Value of PTEN and Echocardiography in Predicting the Efficacy of Trimetazidine Combined with Metoprolol in the Treatment of Heart Failure.

OBJECTIVE: To investigate the predictive value of PTEN and echocardiography in the treatment of heart failure with trimetazidine combined with metoprolol. METHODS: A total of 100 patients with coronary heart disease and HF who admitted to our hospital from August 2018 to August 2020 were enrolled into research. All patients received routine treatment according to the guidelines and were treated with trimetazidine and metoprolol for a total course of 6 months. Echocardiographic parameters and PTEN levels were measured at baseline and after treatment. The patients were divided into groups according to the quartile of basic PTEN level, and the total effective rates were compared. The echocardiographic parameters of patients with different prognosis were analyzed. Bivariate correlation analysis was used to evaluate the correlation between PTEN, echocardiography and treatment effect. RESULTS: Compared with that before treatment, the level of PTEN increased significantly after treatment (P < 0.01). According to the quartile of basic PTEN level, the total effective rate of patients with different levels of basic PTEN was was statistically different (P < 0.01). There was a linear correlation between the level of basic PTEN and the treatment effect, and the total effective rate of patients with high level of basic PTEN was higher than that of patients with low level of PTEN. Compared with before treatment, LVEF, SV, E/A and lvfs increased significantly after treatment (P < 0.01). There was a correlation between the basic echocardiographic parameters and the treatment effect of patients. The basic echocardiographic parameters of patients with poor prognosis were worse than those with good prognosis. PTEN expression in patients' serum was only positively correlated with E/A, but not with LVFE, SV and LVFS (P < 0.01). CONCLUSION: PTEN and echocardiographic parameters serve as a good method to evaluate the short-term therapeutic effect of trimetazidine combined with metoprolol in patients with heart failure.

The benefits of higher LMR for early threatened abortion: A retrospective cohort study.

PROBLEM: To investigate the relation of inflammation-related parameters and pregnancy outcome in women with the early threatened abortion. METHOD OF STUDY: 630 women with early threatened abortion were divided into two groups based on the pregnancy outcome. All of them had the blood routine examination before treating. The differences between two groups were analyzed by the Chi-squared test, Student T test, Mann-Whitney U test, Binary Logistic Regression, Marginal Structural Model and Threshold effect analysis. RESULTS: We found that there is no significant difference in the pregnancy outcome for NLR (OR:0.92, CI95%:0.72, 1.17) and PLR (OR:1.00, CI%:0.99, 1.01). However, a difference had a statistical significance in the pregnancy outcome when LMR less than 2.19 (OR:0.39, CI95%:0.19,0.82). CONCLUSIONS: This study suggested that higher LMR was related to the lower risk of miscarriage in the women with early threatened abortion in a way.

MicroRNA-206 Downregulates Connexin43 in Cardiomyocytes to Induce Cardiac Arrhythmias in a Transgenic Mouse Model.

BACKGROUND: MicroRNAs (miRNAs) are critical modulators of various physiological and pathological processes, but their role in cardiac arrhythmias remains yet to be completely understood. Connexin43 (Cx43) is an important cardiac gap junction protein and a potential target of miR-206, and downregulation of Cx43 induces ventricular tachyarrhythmias. METHODS: We investigated the effects of miR-206 overexpression on the adult mouse heart and in cardiac arrhythmias. Luciferase activity assay was employed to validate Cx43 as a direct target of miR-206. Expression of Cx43 was measured in cardiac muscle cell line HL-1 securely expressing miR-206. An inducible miR-206 overexpression mouse model was established to evaluate the in vivo effect of miR-206 on Cx43 expression and cardiac rhythm. RESULTS: MiR-206 directly recognised 3'-untranslated region of Cx43 mRNA to inhibit its expression in HL-1 cells. Induction of miR-206 in the adult mouse heart suppressed Cx43 expression, particularly in the atria and ventricle. Importantly, miR-206 overexpression also induced abnormal heart-rate and PR interval, and shortened life-span in the experimental mice. CONCLUSIONS: In cardiomyocytes, miR-206 is a upstream regulator of Cx43, and its overexpression downregulates Cx43 to induce abnormal heart-rate and PR interval.

