Prognostic value of the prognostic nutritional index for patients with acute myocardial infarction undergoing percutaneous coronary intervention with variable glucose metabolism statuses: a retrospective cohort study.

BACKGROUND: The prognostic nutritional index (PNI) and different glucose metabolisms have been separately reported to be correlated with long-term prognosis in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). However, PNI application in patients with an impaired glucose metabolism has not been well validated, especially in pre-diabetic patients. This study evaluated whether PNI influences a long-term risk of mortality along different glucose metabolism statuses. METHODS: A total of 17,697 patients with AMI and a history of PCI were enrolled in this retrospective observational cohort study from January 2007 to December 2020. Three subgroups with different glucose metabolism statuses, including normal glucose regulation (NGR), pre-diabetes mellitus (pre-DM), and diabetes mellitus (DM), were divided into three groups according to the tertiles of PNI, respectively. RESULTS: All-cause mortality occurred in 2613 (14.8%) patients within a median of 4.1 years of follow-up. Upon analyzing the Kaplan-Meier plots for the NGR, pre-DM, and DM groups, the incidence of all-cause or cardiovascular mortality in the low PNI (PNI-L, ≤ 42.7) subgroup was significantly higher than that in the median PNI (PNI-M, > 42.7 and ≤ 48.2) and high PNI (PNI-H, > 48.2) subgroups (all, P < 0.001). After adjusting for confounding factors, the hazard ratio (HR) for all-cause mortality in the PNI-L group significantly increased compared to that in the PNI-H subgroups of the NGR group (HR, 1.35; 95% CI 1.14-1.66; P < 0.001), pre-DM group (HR, 1.29; 95% CI 1.02-1.62; P < 0.001), and DM group (HR, 1.36; 95% CI 1.13-1.63; P < 0.001). Given that there was evidence of interactions between PNI and different glucose statuses (P for interaction < 0.001), patients were divided into nine subgroups, and we found that DM patients with PNI-L statuses had the highest risk of all-cause mortality compared to NGR patients with PNI-H statuses (HR, 1.69; 95% CI 1.42-2.01; P < 0.001). CONCLUSION: Lower PNI is a significant and independent risk factor for all-cause mortality in AMI patients undergoing PCI with different glucose metabolism statuses, and this risk further increases with DM compared to NGR or pre-DM statuses.

Characterization of cardiac involvement in patients with LMNA splice-site mutation-related dilated cardiomyopathy and sudden cardiac death.

Introduction: LMNA splicing mutations occur in 9.1% of cases with cardiac involvement cases, but the phenotype and severity of disease they cause have not yet been systematically studied. The aim of this study was to understand the clinical and pathogenic characteristics of the LMNA splice-site mutation phenotype in patients with LMNA-related dilated cardiomyopathy (DCM) and sudden cardiac death (SCD). Methods and Results: First, we reported a novel family with LMNA-related DCM and SCD, and the clinical characteristics of all current patients with LMNA splicing mutations were further summarized through the ClinVar database. Seventeen families with a total of 134 individuals, containing a total of 15 LMNA splicing mutation sites, were enrolled. A total of 42 subjects (31.3%) had SCD. Compared without with the non-DCM group (n = 56), the patients within the DCM group (n = 78) presented a lower incidence of atrioventricular block (AVB) (p = 0.015) and a higher incidence rates of non-sustained ventricular tachycardia (p = 0.004),) and implantable cardioverter defibrillator (ICD) implantation (p = 0.005). Kaplan‒Meier survival analysis showed that the patients with pacemaker (PM) implantation had a significantly reduced the occurrence of SCD compared to patientswith those without PM implantation (log-rank p < 0.001), while there was no significant difference in ICD implantation between the two groups (log-rank p = 0.73). Second, we identified the family that we reported with a mutation in an LMNA c.513+1 G>A mutation in the reported family, and pathogenic prediction analysis showed that the mutation site was extremely harmful. Next, we conducted gene expression levels and cardiac pathological biopsy studies on the proband of this family. We found that the expression of normal LMNA mRNA from the proband was significantly downregulated in peripheral blood mononuclear cells than incompared with healthy individuals. Finally, we comprehensively summarized the pathological characteristics of LMNA-related DCM, including hypertrophy, atrophy, fibrosis, white blood cell infiltration, intercalated disc remodeling, and downregulation of desmin and connexin 43 (Cx43) expression. Discussion: Above all, Cardiaccardiac involvement in patients with LMNA splice-site mutation presented with a high rate of SCD. Implanting a pacemaker significantly reduced the SCD rate in non-DCM patients with AVB. The pathogenic characterization was not only haveinvolved suppressed the expression of the healthy LMNA allele, but was also associated with abnormal expression and distribution of desmin and Cx43.

Predictive value of TRPV2 expression from peripheral blood mononuclear cells on the early recurrence of atrial fibrillation after radiofrequency catheter ablation.

