Biomedical subjects

Jin Li

Publications and source records attributed to Jin Li.

6 recordsLinked to original sources

PubMed2026

Loss of PBRM1 accelerates pancreatic cancer progression by inducing acquisition of mesenchymal phenotype and inflammatory cancer-associated fibroblasts reprogramming.

BACKGROUND: PBRM1 is an important subunit of the SWI/SNF complex, which broadly regulates gene transcription by chromatin remodeling. Genomic alterations of PBRM1 have been found in patients with pancreatic ductal adenocarcinoma (PDAC), but its molecular functions remain unclear. METHODS: Clinical relevance of PBRM1 was analyzed by using human PDAC samples and public genomic datasets. Mice with concomitant pancreas-specific Pbrm1 deletion in Kras-driven genetic PDAC models were generated. Single-cell transcriptomics were performed to determine tumor phenotype and microenvironment reprogramming. RESULTS: Reduction of PBRM1 expression was observed in human PDAC tissues and correlated with poor prognosis and metastasis. Pbrm1 loss promoted ductal metaplasia and delayed epithelial recovery in mice with caerulein-induced pancreatic injury. In PDAC model with either mutant Kras alone or in combination with Trp53 mutation, lack of Pbrm1 markedly accelerated tumor development and progression. Bulk transcriptomics and scRNA-seq identified reprogramming of both tumor compartment with mesenchymal phenotype acquisition and stroma compartment with inflammatory cancer-associated fibroblasts (iCAFs) transformation. Mechanistically, Pbrm1 deletion induced Zeb1 upregulation through epigenetic chromatin remodeling, thereby enhancing epithelial-mesenchymal and basal-like subtype transition. CONCLUSIONS: These findings indicated a tumor-suppressing role of PBRM1 in PDAC. PBRM1-deficient PDAC constitutes a specific subgroup of patients with aggressive phenotype and prognostic significance.

Animals↗

PubMed2026

Matching-adjusted indirect comparison of fruquintinib versus ramucirumab in advanced gastric or gastroesophageal junction adenocarcinoma.

Aim: Fruquintinib (Fruq), a selective VEGFR 1/2/3 inhibitor, showed a significant progression-free survival (PFS) benefit in the Phase III FRUTIGA trial for advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Ramucirumab (RAM), an anti-VEGFR2 antibody, demonstrated efficacy in the RAINBOW-Asia trial. This anchored matching-adjusted indirect comparison (MAIC) evaluated Fruq plus paclitaxel versus RAM plus paclitaxel as second-line therapy for G/GEJ adenocarcinoma in the absence of head-to-head trials. Materials & methods: Data from individual patients in the FRUTIGA study (N = 703) and aggregated data from the RAINBOW-Asia study (N = 440) were analyzed. Baseline characteristics were balanced using entropy balancing. The placebo plus paclitaxel (PBO + PTX) groups served as the common comparators. The primary outcome was PFS; secondary outcomes included overall survival, objective response rate (ORR) and disease control rate (DCR). Rates of treatment-emergent adverse events (TEAEs) were also compared as an exploratory outcome using an adjusted indirect risk difference. Sensitivity analyses included restricted mean survival time and simulated treatment comparison. Results: After weighting (effective sample size = 564), baseline covariates were balanced. The anchored MAIC demonstrated that Fruq + PTX significantly improved PFS compared with RAM + PTX (HR: 0.70; 95% CI: 0.51-0.96; p = 0.0280), corresponding to a 30% reduction in progression risk, with a significant restricted mean survival time benefit of 1.18 months at 20 months (95% CI: 0.08-2.27; p = 0.024). Fruq achieved significantly higher ORR (OR: 1.76, 95% CI: 1.16-2.68; p = 0.008) and DCR (OR: 1.94, 95% CI: 1.33-2.83; p < 0.001). Overall survival was similar (0.97; 95% CI: 0.73-1.30; p = 0.8640). Subgroup analyses showed PFS benefits with Fruq in patients with ECOG PS 1, peritoneal metastases and two or fewer metastatic sites. In sensitivity analysis, the simulated treatment comparison also suggested a PFS benefit for Fruq + PTX (HR: 0.40, 95% CI: 0.32-0.50; p < 0.0001). For any-grade TEAEs, the indirect comparison showed higher adjusted relative incidences of increased bilirubin with Fruq + PTX than with RAM + PTX (RD: 12.3%; 95% CI: 2.3-22.4%, p < 0.05) and of hypokalemia (RD: 9.0%; 95% CI: 1.5-16.4%, p < 0.05). For grade ≥3 TEAEs, the adjusted relative incidence of decreased body weight was higher with Fruq + PTX than with RAM + PTX (RD: 2.9%; 95% CI: 0.6-5.2%, p < 0.05). The adjusted relative incidences of increased AST, ALT and hypocalcemia were numerically lower in the fruquintinib group than in the RAM group. Conclusion: This MAIC indicates that Fruq + PTX may be more effective than RAM + PTX in second-line advanced G/GEJ adenocarcinoma, with potentially improved PFS, ORR and DCR, and similar overall survival. Safety analyses suggested generally comparable safety profiles across the two regimens. Fruq + PTX remains a valuable treatment option, offering important comparative evidence for clinical and health technology assessment decisions. Trial Registration: Clinicaltrials.gov identifiers: NCT07144995.

