Relationship between Quantitative Parameters of Echocardiography and Vascular Endothelial Function in Patients with Chronic Heart Failure and Its Predictive Value for Short-Term MACE Risk.

Objective: To investigate the relationship between quantitative parameters of echocardiography and vascular endothelial function in patients with chronic heart failure (CHF) and the predictive value of short-term major adverse cardiovascular events (MACE). Methods: From February 2018 to February 2020, 86 CHF patients in our hospital were selected as the observation group, and 46 healthy subjects were selected as the control group during the same period. Quantitative parameters of echocardiography (left ventricular ejection fraction (LVEF), left ventricular short-axis shortening rate (FS), and ratio of peak flow velocity between early and late mitral valve diastole (E/A)) and endothelial function indexes (endothelin-1 (ET-1)/nitric oxide (NO)) were compared between the two groups. The correlation between quantitative parameters of echocardiography and vascular endothelial function in patients with CHF was analyzed. A logistic regression equation was used to analyze the risk factors of MACE in patients with CHF. The receiver operating characteristic curve (ROC) was used to analyze the predictive value of quantitative parameters of echocardiography and NO/ET-1 for the risk of MACE in patients with CHF. Result: LVEF, FS, and NO/ET-1 in the observation group were lower than those in the control group, while E/A was higher than that in the control group (P < 0.05). In CHF patients, LVEF and FS were positively correlated with NO/ET-1, while E/A was negatively correlated with NO/ET-1 (P < 0.05). Logistic regression analysis showed that the decrease of LVEF, FS, NO/ET-1, and E/A were risk factors for MACE (P < 0.05) after adjusting for age, body mass index, and cardiac function grading. The AUC value of short-term MACE predicted by quantitative parameters of echocardiography and NO/ET-1 combined was 0.883, with a corresponding sensitivity of 86.21% and specificity of 73.13%. Conclusion: Quantitative parameters of echocardiography in CHF patients are related to vascular endothelial function, and their combination can effectively predict the risk of MACE in the near future, providing reference for clinical treatment.

FK506 protects heart function via increasing autophagy after myocardial infarction in mice.

OBJECTIVE: To investigate the effect of tacrolimus (FK506) on myocardial infarction, and to further explore its function mechanism. MATERIAL AND METHODS: C57BL/6J mice were randomly divided into three groups: the sham group, the control group and the FK506 group. Anterior descending branch ligation was conducted in the control and the FK506 groups, while sham operation was conducted in the sham group. Mice in the sham and the control groups were intragastrical administration with saline, while the FK506 group were with FK506. Heart function were detected by echocardiogram at 3rd day or 21st day after MI. Hearts were harvested at 3rd day or 21st day after MI for the detection of apoptosis, autophagy, mTOR and NF-κB pathway. RESULTS: FK506 treatment increased survival rate and cardiac function in mice after MI. It decreased infarction area, inflammation reaction and apoptosis. To further study the mechanism of FK506 protection effect, we discovered it could increase autophagy via inhibit mTOR pathway. CONCLUSION: FK506 protect heart function after MI as it improved myocardial cells autophagy process via inhibiting mTOR pathway.

Differences in health-related behaviors between middle school, high school, and college students in Jiangsu province, China.

BACKGROUND AND OBJECTIVES: Increasing rates of obesity among Chinese adolescents has become a major public health concern in recent years. Studies have shown that factors such as food choices, physical activity, and screen time play important roles in fostering obesity. We examined a number of biological and social determinants that influence these factors. To determine whether dietary behavior, physical activity, and screen time varied among students in different stages of their education. METHODS AND STUDY DESIGN: Students in 13 cities across Jiangsu Province completed an anonymous survey assessing demographics and various health-related behaviors in a controlled setting. The survey population ranged from middle school students to undergraduates. 55,361 surveys were returned, and 46,611 (84.2%) were usable for the analysis. Multiple linear regression models were used to investigate the relationship between four behavioral factors (dietary behavior, screen time, physical activity, and moderate exercise) and seven predictors (gender, age, BMI, mother's education, nearsightedness, allowance, and geographic region). RESULTS: Baseline characteristics of the survey population analyzed by education level (middle school, high school, college and beyond) showed moderate differences in demographics among the three groups. Physical activity, moderate exercise, and dietary behavior decreased with educational level, while screen time increased. All predictors in the four considered regression models were statistically significant. CONCLUSIONS: This unique, large-scale survey of Chinese students in a region of contrasting economic development revealed numerous relationships between health-related diet and physical-activity, region, and education level. These findings can inform the development of measures to counteract the rise of obesity in China.