BACKGROUND: Recent study has shown that the transient receptor potential vanilloid 2 (TRPV2) channel was exclusively upregulated in patients with atrial fibrillation (AF), and that this overexpression might be detrimental for occurrence and maintenance of AF. We aimed to characterize the expression levels of TRPV2 mRNA in peripheral blood mononuclear cells (PBMCs) with/without early recurrence of atrial fibrillation (ERAF) after radiofrequency catheter ablation (RFCA), and to find a reliable predictor for ERAF. METHODS: 65 patients of AF, who underwent RFCA successfully, then divided into two groups according to ERAF during following 3 months. PBMCs were isolated from whole blood by Ficoll gradient centrifugation before and after RFCA. Gene set enrichment analysis was performed to evaluate TRPV channels expression levels and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping was used for pathway enrichment analysis. RESULTS: There was no significant difference in the TRPV2 mRNA expression level between the two groups before RFCA, while without ERAF group of TRPV2 expression was markedly reduced compared to ERAF group after RFCA. Moreover, the number of TRPV2 expression was confirmed as an independent predictor for the first time through receiver operating characteristic and Kaplan-Meier survival curve analysis. It should be pointed out that the above results were only used to predict ERAF, and have no predictive significance for late recurrence of atrial fibrillation according to the current data. Additionally, ERAF was inversely correlated with P wave dispersion. KEGG mapping further clustered 41 pathways, revealing that ''cyclic guanosine monophosphate-protein kinase G signaling pathway'' was significantly enriched. CONCLUSIONS: We firstly assume that downregulated expression of peripheral TRPV2 appear in patients without ERAF after RFCA. TRPV2 may thus represent a novel predictor of early phase after successful radiofrequency ablation.

Gut microbiome sheds light on the development and treatment of abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disease with high disability and mortality. Its susceptible risk factors include old age, being male, smoking, hypertension, and aortic atherosclerosis. With the improvement of screening techniques, AAA incidence and number of deaths caused by aneurysm rupture increase annually, attracting much clinical attention. Due to the lack of non-invasive treatment, early detection and development of novel treatment of AAA is an urgent clinical concern. The pathophysiology and progression of AAA are characterized by inflammatory destruction. The gut microbiota is an "invisible organ" that directly or indirectly affects the vascular wall inflammatory cell infiltration manifested with enhanced arterial wall gut microbiota and metabolites, which plays an important role in the formation and progression of AAA. As such, the gut microbiome may become an important risk factor for AAA. This review summarizes the direct and indirect effects of the gut microbiome on the pathogenesis of AAA and highlights the gut microbiome-mediated inflammatory responses and discoveries of relevant therapeutic targets that may help manage the development and rupture of AAA.

Role of ferroptosis-related genes in coronary atherosclerosis and identification of key genes: integration of bioinformatics analysis and experimental validation.

BACKGROUND: Coronary atherosclerosis (CA) is the most common type of atherosclerosis. However, the inherent pathogenesis and mechanisms of CA are unclear, and the relationship with ferroptosis-related genes (FRGs) has not been reported. The purpose of this study was to use bioinformatics techniques to evaluate potential therapeutic targets for CA.Please provide the given name for author "Dingshun".Please provide the given name for author "Dingshun". METHODS: First, the GSE132651 dataset was acquired from the Gene Expression Omnibus database. Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and Protein-Protein interaction network were successively conducted. Next, overlapping genes between hub genes and CA genes were found. FRGs were found when comparing the CA group with the normal group. The correlation between overlapping genes and FRGs was further analyzed. At last, we performed Elisa to validate the expression of these genes in human blood specimens. Mice aortic tissues were used for western blot to detect the expression of proteins. RESULTS: Based on the GSE132651 dataset, 102 differentially expressed genes were identified. Five overlapping genes between hub genes and CA genes were found (CCNA2, RRM2, PBK, PCNA, CDK1). TFRC and GPX4 were found to be FRGs. TFRC was positively correlated with CCNA2, PBK, PCNA, CDK1, RRM2, with CDK1 being the strongest correlation. GPX4 was negatively correlated with these genes, among which CCNA2 was the strongest correlation. The ELISA results showed that CCNA2, CDK1, and TFRC expression were markedly increased in serum of the CA samples compared with controls, while GPX4 expression was markedly decreased in the CA samples. The western blot results show that GPX4 expression was lower in the model group, TFRC, CDK1, and CCNA2 protein expression were high in the model group. CONCLUSIONS: Ferroptosis-related genes GPX4 and TFRC were closely correlated with the identified overlapping genes CCNA2 and CDK1, which may serve as targeted therapies for the treatment of CA.

Mammalian Metallothionein-2A and Oxidative Stress.

Mammalian metallothionein-2A (MT2A) has received considerable attention in recent years due to its crucial pathophysiological role in anti-oxidant, anti-apoptosis, detoxification and anti-inflammation. For many years, most studies evaluating the effects of MT2A have focused on reactive oxygen species (ROS), as second messengers that lead to oxidative stress injury of cells and tissues. Recent studies have highlighted that oxidative stress could activate mitogen-activated protein kinases (MAPKs), and MT2A, as a mediator of MAPKs, to regulate the pathogenesis of various diseases. However, the molecule mechanism of MT2A remains elusive. A deeper understanding of the functional, biochemical and molecular characteristics of MT2A would be identified, in order to bring new opportunities for oxidative stress therapy.