Association between venous leg ulcers and chronic heart failure: A Mendelian randomization study.

An association between venous leg ulcers (VLU) and chronic heart failure (CHF) has been suggested by observational research. This study used Mendelian randomization (MR) methods to look into any possible bidirectional causal links between VLU and CHF. The 'TwoSampleMR' R package was employed for MR analyses. The association of VLU and CHF was assessed via methods of inverse variance weighted (IVW), weighted mode, MR Egger and weighted median. Results of IVW suggested no association between VLU and CHF (ß 0.008356; SE 0.01889; p = 0.6582). The weighted median estimator (ß -0.005777; SE 0.02059, p = 0.7791), MR-Egger (ß -0.08955; SE 0.04557; p = 0.07296) and weighted mode (ß -0.01202; SE 0.02467; p = 0.6341) showed consistent results. Conversely, evidence indicating that the presence of CHF increased the risk of VLU was lacking. In conclusion, there is no bidirectional causal relationship between VLU and CHF. Further studies are required to validate the findings of this study.

Mechanisms of QingRe HuoXue Formula in atherosclerosis Treatment: An integrated approach using Bioinformatics, Machine Learning, and experimental validation.

BACKGROUND: Atherosclerosis (AS) is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular disease. QingRe HuoXue Formula (QRHXF), a common prescription of traditional Chinese medicine, has a definite effect on the clinical treatment of AS, but its mechanism remains to be further explored. PURPOSE: The current study aimed to demonstrate the effectiveness of the QRHXF in the treatment of AS and further reveal its potential pharmacological mechanisms. METHODS: Explore the potential mechanisms of QRHXF in treating AS through network pharmacology, machine learning, transcriptome analysis, and molecular docking, then validate them through animal experiments and PCR experiments. RESULTS: The results indicate that through network pharmacology and machine learning methods, 10 genes including COL1A1 and CCR7 have been identified as potential candidate genes for QRHXF treatment of atherosclerosis. Molecular docking indicates that the key active compounds of QRHXF have good binding affinity with the predicted genes. Two key genes, COL1A1 and CCR7, were identified through transcriptome sequencing analysis of the aortic tissue of APOE-/- mice in the AS model. Finally, the animal and PCR experiment found that QRHXF can effectively reduce the formation of aortic plaques in APOE-/- mice of the AS model, lower blood lipid levels in mice, and upregulate the mRNA expression level of COL1A1, promoting the formation of fibrosis within plaques. CONCLUSIONS: We revealed the inflammatory and immune pathways underlying QRHXF treatment for AS, and verified through transcriptome sequencing and experiments that QRHXF can promote the expression of COL1A1, thereby increasing the stability of AS plaques.

Positive Association of Plasma Trimethylamine-N-Oxide and Atherosclerosis in Patient with Acute Coronary Syndrome.

Aim: Atherosclerosis is the major cause of acute coronary syndrome (ACS) which is a significant contributor to both morbidity and mortality in the world. The microbiome-derived metabolite trimethylamine-N-oxide (TMAO) has aroused great interest and controversy as a risk factor of atherosclerosis. Therefore, in this study, we aimed at investigating whether plasma TMAO can be a risk factor of atherosclerosis in coronary artery of patients with ACS and how this relates to lipids and proinflammatory cytokines in plasma. Methods: We enrolled consecutive patients with ACS who underwent percutaneous coronary intervention (PCI). Gensini scoring was used to evaluate angiographic atherosclerosis in the coronary artery of the patients. 13 patients were divided into low (Gensini score < 25), 33 into intermediate (Gensini score 25-50), and 81 into severe atherosclerosis (Gensini score ≥50). Plasma TMAO, vasculitis factors, and cardiovascular biomarkers were measured by clinical biochemistry, intima-media thickness (IMT) of carotid artery was determined by the Color Doppler ultrasound, and the atherosclerotic lesion in coronary artery was assessed in PCI. Results: Plasma TMAO concentrations were positively associated with Gensini score (OR = 0.629, p < 0.001) and Gensini subgroup (R = 0.604, p < 0.001). Plasma TMAO concentrations in patients with severe coronary atherosclerosis were higher than those of patients with moderate coronary atherosclerosis, and the plasma TMAO concentrations of patients with moderate coronary atherosclerosis were higher than those of patients with mild coronary atherosclerosis, the difference was statistically significant [4.73 (3.13, 4.62) versus 1.13 (0.63, 3.34) versus 0.79 (0.20, 1.29), p < 0.001], respectively. Furthermore, ROC analysis showed that plasma TMAO could identify the severity of atherosclerosis (p < 0.001). The AUC of TMAO for severe atherosclerosis was 0.852 (95%CI = 0.779 - 0.925). The sensitivity and specificity of TMAO for identifying severe atherosclerosis are 96.3% and 63.0% when the cut-off value of TMAO was set at 1.2715 pg/ml. Furthermore, logistic regression analysis showed plasma TMAO concentrations were positively associated with severity of atherosclerosis in coronary artery (OR = 1.934, 95%CI = 1.522 - 2.459, p < 0.001). For all that, negatively association was observed between TMAO and age (OR = -0.224, p < 0.05), B-type natriuretic peptide (BNP) (OR = -0.175, p < 0.05), and interleukin-8 (IL-8) (OR = -0.324, p < 0.001), while positive association was observed between TMAO and nitric oxide (NO) (OR = 0.234, p < 0.01). However, there is no obvious association was observed between Gensini score and cardiovascular biomarkers, vasculitis factors, and carotid IMT, respectively. Conclusion: Our cross-sectional observation suggested that plasma TMAO concentrations positively associated with coronary atherosclerosis in ACS patients and serve as a risk factor for severe atherosclerosis. Plasma TMAO also correlated with age, BNP, IL-8, and NO. However, no obvious association was found between atherosclerosis with vasculitis factors and cardiovascular biomarkers in this study, and there was no conclusive evidence showing TMAO enhance atherosclerosis via regulation of inflammation or lipid.