Ad-HGF improves the cardiac remodeling of rat following myocardial infarction by upregulating autophagy and necroptosis and inhibiting apoptosis.

Cell death in MI is the most critical determinant of subsequent left ventricular remodeling and heart failure. Besides apoptosis, autophagy and necroptosis have been recently found to be another two regulated cell death styles. HGF has been reported to have a protective role in MI, but its impact on the three death styles remains unclear. Thus, our study was performed to investigate the distribution of autophagy, apoptosis and necroptosis in cardiac tissues after MI and explore the role and mechanism of Ad-HGF on cardiac remodeling by regulating the three death styles. We firstly showed the distribution of autophagy, apoptosis and necroptosis differs in temporal and spatial context after MI using immunofluorescence. Notably, Ad-HGF treatment improves the cardiac remodeling of SD rats following MI by preserving the heart function, reducing the scar size and aggresomes. Further mechanism study reveals Ad-HGF promotes autophagy and necroptosis and inhibits apoptosis in vivo and in vitro. Co-immunoprecipitation assays showed Ad-HGF treatment significantly decreased the binding of Bcl-2 to Beclin1 but enhanced Bcl-2 binding to Bax in H9c2 cells under hypoxia. Moreover, HGF-induced sequestration of Bax by Bcl-2 allows Bax to become inactive, thereby inhibiting apoptosis. In addition, Ad-HGF markedly increased the formation of Beclin1-Vps34-Atg14L complex, which accounted for promoting autophagy. Both the western blot and activity assay showed Ad-HGF significantly decreased the caspase 8 protein and activity levels, which obligated the cell to undergo necroptosis under hypoxia and block apoptosis. Thus, our findings offer new evidence and strategies for the treatment of MI and post-MI cardiac remodeling.

Necroptosis Induced by Ad-HGF Activates Endogenous C-Kit+ Cardiac Stem Cells and Promotes Cardiomyocyte Proliferation and Angiogenesis in the Infarcted Aged Heart.

BACKGROUND/AIMS: The discovery of c-kit+ cardiac stem cells (CSCs) provided us with new therapeutic targets to repair the damaged heart. However, the precise mechanisms regulating CSC proliferation and differentiation in the aged heart remained elusive. Necroptosis, a type of regulated cell death, has recently been shown to occur following myocardial infarction (MI); however, its effect on c-kit+ CSCs remains unknown. We investigated the effects of hepatocyte growth factor (HGF) and necroptosis on the proliferation and differentiation of endogenous c-kit+ CSCs in aged rat hearts following MI. METHODS: The c-kit+ CSCs and HGF/p-Met expression levels in neonatal, adult and aged rats were compared using immunofluorescence and Western blotting. Immediately after MI, adenovirus carrying the HGF gene (Ad-HGF) was injected into the left ventricular wall surrounding the infarct areas of the aged rat heart. The proliferation and differentiation of the endogenous c-kit+ CSCs were studied using immunofluorescence. The signalling pathways were analysed via Western blotting and ELISA. RESULTS: HGF/p-Met expression levels and c-kit+ CSC abundance gradually decreased with age. Ad-HGF promoted c-kit+ CSC differentiation into precursor cells of cardiomyocyte, endothelial and smooth muscle cell lineages and enhanced cardiomyocyte proliferation and angiogenesis in aged rats; these effects were reversed by the inhibition of necroptosis. Ad-HGF administration induced necroptosis by increasing the expression of receptor interacting protein kinase (RIP) 1 and receptor interacting protein kinase (RIP) 3 proteins in the infarcted heart. Moreover, Ad-HGF-induced necroptosis increased high-mobility group box 1 protein (HMGB1) levels and enhanced the abundance of c-kit+ cells in the bone marrow, which may partly account for the beneficial effect of necroptosis on the c-kit+ CSCs. CONCLUSION: Ad-HGF-induced necroptosis facilitated aged heart repair after MI by promoting c-kit+ CSC proliferation and differentiation. These findings may lead to the development of new methods for the treatment of ischaemic heart disease in aged populations.

Puerarin inhibits cardiac fibrosis via monocyte chemoattractant protein (MCP)-1 and the transforming growth factor-ß1 (TGF-ß1) pathway in myocardial infarction mice.

