Palliative therapy utilizing interventional stents, such as vascular stents, biliary stents, esophageal stents, and other stents, has been a prevalent clinical strategy for treating duct narrowing and partial blockage. However, stent restenosis after implantation usually significantly compromises therapeutic efficacy and patient safety. Clinically, vascular stent restenosis is primarily attributed to endothelial hyperplasia and coagulation, while the risk of biliary stent occlusion is heightened by bacterial adhesion and bile sludge accumulation. Similarly, granulation tissue hyperplasia leads to tracheal stent restenosis. To address these issues, surface modifications of stents are extensively adopted as effective strategies to reduce the probability of restenosis and extend their functional lifespan. Applying coatings is one of the technical routes involving a complex selection of materials, drug loading capacities, release rates, and other factors. This paper provides an extensive overview of state of the art drug-coated stents, addressing both challenges and future prospects in this domain. We aim to contribute positively to the ongoing development and potential clinical applications of drug-coated stents in interventional therapy.

Molecular mechanisms behind potentially inferior prognosis of old cholangiocarcinoma (CCA) patients are unclear. Prevalence of interventional targets and the difference between young and old CCA patients are valuable for promising precision medicine. A total of 188 CCA patients with baseline tumor tissue samples were subgrouped into the young (≤45 years) and old (>45 years) sub-cohorts. Somatic and germline mutation profiles, differentially enriched genetic alterations, and actionable genetic alterations were compared. An external dataset was used for the validation of molecular features and the comparison of overall survival (OS). Compared to young patients, KRAS alterations were more common in old patients (P = .04), while FGFR2 fusions were less frequent (P = .05). TERT promoter mutations were exclusively detected in old patients. The external dataset (N = 392) revealed no significant difference in OS between young and old patients; however, old patient-enriched KRAS (hazard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.37-2.80) and TERT alterations (HR: 2.03, 95% CI: 1.22-3.38) were associated with inferior OS. Approximately 38.3% of patients were identified of actionable oncogenic mutations indicative of a potential response to targeted therapy or immunotherapy. Actionable FGFR2 fusions (P = .01) and BRAF^V600E (P = .04) mutations were more frequent in young females than old patients. The enrichment of KRAS/TERT alterations in CCA patients over 45 years resulted in inferior OS. Approximately one-third of CCA patients were eligible for targeted therapy or immunotherapy given the actionable mutations carried, especially young females.

Macrophages are central regulators of liver immunity and fibrosis; Recent single-cell studies have characterized macrophage heterogeneity in cirrhosis; however, how regulated cell death programs shape their functional transitions across disease progression in human liver remains poorly defined. We integrated scRNA-seq data from 224,529 cells across 31 adult liver samples to define macrophage states and trajectories. Functional activities of regulated cell death pathways were assessed, and key programs were validated by dual immunofluorescence in human liver tissues. Four macrophage subsets with disease-biased distributions were identified. Cirrhotic macrophages exhibited progressive suppression of autophagy, necroptosis, apoptosis, and immunogenic cell death along differentiation, most prominently in terminal states, accompanied by transcriptional exhaustion and reduced immune regulator expression. A disease-associated transitional subpopulation displayed hybrid metabolic-immune features and yielded a six-gene diagnostic signature (LDHB, CD37, S100A10, RNASE1, CXCR4 and CORO1A) validated in bulk RNA-seq data (AUC = 0.936). Spatial analyses confirmed attenuation of autophagy and necroptosis and enrichment of CXCR4- and S100A10-positive macrophages in fibrotic niches. Human cirrhosis is characterized by progressive repression of regulated cell death programs in liver macrophages, providing mechanistic insight into disease progression and identifying macrophage-associated molecular signatures that may aid in patient stratification and serve as potential targets for future therapeutic intervention.

Background: Despite advances in surgical techniques, immunotherapy, the mortality rate associated with pancreatic cancer (PC) has been on the rise in recent years. Understanding the importance of RNA N6-methyladenosine (m6A) in PC is critical for prognosis, tumor microenvironment, and immunotherapy efficacy. The study aims to identify m6A methylation regulators that play an important role in the development and progression of PC by mining databases. The effect of insulin-like growth factor-binding protein 3 (IGFBP3) on pancreatic tumors was explored, and the related mechanisms were explored. Methods: We analyzed the expression of m6A regulators in PC by digging deeper into the datasets of The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases, and analyzed its relationship with the prognosis of patients with PC, looking for m6A methylation regulators that play an important role in the development and progression of PC. Reuse the ConsensusClusterPlus package, Cox analysis, and unsupervised clustering to delineate three distinct m6A clusters – designated as m6A cluster A, m6A cluster B, and m6A cluster C single-sample gene set enrichment analysis, gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses evaluated the different pathway roles of these clusters in the development and progression of PC. Finally, the cell lines with IGFBP3 overexpression and knockdown were constructed by lentivirus transfection, the transfection effect was identified by WB, and the effects of IGFBP3 overexpression/knockdown on the survival and growth of PC cell lines were verified by cell cloning experiments and cell counting kit-8 experiments, and the possible related pathways were explored by KEGG. Results: Most m6A regulatory factors are highly expressed in PC, and their high expression is negatively correlated with the prognosis of patients with PC. Furthermore, m6A regulatory factors may influence the occurrence and development of PC through metabolic pathways, stroma activation pathways, immune regulatory processes, and the immune microenvironment. Finally, the overexpression of IGFBP3 promoted the growth of PC cells, and vice versa. Conclusions: Most m6A regulatory factors are differentially expressed in PC and are associated with the prognosis of patients with PC, potentially influencing the occurrence and development of PC through pathways such as the immune microenvironment. The overexpression of IGFBP3 can promote the growth of PC cells and vice versa.