High serum YKL-40 level positively correlates with coronary artery disease.

AIM: We investigated the predictive value of chitinase-like protein YKL-40 in coronary artery disease (CAD). PATIENTS: Serum YKL-40 levels in 116 CAD patients and 82 healthy controls were analyzed. Severity of CAD was evaluated using Gensini scores. Spearman's correlation was used to evaluate the correlation between Gensini scores and YKL-40 levels. The predictive value of YKL-40 was determined by receivers operating characteristic curve analysis. RESULTS: Serum YKL-40 levels were significantly elevated in CAD group as compared with control group. A positive correlation was found between the serum YKL-40 level and Gensini score. The optimum cut-off value of YKL-40 concentration was 127.7 ng/ml for distinguishing CAD patients from healthy controls with a 75.9% sensitivity and 57.3% specificity. CONCLUSION: A positive correlation exists between YKL-40 levels and CAD, and YKL-40 might be a useful adjunct in the diagnosis of CAD.

MiR-214 regulates the pathogenesis of patients with coronary artery disease by targeting VEGF.

Circulating microRNAs (miRNAs) in patient body fluids have recently been considered to hold the potential of being novel disease biomarkers and drug targets. We aimed to investigate the correlation between the levels of circulating miR-214 and the expression of vascular endothelial growth factor (VEGF) in the pathogenesis of coronary heart disease patients to further explore the mechanism involved in the vasculogenesis. Three different cohorts, including 13 acute myocardial infarction patients, 176 angina pectoris patients, and 127 control subjects, were enrolled to investigate the expression levels of circulating miR-214 in patients with myocardial ischemia and also the relationship between plasma miR-214 and severity of coronary stenosis. Plasma miR-214 levels of participants were examined by real-time quantitative PCR. Simultaneously, plasma cardiac troponin I concentrations were measured by ELISA assays. We further detected the correlation of miR-214 and VEGF by molecular and animal assays. MiR-214 was enriched in not only diseased endothelial progenitor cells (EPCs) but also the plasma of coronary artery disease (CAD) patients. Besides, we found out miR-214 was able to suppress VEGF expression and EPC activities. Reporter assays confirmed the direct binding and repression of miR-214 to the 39-UTR of VEGF mRNA. Knockdown of miR-214 not only restored VEGF levels and angiogenic activities of diseased EPCs in vitro, but also further promoted blood flow recovery in ischemic limbs of mice. Circulating miR-214 may be a new biomarker for CAD and as a potential diagnostic tool. And increased miR-214 level may be used to predict the presence and severity of coronary lesions in CAD patients.

PDK1 plays a critical role in regulating cardiac function in mice and human.

BACKGROUND: PDK1 is an essential protein kinase that plays a critical role in mammalian development. Mouse lacking PDK1 leads to multiple abnormalities and embryonic lethality at E9.5. To elucidate the role of PDK1 in the heart, we investigated the cardiac phenotype of mice that lack PDK1 in the heart in different growth periods and the alteration of PDK1 signaling in human failing heart. METHODS: We employed Cre/loxP system to generate PDK1(flox/flox): α-MHC-Cre mice, which specifically deleted PDK1 in cardiac muscle at birth, and tamoxifen-inducible heart-specific PDK1 knockout mice (PDK1(flox/flox):MerCreMer mice), in which PDK1 was deleted in myocardium in response to the treatment with tamoxifen. Transmural myocardial tissues from human failing hearts and normal hearts were sampled from the left ventricular apex to analyze the activity of PDK1/Akt signaling pathways by Western blotting. RESULTS: PDK1(flox/flox): α-MHC-Cre mice died of heart failure at 5 and 10 weeks old. PDK1(flox/flox) -MerCreMer mice died of heart failure from 5 to 21 weeks after the initiation of tamoxifen treatment at 8 weeks old. We found that expression levels of PDK1 in human failing heart tissues were significantly decreased compared with control hearts. CONCLUSION: Our results suggest that PDK1 signaling network takes part in regulating cardiac viability and function in mice, and may be also involved in human heart failure disease.