BackgroundMicroRNAs (miRNAs) are a recently discovered class of posttranscriptional regulators of gene expression with critical functions in the angiogenesis and cardiovascular diseases; however, the details of miRNAs regulating mechanism of angiogenesis of ischemic cardiac microvascular endothelial cells (CMECs) are not yet reported.Methods and ResultsThis study analyzes the changes of the dynamic expression of miRNAs during the process of angiogenesis of ischemic CMECs by applying miRNA chip and real-time PCR for the first time. Compared with normal CMECs, ischemic CMECs have a specific miRNAs expression profile, in which mir-223-3p has the most significant up-regulation, especially during the process of migration and proliferation, while the up-regulation is the most significant during migration, reaching 11.02 times. Rps6kb1 is identified as a potential direct and functional target of mir-223-3p by applying bioinformatic prediction, real-time PCR and Western blot. Pathway analysis report indicates Rps6kb1 regulates the angiogenesis by participating into hif-1a signal pathway. Further analysis reveals that both the gene and protein expression of the downstream molecules VEGF, MAPK, PI3K and Akt of Rps6kb1/hif-1a signal pathway decrease significantly during the process of migration and proliferation in the ischemic CMECs. Therefore, it is confirmed that mir-223-3p inhibits the angiogenesis of CMECs, at least partly, via intervening RPS6KB1/hif-1a signal pathway and affecting the process of migration and proliferation.ConclusionThis study elucidates the miRNA regulating law in the angiogenesis of CMECs; mir-223-3p inhibits the process of migration and proliferation of ischemic CMECs probably via affecting RPS6KB1/hif-1a signal pathway, which in turn suppresses the angiogenesis. It is highly possible that mir-223-3p becomes a novel intervention core target in the treatment of angiogenesis of ischemic heart diseases.

Objective. This study aimed to construct a 5-year survival prediction model of coronary heart disease (CHD) induced chronic heart failure (CHF), which is supported by the traditional Chinese medicine (TCM) factor, and to verify the model. Methods. Inpatients from January 1, 2012, to December 31, 2017, in seven hospitals in Shandong Province were studied. The random number table was used to randomly divide the seven hospitals into two groups (training set and verification set). In the training set, the least absolute shrinkage selection operator regression was first used to screen the independent variables. Logistic regression was then applied to construct a survival prediction model. The following nomogram visualizes the prediction model results. Finally, C-indices, calibration curves, and decision curves were used to discriminate and calibrate the established model and evaluate its practicability in the clinic. Bootstrap resampling and the verification set were used for internal and external verification, respectively. Results. A total of 424 eligible patients were included in the model construction and verification. In this 5-year survival prediction model of patients with CHF induced by CHD, eight independent predictors were included. The series of C-indices for the training set, bootstrap resamples, and verification set was 0.885, 0.867, and 0.835, respectively, demonstrating the credibility of our model. Additionally, the receiver operating characteristic curve, calibration curve, and clinical decision curve analysis of the training and verification sets showed that this 5-year survival prediction model was good in discrimination, calibration, and clinical practicability. Conclusion. This work highlights eight independent factors affecting 5-year mortality in patients with CHF induced by CHD after discharge and further helps reallocate medical resources rationally by precisely identifying high-risk groups. The constructed prediction model not only plays a credible role in prediction but also demonstrates TCM intervention as a protective factor for the 5-year death of patients with CHF induced by CHD, thereby advancing the use of TCM in CHF.

Traditional Chinese medicine (TCM) research shows that Qi-Shen-Yi-Qi Dripping Pills (QSYQ) can promote ischemic cardiac angiogenesis. Studies have shown that microRNAs (miRNAs) are the key component of gene regulation networks, which play a vital role in angiogenesis and cardiovascular disease. Mechanisms involving miRNA by which TCM promotes ischemic cardiac angiogenesis have not been reported. We found that microRNA-223-3p (mir-223-3p) was the core miRNA of angiogenesis of rats ischemic cardiac microvascular endothelial cells (CMECs) and inhibited angiogenesis by affecting RPS6KB1/HIF-1α signal pathway in previous study. Based on the results, we observed biological characteristics and optimal dosage for QSYQ intervening in rats ischemic CMECs angiogenesis and concluded that QSYQ low-dose group had the strongest ability to promote angiogenesis of ischemic myocardium. Using miRNA chip and real-time PCR techniques in this study, we identified mir-223-3p as the pivotal miRNA in QSYQ that regulated angiogenesis of ischemic CMECs. From real-time PCR and western blot analysis, research showed that gene and protein expression of factors located RPS6KB1/HIF-1α signaling pathway, including HIF-1α, VEGF, MAPK, PI3K, and AKT, were significantly upregulated by QSYQ to regulate angiogenesis of ischemic CMECs. This study showed that QSYQ promote ischemic cardiac angiogenesis by downregulating mir-223-3p expression in rats ischemic CMECs.

