Exploring the mechanisms of glycolytic genes involvement in pulmonary arterial hypertension through integrative bioinformatics analysis.

The purpose of this study was to identify the mechanisms underlying the involvement of glycolytic genes in pulmonary arterial hypertension (PAH). This study involved downloading 3 datasets from the GEO database at the National Center for Biotechnology Information. The datasets were processed to obtain expression matrices for analysis. Genes involved in glycolysis-related pathways were obtained, and genes related to glycolysis were selected based on significant differences in expression. Gene Ontology functional annotation analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and GSEA enrichment analysis were performed on the DEGs. Combining LASSO regression with SVM-RFE machine learning technology, a PAH risk prediction model based on glycolysis related gene expression was constructed, and CIBERSORTx technology was used to analyse the immune cell composition of PAH patients. Gene enrichment analysis revealed that the DEGs work synergistically across multiple biological pathways. A total of 6 key glycolysis-related genes were selected using LASSO regression and SVM. A bar plot was constructed to evaluate the weights of the key genes and predict the risk of PAH. The clinical application value and predictive accuracy of the model were assessed. Immunological feature analysis revealed significant correlations between key glycolysis-related genes and the abundances of different immune cell types. The glycolysis genes (ACSS2, ALAS2, ALDH3A1, ADOC3, NT5E, and TALDO1) identified in this study play important roles in the development of pulmonary arterial hypertension, providing new evidence for the involvement of glycolysis in PAH.

Monocyte-to-lymphocyte ratio predicts mortality and cardiovascular mortality in the general population.

BACKGROUND: Systemic chronic inflammation (SCI) is closely involved in the pathogenesis of many diseases. This study aims to investigate the association between MLR with mortality and cardiovascular disease (CVD) mortality in US adults. METHODS: 35,813 adults were enrolled from the 1999-2014 National Health and Nutrition Examination Survey (NHANES) cycle. Individuals were categorized according to MLR tertiles and followed until 31 December 2019. Kaplan-Meier plots and log-rank tests were utilized to explore survival differences among the MLR tertiles. Adjusted multivariable Cox analysis was employed to investigate the relationship of MLR with mortality and CVD mortality. Restricted cubic spline and subgroup analysis were further used to discern non-linear relationship and the relationship in categories. RESULTS: During a median follow-up of 134 months, 5865 (16.4%) all-cause deaths and 1602 (4.5%) cardiovascular deaths occurred. Kaplan-Meier plots revealed significant differences in all-cause and cardiovascular mortality among the MLR tertiles. In the fully-adjusted Cox regression model, individuals in the highest tertile of MLR had higher risk of mortality (HR = 1.26, 95% CI: 1.17-1.35) and CVD mortality (HR = 1.41, HR, 95% CI: 1.23-1.62) than those in the lowest tertile. The restricted cubic spline exhibited a J-shaped relationship between MLR with mortality and CVD mortality (P for non-linearity <0.001). The further subgroup analysis demonstrated a robust trend across categories. CONCLUSION: Our study demonstrated that increased baseline MLR was positively associated with a higher risk of death in US adults. MLR was a strong independent predictor of mortality and CVD mortality in the general population.

Clinical outcomes of bariatric surgery - Updated evidence.

Obesity has grown to become a major health problem over the past few decades. Obesity-related comorbidities, such as diabetes mellitus, hypertension, obstructive sleep apnea, and dyslipidemia, are inextricably linked with increased adverse clinical consequences and mortality. Compared with other strategies for obesity, bariatric surgery is efficient in weight loss and has been proved to exert positive effects on obesity-related risk factors. This broad improvement in risk factors has resulted in substantial remission or reductions of comorbidities and better performance on clinical outcomes, including cardiovascular diseases, cancer, and mortality. With the development of surgical procedures, the safety of bariatric surgery has been validated and the rate of peri-operative death is low all over the world. Nonetheless, surgeons ought to be careful about potential complications, such as nutrition deficiencies, psychological disorders, or new digestive tract tumors after surgery. For patients with obesity, bariatric surgery might be a precious and crucial tool to bring additional benefits including comorbidities protection and life span extension. All patients with obesity should be engaged in a union consultation group to select a suitable treatment.

Cardiotoxicity in cancer immune-checkpoint therapy: Mechanisms, clinical evidence, and management strategies.

Immune-checkpoint inhibitors (ICIs), a unique antibody-based therapeutic strategy, have revolutionized the treatment landscape of solid and hematological cancers. Despite the proven benefits of ICIs, the cardiotoxicity from unspecific immune activation (uncommon but potentially fatal) is a continuing concern. Accumulating preclinical research has demonstrated that ICIs initiate inflammation in the myocardium, while clinically significant cardiotoxicity were reported in few patients receiving ICI therapy, probably due to the low incidence and unspecific symptoms. The subtle signs and symptoms (e.g., chest pain, dizziness, and dyspnea) were likely attributed to cancer and/or non-cardiac events by previous studies, thus limiting the understanding of the incidence, outcomes, risk factors, and management of ICI-related cardiotoxicity. The heterogeneous clinical presentation and complex diagnostic procedure further make it challenging to accurately identify ICI-related cardiac events in clinical trials. Therefore, ICI-related cardiotoxicity, whose incidence is probably underestimated, has not been well recognized. In this article, we provide an overview of potential mechanisms underlying ICI-related cardiotoxicity and review accumulating clinical evidence of ICI-related cardiotoxicity, with a focus on myocarditis. Moreover, we discuss possible strategies to manage ICI-related cardiotoxicity and highlight the importance of developing cardio-oncology.