MiR-20b-5p involves in vascular aging induced by hyperhomocysteinemia.

Hyperhomocysteinemia (HHcy) is an independent risk factor of atherosclerosis (AS). Some reports have shown that homocysteine (Hcy) could accelerate the development of AS by promoting endothelial cell senescence. miRNAs were widely involved in the pathophysiology of HHcy. However, few studies have focused on the changes of miRNA-mRNA networks in the artery of HHcy patients. For this reason, RNA-sequencing was adopted to investigate the expression of miRNA and mRNA in HHcy model mouse arteries. We found that the expression of 216 mRNAs and 48 miRNAs were significantly changed. Using TargetScan and miRDB web tools, 29 miRNA-mRNA pairs were predicted. Notably, miR-20b-5p and FJX1 shared the highest predicted score in TargetScan, and further study indicated that the miR-20b-5p inhibitor significantly upregulated the FJX1 expression in HHcy human umbilical vein endothelial cells (HUVECs) model. PPI analysis revealed an important sub-network which was centered on CDK1. Gene ontology (GO) enrichment analysis showed that HHcy had a significant effect on cell cycle. Further experiments found that Hcy management increased reactive oxygen species (ROS) generation, the activity of senescence associated ß-galactosidase (SA-ß-gal) and the protein expression of p16 and p21 in HUVECs, which were rescued by miR-20b-5p inhibitor. In general, our research indicated the important role of miR-20b-5p in HHcy-related endothelial cell senescence.

New Insights into the Role of HMGB2 in ST-Segment Elevation Myocardial Infarction.

Background: Ischemic heart disease is one of the leading causes of death in the world, of which ST-segment elevation myocardial infarction (STEMI) is an important type. Inappropriate activation and accumulation of platelets typically induced thrombosis, which may result in acute vessel occlusion and STEMI. Multiple cytokines have been shown to regulate platelet activation, but the relationship between HMGB2 and platelet activation has not been elucidated. Methods: We collected peripheral blood of STEMI patients and healthy adults, and mass spectrometry analysis of platelet proteins was conducted. The "edgeR" package was used to identify the differentially expressed proteins (DEPs). The Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO) and Gene Set Enrichment Analysis (GSEA) were used to identify the significantly changed pathways. Western blot and ELISA were used to detect the expression of a high mobility group box 2 (HMGB2). Flow cytometric analysis and platelet aggregation rate were performed to evaluate the activation of platelets. Results: We identified ALOX5, HIST1H1B, S100A11, HMGB2, and RPS15A were the top five up-regulated proteins by differential expression analysis. Western blot verified that the relative protein expression of HMGB2 in platelet was significantly higher in STEMI patients compared with control adults, and the results of ELISA indicated that the serum HMGB2 level increased and significantly correlated with neutrophil count in STEMI patients. Further investigation showed that the platelet aggregation induced by ADP, the activation of integrin αIIbß3 and CD62P expression on platelet surface were all enhanced by the recombinant HMGB2 (rHMGB2). Conclusion: In conclusion, HMGB2 may be the key molecule to regulate platelet activation in patients with STEMI, which may serve as a potential therapeutic target for STEMI.

One hundred most cited articles related to Endoscopic retrograde cholangiopancreatography: A bibliometric analysis.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) has developed over the past few decades into a reliable technology for diagnostic and therapeutic purposes. Through a bibliometric analysis, this research attempted to evaluate the characteristics of the top 100 articles on ERCP that had the most citations. Methods: We extracted pertinent publications from the Web of Science Core Collection (WoSCC) on July 9, 2022. The top 100 ERCP articles with the most citations were identified and analyzed. The following data were extracted: publication year, country/region, organization, total citation times, annual citation times, research type and research field, etc. To implement the network's visual analysis, a bibliographic coupling network based on keywords was built using the VOSviewer 1.6.17 program. Results: The journal with the most publications were GASTROINTESTINAL ENDOSCOPY, with 45 articles. Most of the top 100 articles came from the United States (n = 47) and Italy (n = 14). Indiana University and the University of Amsterdam were among the most important institutions in ERCP research. ML Freeman of the University of Minnesota contributed the highest number (n = 9) and the most highly cited paper. The age of the paper and article type is closely related to citation frequency. Of the 100 most-cited articles, clinical application in the field of ERCP has focused on three aspects: diagnosis, treatment, and complications. Clinical use of ERCP has shifted from diagnosis to treatment. Post-ERCP pancreatitis is the focus of attention, and the clinical application of technically complex therapeutic ERCP is the future development trend. Conclusion: This study lists the most influential articles in ERCP by exposing the current state of the field, and showing the evolution of research trends to provide perspective for the future development of ERCP.

LncRNA DUXAP8 as a prognostic biomarker for various cancers: A meta-analysis and bioinformatics analysis.

