenzyme Q10 + routine treatment: RR = 1.20, 95% Cl: 1.14∼1.27, P < 0.00001; QY + trimetazidine + acyclovir vs trimetazidine + acyclovir: RR = 1.59, 95% Cl: 1.38∼1.83, P < 0.00001; QY + routine treatment vs routine treatment: RR = 1.09, 95% Cl: 1.03∼1.15, P < 0.003). A study on posttreatment myocardial enzyme levels revealed that QY with western medicine downregulated creatine kinase isoenzyme (CK-MB) (QY + antiviral treatment + routine treatment vs antiviral treatment + routine treatment group: MD = -11.28, 95% CI: -13.33∼-9.22, P < 0.00001; QY + routine treatment vs routine treatment: MD = -4.96, 95% CI: -5.56∼-4.32, P < 0.00001), creatine kinase (CK) (MD = -32.10, 95% CI: -35.63∼-28.57, P < 0.00001), and lactate dehydrogenase (LDH) (QY + antiviral treatment + routine treatment vs antiviral treatment + routine treatment: MD = -48.76 95% CI: -58.18∼-39.33, P < 0.00001; QY + routine treatment vs routine treatment: MD = -23.52, 95% CI: -30.10-16.94, P < 0.00001) rather than western medicine alone, with no evidence of aspartate aminotransferase (AST) downregulation on treatment with QY with western medicine (MD = 2.88, 95% CI: -0.95∼6.71, P < 0.00001) in patients. Two studies reported adverse events, indicating that QY is relatively safe. CONCLUSION: Although QY may have potential advantages in treating VMC, they remain unclear owing to the poor methodological quality of most studies. Larger, multicenter, high-quality randomized controlled trials are required to verify the effectiveness of QY.

[Effect of traditional Chinese medicine in attenuating coronary heart disease and main risk factors by regulating gut micro-biota].

Ischemic heart disease has became the world's most common deadly disease, and coronary heart disease(CHD) is the most common type of ischemic heart disease. The pathological mechanism of CHD has not been fully elucidated. In recent years, scientific studies have found that gut micro-biota are closely related to the occurrence and development of CHD, and CHD could be intervened by regulating gut micro-biota because of the correlation between CHD and intermediate metabolite of gut micro-biota. Current intervention strategies mainly include probiotics supplementation, reduction of TMAO and increase of SCFAs, which can achieve the effect of stabilizing plaques, and controlling blood pressure, blood lipids, blood glucose and obesity. Traditional Chinese medicine(TCM) has the multi-component and multi-target effects, which is correlated to its role in the prevention and treatment of CHD. This paper summarizes the domestic and foreign researches on the effect of TCM in attenuating CHD and its main risk factors by regulating gut micro-biota. The article aims to explore the correlation between gut micro-biota and CHD, and propose three main intervention strategies. Furthermore, the research progress of TCM on CHD, hypertension, dyslipidemia, hyperglycemia and obesity is reviewed by the categories of Chinese medicine monomer and compound, in the hope to provide more theoretical basis for TCM therapy on CHD and guidance for further studies in this field.

The effect of auricular therapy on blood pressure: A systematic review and meta-analysis.

