Wei Zhu

Objective: Bacterial infections (BIs) in decompensated cirrhosis are associated with high morbidity and mortality but remain diagnostically challenging due to limited conventional biomarker accuracy. We aim to evaluate the utility of serum Delta-like ligand 1 (DLL1) for BI detection in patients with decompensated cirrhosis. Methods: In this dual-cohort prospective study, 320 hospitalized patients with decompensated cirrhosis were consecutively enrolled and stratified into derivation (n = 224) and independent validation (n = 96) cohorts. Serum DLL1 levels were quantified at admission with an enzyme-linked immunosorbent assay. Diagnostic performance was assessed through receiver operating characteristic (ROC) curve analysis and multivariable logistic regression. Results: Compared with their noninfected counterparts, patients with decompensated cirrhosis and BI had elevated serum DLL1 levels (P < 0.001). DLL1 was an independent predictor of BIs (adjusted odds ratio (OR) = 5.495, 95% confidence interval (CI): 3.022–9.992) in multivariate analysis. DLL1 demonstrated robust diagnostic performance (area under the curve (AUC) = 0.863, 95% CI: 0.814–0.911), which was further improved when combined with C-reactive protein (CRP) in a dual-marker model (AUC = 0.918, P < 0.001) and validated in an independent cohort (AUC = 0.925). Decision curve analysis confirmed the clinical utility of this combination across threshold probabilities of 10% to 80%. Notably, DLL1 levels were weakly correlated with total bilirubin levels (Spearman's ρ=0.24, P < 0.001), suggesting limited confounding effects from hepatic inflammation. Conclusion: Serum DLL1 was a clinically viable diagnostic biomarker for BIs in patients with decompensated cirrhosis and demonstrated weak confounding effects from hepatic dysfunction. The CRP–DLL1 combined model achieved superior diagnostic accuracy with cross-cohort validation robustness.

Chloride intracellular channel (CLIC) proteins are novel Cl-channels with 6 family members (CLIC1–6) that are known to play crucial roles in multiple physiological functions, such as neurological, cardiovascular, pulmonary, and auditory functions, and in various malignancies, including hepatocellular carcinoma (HCC). However, considerable challenges exist in identifying appropriate CLICs as therapeutic target molecules and prognostic biomarkers for HCC because the transformation of soluble or integral membrane protein forms, and specific pharmacological agents (agonists and antagonists) for distinct CLICs remains enigmatic. To address this issue and the possible molecular basis and the signaling networks activated by CLICs in HCC, we examined the transcriptional, promoter methylation, DNA mutation, survival, and immune infiltration data of CLICs in patients with HCC using the ONCOMINE, UALCAN, GEPIA, cBioPortal, and TIMER databases. The data showed that the expression levels of CLIC family members were differed between tumor and normal tissues. High expression levels of CLIC1 and CLIC3 were associated with advanced cancer stage in HCC patients. Low CLIC1 expression was associated with a better overall survival (OS). The DNA methylation levels of the CLIC1–3 and CLIC5–6 promoters in tumor tissue with HCC were significantly lower in HCC tissues than in normal tissues. Patients with CLIC1 alterations had a shorter OS than patients with unaltered CLIC1. Moreover, the expression levels of CLICs correlated with the infiltration of 6 different immune cells (B cells, CD4⁺ T cells, CD8⁺ T cells, neutrophils, macrophages, and dendritic cells). These results indicate that the increased mRNA expression and decreased promoter DNA methylation level of CLICs may play crucial roles in HCC tumorigenesis. The expression of CLIC family members was significantly correlated with the tumor immune status. High CLIC1 and CLIC3 expression levels could serve as biomarkers for identifying advanced-stage HCC. Moreover, a CLIC1 mutation rate of 18% was also observed and CLIC1 genetic alterations were significantly associated with lower OS in HCC patients.

This study investigated the expression change, prognostic values, and potential regulatory mechanisms of mortality factor on chromosome 4 (MORF4)-related gene-binding protein (MRGBP) in hepatocellular carcinoma (HCC). MRGBP expression and clinical data from The Cancer Genome Atlas were used to evaluate the associations between MRGBP expression and clinicopathological characteristics. Kaplan–Meier and Cox regression analyses were performed to assess the factors contributing to prognosis. Gene set enrichment analysis (GSEA) was used to identify pathways associated with MRGBP expression. Single-sample gene set enrichment analysis (ssGSEA) was used to comprehensively analyze the relative immune infiltration levels. High MRGBP expression was significantly associated with a higher T stage, pathologic stage, histologic grade, vascular invasion, tumor protein p53 status, and worse overall survival. MRGBP exhibited high diagnostic accuracy with an area under the receiver operating characteristic curve value of 0.980. GSEA revealed the enrichment of pathways related to tumorigenesis in the MRGBP high-expression phenotype, such as cell cycle and DNA replication pathways. ssGSEA revealed that MRGBP expression was significantly correlated with 15 types of immune cell infiltration levels. The Wilcoxon rank sum test revealed significantly high T helper (Th), T follicular helper, CD56 bright natural killer, and Th2 cell enrichment scores in the high MRGBP expression group and significantly low neutrophil, Th17, dendritic cell (DC), gamma delta T, cytotoxic cell, regulatory T cell, plasmacytoid DC, and immature DC enrichment scores. MRGBP may be a novel prognostic biomarker and a therapeutic target correlated with immune infiltrates in HCC.

Rationale: Diffuse giant cell tumors of the tendon sheath (GCT-TS) in the temporomandibular joint (TMJ) are extremely rare. Patient concerns: We reported the imaging appearance and the pathological findings of 2 male cases with diffuse GCT-TS in the TMJ (52 years for the case 1 and 50 years for the case 2) who complain of the hearing disorders of left ear when presenting to our hospital. Diagnosis: Preoperative computerized tomography (CT) scan revealed an irregular mass in the left temporal fossa with the sizes of approximately 5.8 × 3.8 × 4.6 cm for case 1 and 4.2 × 3.2 × 4.3 cm for case 2, respectively. Magnetic resonance imaging (MRI) findings showed a mass of 6.1 × 4.0 × 5.1 cm and 5.3 × 3.6 × 3.3 cm, respectively. Postoperative pathological examination revealed the diffuse multinucleated giant cells accompanied with synovial cells in the diffuse arrangement. Immunohistochemical examination showed CD68 (+), Vim (+), S-100 (-) and 2% of Ki-67 proliferation index. These characteristics are in line with the diagnosis of the diffuse GCT-TS in the TMJ. Interventions: Both cases underwent the gross total resection followed by radiation therapy. Outcomes: Two patients experienced no recurrence after follow-up of 1 to 2 year(s). Lessons: Diffuse GCT-TS in the TMJ is very rare. Clinicians should keep in mind the possibility of the GCT-TS when aggressive lesions involve the TMJ and adjacent bone destruction was found. Careful pre- and postoperative examinations and complete resection are the factors that lead to its optimal treatment, significantly reducing its recurrence rate.