Background. Acupuncture is widely used in the clinical treatment of essential hypertension (EH). This overview is aimed at summarizing current systematic reviews of acupuncture for EH and assessing the methodological bias and quality of evidence. Methods. Two researchers searched and extracted 7 databases for systematic reviews (SRs)/meta-analyses (MAs) and independently assessed the methodological quality, risk of bias, reporting quality, and quality of evidence of randomized controlled trials (RCTs) included in the SRs/MAs. Tools used included the measurement tool to assess systematic reviews 2 (AMSTAR-2), the risk of bias in systematic (ROBIS) scale, the checklist of preferred reporting items for systematic reviews and meta-analyses (PRISMA), and the grading of recommendations assessment, development, and evaluation (GRADE) system. Results. This overview included 14 SRs/MAs that use quantitative calculations to comprehensively assess the various effects of acupuncture in essential hypertension interventions. The methodological quality, reporting quality, risk of bias, and quality of evidence for outcome measures of SRs/MAs were all unsatisfactory. According to the results of the AMSTAR-2 assessment, all SRs/MAs were of low or very low quality. According to the results of the ROBIS evaluation, a few SRs/MAs were assessed as low risk of bias. According to the results of the PRISMA checklist assessment, SRs/MAs that were not fully reported on the checklist accounted for the majority. According to the GRADE system, 86 outcomes were assessed under different interventions in SRs/MAs, and 2 were rated as moderate-quality evidence, 23 as low-quality evidence, and 61 as very low-quality evidence. Limitations of the included SRs/MAs included the lack of necessary items, such as not being registered in the protocol, not providing a list of excluded studies, and not analyzing and addressing the risk of bias. Conclusion. Currently, acupuncture may be an effective and safe treatment for EH, but the quality of evidence is low, and caution should be exercised when applying this evidence in clinical practice.

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Background: Heart failure (HF) has become a serious global public health issue due to its high incidence, high mortality and extremely low quality of life. According to several clinical trials, Qishen Yiqi Dripping pills (QSYQ) combined with routine western medicine treatment can further enhance the curative effect of HF patients. However, most of the trials are small in sample size and poor in quality, which can only provide limited evidence-based medicine. The existing systematic reviews of efficacy and safety has provided evidence for the clinical application of QSYQ to a certain extent, but there are still 3 major defects. Here, we will perform a systematic review and meta-analysis that include the randomized clinical trial (RCT) of CACT-IHF, apply meta-regression and subgroup analysis to cope with multiple confounding factors, and add the clinical efficacy standards of TCM, all-cause death and readmission rates as reliable efficacy evaluation indicators. The purpose of this study was to rigorously evaluate the clinical efficacy and safety of QSYQ in the complementary treatment of HF with a well-designed systematic review and meta-analysis. Methods: Following the strict search strategy, 9 databases will be searched to ensure a comprehensive search. We search the database from the establishment until November 30, 2020. This study will include RCTs of QSYQ in HF patients’ complementary treatment. Two searchers will independently draft and carry out the search strategy, and the third member will further complete it. Two members independently screen literature, extract data and cross-check, and solve different opinions through discussion or negotiation with the third member. The risk bias will be evaluated based on Cochrane tool of risk of bias. Meta-regression and subgroup analysis are used to check and deal with the heterogeneity. The data analysis will be conducted by the statistical software Stata 16.0. Results: The results of this research will be delivered in a peer-reviewed journal. Conclusion: This study expects to provide credible and scientific evidence for the efficacy and safety of QSYQ in HF's complementary treatment, and at the same time provide a convenient and effective choice for decision-makers and patients. Protocol registration number: INPLASY 2020120106. Ethical approval: Since this study is on the basis of published or registered RCTs, ethical approval and informed consent of patients are not required.

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