Transforming growth factor-ß1 (TGF-ß1) and inflammation play important roles in the cardiac fibrosis development associated with myocardial infarction (MI). Puerarin is wildly used for treatment of diabetes, cardiovascular disease and cerebrovascular disease in China, and recently some studies have shown its anti-cardiac fibrotic effect on myocardial hypertrophy. The purpose of our study was to determine whether puerarin has an anti-cardiac fibrotic effect after MI and find the potential mechanism. A mouse model of MI was established by standard LAD coronary artery ligation, and cardiac fibrosis was confirmed by Masson's staining and the expression of collagen I, III and α-SMA. The expression level of F4/80 (macrophage/monocyte marker in mouse), monocyte chemoattractant protein (MCP)-1 and TGF-ß1 in cardiac tissue treated with or without puerarin was evaluated by immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR). The downstream protein phospho-Smad (small mother against decapentaplegic) 2/3 was evaluated by westernblot. The results displayed that puerarin could inhibit the recruitment and activation of monocytes/macrophages, decrease the expression of TGF-ß1 in the cardiac tissues, and consequently significantly attenuated cardiac fibrosis after MI. Our results also displayed a strong positive correlation between MCP-1 and TGF-ß1 expression in MI. Thus, this study revealed the mechanism by which prevented cardiac fibrosis after MI through a decrease in MCP-1 expression and an inhibition TGF-ß1 pathway, and indicated puerarin could be a potential agent in attenuating MI-induced cardiac fibrosis.

Exogenous HGF Prevents Cardiomyocytes from Apoptosis after Hypoxia via Up-Regulating Cell Autophagy.

BACKGROUND: Hepatocyte growth factor (HGF) is widely known as a protective factor in ischemic myocardium, however HGF sensitive cellular mechanism remained ill-defined. Autophagy at early stage of hypoxia has been demonstrated to play a role in protecting myocardium both in vivo and vitro. We performed this study to investigate the association between the protective effect of HGF and autophagy. METHODS: Ventricular myocytes were isolated from neonatal rat heart (NRVMs). We evaluated cardiomyocytes apoptosis by Hoechst staining and flow cytometry. Autophagy was assessed by transmission electron microscope and mRFP-GFP-LC3 adenovirus infection. Mitochondrial membrane potential was estimated by JC-1 staining. Western blotting and ELISA assay were used to quantify protein concentrations. RESULTS: We found that autophagy in NRVMs increased at early stage after hypoxia and HGF release was consistent with the change of autophagy. Exogenous HGF enhanced autophagy and decreased apoptosis, while neutralizing HGF yielded opposite effects. Besides, inhibition of autophagy increased apoptosis of myocytes. Furthermore, exogenous HGF induced Parkin, the marker of mitochondrial autophagy, indicating increased clearance of injured mitochondria. CONCLUSIONS: Our results revealed a potential mechanism in which exogenous HGF prevented NRVMs from apoptosis after hypoxia. Upregulation of Parkin through administration of exogenous HGF may be a potential therapeutic strategy ptotecting myocytes during ischemia.

A systematic review and meta-analysis of conventional laparoscopic sacrocolpopexy versus robot-assisted laparoscopic sacrocolpopexy.

BACKGROUND: Robot-assisted laparoscopic sacrocolpopexy (RALSC) has spread rapidly without the availability of comprehensive and systematically recorded outcome data. OBJECTIVE: To systematically review and compare the outcomes of laparoscopic sacrocolpopexy (LSC) and RALSC. SEARCH STRATEGY: PubMed and Scopus were searched for reports published from 2000 to 2014, using the search terms "robotic sacrocolpopexy," "laparoscopic sacrocolpopexy," and "sacral colpopexy." SELECTION CRITERIA: Studies were included if they directly compared the outcomes of RALSC and LSC, the sample size in each group was more than 15, the follow-up duration was longer than 3 months, and the report was in English. DATA COLLECTION AND ANALYSIS: The studies' characteristics, quality, and outcomes were recorded. Random-/fixed-effects models were used to combine data. MAIN RESULTS: Data on 264 RALSC and 267 LSC procedures were collected from seven studies. The mean operative time was longer in the RALSC group (245.9 minutes vs 205.9 minutes; P<0.001). The estimated blood loss in the two groups was similar (114.4 mL vs 160.1 mL; P=0.36). The differences in incidence of intraoperative/postoperative complications were also similar (P=0.85 vs P=0.92). The costs of RALSC were significantly higher than were those of LSC series in each of three studies (P<0.01 for all). CONCLUSIONS: The clinical outcomes of prolapse surgery are similar with RALSC and LSC, but RALSC is less efficient in terms of cost and time.

Puerarin improves cardiac function through regulation of energy metabolism in Streptozotocin-Nicotinamide induced diabetic mice after myocardial infarction.

