Discussion on operation: To compare the curative effect of PMT and CDT in the treatment of middle and high risk stratified APE and the clinical application value of serum BNP, TnI and plasma DFR levelse.

Objective: To compare the efficacy of Percutaneous mechanical thrombectomy (PMT) and Catheter directed thrombolysis (CDT) in the treatment of patients with moderate and high-risk ape and explore the clinical application value of biomarkers in the treatment of moderate and high-risk ape. Method: A total of 84 patients with ape were selected from the Department of vascular surgery of the Second Affiliated Hospital of Shandong First Medical University and the Department of vascular surgery of Shanghai Ninth People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine. According to the relevant guidelines, they were divided into high-risk and medium-risk groups, including PMT groups (35 cases) and CDT groups (49 cases). To detect the changes of serum B-type brain natriuretic peptide (BNP),Troponin I (TnI) and plasma D-dimer/fibrinogen ratio (DFR) levels in different risk stratification before and after PMT and CDT, the correlation and diagnostic value of each index, and compare the thrombus clearance rate, pulmonary artery pressure, average dosage of urokinase, effective thrombolytic time, average hospitalization time and complications of PMT and CDT. Result: Under different treatment methods and risk stratification, there was no statistically significant difference in the clinical data of patients at general baseline;The preoperative BNP, TnI and DFR levels of PMT and CDT in the middle and high risk stratification were significantly lower than those in the other groups (P < 0.005),Compared with the CDT group, PMT has significantly better therapeutic effect on ape than the CDT group in terms of thrombus clearance rate, pulmonary artery pressure, average dosage of urokinase, effective thrombolytic time and average hospitalization time (P < 0.05),meanwhile,there was no significant difference in postoperative complications between the two groups (P < 0.05). After half a year of follow-up, the levels of BNP, TnI and DFR in the cured group were significantly lower than those in the effective group and the ineffective group. The areas under the curve of serum BNP, TnI and plasma DFR were 0.91, 0.87 and 0.93 and the area under the curve DFR has higher diagnostic efficiency than BNP and TnI, while the sensitivity and specificity of TnI are significantly higher than BNP and DFR. Conclusion: Serum BNP, TnI and plasma DFR levels can reflect the risk stratification and better clinical diagnostic value of ape,PMT and CDT are used to treat high-risk ape. For hospitals with medical conditions, PMT is more worthy of clinical recommendation.

Novel Diagnostic Biomarkers Related to Oxidative Stress and Macrophage Ferroptosis in Atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory disease, which has a complex interplay between altered immune metabolism and oxidative stress. Therefore, we aimed to determine the oxidative stress and immune-related biomarkers in AS. Differential gene expression analyses are based on the GSE100927 dataset in the Gene Expression Omnibus (GEO), and 389 oxidative stress (OS) genes are identified based on gene set enrichment analysis (GSEA). We identified 74 differentially expressed genes related to oxidative stress (DEOSGs). "CIBERSORT" and "WGCNA" R Packages were used to compare the differences in immune infiltration levels between AS and control samples. The DEOSGs (N = 74) were intersected with the key module's genes of WGCNA (N = 972), and 27 differentially expressed immune-related oxidative stress genes (DEIOSGs) were obtained. To identify the pivotal genes, a protein-protein interaction (PPI) network was constructed using the STRING database and the Cytoscape software. MMP9, ALOX5, NCF2, NCF, and NCF4 were identified as diagnostic markers of AS, and we validated them in the GSE57691 dataset. The expression levels of the five diagnostic genes were significantly highly expressed in the AS group. Correlation analysis and single-cell analysis revealed that five diagnostic genes were mainly correlated with macrophages M1. We, respectively, intersected differentially expressed genes (DEGs) with ferroptosis gene set, necroptosis gene set, and pyroptosis gene set. The findings suggested that ALOX5 and NCF2 were differentially expressed genes of ferroptosis. High expression of five hub genes in RAW264.7 macrophages were confirmed by PCR. High ALOX5 and NCF2 expression levels in plaque tissues were confirmed by immunohistochemistry (IHC) and western blotting. Our study identified that MMP9, ALOX5, NCF2, NCF1, and NCF4 were diagnostic genes of AS and associated with oxidative stress. ALOX5 and NCF2 may be involved in the formation of the necrotic core in AS by regulating macrophage ferroptosis.

Prediction of Necroptosis-Related Markers in Head and Neck Carcinoma by Bioinformatics.

