Shengjie Tongyu Decoction Regulates Cardiomyocyte Autophagy Through Modulating ROS-PI3K/Akt/mTOR Axis by LncRNA H19 in Diabetic Cardiomyopathy.

Context: Diabetic cardiomyopathy (DCM) is particularly dangerous in diabetes mellitus (DM). The Shengjie Tongyu decoction (SJTYD) is a well-known, traditional Chinese medicinal formulation that practitioners use to treat myocardial diseases in China; however, its role in DCM remain unclear. Objective: The study intended to investigate: (1) SJTYD's role in the treatment of DCM and its underlying mechanisms, (2) the association of autophagy with DCM, and (3) the involvement of mammalian target of rapamycin (mTOR) signaling in the regulation of DCM. Design: The research team performed an animal study. Setting: The study took place in the Department of Endocrinology in the No. 2 ward-Traditional and Complementary Medicine(TCM) of the China-Japan Friendship Hospital in Beijing, China. Animals: The animals were 60 C57/BL6 mice weighing 200-250 g. Intervention: To determine the role of SJTYD in treating DCM, the research team established a mouse model of DM using streptozotocin (STZ). The team randomly divided the mice into three groups with 20 mice each: (1) a negative control group, which didn't receive injections of STZ or treatment with SJTYD; (2) a model group, the Model group, which received injections of STZ but didn't receive treatment with SJTYD; and (3) an SJTYD group, which received injections of STZ and treatment with SJTYD. Outcome Measures: The research team: (1) conducted a differential analysis to identify the differentially expressed genes; (2) performed deep sequencing of the long noncoding RNAs (lncRNAs) expressed in cardiomyocytes from the control, Model, and SJTYD groups ; (3) performed a bioinformatics analysis; (4) used the ultrasonic and pathological, transmission electron microscopy (TEM) test as well as a Western blot to evaluate cardiac function, myocardial-injury areas, and autophagy in vivo; (5) transfected primary cardiomyocytes treated them with lncRNA H19 and SJTY 3-MA to establish SJTYD subgroups in which the H19 protected against DCM and the 3-MA inhibited autophagy; and (6) carried out immunofluorescence staining and Western blot to test the phosphorylated levels of phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) as well as autophagy levels in vitro. Results: The bioinformatics analysis indicated that SJTYD significantly modulated lncRNA H19 as well as the mTOR pathway. The vevo2100's results indicated the SJTYD reversed the cardiac-dysfunction parameters in DCM. The Masson' staining, TEM, and Western blot demonstrated that the SJTYD could suppress the myocardial-injury areas as well as the numbers of autophagosomes and the expression proteins of autophagy in vivo. The SJTYD promoted the phosphorylated-levels of PI3K, AKT, and mTOR and decreased the levels of autophagy proteins. LC3A-II and Beclin-1; lncRNA H19 amplified the SJTYD's role; and 3-MA reversed those effects, as tested using immunofluorescence and Western blot in primary cardiomyocytes. Conclusions: The SJTYD can protect against diabetic myocardial injury by inhibiting cardiomyocyte autophagy through the activation of lncRNA H19, reactive oxygen species (ROS), and the PI3K/Akt/mTOR signaling pathway. SJTYD may be an effective strategy to ameliorate diabetic myocardial injuries.

Mapping the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to SF-6Dv2 in Chinese patients with heart failure.

PURPOSE: Mapping the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to SF-6Dv2 in Chinese patients with chronic heart failure, and to obtain the health utility value for health economic assessment. METHODS: Four statistical algorithms, including ordinary least square method (OLS), Tobit model, robust MM estimator (MM) and censored least absolute deviations (CLAD), were used to establish the alternative model. Models were validated by using a tenfold cross-validation technique. The mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate the prediction performance of the model. The Spearman correlation coefficient and Intraclass Correlation Coefficients (ICC) were used to examine the relationship between the predicted and observed SF-6Dv2 values. RESULTS: A total of 195 patients with chronic heart failure were recruited from 3 general hospitals in Beijing. The MLHFQ summary score and domain scores of the study sample were negatively correlated with SF-6Dv2 health utility value. The OLS regression model established based on the MLHFQ domain scores was the optimal fitting model and the predicted value was highly positively correlated with the observed value. CONCLUSION: The MLHFQ can be mapped to SF-6Dv2 by OLS, which can be used for health economic assessment of cardiovascular diseases such as chronic heart failure.

