Tianyou Li

Background: The risk-benefit balance of early metoprolol administration in critically ill patients with congestive heart failure (CHF) admitted to the intensive care unit (ICU) remains controversial. However, high-quality causality clinical evidence is still lacking. This study utilized real-world data and causal forest algorithm to investigate the average treatment effect (ATE) of early metoprolol use on 30-day mortality in ICU patients with CHF. We also explored the heterogeneity of individual treatment effects (ITE) to identify clinical characteristics across different treatment-effect populations. Method: Study population and their clinical characteristics were obtained from the MIMIC-IV database (version 3.1). Propensity score matching (PSM) was performed to balance baseline confounders. Causal forest models estimated the ATE and ITE. Variable importance, conditional average treatment effect (CATE), and ITE-based quartile analysis were performed to identify heterogeneity and clinical characteristics of patients. Results: A total of 5,758 patients were included in the initial cohort, with 3,934 patients entering the final analysis after PSM. The causal forest model indicated that early metoprolol use increased the risk of 30-day ICU mortality by 2% compared with no use group (ATE = 0.02, 95% CI: 0.0004–0.0396, P = 0.045). APSIII, age, and SOFA were the top three variables contributing to the ATE. The causal forest model estimated the conditional average treatment effects for every variable. Individual treatment effects exhibited a right-skewed distribution. The highest ITE percentile was associated with APSIII >64, age >78 years, SOFA >8, WBC >13.95 × 10 ⁹ /L, and BUN >43.06 mg/dL. Conclusion: Early metoprolol use within 24 h of ICU admission in CHF patients is associated with increased 30-day mortality. Therapeutic effects were heterogeneous, with the adverse effects being particularly pronounced in patients with high APSIII, advanced age, elevated SOFA, high white blood cell counts, and elevated blood urea nitrogen levels. These findings suggest careful consideration should be given to the early use of metoprolol in high-risk patients.

Background Exercise is an important method of promoting health. But unscientific high-intensity exercise is harmful to health. Extreme high-intensity exercise could lead to serious cardiac events such as sudden cardiac death. However, myocardial injury and the metabolic changes have been little studied. Our study aimed to explore the changes in myocardial tissue and metabolism after high-intensity exercise, while investigating the relationship between key metabolites and diseases that cause myocardial injury in population. Methods We investigated myocardial injury through serum myocardial injury markers and myocardial pathology in mice after single exhaustion swimming. Machine learning combined with metabolomics were used to study myocardial metabolic changes and select key metabolites. Mendelian randomization was utilized to test the applicability of the results of animal experiments in the population. Results Our study found that high-intensity exercise resulted in significant elevation of serum markers of myocardial injury, significant pathological changes in the myocardium, and significant alterations in myocardial metabolism. Mendelian randomization revealed that decreased expression of the key metabolite asparagine might associate with chronic ischemic heart disease, consistent with the results of animal experiments. Conclusions This study found that high-intensity exercise could cause myocardial injury and significantly affect myocardial metabolic profiles. The selected key metabolite asparagine was a protective factor against chronic ischemic heart disease in population. Our study provides new insights into high-intensity exercise-associated myocardial injury and new strategies for human health protection. Graphical abstract

As the number of HIV-infected patients increased, the number of patients requiring general surgery has subsequently increased. However, impairment of immune function due to HIV infection increases the risk of postoperative surgical-site infection and significant harm to patient health. This study aimed to examine the risk factors for surgical-site infection after general surgery. The patients’ data were from Zunyi fourth hospital medical information system. Machine learning based Boruta algorithm were used for variable screening. Univariable and multivariable logistic regression and restricted cubic spline analysis were performed to examine the relationship between significant variables and surgical-site infection. A total of 125 general surgery postoperative HIV-infected patients participated in the study. Surgical-site pathogen culture identified Escherichia coli, Klebsiella pneumoniae, and mixed bacteria as the three most common pathogens causing Surgical-site infection. Univariable and multivariable logistic regression analysis to adjust for risk factors identified type III surgical incision (OR = 9.92, 95% CI = 1.28–76.75) and elevated preoperative white blood cell (WBC) count (OR = 1.30, 95% CI = 1.12–1.51) as independent risk factors for postoperative surgical-site infection, whereas CD4 + T lymphocyte count greater than 400 cells/µL was identified as a protective factor (OR = 0.23, 95% CI = 0.09–0.60) while. The restricted cubic spline analysis results directly reflected the dose-response relationship between continuous variables and postoperative surgical-site infection. Type III incision and an elevated WBC count pose a higher risk of postoperative surgical-site infection. A CD4 + T lymphocyte counts greater than 400 cells/µL provided a protective effect of lower risk of surgical site infection. Preoperative serum neutrophil percentage, albumin level, red blood cell count, and serum urea level within a specific range were beneficial in reducing the risk of incisional infections. Our research provides a theoretical basis for clinical practice.

Cardiovascular adverse effects caused by high-intensity exercise (HIE) have become a public health problem of widespread concern. The therapeutic effect and metabolic regulation mechanism of myricetin, a phytochemical with potential therapeutic effects, have rarely been studied. In this study, we established mice models of different doses of myricetin intervention with 1 week of HIE after intervention. Cardiac function tests, serology, and pathological examinations were used to evaluate the protective effect of myricetin on the myocardium. The possible therapeutic targets of myricetin were obtained using an integrated analysis of metabolomics and network pharmacology and verified using molecular docking and RT-qPCR experiments. Different concentrations of myricetin improved cardiac function, significantly reduced the levels of myocardial injury markers, alleviated myocardial ultrastructural damage, reduced the area of ischemia/hypoxia, and increased the content of CX43. We obtained the potential targets and regulated metabolic network of myricetin by combined network pharmacology and metabolomics analysis and validated them by molecular docking and RT-qPCR. In conclusion, our findings suggest that myricetin exerts anti-cardiac injury effects of HIE through the downregulation of PTGS2 and MAOB and the upregulation of MAP2K1 and EGFR while regulating the complicated myocardial metabolic network.

The purpose of this study was to examine whether endogenous GLP-1 (glucagon-like peptide-1) could respond to exercise training in mice, as well as whether dihydromyricetin (DHM) supplementation could enhance GLP-1 levels in response to exercise training. After 2 weeks of exercise intervention, we found that GLP-1 levels were significantly elevated. A reshaped gut microbiota was identified following exercise, as evidenced by the increased abundance of Bifidobacterium, Lactococcus, and Alistipes genus, which are involved in the production of short-chain fatty acids (SCFAs). Antibiotic treatment negated exercise-induced GLP-1 secretion, which could be reversed with gut microbiota transplantation. Additionally, the combined intervention (DHM and exercise) was modeled in mice. Surprisingly, the combined intervention resulted in higher GLP-1 levels than the exercise intervention alone. In exercised mice supplemented with DHM, the gut microbiota composition changed as well, while the amount of SCFAs was unchanged in the stools. Additionally, DHM treatment induced intracellular cAMP in vitro and down-regulated the gene and protein expression of dipeptidyl peptidase-4 (DPP-4) both in vivo and in vitro. Collectively, the auxo-action of exercise on GLP-1 secretion is associated with the gut-microbiota-SCFAs axis. Moreover, our findings suggest that DHM interacts synergistically with exercise to enhance GLP-1 levels by stimulating cAMP and inhibiting DPP-4.