Background: Dual homeoboxes A pseudogene 8 (DUXAP8) is a newly discovered long noncoding RNA that has been shown to function as an oncogene in a variety of human malignant cancers. By integrating available data, this meta-analysis sought to determine the relationship between clinical prognosis and DUXAP8 expression levels in diverse malignancies. Materials and methods: A systematic search was performed to identify eligible studies from several electronic databases from their inception to 25 October 2021. Pooled odds ratios and hazard ratios with 95% CI were used to estimate the association between DUXAP8 expression and survival. For survival analysis, the Kaplan-Meier method and COX analysis were used. Furthermore, we utilized Spearman's correlation analysis to explore the correlation between DUXAP8 and tumor mutational burden (TMB), microsatellite instability (MSI), the related genes of mismatch repair (MMR), DNA methyltransferases (DNMTs), and immune checkpoint biomarkers. Results: Our findings indicated that overexpression of DUXAP8 was related to poor overall survival (OS) (HR = 1.63, 95% CI, 1.49-1.77, p < 0.001). In addition, elevated DUXAP8 expression was closely related to poor OS in several cancers in the TCGA database. Moreover, DUXAP8 expression has been associated with TMB, MSI, and MMR in a variety of malignancies. Conclusion: This study revealed that DUXAP8 might serve as a prognostic biomarker and potential therapeutic target for cancer. It can be used to improve cancer diagnosis, discover potential treatment targets, and improve prognosis.

Incidence of coronary drug-eluting stent fracture: A systematic review and meta-analysis.

Background: Reported evidence of coronary stent fracture (CSF) has increased in recent years. The purpose of this study was to determine reliable estimates of the overall incidence of CSF. Methods and results: The MEDLINE, Embase and Cochrane databases were searched until March 18, 2022. Pooled estimates were acquired using random effects models. Meta-regression and subgroup analysis were used to explore sources of heterogeneity, and publication bias was evaluated by visual assessment of funnel plots and Egger's test. Overall, 46 articles were included in this study. Estimates of CSF incidence were 5.5% [95% confidence interval (CI): 3.7-7.7%] among 39,953 patients based on 36 studies, 4.8% (95% CI: 3.1-6.8%) among 39,945 lesions based on 29 studies and 4.9% (95% CI: 2.5-9.4%) among 19,252 stents based on 8 studies. There has been an obvious increase in the incidence of CSF over the past two decades, and it seems that the duration of stent placement after stent implantation has no impact on incidence estimation. Conclusion: The incidence of CSF was 5.5% among patients, 4.8% for lesions and 4.9% for stents and increased over the past 20 years. The duration of stent placement after stent implantation was found to have no impact on the incidence of CSF, but drug-eluting stent (DES) types and right coronary artery (RCA) lesions influenced the pooled incidence. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022311995], identifier [CRD42022311995].

Lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients: an integrated bioinformatic analysis.

BACKGROUND: Hyperlipidaemia is an important factor that induces coronary artery disease (CAD). This study aimed to explore the lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients. METHODS: In the current study, datasets were fetched from the Gene Expression Omnibus (GEO) database and nonnegative matrix factorization clustering was used to establish a new CAD classification based on the gene expression profile of lipid metabolism genes. In addition, this study carried out bioinformatics analysis to explore intrinsic biological and clinical characteristics of the subgroups. RESULTS: Data for a total of 615 samples were extracted from the Gene Expression Omnibus database and were associated with clinical information. Then, this study used nonnegative matrix factorization clustering for RNA sequencing data of 581 lipid metabolism relevant genes, and the 296 patients with CAD were classified into three subgroups (NMF1, NMF2, and NMF3). Subjects in subgroup NMF2 tended to have an increased severity of CAD. The CAD index and age of group NMF1 were similar to those of group NMF3, but their intrinsic biological characteristics exhibited significant differences. In addition, weighted gene coexpression network analysis (WGCNA) was used to determine the most important modules and screen lipid metabolism related genes, followed by further analysis of the DEGs in which the significant genes were identified based on clinical information. The progression of coronary atherosclerosis may be influenced by genes such as PTGDS and DGKE. CONCLUSION: Different CAD subgroups have their own intrinsic biological characteristics, indicating that more personalized treatment should be provided to patients in each subgroup, and some lipid metabolism related genes (PDGTS, DGKE and so on) were related significantly with clinical characteristics.

Efficacy and safety of sacubitril/valsartan on heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials.

