Predictors of permanent pacemaker implantation in aortic valve diseases after TAVI with vitaFlow liberty system.

Introduction: Permanent pacemaker implantation (PPI) is a known complication in patients with aortic stenosis following transcatheter aortic valve implantation (TAVI). However, there is limited research on TAVI for pure aortic regurgitation (PAR), and more investigation is needed to determine the occurrence of postoperative cardiac conduction block and the need for PPI in this population. Therefore, this retrospective analysis aimed to evaluate the incidence of cardiac conduction block and the necessity of PPI after TAVI in patients with different types of aortic valve disease, including pure aortic stenosis (PAS), aortic stenosis with regurgitation (ASR), and PAR. Methods: Clinical data of 100 patients who TAVI were analyzed retrospectively. The incidence of conduction block was assessed, and clinical factors were examined to predict the necessity of PPI. Results: Cardiac conduction block was found to be a common complication following TAVI, particularly in patients with PAR. PAR was identified as an independent risk factor for requiring PPI. Additionally, first-degree atrioventricular block emerged as a sensitive predictor for PPI in patients with PAR. Discussion: These findings provide valuable insights into the safety and effectiveness of TAVI, which can help enhance patient management and reduce complications.

Integrated bioinformatics analysis reveals marker genes and immune infiltration for pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a chronic cardiopulmonary syndrome with high pulmonary vascular load and eventually causing RV heart failure even death. However, the mechanism of pulmonary hypertension remains unclear. The purpose of this research is to detect the underlying key genes and potential mechanism of PAH using several bioinformatic methods. The microarrays GSE22356, GSE131793 and GSE168905 were acquired from the GEO. Subsequently, a host of bioinformatics techniques such as DAVID, STRING, R language and Cytoscape were utilized to investigate DEGs between PAH and healthy controls and conduct GO annotation, KEGG enrichment analysis and PPI network construction etc. Additionally, we predicted the transcription factors regulating DEGs through iRegulon plugin of Cytoscape and CIBERSORT was used to conduct immune infiltration analysis. One thousand two hundred and seventy-seven DEGs (403 up-regulated and 874 down-regulated) were identified from peripheral blood samples of 32 PAH patients and 29 controls, among which SLC4A1, AHSP, ALAS2, CA1, HBD, SNCA, HBM, SELENBP1, SERPINE1 and ITGA2B were detected as hub genes. The functional enrichment changes of DEGs were mainly enriched in protein binding, extracellular exosome, extracellular space, extracellular region and integral component of plasma membrane. The hub genes are chiefly enriched at extracellular exosome, hemoglobin complex, blood microparticle, oxygen transporter activity. Among TF-DEGs network, 42 target DEGs and 6 TFs were predicted with an NES > 4 (TEAD4, TGIF2LY, GATA5, GATA1, GATA2, FOS). Immune infiltration analysis showed that monocytes occupied the largest proportion of immune cells. The trend analysis results of infiltration immune cells illustrated that PAH patients had higher infiltration of NK cell activation, monocyte, T cell CD4 memory activation, and mast cell than healthy controls and lower infiltration of T cell CD4 naive. We detected SLC4A1, AHSP, ALAS2, CA1, HBD, SNCA, HBM, SELENBP1, SERPINE1 and ITGA2B as the most significant markers of PAH. The PAH patients had higher infiltration of NK cell activation, monocyte, T cell CD4 memory activation, and mast cell than healthy controls and lower infiltration of T cell CD4 naive. These identified genes and these immune cells probably have precise regulatory relationships in the development of PAH.

Exploration of Mechanisms of Sacubitril/Valsartan in the Treatment of Cardiac Arrhythmias Using a Network Pharmacology Approach.

Significant reductions in the incidence of cardiac arrhythmia (CA) and sudden cardiac death (SCD), along with amelioration of heart failure, have been reported for treatment with Sacubitril/valsartan (SV). However, its anti-arrhythmic mechanism remains unclear. The current study aims to explore the anti-arrhythmic molecular mechanism of SV. The direct protein targets (DPT) of SV were extracted from DrugBank. The protein-protein interaction (PPI) network of SV DPTs was constructed using STRING, and the indirect protein targets (IPTs) were also identified. A search for arrhythmia-related genes was conducted using GeneCards and the Comparative Toxicogenomics Database (CTD). The DTPs, ITPs, and arrhythmia-related genes from the two datasets were combined in a Venn diagram, and the overlapping genes were identified as core target genes. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses identified the top 20 biological processes and signaling pathways related to disease and the therapeutic effects of SV. The renin-angiotensin system, adrenergic signaling in cardiomyocytes, and gap junction pathways are strongly implicated in the effects of SV on CA. In conclusion, our bioinformatics analyses provided evidence pertaining to the possible antiarrhythmic mechanisms of SV and may contribute to the development of novel drugs for CA.

Rho/ROCK Pathway Regulates Migration and Invasion of Esophageal Squamous Cell Carcinoma by Regulating Caveolin-1.

BACKGROUND Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. Caveolin-1 (Cav1) and Rho/ROCK pathway play important roles in tumor metastasis, separately. However, less research was focused on the relationship between Cav1 and Rho/ROCK in ECSS metastasis. Therefore, we investigated the relationship between Cav1 and Rho/ROCK pathway in ESCC metastasis. MATERIAL AND METHODS Cav1 and phosphorylated Cav1 (PY14Cav1) were examined in ESCC and in adjacent and non-tumorous tissues from ESCC patients by immunohistochemistry (IHC). Small interfering RNA (siRNA) targeting Cav1 or Rho/ROCK inhibitor was used to treat EC109, Eca109, TE1, and TE13 cells. Western blotting (WB) was used to detect Cav1 and PY14Cav1 expression. The wound healing scratch test and transwell assays were used to assess migration and invasion. RESULTS Cav1 and PY14Cav1 were gradually expressed at higher levels in ECSS than in adjacent and non-tumor tissues as ESCC stage and lymphatic metastasis increased, and this difference was significant (P<0.05). Cav1 was expressed at higher levels in TE1 and TE13 than in EC109 and Eca109, while PY14Cav1 was enhanced in TE1 and TE13 cells but not in EC109 and Eca109, and the difference was significant (P<0.05). TE1 and TE13 had significantly (P<0.05) stronger motility, migratory, and invasion abilities than EC109 and Eca109 cells. Silencing Cav1 decreased PY14Cav1 expression in TE1 and TE13 cells, as well as suppressing the migration and invasion of all ECSS cells, and these differences were significant (P<0.05). Suppressing the Rho/ROCK pathway obviously inhibited Cav1 and PY14Cav1 expressions, as well as significantly (P<0.05) decreasing migration and invasion of ESCC cells. CONCLUSIONS Cav1 and PY14Cav1 were positively correlated with ESCC lymphatic metastasis and cancer stages. Rho/ROCK pathway activation promoted ESCC metastasis by regulating Cav1.