BACKGROUND: Although a number of clinical studies have investigated the effectiveness and safety of auricular therapy for treating hypertension, the overall evidence remains uncertain. AIMS: We aimed to evaluate the evidence for the effect of auricular therapy on blood pressure using meta-analysis methodology. METHODS: We searched PubMed, Embase, Cochrane Library databases, Clinicalkey, China National Knowledge Infrastructure, China Scientific Journal Database and Wanfang Database and Chinese Biomedicine for trials that compared the effects of auricular therapy to that of sham auricular therapy, antihypertensive drugs, or no intervention on blood pressure. Blood pressure values before and after treatment, magnitude of blood pressure change between baseline and post-intervention, and the efficacy rate, as outcomes, were synthesized by RevMan 5.3. Continuous outcomes were expressed as weighted mean differences, and dichotomous data were expressed as relative risks with 95% confidence intervals. RESULTS: We systematically reviewed 44 randomized controlled trials (involving 5022 patients through June 2018). Auricular acupressure plus antihypertensive drugs might be more effective than antihypertensive drugs alone in both reducing systolic blood pressure value after treatment (n=464 patients; mean difference, -5.06 mm Hg; 95% confidence interval, -6.76- -3.36, p<0.00001; I2=32%), decreasing diastolic blood pressure after treatment (n=464 patients; mean difference, -5.30 mm Hg; 95% confidence interval, -6.27- -4.33, p<0.00001; I2=0%) and the efficacy rate (relative risk, 1.22; 95% confidence interval, 1.17-1.26; p<0.00001; I2=0%). CONCLUSION: Auricular therapy could be provided to patients with hypertension as an adjunct to antihypertensive drugs for lowering blood pressure value and achieving blood pressure targets.

Sensitive Biomarker Analysis of Xue-Fu-Zhu-Yu Capsule for Patients with Qi Stagnation and Blood Stasis Pattern: A Nested Case-Control Study.

OBJECTIVES: To identify the sensitive biomarker to predict the effectiveness of Xue-Fu-Zhu-Yu capsules (XFZYC). METHODS: This nested case-control study included 5 patients with response to XFZYC in the treatment group, 5 patients with no response to XFZYC also in the treatment group, and 5 patients in the control group treated with placebo who participated in the previous RCT. The mRNAs, miRNAs, lncRNAs, and circRNAs were sequenced by next-generation sequencing and differential-expressed (DE) RNAs were identified if p value ≤ 0.05 and fold change ≥2, bioinformatics analysis was conducted in terms of function annotations and signaling pathways, and then sensitive biomarker was analyzed based on real-time PCR. RESULTS: The distributions of clinical characteristics between the selected participants from treatment group and placebo group were well balanced. A total of 1156 DE RNAs, 388 miRNAs, 1954 lncRNAs, and 560 circRNAs were identified, which was associated the mechanism of XFZYC and composed the targeted potential biomarkers for further real-time PCR. The DE RNAs were enriched in KEGG pathways pertaining to pathogenesis of Qi Stagnation and Blood Stasis- (QS & BS-) & associated diseases such as coronary heart disease and digestive diseases. The expression level of FZD8 was significantly higher in response patients than that in nonresponse patients (p = 0.041) and circRNA_13799 significantly lower in response patients than that in nonresponse patients (p = 0.040) based on real-time PCR. Patients with higher expression level of FZD8 with 75% stratification have significantly higher reduction in the questionnaire score (p = 0.010), and the area under the curve (AUC) was 0.765 (95%CI = 0.593-0.936; p = 0.014). CONCLUSIONS: FZD8 might perform the sensitive biomarker for predicting the effectiveness of XFZYC. However, further prospective cohort study was warranted to confirm the exact specificity and sensitivity of this biomarker.

Effectiveness and safety of Chinese herbal medicine xuanbi antong granules for the treatment of borderline coronary lesions: study protocol for a randomised, double-blinded, placebo-controlled, multicentre clinical trial.

INTRODUCTION: As the early stage of coronary heart disease (CHD), borderline coronary lesion (BCL) is defined as a 30%-70% diameter stenosis. Previous studies have demonstrated that BCL may progress to acute coronary syndrome easily. However, routine medications available for the treatments of BCL have some limitations. Xuanbi antong granule (XAG) has been used for the treatment of BCL in China for many years. Previous studies have shown that XAG has effectiveness in improving clinical symptoms and quality of life in patients with CHD. This study aims to evaluate the effectiveness and safety of XAG in patients with BCL. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blinded, placebo-controlled clinical trial. A total of 300 participants will be randomly assigned to the intervention group and the placebo group. Based on routine medications, the intervention group will be treated with XAG and the placebo group will be treated with XAG placebo. All participants will receive a 6-month treatment and then be followed-up for another 6 months. The primary outcomes are the changes of target plaque characteristics (including target plaque volume, degree of stenosis, CT value and calcification score) measured by dual source CT angiography. The secondary outcomes include blood lipid indicators, efficacy of angina symptoms, Seattle Angina Questionnaire, high-sensitivity C-reactive protein and occurrence of major adverse cardiac events. All the data will be recorded in electronic case report forms and analysed by SPSS V.20.0. ETHICS AND DISSEMINATION: This study has been approved by Research Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (No. 2017-083-KY-01). Written informed consent will be obtained from all participants. The results of this study will be disseminated to the public through academic conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17013189; Pre-results.