Aims: The efficacy and safety of sacubitril/valsartan for patients with heart failure with preserved ejection fraction (HFpEF) are controversial. Hence, the primary objective of the study was to evaluate the efficacy and safety of sacubitril/valsartan treatment for patients with HFpEF. Methods and results: We used the PubMed, Embase, and Web of Science databases to search for randomized controlled trials of sacubitril-valsartan in patients with HFpEF. Three studies, involving a total of 7,663 patients, were eligible for inclusion. Sacubitril-valsartan reduced the risk of hospitalization for heart failure (HF) [odds ratio (OR): 0.78; 95% CI: 0.70-0.88; p < 0.0001] and the incidence of worsening renal function [risk ratio (RR): 0.79, p = 0.002] among patients with HFpEF in the three trials, but there was no significant reduction in all-cause mortality (0.99, 95% CI: 0.84-1.15; p = 0.86) or cardiovascular mortality (0.95, 95% CI: 0.78-1.15; p = 0.16). Moreover, sacubitril/valsartan was associated with an increased risk of symptomatic hypotension (RR: 1.44; p < 0.00001) and angioedema (RR: 2.66; p < 0.04); there was no difference for decreasing the incidence of hyperkalemia (RR: 0.89; p = 0.11). Conclusion: Compared with valsartan or individualized medical therapy (IMT), sacubitril/valsartan significantly decreased the risk of hospitalization for HF and reduced the incidence of renal dysfunction.

Association between baseline serum uric acid and development of LDL-C level in patients with first acute myocardial infarction.

BACKGROUND: Data on the relationship of baseline serum uric acid (SUA) with development of low-density lipoprotein cholesterol (LDL-C) level in patients with first acute myocardial infarction (AMI) are limited. The present study is to evaluate whether elevated SUA predicts the development of LDL-C in the first AMI. METHODS: This is a retrospective 6-month cohort study of 475 hospitalized Chinese patients who underwent first AMI between January 2015 and December 2019 and were reevaluated half a year later at the Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Jiangxi Province, China. The associations of baseline SUA with the percentage decrease of LDL-C (%) and LDL-C control were analyzed by using logistic regression analyses, multivariate linear regression analyses and the restricted cubic spline. RESULTS: Over the 6-month follow-up, baseline SUA was independently and positively associated with the percentage decrease of LDL-C (%) and LDL-C control in a dose response fashion. After multivariable adjustment, per SD increment of baseline SUA (120.58 µmol/L) was associated with 3.96% higher percentage decrease of LDL-C(%). The adjusted OR (95% CI) for LDL-C control was 5.62 (2.05, 15.36) when comparing the highest tertile (SUA ≥ 437.0 µmol/L) to the lowest tertile (< 341.7 µmol/L) of baseline SUA. CONCLUSIONS: Among Chinese patients with first AMI, higher baseline SUA was associated with higher LDL-C deduction percentage (%), and higher rate of LDL-C control in the short-term follow-up, respectively. SUA acquired when AMI occurred was prone to be profitable in predicting the risk stratification of uncontrolled LDL-C and dyslipidemia management.

Clinicopathological and Prognostic Significance of Long Non-coding RNA MIAT in Human Cancers: A Review and Meta-Analysis.

Background: Although the treatment of cancer has made evident progress, its morbidity and mortality are still high. A tumor marker is a critical indicator for early cancer diagnosis, and timely cancer detection can efficiently help improve the prognosis of patients. Therefore, it is necessary to identify novel markers associated with cancer. LncRNA myocardial infarction associated transcript (MIAT) is a newly identified tumor marker, and in this study, we aimed to explore the relationship between MIAT and clinicopathological features and patient prognosis. Methods: We searched PubMed, Embase, Web of Science, and The Cochrane Library from inception to September 2020 to identify correlational studies. Then, we extracted valid data and used Stata software to make forest plots. We used the hazard ratio (HR) or odds ratio (OR) with 95% CI to evaluate the relationship between aberrant expression of MIAT and patients' prognosis and clinicopathological features. Results: The study included 21 studies, containing 2,048 patients. Meta-analysis showed that overexpression of lncRNA MIAT was associated with poor overall survival (OS) (HR = 1.60, 95% CI, 1.31-1.96, p < 0.001). In addition, high expression of MIAT could forecast tumor size (OR = 2.26, 95% CI 1.34-3.81, p = 0.002), distant metastasis (OR = 2.54, 95% CI 1.84-3.50, p < 0.001), TNM stage (OR = 2.38, 95% CI 1.36-4.18, p = 0.002), lymph node metastasis (OR = 2.59, 95% CI 1.25-5.36, p = 0.011), and the degree of differentiation (OR = 2.65, 95% CI 1.54-4.58, p < 0.001). However, other clinicopathological features, including age (OR = 1.07, 95% CI 0.87-1.32, p = 0.516), gender (OR = 0.95, 95% CI 0.77-1.19, p = 0.668), and histology (OR = 0.72, 95% CI 0.48-1.10, p = 0.128) were not significantly different from high expression of MIAT. Conclusions: Our study showed that overexpression of MIAT is related to poor overall survival and clinicopathological features. MIAT can be considered a novel tumor marker to help diagnose tumors earlier and improve patient prognosis.