The Effect of Shen-Yuan-Dan Capsule on Autophagy-Related Gene Atg13 Promoter Methylation and Genomic Methylation Levels in Atherosclerotic Mice.

BACKGROUND: Moderate autophagy plays a positive role in the prevention of atherosclerosis. Aberrant promoter methylation of autophagic genes can affect autophagy. Shen-Yuan-Dan Capsule (SYDC), a traditional Chinese medicine, can prevent atherosclerosis in high-fat-fed mice. However, its precise mechanism remains unclear. This study investigated the mechanism of SYDC in ameliorating atherosclerosis in a mice model. METHODS: After 6 weeks of a high-fat diet, apolipoprotein E knockout (apoE-/-) mice were randomly grouped into control, Lipitor, and SYDC groups (n = 10). The mice were intragastrically administered with the respective drugs for 6 weeks. The expressions of Beclin1 and Atg5-Atg12 complex in atherosclerotic plaques of the mice were measured. The levels of 5-mC and DNA methyltransferase 1 (DNMT1) in the plasma of the mice were determined. The average methylation rate of CpG islands in the promoter region of autophagy-related protein (Atg13) and the mRNA expression of Atg13 in the aortas of the mice were determined. RESULTS: SYDC up-regulated the expressions of Atg5-Atg12 complex and Beclin-1 in atherosclerotic plaques (p < 0.01). Moreover, SYDC decreased the 5-mC and DNMT1 levels in plasma and atherosclerotic plaques of the mice (p < 0.01), and also decreased the average methylation rate of CpG islands in the promoter region of Atg13 and increased the mRNA levels of Atg13 in the aortas of atherosclerotic mice (p < 0.01). CONCLUSIONS: SYDC attenuates atherosclerosis by promoting autophagy, probably through regulating genomic DNA methylation and Atg13 promoter demethylation.

Association of ankylosing spondylitis with cardiovascular disease: a bidirectional two-sample mendelian randomization study.

Backgrounds: Current observational investigations hint at a potential linkage between ankylosing spondylitis and cardiovascular wellness. However, the nature of this causality remains to be elucidated. Consequently, this study is designed to evaluate the causal interconnection between ankylosing spondylitis and cardiovascular-related conditions utilizing a bidirectional two-sample Mendelian Randomization (MR) methodology. Methods: In this study, we conducted Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data. The fixed-effects inverse variance weighted (IVW) model was used as the primary analysis method, and MR-Egger regression and the weighted median method were employed as supplementary approaches. Horizontal pleiotropy and heterogeneity were evaluated using various statistical tests, including MR-PRESSO global test, MR-Egger intercept, and Cochran's Q test. Results: The MR result demonstrated an increased risk of heart failure in individuals with ankylosing spondylitis (OR: 1.0132, 95% CI = 1.0043-1.0221, p = 0.003). The MR analysis results did not demonstrate a causal relationship between ankylosing spondylitis and other cardiovascular diseases, such as atrial fibrillation, coronary artery disease, ischemic stroke, myocardial infarction, and valvular heart disease (all p > 0.05). No evidence of reverse causality was found between ankylosing spondylitis and mentioned cardiovascular diseases in reverse MR analyses. Sensitivity analysis verified the reliability of the results. Conclusion: Our MR study indicates a relationship between ankylosing spondylitis and an increased risk of heart failure. Further research is needed to confirm these findings and elucidate the underlying mechanisms involved.

Effect of Traditional Chinese Medicine Cutaneous Regions Therapy as adjuvant treatment of chronic heart failure: A systematic review and meta-analysis.