Identification of differentially expressed non-coding RNAs and mRNAs involved in Qi stagnation and blood stasis syndrome.

Qi stagnation and blood stasis syndrome (QSBSS) is a common Zheng in Traditional Chinese Medicine (TCM), describes the condition of unsmooth flow of Qi and blood, which manifests as distending pain in a fixed body part and emotional disorders, including irritability and depression. However, the underlying molecular mechanisms remain largely elusive. RNAs are the connection between DNA and proteins, which reflect the interaction between the genotypes and the phenotype. Of note, non-coding (nc)RNA is a type of RNA that is not translated into any protein, but has regulatory functions. Despite the growing interest in exploring the biological basis of TCM Zhengs, the specific roles of ncRNAs in QSBSS have remained largely elusive. In the present study, next-generation sequencing was performed to investigate the ncRNA profile in patients with three different types of disease, but who had QSBSS. A total of 104 long non-coding RNAs, 2 circular RNAs and 697 mRNAs were identified to be significantly differentially expressed in QSBSS patients. Further bioinformatics analysis revealed that the most significantly enriched pathways by the differentially expressed RNAs in QSBSS were the sphingolipid signaling pathway, the neurotrophin signaling pathway, 5'AMP-activated protein kinase and endocytosis. In addition, a network pharmacology analysis indicated that several of the differentially expressed RNAs were included in the targets of TCM herbs for treating QSBSS. The present study was the first to identify ncRNAs that are deregulated in QSBSS by next-generation sequencing technology. The results may offer insight into the biological basis of TCM Zheng and the optimization of ancient formulae, as well as the discovery of novel drugs, to pave the way toward advanced TCM theory and improved health care delivery.

Xue-Fu-Zhu-Yu capsule in the treatment of qi stagnation and blood stasis syndrome: a study protocol for a randomised controlled pilot and feasibility trial.

BACKGROUND: Qi stagnation and blood stasis syndrome (QS&BSS) is one of the common Zhengs in traditional Chinese medicine (TCM), which manifests as various symptoms and signs, such as distending pain or a tingling sensation in a fixed position. In recent years, a number of clinical trials have focused on the effectiveness and safety of XFZYC in patients with a QS&BSS subtype disease, such as coronary heart disease, hyperlipidaemia, ischaemic cerebrovascular disease, gastritis, dysmenorrhoea, or arthritis, in terms of the outcomes of relevant diseases. However, there is lack of evidence of the effects of XFZYC in patients with QS&BSS with different diseases, focusing on the outcomes of Zhengs. METHODS/DESIGN: A randomised, controlled, pilot and feasibility trial will be employed in this study, using a 7-week study period. Participants will be recruited from Guang'anmen Hospital, Huguosi TCM Hospital, Wangjing Hospital in China. One hundred and twenty participants will be randomised to a treatment group (Xue-Fu-Zhu-Yu Capsule (XFZYC)) and placebo group in a 1:1 ratio. Participants included in the study must be diagnosed with Qi stagnation and blood stasis syndrome criteria. The outcome measurements will include the traditional Chinese medicine patient-reported outcome (PRO) scale for QS&BSS, the single symptom and sign scale of QS&BSS, and the pain scale of QS&BSS. The clinical data management system ( http://www.tcmcec.net /) will be used to collect and manage the data. Quality control will be used, according to Good Clinical Practice (GCP). DISCUSSION: Previous studies were expected to evaluate whether the addition of XFZYC to standard routine treatment would enhance the treatment effectiveness and improve the biomedical parameters pertaining to relevant disease. However, this trial is focused on the outcome of Zhengs, and we chose a range of outcome measurements to assess the improvement of relevant symptoms and signs. This trial is the first study designed to define and optimise the outcome measurements of Zhengs of XFZYC in the treatment of patients with QS&BSS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03091634 . Registered on 12 August 2018. Release date 6 May 2017.

