The dysregulation of plasma miR-497/FGF23 axis, and its association with clinical characteristics and major adverse cardiovascular event in female premature acute coronary syndrome patients.

AIM: MicroRNA-497 (miR-497) directly targets fibroblast growth factor 23 (FGF23) to participate in the pathology of acute coronary syndrome (ACS) by regulating atherosclerosis, inflammatory response, lipid metabolism, etc. This study intended to investigate the dysregulation of the miR-497/FGF23 axis, and its association with the major adverse cardiovascular event (MACE) in female premature ACS. METHODS: MiR-497 and FGF23 from plasma samples were detected by RT-qPCR and ELISA in 979 newly diagnosed female premature ACS patients and 100 healthy controls (HCs). MACE was recorded during follow-up (median: 27.0, range: 1.0-54.0 months) in female premature ACS patients. RESULTS: MiR-497/FGF23 axis was reduced in female premature ACS patients versus HCs [median (interquartile range): 0.7 (0.1-1.2) versus 1.9 (1.1-3.4)] (P < 0.001). Meanwhile, miR-497 negatively correlated with FGF23 in femal e premature ACS patients (P < 0.001), but not in HCs (P = 0.157). In female premature ACS patients, the miR-497/FGF23 axis was negatively associated with serum creatinine (P < 0.001), serum uric acid (P = 0.003), high-sensitivity C-reactive protein (P < 0.001), total cholesterol (P = 0.031), and low-density lipoprotein cholesterol (P = 0.003). The 1-year, 2-year, 3-year, and 4-year accumulating MACE rate was 2.9%, 8.6%, 16.7%, and 26.0%, respectively. Interestingly, a high level of miR-497/FGF23 axis predicted decreased accumulating MACE risk (P < 0.001). After adjustment by multivariate Cox's regression analysis, the high miR-497/FGF23 axis (hazard ratio (HR) = 0.005, P = 0.001) independently correlated with reduced accumulating MACE risk. CONCLUSION: The plasma miR-497/FGF23 axis represents favorable kidney function, decreased inflammation, and reduced lipid level; meanwhile, this axis possesses prognostic value in predicting decreased accumulating MACE risk in female premature ACS patients.

Predicted visceral adiposity index in relation to risk of coronary heart disease and all-cause mortality: insights from NHANES.

Background and aims: The Visceral Adiposity Index (VAI) is a straightforward and gender-specific marker that combines anthropometric measurements with lipid profiles. The objective of this study was to evaluate the relationship between VAI and coronary heart disease (CHD). Methods and results: The study examined data collected from adults during the NHANES 1999-2018 cycle. The analyses were weighted, and multivariable logistic regression models were employed to investigate the association between VAI and CHD. Additionally, subgroup analyses stratified by age were conducted. To evaluate the impact of VAI levels on survival outcomes, the study utilized the Kaplan-Meier method and performed the log-rank test to evaluate the survival outcome of participants with different VAI levels. The study findings revealed a significant association between VAI and CHD, indicating a non-linear relationship where an increase in VAI was associated with an elevated risk of CHD. High levels of VAI were linked to an increased prevalence of CHD (Q4 vs Q1, OR 1.50, 95% CI 1.12-2.01, P=0.01). Additionally, higher levels of VAI were associated with a poorer overall prognosis in terms of survival outcomes. There were no statistically significant differences in survival outcomes among the population with CHD. Conclusion: The results of this study highlighted a significant association between VAI and CHD, with a non-linear relationship observed. High VAI levels were associated with an increased risk of CHD and poor survival outcomes, emphasizing the importance of understanding and managing this risk factor, particularly in older age groups.

Metformin reduces proteinuria in spontaneously hypertensive rats by activating the HIF-2α-VEGF-A pathway.