Xuefuzhuyu decoction for hyperlipidemia: a systematic review and meta-analysis of randomized clinical trails.

OBJECTIVE: To evaluate the efficacy and safety of Xuefuzhuyu decoction for hyperlipidemia. METHODS: Randomized clinical trials on hyperlipidemia treated by Xuefuzhuyu decoction, either alone or with Western Medicine, were searched in electronic databases. Databases searched were: MEDLINE, Allied and Complementary Medicine Database, EMBASE, The Cochrane Library 2013 (Issue 4), China National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, and Wanfang Database up to 2 May, 2013. Study selection, data extraction, quality assessment, and data analysis were conducted according to the Cochrane standards. RESULTS: Six randomized clinical trials involving 748 patients (373 patients in the treatment group, 375 patients in the control group) were included in the analysis. The studies were of low methodological quality. Meta-analysis indicated that the effect of Xuefuzhuyu decoction on hyperlipidemia was better than that in the control group [n = 748, OR = 5.07, 95% CI (3.40, 7.58), P < 0.01]. Weighted mean differences in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and high-density lipoprotein cholesterol were - 0.79, - 0.74, - 0.44, 0.16, respectively, and Meta-analysis revealed that the treatment group was better than the control group with 95% CI (- 1.21, - 0.36),(- 0.94, - 0.55), (- 0.77, - 0.11), (0.04, 0.27), respectively (all P < 0.05). Some adverse events in evaluated studies were recorded. CONCLUSION: Xuefuzhuyu decoction may be effective for treating hyperlipidemia. The studies we analyzed were of low methodological quality, which indicates that the above findings should be considered cautiously. Therefore, more strictly designed large-scale randomized clinical trials are needed to evaluate the efficacy of Xuefuzhuyu decoction in hyperlipidemia.

Minimum clinically important differences in the Minnesota Living with Heart Failure questionnaire: from a study of heart failure patients treated with integrated Chinese and Western medicine.

Objective: The purpose of this study was to estimate the minimum clinically important differences (MCIDs) in the Minnesota Living with Heart Failure questionnaire (MLHFQ), which targeted patients with heart failure treated with integrated Chinese and Western medicine, as a means of helping doctors and patients judge the effectiveness of intervention. Methods: A total of 194 patients with chronic heart failure were recruited from three general hospitals in Beijing. Anchor-based and distribution-based approaches were used to estimate MCID. The anchor was SF-36 item 2 (HT, Health Transition), and the calculation methods included the mean change method, receiver operating characteristic (ROC) curve analysis, and linear regression model. For the distribution-based approaches, 0.2, 0.5, and 0.8 standardized response mean (SRM) values and standard error of measurement (SEM) value of 1 were used. Results: The correlation coefficients of the MLHFQ scale information and HT were 0.346-0.583. Different MCIDs were obtained by the mean change method, ROC curve, and linear regression model. The minimum MCID in the physical domain, emotional domain, and total scores were 3.6, 2.0, and 7.4, respectively; the maximum estimates were 9.5, 2.5, and 13.0, respectively; and the average estimates were 5.7, 2.2, and 10.0, respectively. The average estimates were close to the result of the 0.5 SRM or 1 SEM. Conclusion: We established MCIDs in the MLHFQ using anchor-based and distribution-based approaches. It was recommended to round the average estimates of anchor-based approaches up to the nearest whole number for the MCIDs of the MLHFQ physical domain, emotional domain, and total scores. The results were 6.0, 2.0, and 10.0, respectively.

Xuesaitong promotes myocardial angiogenesis in myocardial infarction mice by inhibiting MiR-3158-3p targeting Nur77.