It is well recognized that the incidence of heart failure and the risk of death is high in diabetic patients after myocardial infarction (MI). Accumulating evidence showed that puerarin (PUE) has protecting function on both cardiovascular disease and diabetes. The aim of this study is to explore whether puerarin could improve cardiac function in diabetic mice after MI and the underlying mechanism. The left anterior of Streptozotocin (STZ)-Nicotinamide (NA) induced diabetic mice were ligated permanently except for the Shame group. Then the operated mice were randomly treated with PUE or saline. Cardiac function was evaluated by echocardiograph before and at 1, 2, 4 weeks after MI. GLUT4/CD36/p-Akt/PPAR α of the heart was examined after treatment for 4 weeks. The results indicated that PUE significantly increased survival rate, improved cardiac function compared with MI group. Moreover, PUE increased expression and translocation of GLUT4 while attenuated expression and translocation of CD36. Western blot analysis showed that PUE enhanced phosphorylation of Akt and decreased PPAR α. This study demonstrated that PUE improved cardiac function after MI in diabetic mice through regulation of energy metabolism, the possible mechanism responsible for the effect of PUE was increasing the expression and translocation of GLUT4 while attenuating the expression and translocation of CD36.

p27 kip1 haplo-insufficiency improves cardiac function in early-stages of myocardial infarction by protecting myocardium and increasing angiogenesis by promoting IKK activation.

p27(kip1) (p27) is widely known as a potent cell cycle inhibitor in several organs, especially in the heart. However, its role has not been fully defined during the early phase of myocardial infarction (MI). In this study, we investigated the relationships between p27, vascular endothelial growth factor/hepatocyte growth factor (VEGF/HGF) and NF-κB in post-MI cardiac function repair both in vivo and in the hypoxia/ischemia-induced rat myocardiocyte model. In vivo, haplo-insufficiency of p27 improved cardiac function, diminished the infarct zone, protected myocardiocytes and increased angiogenesis by enhancing the production of VEGF/HGF. In vitro, the presence of conditioned medium from hypoxia/ischemia-induced p27 knockdown myocardiocytes reduced the injury caused by hypoxia/ischemia in myocardiocytes, and this effect was reversed by VEGF/HGF neutralizing antibodies, consistent with the cardioprotection being due to VEGF/HGF secretion. We also observed that p27 bound to IKK and that p27 haplo-insufficiency promoted IKK/p65 activation both in vivo and in vitro, thereby inducing the NF-κB downstream regulator, VEGF/HGF. Furthermore, IKKi and IKK inhibitor negated the effect of VEGF/HGF. Therefore, we conclude that p27 haplo-insufficiency protects against heart injury by VEGF/HGF mediated cardioprotection and increased angiogenesis through promoting IKK activation.

Association of admission serum calcium levels and in-hospital mortality in patients with acute ST-elevated myocardial infarction: an eight-year, single-center study in China.

OBJECTIVE: The relationship between admission serum calcium levels and in-hospital mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) has not been well definitively explored. The objective was to assess the predictive value of serum calcium levels on in-hospital mortality in STEMI patients. METHODS: From 2003 to 2010, 1431 consecutive STEMI patients admitted to the First Affiliated Hospital of Nanjing Medical University were enrolled in the present study. Patients were stratified according to quartiles of serum calcium from the blood samples collected in the emergency room after admission. Between the aforementioned groups,the baseline characteristics, in-hospital management, and in-hospital mortality were analyzed. The association of serum calcium level with in-hospital mortality was calculated by a multivariable Cox regression analysis. RESULTS: Among 1431 included patients, 79% were male and the median age was 65 years (range, 55-74). Patients in the lower quartiles of serum calcium, as compared to the upper quartiles of serum calcium, were older, had more cardiovascular risk factors, lower rate of emergency revascularization,and higher in-hospital mortality. According to univariate Cox proportional analysis, patients with lower serum calcium level (hazard ratio 0.267, 95% confidence interval 0.164-0.433, p<0.001) was associated with higher in-hospital mortality. The result of multivariable Cox proportional hazard regression analyses showed that the Killip's class≥3 (HR = 2.192, p = 0.026), aspartate aminotransferase (HR = 1.001, p<0.001), neutrophil count (HR = 1.123, p<0.001), serum calcium level (HR = 0.255, p = 0.001), and emergency revascularization (HR = 0.122, p<0.001) were significantly and independently associated with in-hospital mortality in STEMI patients. CONCLUSIONS: Serum calcium was an independent predictor for in-hospital mortality in patients with STEMI. This widely available serum biochemical index may be incorporated into the current established risk stratification model of STEMI patients. Further studies are required to determine the actual mechanism and whether patients with hypocalcaemia could benefit from calcium supplement.