Objective: To systematically evaluate the effectiveness of Traditional Chinese Medicine Cutaneous Regions Therapy (TCMCRT) as an adjunctive treatment for chronic heart failure. Methods: China National Knowledge Infrastructure (CNKI), Wanfang database, China Science and Technology Journal Database (VIP), Chinese BioMedical Literature Database (CBM), Cochrane Library, PubMed, Web of Science, and EMBASE database were searched to screen randomized controlled trials (RCTs) of TCMCRT for chronic heart failure versus conventional western treatment for chronic heart failure. The Cochrane Risk of Bias Collaboration tool was used to assess the risk of bias in RCTs. Meta-analysis was performed using RevMan 5.3 software to systematically evaluate the effects of conventional western treatment combined with TCMCRT on the cardiac function efficacy, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-min walk test (6MWT), Minnesota Heart Failure Quality of Life Scale (MLHFQ) and Adverse effects, as well as to evaluate the safety of this treatment modality. Results: 18 RCT studies were finally included, with a total of 1388 patients, including 695 in the experimental group and 693 in the control group. The results of the Meta-analysis showed that the efficacy of improved cardiac function was better in the experimental group than in the control group [RR = 1.24, 95%CI (1.16, 1.32), P < 0.00001]. Improvement of LVEF in the experimental group was better than the control group [MD = 0.04, 95%CI (0.02, 0.05), P < 0.00001]. LVEDD were better in the experimental group than in the control group after treatment [MD = -3.63, 95% CI (-6.14, -1.12), P = 0.005]. The experimental group improved NT-proBNP better than the control group [MD = -586.26, 95%CI (-857.83, -314.68), P < 0.0001]. The experimental group improved 6MWT better than the control group [MD = 38.76, 95%CI (20.77, 56.75), P < 0.0001]. The experimental group improved MLHFQ values better than the control group [MD = -5.93, 95%CI (-7.70, -4.16), P < 0.00001]. Nine of the included studies mentioned the occurrence of adverse reactions, but none reported serious adverse reactions. Conclusion: The available evidence suggests that TCMCRT has good efficacy in the adjuvant treatment of chronic heart failure. However, due to the limitations of this study, more high-quality studies are needed to further validate this conclusion.

Pharmacological Effects of Botanical Drugs on Myocardial Metabolism in Chronic Heart Failure.

Although there have been significant advances in the treatment of heart failure in recent years, chronic heart failure remains a leading cause of cardiovascular disease-related death. Many studies have found that targeted cardiac metabolic remodeling has good potential for the treatment of heart failure. However, most of the drugs that increase cardiac energy are still in the theoretical or testing stage. Some research has found that botanical drugs not only increase myocardial energy metabolism through multiple targets but also have the potential to restore the balance of myocardial substrate metabolism. In this review, we summarized the mechanisms by which botanical drugs (the active ingredients/formulas/Chinese patent medicines) improve substrate utilization and promote myocardial energy metabolism by activating AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptors (PPARs) and other related targets. At the same time, some potential protective effects of botanical drugs on myocardium, such as alleviating oxidative stress and dysbiosis signaling, caused by metabolic disorders, were briefly discussed.

Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium.

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION: DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.

Efficacy of Chinese Medicine Injection for Cardiotoxic Injury of Anthracycline Chemotherapy Drugs: A Network Meta-Analysis of Randomized Controlled Trials.

Background: Chinese medicine injections (CMIs) are widely used in the prevention and treatment of cardiotoxicity caused by anthracycline chemotherapeutic drugs. However, it is uncertain that CMIs are more effective in combating the cardiotoxicity of anthracyclines. The aim of this Network Meta-analysis (NMA) was to compare the treatment effects of various CMIs in order to determine the best CMI for the prevention and treatment of cardiac damage from anthracyclines. Methods: The Chinese Journal Full Text Database (CNKI), Wanfang Database, Chinese Science and Technology Journal Full Text Database (VIP), Chinese Biomedical Literature Database (CBM), PubMed, Web of Science, and Cochrane Library databases were searched to screen randomized controlled trials (RCTs) of CMIs against cardiotoxicity of anthracycline-based chemotherapeutic drugs. The search time frame was all from the establishment of the database to October 1, 2021. After independent screening of the literature, extraction of information and evaluation of the risk of bias of the included studies by two evaluators, mesh meta-analysis was performed using RevMan 5.3, Stata 15.1, and ADDIS 1.16.8 software. Results: A total of 33 studies including 2783 patients, including 1410 cases in the experimental group and 1373 cases in the control group were included, and six CMIs were extracted, namely, Shenfu injection, Shenmai injection, Shenqi Fuzheng injection, Shengmai injection, Xinmailong injection, and Haungqi injection. The results of the reticulated meta-analysis showed that in terms of ST-T segment (ECG change) change rate, Haungqi injection, Shenfu injection, and Xinmailong injection were superior. In terms of lowering CK-MB, Huangqi Injection and Shenqi Fuzheng injection were superior. In terms of improving Left ventricular ejection fraction (LVEF), Shenfu injection, Huangqi Injection, and Shengmai injection were more effective than other injections. In terms of improving LVEDD, Shengmai injection, Huangqi Injection, and Xinmailong injection have advantages. Conclusion: The six CMIs included in this study are effective against cardiotoxicity caused by anthracycline-based chemotherapeutic agents. Huangqi Injection and Shenfu injection are both superior in improving various outcome indicators. There is still a need for larger, high-quality randomized controlled trials (RCTs) to compare the various CMIs in a more refined way.