This study aims to investigate the regulatory effect of Xuesaitong (XST) and miR-3158-3p on angiogenesis. All mice were randomly assigned into Sham group, Model group, XST group, XST + miR-3158-3P-overexpression (miRNA-OE) group. XST was found to increase the left ventricular anterior wall thickness at end diastole and end systole (LVAWd and LVAWs), left ventricular internal dimension at end diastole and end systole (LVIDd and LVIDs), fractional shortening (FS), and ejection fraction (EF) and decrease the proportion of fibrotic areas in mice. In contrast to those in Sham group, the protein expressions of Nur77, p-PI3K, HIF-1α, VEGFs, COX-2 in the heart tissues of mice in Model group were elevated and further increased after XST treatment in comparison with those in Model group. Nur77-/- mice were utilized. It was found that XST enhanced cell viability through a methyl thiazolyl tetrazolium assay and facilitated angiogenesis in each group, as assessed by a catheter formation assay. Specifically, XST was shown to promote the formation of blood vessels. Moreover, the protein expression levels of Associated proteins in the heart tissues of Nur77-/- mice were dramatically reduced in mice in Model and XST group compared with those in WT mice. Additionally, the above-mentioned protein expressions in the heart tissues of Nur77-/- mice did not change significantly in mice in Model + miRNA-OE + XST group compared with those in WT mice, suggesting that miR-3158-3p can specifically inhibit the expression of Nur77. In conclusion, XST inhibits miR-3158-3p targeting Nur77 to facilitate myocardial angiogenesis in mice with myocardial infarction.

An unusual contrast-induced encephalopathy following percutaneous coronary intervention in patients with cerebrovascular abnormalities: A case report.

Introduction: Contrast-induced encephalopathy (CIE) is a complication associated with the administration of iodinated contrast, which usually happens minutes to hours after contact with contrast, and fully recovers within 72 h. The clinical manifestations of CIE are diverse, and the pathological mechanism is not explicit. Methods: We report the case of a 66-year-old female who suffered from a delayed CIE following the administration of iodinated contrast agent. Symptoms were severe. Imaging examination, biochemical and etiological detection were performed timely. The course of neurological symptoms was atypical. Her complex complications of hypothyroidism and cerebrovascular abnormalities contributed to more challenges, which were also clues to the diagnosis. With prompt and active treatment, the patient recovered fully over 10 days. Discussion: The diagnosis standard of CIE highly depends on the association with the contact of contrast and the exclusion of other nervous system diseases. Complicated clinical circumstances and individual specificity can lead to different clinical manifestations of CIE, making it even more difficult to diagnose and treat. Prompt and dynamic imaging examination would provide great value in the diagnosis and evaluation of CIE. Timely diagnosis and intervention may be the key to its satisfying prognosis.

LncRNA H19 inhibits ER stress induced apoptosis and improves diabetic cardiomyopathy by regulating PI3K/AKT/mTOR axis.

OBJECTIVE: Extensive studies have shown that ERS may be implicated in the pathogenesis of DCM. We explored the therapeutic effects of lncRNAH19 on DCM and its effect on ERS-associated cardiomyocyte apoptosis. METHODS: C57/BL-6j mice were randomly divided into 3 groups: non-DM group (controls), DM group (DCM), and lncRNAH19 overexpression group (DCM+H19 group). The effect of H19 on cardiac function was detected. The effect of H19 on cardiomyocyte apoptosis and cardiac fibrosis in DM was examined. Differentially expressed genes (DEGs) and activated pathways were examined by bioinformatics analysis. STRING database was applied to construct a PPI network using Cytoscape software. The expression of p-PERK, p-IRE1, ATF6, CHOP, cleaved caspase-3, -9, -12 and BAX proteins in cardiac tissue was used to determine the ERS-associated apoptotic indicators. We established the HG-stimulated inflammatory cell model. The expression of p-PERK and CHOP in HL-1 cells following HG was determined by immunofluorescence labeling. The effects of H19 on ERS and PI3K/AKT/mTOR pathway were also detected. RESULTS: H19 improved left ventricular dysfunction in DM. H19 could reduce cardiomyocytes apoptosis and improve fibrosis in vivo. H19 could reduce the expression of p-PERK, p-IRE1α, ATF6, CHOP, cleaved caspase-3, cleaved caspase-9, cleaved caspase-12, and BAX proteins in cardiac tissues. Furthermore, H19 repressed oxidative stress, ERS and apoptosis in vitro. Moreover, the effect of H19 on ERS-associated apoptosis might be rescued by LY294002 (the specific inhibitor for PI3K and AKT). CONCLUSION: H19 attenuates DCM in DM and ROS, ERS-induced cardiomyocyte apoptosis, which is associated with the activation of PI3K/AKT/mTOR signaling pathway.

Efficacy and Safety of Chinese Herbal Medicine Compared With Losartan for Mild Essential Hypertension: A Randomized, Multicenter, Double-Blind, Noninferiority Trial.

