This meta-analysis aims to evaluate the efficacy and safety of colchicine for the secondary prevention of cardiovascular and cerebrovascular diseases, and examines how dose and treatment duration modify its risk–benefit profile. A meta-analysis comparing colchicine to placebo or standard care was performed. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. The secondary endpoint was expanded MACE (eMACE), defined as MACE plus ischemia-driven coronary revascularization. Colchicine significantly reduced the risk of MACE (relative risk [RR] 0.83, 95
Inflammatory bowel disease (IBD) is a chronic and relapsing gastrointestinal disorder marked by persistent inflammation and disruption of the intestinal barrier. Current treatments often focus solely on inflammation control and lack effective mucosal repair capabilities, leading to suboptimal outcomes and adverse effects. To address this, we developed tea polyphenol and serotonin nanoparticles (TPSNs) through oxidative copolymerization of epigallocatechin gallate (EGCG) and serotonin (5-HT), combining the anti-inflammatory, antioxidant, and mucosal repair functions of both components. The therapeutic efficacy was systematically evaluated in dextran sulfate sodium (DSS)-induced acute colitis models in both zebrafish and mice, as well as in IL-10 knockout mice models of chronic colitis. Mechanistic studies revealed that TPSNs effectively scavenged reactive oxygen and nitrogen species (RONS), promoted M1-to-M2 macrophage repolarization, inhibited pyroptosis and NF-κB signaling, and activated MAPK and PI3K-AKT pathways to enhance epithelial cell proliferation and migration. TPSNs were further incorporated into a thermosensitive in situ forming gel for rectal delivery to enhance localized and sustained drug release. In vivo administration demonstrated significant amelioration of disease symptoms and histopathological features, while biosafety assessments confirmed no considerable toxicity to major organs or disruption of liver and kidney function. These findings highlight TPSNs as a safe and effective nanotherapeutic candidate for integrated IBD treatment by addressing inflammatory and mucosal repair pathways.
4059 Background: Anti-PD1 antibody has significantly improved survival in patients with HER2-overexpressing and PD-L1 combined positive score (CPS) ≥1 GC/GEJC when added to trastuzumab and chemotherapy. Recent trials revealed that HER2-targeted antibody-drug conjugates, including RC48 and Trastuzumab Deruxtecan, combined with anti-PD1 antibody, have also shown promising efficacy in this population. This study reports updated survival results of RC48 combined with tislelizumab and the oral fluoropyrimidine S-1 as first-line therapy for patients with HER2-overexpressing GC/GEJC. Methods: This single-arm, multicenter clinical trial enrolled patients with unresectable or metastatic HER2-overexpressing (IHC 3+ or 2+, regardless of FISH status) first-line GC/GEJC. Patients received RC48 (2.5 mg/kg), tislelizumab (200 mg), and S-1 (40-60 mg BID for 14 days) every 3 weeks until disease progression (PD) or intolerable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results: 57 patients from 9 centers were enrolled, 71.9% HER2 IHC 3+, 17.5% IHC 2+/FISH+, and 10.5% IHC 2+/FISH-. 14.9% and 36.2% had CPS≥5 and ≥1, respectively. Median follow-up was 11.8 months. In the intent-to-treat population, the confirmed ORR (cORR) was 89.4% (51/57, 95% CI: 78.5-96.0%), the median PFS (mPFS) was 12.7 months (95% CI: 10.9-NA), and the 18-month OS rate (18m-OSr) was 72.7% (95% CI: 60.0-88.5%). In the per-protocol set (excluding patients with no PD at the first assessment but refused a second evaluation), the cORR was 92.7% (51/55, 95% CI: 82.4-98.0%), the mPFS was 13.2 months (95% CI: 10.9-NA), and the 18m-OSr was 76.3% (95% CI: 63.0-91.7%). In the HER2-positive and -negative subgroups, the ORRs were 92.1% (95% CI: 81.1-97.8%) and 66.7% (95% CI: 22.3-95.7%), the mPFS was 12.6 months (95% CI: 11.0-NA) and 7.7 months (95% CI: 7.1-NA), and the 18m-OSr was 74.7% (95% CI: 61.3-91.1%) and 62.5% (95% CI: 32.0-100%), respectively. In the CPS ≥1 and CPS < 1 subgroups, ORRs were 92.3% (95% CI: 74.9-99.1%) and 87.1% (95% CI: 70.2-96.4%), the mPFS was 16.8 months (95% CI: 11.3-NA) and 11.4 months (95% CI: 8.5-NA), and the 18m-OSr was 80.4% (95% CI: 62.1-100%) and 67.4% (95% CI: 50.7-89.5%), respectively. The grade 3-4 treatment-related adverse events (AEs) was 63.2%. The most common AEs were neutropenia, fatigue, and leukopenia. An exploratory study with longitudinal sequencing of circulating tumor DNA is ongoing. Conclusions: The combination of RC48, tislelizumab and S-1 as a first-line therapy shows encouraging response rates and survival benefits in HER2-overexpressing GC/GEJC, especially in HER2-positive or CPS ≥1 patients, supporting further evaluation in randomized controlled trials. Clinical trial information: NCT05586061 .