Efficacy and safety of eight types Salvia miltiorrhiza injections in the treatment of unstable angina pectoris: A network meta-analysis.

Background: Salvia miltiorrhiza Bunge. [Lamiaceae, danshen] injection classes (SMIC) is widely used in the treatment of unstable angina (UA). However, it is uncertain which SMIC is more effective in terms of UA efficacy. The purpose of this Network Meta-analysis (NMA) was to compare the treatment effects of various SMIC to determine the best SMIC for the treatment of UA. Methods: The China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), Chinese Biomedical Literature Database (CBM), PubMed, Web of Science, and Cochrane Library databases were searched to screen randomized controlled trials (RCTs) of SMIC for UA. The search time frame was all from the establishment of the database to May 2022. RevMan 5.3 and Stata 14.0 software were used for NMA. Results: A total of 148 studies including 14,979 patients, including 7,584 cases in the experimental group and 7,395 cases in the control group were included, and eight SMIC were extracted, namely:Danshen injection, Fufang Danshen injection, Guanxinning injection, Danshenchuanxiongqin injection, Danhong injection, Danshentong IIA Huangsuanna injection, Shenxiong Putaotang injection, and Danshenduofensuanyan injection. The results of NMA showed that, in terms of total effective rate, Shenxiong Putaotang injection and Danshenchuanxiongqin injection have the advantage; In terms of ECG efficiency, Danshentong IIA Huangsuanna injection and Danshen injection have an advantage; Danshenchuanxiongqin injection and Danshenduofensuanyan injection were more effective than other SMIC in improving angina pectoris attacks; Shenxiong Putaotang injection has an advantage in improving hs-CRP; Shenxiong Putaotang injection and Danshentong IIA Huangsuanna injection have advantages in improving TC and TG, respectively. Conclusion: The eight SMIC included in the current study were effective in treating UA, Shenxiong Putaotang injection and Danshentong IIA Huangsuanna injection were both superior in improving all outcome indicators. However, there is still a need for larger samples and high-quality randomized controlled trials for more refined comparisons of various SMIC. Systematic Review Registration: [PROSPERO], identifier [CRD42022350872].

Clinical Characteristics and Risk Factors of Periprocedural Myocardial Injury in Patients with Elective PCI in a TCM Hospital.

Objective: To investigate the clinical characteristics of patients with unstable angina (UA) who received elective percutaneous coronary intervention (PCI) in a traditional Chinese medicine (TCM) hospital and to analyze the related risk factors of periprocedural myocardial injury (PMI). Methods: On the basis of cross-sectional investigation, the case-control method was adopted. We retrospectively collected clinical data of patients with UA who successfully received elective PCI in Beijing Hospital of TCM from February 2017 to February 2019. Based on the occurrence of PMI, the case-control was formed. The influence of related factors on PMI occurrence was analyzed using the logistic multiple regression equation based on the parameters between the comparison groups. Results: 1. Incidence of PMI and related clinical features: Of the 265 UA patients, the incidence of PMI was 26.4%, nearly one quarter (23.4%) had old myocardial infarction, nearly half (45.3%) had previously received coronary intervention. The prevalence of patients with previous hypertension (75.8%), type 2 diabetes (57%), and high-low-density lipoprotein cholesterolemia (69.3%) exceeded 50%, more than 50% of the patients have triple-vessel disease (50.2%). 2. Features of TCM syndrome elements: The main TCM syndromes of the investigated patients are blood stasis syndrome (81.1%) and Qi deficiency syndrome (77.3%), the others include Phlegm turbidity syndrome (53.2%), Yang deficiency syndrome (50.9%), Yin deficiency syndrome (50.1%), Qi stagnation syndrome (30.1%), and coagulated cold syndrome (17.1%). 3. Factors of PMI occurrence: According to the occurrence of PMI, 265 patients were divided into PMI group (n = 70) and non-PMI group (n = 195). The comparison between groups shows that the preoperative SYNTAX score, the number of stents, and the total length of stents of the patients in the PMI group were higher than those in the non-PMI group (P < 0.05); the patients in the PMI group treated by Shen-Yuan-Dan (SYD), a Chinese medicine prescription with Qi-supplementing and blood stasis-purging, were significantly lower than those in the non-PMI group (P < 0.05). Brought these four factors (preoperative SYNTAX score, number of stents implanted, total length of implanted stents, and treated by SYD) into the binary logistic regression equation, those who were only treated by SYD have statistical significance in the equation as a protective factor (OR 0.327, 95% CI 0.117-0.916, P=0.033). Conclusion: Patients with UA who received elective PCI in TCM institutions may have clinical characteristics including multiple accompanying diseases and high stenosis coronary artery, in which the incidence of poor blood glucose control and high rate of three-vessel coronary disease are particularly significant. The TCM syndromes are mainly Qi deficiency and blood stasis syndromes. The decrease of PMI may be attributed to the application of SYD in the real world. This trial is registered at ChiCTR2100043465.