BACKGROUND: Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Songling Xuemaikang capsule (SXC)-a Chinese herbal formula-was effective for essential hypertension. However, the efficacy of SXC monotherapy for hypertension remains unclear. We aimed to compare the blood pressure (BP)-lowering efficacy and safety of SXC versus losartan in patients with essential hypertension. METHODS: In this multicenter, randomized, double-blind, noninferiority trial in China, patients 18 to 65 years of age with mild essential hypertension were randomly allocated to receive either SXC or losartan for 8 weeks. The primary outcome was the change in sitting diastolic BP from baseline to 8 weeks, with a predefined noninferiority margin of -2.5 mm Hg. RESULTS: Of the 755 patients who entered a 2-week run-in period, 628 patients (327 women and 301 men; mean [SD] age, 52.6 [9.2] years) were randomly assigned to the SXC (n=314) or losartan (n=314) group. The primary analysis based on the intention-to-treat principle showed that the change in diastolic BP from baseline to 8 weeks was similar between the SXC and losartan groups (-7.9 [8.0] versus -8.1 [7.9]). The lower boundary of 95% CI (mean difference, -0.24 [95% CI, -1.51 to 1.03]) was above the margin of -2.5 mm Hg, showing noninferiority. Results were consistent with per-protocol analysis. SXC produced greater improvements in total hypertension symptom score (-5.7 [4.2] versus -5.0 [4.0]; P=0.020) and total cholesterol (-0.1 [1.0] versus 0.1 [1.2]; P=0.025). There were no differences between groups in the other BP and patient-reported outcomes. Incidence and severity of adverse events were similar between groups. CONCLUSIONS: SXC was well tolerated and demonstrated noninferior to losartan in BP lowering in patients with mild hypertension. SXC might be an alternative for mild hypertension, particularly for patients with a preference for natural medicine. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR-IPR-16008108.

Xuesaitong injection treating acute myocardial infarction: A systematic review and meta-analysis.

BACKGROUND: Although the incidence of acute myocardial infarction (AMI) is decreasing, the mortality in AMI patients remains substantial. Traditional Chinese medicine has shown its role in the prevention and management of AMI. The purpose of this study is to evaluate the clinical efficacy of Xuesaitong injection (XST) for the treatment of AMI by a meta-analysis. METHODS: A literature search was performed in 5 medical databases up to June 1, 2020. Randomized controlled trials involving XST combined with conventional treatment versus conventional treatment were included. A meta-analysis of clinical efficacy, left ventricular function and other objective parameters was performed to evaluate the effects of XST on AMI. RESULTS: Five randomized controlled trials involving 539 participants were eventually included. Meta-analysis showed that the combination of XST and conventional treatment could achieve significantly better effect on improving clinical efficacy (risk ratio: 1.09 [1.01, 1.17]; P = .04), left ventricular ejection fraction (mean difference [MD]: 3.18 [1.69, 4.67]; P < .0001), hypersensitive C-reactive protein (MD: -2.58 [-5.04, -0.12]; P = .04), interleukin 6 (MD: -26.00 [-38.85, -13.16]; P < .0001), cardiac troponin T (MD: -15.85 [-18.09, -13.61]; P < .00001) and creatine kinase myocardial isoenzyme (MD: -73.06 [-79.74, -66.37]; P < .00001). CONCLUSION: XST combined with conventional treatment can achieve better efficacy on clinical performance and some of the AMI related parameters. However the interpretation of the results should be cautious, due to the relatively low quality of included trials. More rigorously designed, large-scaled, randomized controlled trials are warranted to support its clinical use in the future.

Traditional Chinese medicine for acute coronary syndrome: A meta-analysis of clinical manifestations and objective indicators.

BACKGROUND: Modern clinical trials and experimental researches of traditional Chinese medicine (TCM) have been conducted for decades and provided support for the prevention and treatment of acute coronary syndrome (ACS). However the level of evidence and the proper application of TCM were still barely satisfactory. METHODS: In this study, we divided ACS into 3 different stages, including unstable angina, acute myocardial infarction, and post myocardial infarction. Then we systematically reviewed and meta-analyzed the existing randomized controlled trials on both clinical manifestations and objective indicators, in these 3 aspects. RESULTS: The results indicate that TCM can both improve the clinical manifestations and ameliorate the objective parameters in different courses of ACS, including C-reactive protein in unstable angina, left ventricular ejection fraction in acute myocardial infarction and post myocardial infarction. And the incidence of short-term cardiovascular events are lower in TCM intervention group. Some of the improvements lead to potential long-term benefits. CONCLUSION: TCM treatment is beneficial to different courses of ACS. To acquire more solid and comprehensive evidence of TCM in treating ACS, more rigorously designed randomized controlled trials with longer follow-up duration are warranted.