Background:Glioma is a highly heterogeneous and aggressive malignancy of the central nervous system, and reliable molecular biomarkers are urgently needed to improve prognostic stratification and guide therapeutic decision-making. The MEX3 family of RNA-binding proteins has been implicated in tumorigenesis and post-transcriptional regulation; however, their comprehensive roles in glioma remain poorly understood. Methods:Integrated bioinformatic analyses were performed using transcriptomic and clinical data from TCGA, CGGA, and GEO cohorts to evaluate the expression profiles, diagnostic and prognostic value, genetic alterations, molecular interactions, immune infiltration characteristics, and functional pathways associated with MEX3A, MEX3B, MEX3C, and MEX3D. Protein-protein interaction networks, gene set enrichment, and co-expression analyses were conducted to explore potential biological mechanisms. A MEX3-related prognostic risk model was constructed and validated in independent datasets. Drug sensitivity correlations were analyzed using public pharmacogenomic resources. In addition, in vitro experiments, including qRT-PCR, western blotting, proliferation, migration, and invasion assays, were performed in U251 and LN229 glioma cell lines to functionally validate the bioinformatic findings. Results:All four MEX3 family members were significantly upregulated in glioma tissues compared with normal controls and demonstrated strong diagnostic performance. Distinct prognostic patterns were observed, with MEX3D consistently identified as an independent predictor of poor overall, disease-specific, and progression-free survival. MEX3 genes were associated with diverse genetic alterations and were enriched in pathways related to RNA processing, cell cycle regulation, and cancer-associated signaling. Immune analyses revealed significant correlations between MEX3 expression and multiple immune cell populations as well as immune checkpoint molecules, suggesting potential roles in shaping the glioma immune microenvironment. A MEX3-related co-expression-based prognostic model showed robust survival-predictive ability and remained effective in external validation cohorts. Functional assays confirmed that silencing individual MEX3 genes significantly inhibited glioma cell proliferation, migration, and invasion in vitro. Conclusions:This study provides a comprehensive characterization of the MEX3 family in glioma, demonstrating their dysregulation, prognostic relevance, immune associations, and functional contributions to malignant phenotypes. Among them, MEX3D emerges as a particularly promising prognostic biomarker. These findings establish a foundation for future mechanistic and translational studies exploring MEX3 family members as potential biomarkers or therapeutic targets in glioma.
RATIONALE:Ingestion of removable dentures leading to gastrointestinal perforation is a rare but potentially life-threatening emergency, particularly in the elderly population due to diminished oral sensation and swallowing reflex. This article reports the management of a patient who developed sigmoid colon necrosis and perforation. PATIENT CONCERNS:A 76-year-old female presented to the emergency department with a 2-day history of nausea and left lower abdominal pain. Medical history collection confirmed that the patient had accidentally swallowed her removable denture 3 days ago. DIAGNOSES:Abdominal computed tomography identified a high-density foreign body in the sigmoid colon and pneumoperitoneum with dilated bowel loops. Combined with the medical history, the diagnosis of sigmoid colon perforation caused by ingested dentures was confirmed. INTERVENTIONS:Emergency treatment involved Hartmann procedure for resection of the necrotic bowel segment and colostomy. Four months later, laparoscopic-assisted stoma reversal was successfully performed to restore intestinal continuity. OUTCOMES:The patient recovered uneventfully and was discharged without complications. Hartmann procedure is an effective and safe treatment for colonic perforation that needs emergency treatment and cannot be anastomozed in 1 stage. LESSONS:Early identification and individualized treatment are critical for patients with ingested dentures. Denture restoration for high-risk groups should be reconsidered or replaced with safer alternatives.