A randomized, placebo-controlled, double-blind trial to evaluate efficacy and safety of Shen-Yuan-Dan capsules, a traditional Chinese medicine, for treatment of peri-procedure myocardial injury following percutaneous coronary intervention.

BACKGROUND: Peri-procedural myocardial injury (PMI) is a common complication of percutaneous coronary intervention (PCI), which cannot be entirely avoided using available treatments. The findings of earlier research have shown that Shen-Yuan-Dan (SYD) capsules, a traditional Chinese medicine, can potentially alleviating PMI. This study aimed to confirm further this hypothesis in a rigorous, well-designed randomized controlled study. METHODS: Our clinical trial was randomized, double-blinded, and placebo-controlled. A total of 181 patients with unstable angina (UA) undergoing elective PCI were randomized to pretreatment with SYD or a placebo under the basis of conventional treatment; 87 patients were pretreated with SYD (4 capsules, 3 times a day, with a further 4 capsules 2 h before PCI) 3 days before the procedure, and 94 patients were given a placebo. No patients received reloading statins before PCI, and SYD or placebo was maintained for 1 month after PCI. The primary endpoint was the incidence of PMI. The secondary endpoint was calculating the incidence rate of all 30-day major adverse cardiovascular events (all-cause mortality, non-fatal myocardial infarction, unplanned revascularization). The safety outcomes, including abnormalities in electrocardiogram and serum biochemical examinations caused by drug use, were also tested. RESULTS: The levels of creatine kinase-myocardial band (CK-MB) in both the SYD and placebo groups were increased at 4 h and 24 h after PCI compared with before the procedure (P < 0.05). The incidence rate of PMI in the SYD group (10.3 %) was lower than that in the placebo group (34 %) (absolute difference, 23.7 % [95 % CI, 11.7-34.8 %], P < 0.01). After taking SYD, the relative risk reduction (RRR) and absolute risk reduction (ARR) were 69.7 % and 24.3 %, respectively; further, number needed to treat (NNT) was 4.2. The 30-day major adverse cardiovascular event (MACE) rate was not statistically different between the SYD and placebo groups (6.9 % vs. 9.6 %, P = 0.352). There were no abnormal situations during the trial. CONCLUSION: These findings showed that pretreatment with SYD could safely reduce the incidence rate of PMI in patients with UA undergoing elective PCI. Further study on the effects of SYD and how it can improve adverse cardiovascular events outcomes is needed.

Efficacy and safety of Tonifying Qi and activating blood Chinese herbal prescriptions for myocardial infarction: Study protocol for a multi-centered RCT.

INTRODUCTION: Acute myocardial infarction (AMI) is a common cause of death worldwide and heart failure (HF) is the main complication. Although the increase in percutaneous coronary intervention and drug treatment can reduce in-hospital mortality after AMI, the incidence of HF after AMI and the resulting risk of death are still rising, which causes difficulties in the rehabilitation of AMI patients after reperfusion. METHODS: In this prospective, multicenter, randomized, double-blind, double-dummy, placebo-controlled trial, we will assigned 673 eligible patients with AMI after reperfusion into 4 groups: receiving Nao-Xin-Tong capsule (NXT), Bu-Yang-Huan-Wu (BYHW) granule (BYHW), Yang-Yin-Tong-Nao granule (YYTN), or placebo. The course of treatment will be 3 months. The primary outcome is HF incidence within 180 days. Nao-Xin-Tong capsule, BYHW granule, and Yang-Yin-Tong-Nao granule are different traditional Chinese medicines used for tonifying Qi and activating blood (TQAB). RESULTS: Three months of TQAB combined with Western medicine may reduce the incidence of HF after reperfusion of AMI and improve patients' quality of life. DISCUSSION: This study will provide an important basis for the application of traditional Chinese medicine in patients with AMI after reperfusion and provide an evidence-based basis for the prevention and treatment strategy of HF after AMI.