Bibliometric Analysis of the Results of Cardio-Oncology Research.

OBJECTIVE: To analyze the development of cardio-oncology, summarize the research achievements, and provide proposals for its future research. METHODS: The web of science database was used to search for "cardio-oncology" and "oncocardiology" related articles from the beginning of the database (1970) to April 5, 2019. Excel 2016 and Cytoscape were used to analyze the trend of cardio-oncology research. RESULTS: A total of 356 articles were obtained. The number of articles has grown rapidly in recent years. Cardiac injury caused by tumor therapy was a research hotspot (n = 107). Researchers paid more attention to the prevention and treatment of cardiotoxicity (n = 54). Experimental researches were a small part of all studies (n = 72), mainly focusing on the study of cancer drugs' cardiac injury, test indicators of cardiotoxicity, and preventive drugs. The United States (n = 156.25), Italy (n = 48.5), and Canada (n = 23.5) published the most articles, making a great contribution to the development of cardio-oncology. CONCLUSIONS: Cardio-oncology has been developing rapidly and receiving a large amount of research efforts in recent years. Most articles on cardio-oncology were published by the authors from the United States (44%) and Italy (17%), while other countries need to pay more attention to cardio-oncology. As an independent discipline, cardio-oncology is certainly in need of significant progress, but it has formed a basic framework, which has obtained many leading theories and meaningful achievements in diagnostic criteria, diagnostic methods, prevention and treatment, mechanism research, and influencing factor. Cardiac injury of tumor drugs has always been a research hotspot in this discipline, and there is still a lot of research space. The research about detection methods of cardiotoxicity and preventive drugs is gradually increasing. Basic research lags behind, and many mechanisms are still unclear.

Efficacy and safety of tangshen formula on patients with type 2 diabetic kidney disease: a multicenter double-blinded randomized placebo-controlled trial.

BACKGROUND: Persons with diabetes are at high risk of developing diabetic kidney disease (DKD), which is associated with high morbidity and mortality. Current drug therapies for DKD, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are not entirely satisfactory. This study aimed to evaluate the additional benefit and safety of the Chinese herbal granule Tangshen Formula (TSF) in treating DKD. METHODS: The study was designed as a six-center randomized, double-blind, placebo-controlled trial. From April 2007 through December 2009, 180 patients with DKD were enrolled. In addition to conventional treatment with ACEIs or ARBs, 122 participants were randomly assigned to receive TSF and 58 participants to receive placebo for 24 weeks. Primary outcome was urinary protein level, measured by urinary albumin excretion rate (UAER) for participants with microalbuminuria, 24-hour urinary protein (24h UP) for participants with macroalbuminuria. Secondary outcomes included renal function, serum lipids, quality of life, symptoms, and adverse events. FINDINGS: After 24 weeks of treatment, no statistically significant difference in UAER (TSF -19.53 µg/min compared with placebo -7.01 µg/min, with a mean difference of -12.52 µg/min; 95%CI, -68.67 to 43.63, P = 0.696) was found between TSF and placebo groups. However, TSF displayed a statistically significant decrease in 24h UP (TSF-0.21 g compared with placebo 0.36 g, with a mean difference of -0.57g; 95%CI, -1.05 to -0.09, P = 0.024). Estimated glomerular filtration rate (eGFR) was improved in both patients with microalbuminuria and macroalbuminuria, with a mean difference of 15.51 ml/min/1.73 m2 (95%CI, 3.71 to 27.31), 9.01 ml/min/1.73 m2 (95%CI, -0.10 to 18.13), respectively. Other secondary outcomes showed no statistically significant difference between groups or in the incidence of adverse events. CONCLUSIONS: Based on conventional treatments, TSF appears to provide additional benefits compared with placebo in decreasing proteinuria and improving eGFR in DKD patients with macroalbuminuria. Nevertheless, further study is needed to evaluate TSF treating patients with microalbuminuria. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-10000843.