Metformin has protective effects on diabetic nephropathy. However, the mechanism underlying the renoprotective action of metformin in spontaneously hypertensive rats (SHR) is not completely understood. We determined the role of metformin in proteinuria and investigated the mechanism. We measured the urinary protein concentration (mg/day) in 48-week-old SHR. Matched control animals were of the same genetic strain, Wistar-Kyoto (WKY). The rats received metformin (100 mg/kg/day) or vehicle for 10 months. Metformin improved renal function and reduced the proteinuria (urine protein: 48.4 ± 3.7 vs. 25.4 ± 1.8 mg, P < 0.01) induced by long-term high blood pressure. Metformin increased the production of vascular endothelial growth factor (VEGF)-A in rat kidneys and cultured rat podocytes. Metformin activated hypoxia-inducible factor-2α (Hif-2α) in response to VEGF but did not affect Hif-1α in rat kidneys and cultured rat podocytes. Metformin reduced the proteinuria induced by long-term high blood pressure in vivo and increased the VEGF-A production in rat kidneys and cultured rat podocytes, probably by activating the Hif-2α-VEGF signaling pathway. These findings provide a new mechanism for the renoprotective effects of metformin.

[Effect of testosterone propionate on condition and prognosis of sepsis patients].

OBJECTIVE: To investigate the effect of testosterone propionate injection on the condition and prognosis of patients with sepsis. METHODS: The clinical data of 61 sepsis patients admitted to the department of intensive care medicine, Weinan Central Hospital from June 2009 to October 2019 were retrospectively analyzed. All patients were treated with anti-infection, control of infection sources, organ function support, nutrition enhancement and supportive treatment. On the basis of routine treatment, observation group was given 100 mg of testosterone propionate injection for deep intramuscular injection twice a week (twice in total), and control group was not given testosterone propionate injection. The general information and laboratory indexes before treatment were observed, and the testosterone, albumin, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) score after treatment, intensive care unit (ICU) hospitalization time, total hospitalization cost, mechanical ventilation time, 28-day all-cause mortality and other indicators of the patients in two groups were compared. RESULTS: There were no significant differences between the two groups in gender, age and other baseline data and laboratory indexes before treatment. After treatment, in observation group the testosterone (µg/L: 3.69±2.38 vs. 2.85±0.90) and albumin (g/L: 39.87±1.98 vs. 26.25±4.13) were significantly higher than those in control group. Total hospitalization expenses (ten thousand Yuan: 10.14±3.22 vs. 12.10±3.91), APACHE II (13.71±2.13 vs. 23.23±2.52), SOFA (4.45±1.57 vs. 9.97±2.65), ICU hospitalization time (days: 12.36±4.37 vs. 14.03±3.86) and mechanical ventilation time (days: 3.00±1.85 vs. 7.00±2.50) were significantly lower than those in control group (all P < 0.05), and the difference in 28-day all-cause mortality of two groups was not significant [3.2% (1/31) vs. 13.3% (4/30), P > 0.05]. CONCLUSIONS: Testosterone propionate injection can increase albumin level, shorten the time of mechanical ventilation, and improve the condition and prognosis of patients with sepsis.

The carboxyl terminus of heat shock protein 70-interacting protein (CHIP) participates in high glucose-induced cardiac injury.

The carboxyl terminus of heat shock protein 70-interacting protein (CHIP) is confirmed to have a protective effect on the myocardium, but its effect on diabetic cardiomyopathy is unclear. Small interfering RNA (siRNA) was used for knockdown experiments in neonatal rat cardiomyocytes to examine the function of CHIP in high glucose-induced injury. High glucose stimulated the production of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate oxidase (NOX), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) production. However, cardiomyocytes lacking CHIP suffered from increased oxidative stress and inflammatory responses. High glucose increased the expression of Bax and caspase-3 mRNAs, decreased the expression of Bcl-2 mRNA, and up-regulated the expression of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) proteins. However, upon CHIP knockdown, the expression of Bax and caspase-3 mRNAs increased even further, and the expression of Bcl-2 mRNA was further suppressed. The expression of the phosphorylated p65 and p38 proteins (p-p65 and p-p38) was also further enhanced. Thus, CHIP is a potent cardioprotective molecule.