Acute Myocardial Infarction in Chinese Medicine Hospitals in China from 2006 to 2013: An Analysis of 2311 Patients from Hospital Data.

OBJECTIVE: To assess the trends in characteristics, treatments, and outcomes of acute myocardial infarction (AMI) patients in tertiary Chinese medicine (CM) hospitals in China between 2006 and 2013. METHODS: This retrospective study was based on two nationwide epidemiological surveys of AMI in tertiary CM hospitals during 2 years (2006 and 2013). Patients admitted to the hospital for AMI were enrolled. Hospital records were used as the data source. Case data were derived regarding baseline characteristics, treatments, and outcomes of patients to assess changes from 2006 to 2013. Logistic regression was used to analyze the relationship between prognosis, general influencing factors of disease, and various treatment measures. RESULTS: Totally 26 tertiary CM hospitals in 2006 and 29 tertiary CM hospitals in 2013 (18 were repetitive) were surveyed. A total of 2,311 patients with AMI were enrolled (1,094 cases in 2006 and 1,217 cases in 2013). From 2006 to 2013, the mean age did not significantly change, but the proportion of patients younger than 65 years increased. The prevalence of risk factors such as hypertension, diabetes, and hyperlipidemia also increased. Significant increases were observed in primary percutaneous coronary intervention [20.48% (2006) vs. 24.90% (2013)] and revascularization [36.11% (2006) vs. 52.42% (2013)]. In-hospital mortality decreased from 11.15% in 2006 to 10.60% in 2013. A mortality logistic regression analysis identified reperfusion therapy [odds ratio (OR), 0.222; 95% confidence interval (CI), 0.106-0.464], Chinese patent medicines (OR, 0.394; 95% CI, 0.213-0.727), and CM decoctions (OR, 0.196; 95% CI, 0.109-0.353) as protective factors. CONCLUSION: Reperfusion and revascularization capabilities of tertiary CM hospitals have improved significantly, but in-hospital mortality has not significantly decreased. Efforts are needed to improve medical awareness of AMI and expand the use of CM to reduce in-hospital mortality in China.

Efficacy and safety of Shen-Yuan-Dan capsules for peri-procedural myocardial injury following percutaneous coronary intervention: study protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Peri-procedural myocardial injury (PMI) during percutaneous coronary intervention (PCI) will result in an unfavorable clinical prognosis in patients, thus urgently necessitating effective drug treatment measures. Shen-Yuan-Dan (SYD) capsules are a traditional Chinese medicine (TCM) preparation that have been found to have potential myocardial protection effects during the peri-procedural phase of PCI in previous clinical and basic research; however, there is a lack of rigorous, randomized, and controlled studies. The aim of this study is to evaluate the efficacy and safety of SYD in decreasing PMI. METHODS: This is a randomized, double-blind, placebo-controlled clinical trial. A total of 284 patients with unstable angina will be randomized into test and control groups. The two groups will be given SYD or a placebo (three times each day, four capsules each time) 3 days before PCI on the basis of conventional treatment. Twelve hours before PCI, an additional 4 capsules will be given, and drug treatment is planned to be maintained for 1 month after surgery. Dynamic changes in the myocardial enzyme in four time-points (before PCI, and 4, 24, 48 hours after PCI) in both groups of patients that will be observed. The follow-up period will be 1 month. The primary observation markers are planned to evaluate the efficacy and safety of SYD in decreasing PMI. The secondary observation markers will be to evaluate the major adverse cardiovascular events (MACEs) status at day 30 after PCI, (all-cause mortality, non-fatal myocardial infarction, repeated revascularization of target blood vessel) and Seattle Angina Questionnaire scores. GRACE scores will be used for risk stratification, and the intervention efficacy of SYD on PMI patients with different risks will be retrospectively evaluated. DISCUSSION: This study will provide a rigorous clinical evidence to evaluate the efficacy and safety of SYD in decreasing PMI and the results are worth anticipating. TRIAL REGISTRATION: The design of this trial has been registered with the Chinese Clinical Trial Registry (No. ChiCTR-IPR-17011069).