Coronary Heart Disease (CHD) and Non-Alcoholic Fatty Liver Disease (NAFLD) share overlapping pathogenic mechanisms including adipose tissue dysfunction, insulin resistance, and systemic inflammation mediated by adipokines. However, the specific impact of inflammation and immune responses on CHD risk in NAFLD patients remains poorly understood. This study evaluated the predictive value of ten immunoinflammatory indexes for CHD risk in NAFLD patients using an interpretable machine learning framework. We retrospectively analyzed 407 NAFLD patients undergoing coronary angiography, and stratifying them into NAFLD + CHD (n = 250) and NAFLD (n = 157) groups. Ten immunoinflammatory indexes were derived from the blood laboratory results. Lasso regression analysis and propensity score matching (PSM) were employed to mitigate confounding effects. Subsequently, univariate and multivariate logistic regression analyses were used to identify independent risk factors for CHD occurrence among NAFLD patients. While restricted cubic splines (RCS) and Receiver operating characteristic (ROC) curve evaluated the relationship between each immunoinflammatory indexes and CHD risk. Linear correlation methods were employed to evaluate the relationship between Gensini score and immunoinflammatory indexes. Finally, three machine learning algorithms (RF, SVM and GLM) were used to identify significant risk factors. To interpret the diagnostic model built by Random Forest, the SHapley Additive exPlanations (SHAP) method was employed, and features were ranked according to their SHAP values. Based on these rankings, a diagnostic nomogram was further constructed and the accuracy of the diagnostic model was evaluated using ROC curves. After PSM, among the 282 included patients with NAFLD, 141 cases (50%) were complicated with CHD. Multivariate logistic regression analysis revealed that after adjusting for age, sex, hypertension, and smoking history, the NHR index was identified as the most significant risk factor for CHD in NAFLD patients (OR, 1.375; 95% CI, 1.021–1.852; P < 0.001). Additionally, NLR, SII, SIRI and NMR were also identified as risk factors. PNR was a protective factor for CHD events in patients with NAFLD. RCS analysis demonstrated linear relationships between the NHR, NLR, and PNR index with CHD occurrence, whereas the SII index exhibited a non-linear J-shaped relationship with CHD risk (non-linear P = 0.025). Correlation analysis with Gensini score showed that the NHR index had the highest correlation with the severity of CHD (R = 0.256, P < 0.001). ROC curves indicated that the NHR index had good predictive and diagnostic performance (AUC = 0.703,95% CI, 0.652–0.754). Finally, the diagnostic nomogram constructed based on SHAP values demonstrated good accuracy and predictive performance (AUC = 0.834,95% CI, 0.795–0.873; P < 0.001). Six immunoinflammatory markers demonstrated significant associations with CHD risk in NAFLD populations, among which the NHR index exhibited particularly promising predictive potential.

Acute aortic dissection (AAD) is a life-threatening disease. Despite the higher risk of mortality, currently there are no effective therapies that can ameliorate AAD development or progression. Identification of meaningful clusters of co-expressed genes or representative biomarkers for AAD may help to identify new pathomechanisms and foster development of new therapies. To this end, we performed a weighted gene co-expression network analysis (WGCNA) and calculated module-trait correlations based on a public microarray dataset (GSE 52093) and discovered 9 modules were found to be related to AAD. The module which has the strongest positive correlation with AAD was further analyzed and the top 10 hub genes SLC20A1, GINS2, CNN1, FAM198B, MAD2L2, UBE2T, FKBP11, SLMAP, CCDC34, and GALK1 were identified. Furthermore, we validated the data by qRT-PCR in an independent sample set originated from our study center. Overall, the qRT-PCR results were consistent with the results of the microarray analysis. Intriguingly, the highest change was found for FKBP11, a protein belongs to the FKBP family of peptidyl-prolyl cis/trans isomerases, which catalyze the folding of proline-containing polypeptides. In congruent with the gene expression analysis, FKBP11 expression was induced in cultured endothelial cells by angiotensin II treatment and endothelium of the dissected aorta. More importantly we show that FKBP11 provokes inflammation in endothelial cells by interacting with NF-kB p65 subunit, resulting in pro-inflammatory cytokines production. Accordingly, siRNA mediated knockdown of FKBP11 in cultured endothelial cells suppressed angiotensin II induced monocyte transmigration through the endothelial monolayer. Based on these data, we hypothesize that pro-inflammatory cytokines elicited by FKBP11 overexpression in the endothelium under AAD condition could facilitate transendothelial migration of the circulating monocytes into the aorta, where they differentiate into active macrophages and secrete MMPs and other extracellular matrix (ECM) degrading proteins, contributing to sustained inflammation and AAD. Taken together, our data identify important role of FKBP11 which can serve as biomarker and/or therapeutic target for AAD.

Aims: Obstructive sleep apnea syndrome (OSAS) has been increasingly recognized as an independent risk factor for aortic dissection (AD) and it is strongly associated with the extent of intermittent hypoxia and re-oxygenation (IH). This study aimed to clarify role of ROS- HIF-1α-MMPs pathway in the pathogenesis of AD and whether the HIF-1α inhibitor attenuates AD formation.

Pulmonary arterial hypertension (PAH) is a group of devastating and progressive disorders, resulting in relentless increases in pulmonary vascular resistance. The number of studies related to PAH has been increasing in recent years. Our study aims to illustrate trends in PAH research over the past decade using bibliometric analysis. Science Citation Index-Expanded was adopted to search studies concerning PAH between 2011 and 2020. The bibliographic information was converted and analyzed automatically using a bibliometric package in R software and citespace. The annual quantity of publications on PAH showed an overall increase last decade. The United States was the most prolific country with 2,479 publications, and it was also the country that cooperated most with other countries. Hôpital Bicêtre made important research achievements on PAH and was a leader in study cooperation. Marc Humbert led the PAH field by publishing 150 articles in the past decade. During the past decade, there was a close transnational relation among countries or regions, institutions and authors. Further, Circulation was the most cited journal, followed by the Journal of the American College of Cardiology and the American Journal of Respiratory and Critical Care Medicine, with 3,895, 3,406, and 3,170 citations, respectively. The global research status and trend of PAH are deeply understood for the first time using bibliometric and visual methods, and the results of our study bring us a valuable reference for clinical researchers. Graphical abstract

Background: Chronic diabetes accelerates vascular dysfunction often resulting in cardiomyopathy but underlying mechanisms remain unclear. Recent studies have shown that the deregulated unfolded protein response (UPR) dependent on highly conserved IRE1α-spliced X-box- binding protein (XBP1s) and the resulting endoplasmic reticulum stress (ER-Stress) plays a crucial role in the occurrence and development of diabetic cardiomyopathy (DCM). In the present study, we determined whether targeting MAPK/ERK pathway using MEK inhibitor U0126 could ameliorate DCM by regulating IRE1α-XBP1s pathway.