Necroptosis is a form of programmed cell death that has recently been shown to be important in the progression of head and neck cancer (HNC). Noncoding RNAs (ncRNAs) are known to function in cell death and tumor formation. In this study, we focused on microRNAs (miRNA) that play roles in necroptosis and the progression of HNC. We collected miRNA expression data, related clinical data of patients with HNC, and miRNA data related to necroptosis. A prognostic multimiRNA molecular marker was generated based on differential expression analysis and univariate and multivariate Cox regression analyses. Target genes of the prognosis-related miRNAs were identified, and their functions were evaluated by Gene Ontology Enrichment Analysis to reveal the processes the miRNAs may be involved in. Eight potentially prognostic miRNAs were identified through differential expression analysis: miR-331-3p, miR-181d-5p, miR-181b-5p, miR-500a-3p, miR-425-5p, miR-181a-5p, miR-141-3p, and miR-200a-5p. Multivariate Cox regression identified the risk score as an independent prognostic factor (univariate Cox regression results: hazard ratio (HR): 2.2028, 95% confidence interval (CI): 1.2640-3.8388, P = 0.0053; multivariate Cox regression results: HR: 2.4168, 95% CI: 1.3743-4.2501, P = 0.0022). Survival curve analysis revealed that patients with a high risk score had a bad prognosis (P = 0.0109). A receiver operating characteristic curve showed that the model has a certain prediction ability. We identified 187 miRNA-related genes, which were enriched in "cell cycle" and "cellular senescence." In conclusion, this study identified eight novel miRNA markers for predicting the prognosis of patients with HNC and paved the way for future research on necroptosis-related genes.

Deciphering the Intercellular Communication Between Immune Cells and Altered Vascular Smooth Muscle Cell Phenotypes in Aortic Aneurysm From Single-Cell Transcriptome Data.

Background: Vascular smooth muscle cell (VSMC) phenotype switching has been preliminarily found in aortic aneurysms. However, two major questions were raised: (1) What factors drive phenotypic switching of VSMCs in aortic aneurysms? (2) What role does VSMC phenotype transformation play in aortic aneurysms? We speculated that the interaction between infiltrated immune cells and VSMCs played a pivotal role in aortic aneurysm expansion. Materials and Methods: We obtained single-cell transcriptome data GSE155468 that incorporate eight aortic aneurysm samples and three normal aorta samples. A standard single-cell analysis procedure was performed by Seurat (v3.1.2) for identifying the general cell components. Subsequently, VSMCs were extracted separately and re-clustered for identifying switched VSMC phenotypes. VSMC phenotype annotation was relied on the definitions of specific VSMC phenotypes in published articles. Vital VSMC phenotypes were validated by immunofluorescence. Next, identified immune cells and annotated vital VSMC phenotypes were extracted for analyzing the intercellular communication. R package CellChat (v1.1.3) was used for investigating the communication strength, signaling pathways, and communication patterns between various VSMC phenotypes and immune cells. Result: A total of 42,611 cells were identified as CD4 + T cells, CD8 + T cells, VSMC, monocytes, macrophages, fibroblasts, endothelial cells, and B cells. VSMCs were further classified into contractile VSMCs, secreting VSMCs, macrophage-like VSMCs, mesenchymal-like VSMCs, adipocyte-like VSMCs, and T-cell-like VSMCs. Intercellular communication analysis was performed between immune cells (macrophages, B cells, CD4 + T cells, CD8 + T cells) and immune related VSMCs (macrophage-like VSMCs, mesenchymal-like VSMCs, T-cell-like VSMCs, contractile VSMCs). Among selected cell populations, 27 significant signaling pathways with 61 ligand-receptor pairs were identified. Macrophages and macrophage-like VSMCs both assume the roles of a signaling sender and receiver, showing the highest communication capability. T cells acted more as senders, while B cells acted as receivers in the communication network. T-cell-like VSMCs and contractile VSMCs were used as senders, while mesenchymal-like VSMCs played a poor role in the communication network. Signaling macrophage migration inhibitory factor (MIF), galectin, and C-X-C motif chemokine ligand (CXCL) showed high information flow of intercellular communication, while signaling complement and chemerin were completely turned on in aortic aneurysms. MIF and galectin promoted VSMC switch into macrophage-like phenotypes, CXCL, and galectin promoted VSMCs transform into T-cell-like phenotypes. MIF, galectin, CXCL, complement, and chemerin all mediated the migration and recruitment of immune cells into aortic aneurysms. Conclusion: The sophisticated intercellular communication network existed between immune cells and immune-related VSMCs and changed as the aortic aneurysm progressed. Signaling MIF, galectin, CXCL, chemerin, and complement made a significant contribution to aortic aneurysm progression through activating immune cells and promoting immune cell migration, which could serve as the potential target for the treatment of aortic aneurysms.