Observational Study of the Association between TCM Zheng and Types of Coronary Artery Stenosis: Protocol of a Multicenter Case Series Study.

BACKGROUND: Coronary artery stenosis is the major pathological change of coronary heart disease (CHD). Within the framework of traditional Chinese medicine (TCM) theory, some kinds of TCM Zheng could exist in patients with CHD; accordingly, TCM practitioners could provide appropriate TCM therapy. However, little is known about the association between TCM Zheng and types of coronary artery stenosis. Such knowledge could help improve the accuracy and effectiveness of efforts to combine CHD treatment with TCM therapy. Therefore, the aim of this study is to determine the association between TCM Zheng and types of coronary artery stenosis. METHODS AND DESIGN: This is a multicenter, large sample, case series study in 4 tertiary A hospitals from 3 provinces in China. A total of 3,000 eligible patients diagnosed with atherosclerosis or CHD and selected to undergo coronary angiography (CAG) will be enrolled in this study. We will use electronic case report forms (eCRF) to collect information, including baseline characteristics, TCM symptoms, CAG results, and GRACE scores according to standard operating procedures (SOP). Data will be analyzed by SPSS 20.0. ETHICS: This study is approved by the Ethics Committee of Guang'anmen Hospital of the China Academy of Chinese Medical Sciences (no. 2017-058-KY-01) and is registered with chictr.org (registration number ChiCTR-ROC-17013221).

[CircRNA as a new field in human disease research].

For the characteristics of high stability， high conservation between species， and tissue specificity， circular RNA(circRNA) has been expected to become a new molecular biomarker for the clinical diagnosis， treatment and prognosis， and the potential target for targeted therapy. Study on the traditional Chinese medicine(TCM) syndrome includes not only the macro indexes collected by using four traditional methods of diagnosis， but also contains some micro information that can not be achieved by using the four traditional diagnosis methods. The questions such as how to deal with the relationship between the holistic concept of TCM and micro research， and how to solve the contradiction between the fuzziness of syndrome description and the accuracy of microscopic research， need to be considered before the micro research in TCM syndrome. circRNA as a new field of understanding human disease， may provide some ideas for the TCM syndrome research due to its characteristics. Overall， it is necessary to pay attention to explore the molecular level with same syndrome in different diseases and reveal the connotation and essence of syndromes by understanding of circRNA.

Therapeutic Effects of Breviscapine in Cardiovascular Diseases: A Review.

Breviscapine is a crude extract of several flavonoids of Erigeron breviscapus (Vant.) Hand.-Mazz., containing more than 85% of scutellarin, which has been traditionally used in China as an activating blood circulation medicine to improve cerebral blood supply. Accumulating evidence from various in vivo and in vitro studies has shown that breviscapine exerts a broad range of cardiovascular pharmacological effects, including vasodilation, protection against ischaemia/reperfusion (I/R), anti-inflammation, anticoagulation, antithrombosis, endothelial protection, myocardial protection, reduction of smooth muscle cell migration and proliferation, anticardiac remodeling, antiarrhythmia, blood lipid reduction, and improvement of erectile dysfunction. In addition, several clinical studies have reported that breviscapine could be used in conjunction with Western medicine for cardiovascular diseases (CVDs) including coronary heart disease, myocardial infarction, hypertension, atrial fibrillation, hyperlipidaemia, viral myocarditis, chronic heart failure, and pulmonary heart disease. However, the protective effects of breviscapine on CVDs based on experimental studies along with its underlying mechanisms have not been reviewed systematically. This paper reviewed the underlying pharmacological mechanisms in the cardioprotective effects of breviscapine and elucidated its clinical applications.