Adult↗

PubMed2026

Shared genetic architecture and therapeutic targets across paediatric immune-mediated diseases.

OBJECTIVES: Paediatric-onset immune-mediated inflammatory diseases (IMIDs), including juvenile idiopathic arthritis and related rheumatic diseases, remain genetically undercharacterised. We aimed to define shared and category-specific genetic architecture across paediatric IMIDs, compare signals with adult IMIDs, and identify therapeutic opportunities. METHODS: We analysed 24 paediatric IMIDs classified as autoimmune, polygenic-autoinflammatory, mixed-pattern, or allergic. Genome-wide association analyses included 18,086 cases and 131,019 controls of European ancestry. We estimated single nucleotide polymorphism (SNP)-based heritability, genetic correlations, and polygenic overlap; performed subset-based meta-analysis; and conducted functional annotation, gene prioritisation, pathway and protein network analyses, adult-IMID comparison, and drug-target prioritisation. RESULTS: SNP-based heritability ranged from 28.9% for allergic IMIDs to 61.9% for autoimmune IMIDs. Genetic correlation and polygenic modelling supported partial sharing across categories with category-specific components. Meta-analysis identified 39 genome-wide significant loci outside the Major Histocompatibility Complex (MHC) region, including 15 previously unreported loci; 19 loci were shared between categories. Gene-prioritisation and protein interaction analyses identified a core MHC-centred antigen-presentation network, with category-enriched modules involving complement, innate/barrier pathways, epithelial biology, and type 2 immunity. Enriched pathways included nuclear factor κB signalling, T helper 17 related pathways, Janus kinase-signal transducer and activator of transcription signalling, programmed cell death protein 1/programmed death‑ligand 1, cytotoxic T‑lymphocyte associated protein 4 regulation, and osteoclast differentiation, several of which are relevant to rheumatic diseases. Paediatric IMIDs shared broad polygenic architecture with adult IMIDs, whereas top-ranked genes converged strongly with adult rheumatic diseases. Priority Index analysis identified 178 high-scoring genes, including 43 approved or investigational IMID drug targets. CONCLUSIONS: Paediatric-onset IMIDs share core pathways with adult forms but exhibit distinct genetic architecture shaped by age-specific immune and neurodevelopmental biology. These findings provide a genomic framework for paediatric precision medicine, guiding classification, risk prediction, and therapeutic development.

Humans↗

PubMed2026

Risk Factors and Predictive Model for Postoperative High Myopia in Children Undergoing Congenital Cataract Surgery With Intraocular Lens Implantation.

PURPOSE: To identify risk factors associated with the development of high myopia following congenital cataract surgery and to establish a robust predictive model. DESIGN: Retrospective clinical cohort study. SUBJECTS: This retrospective study included 106 pediatric patients who underwent congenital cataract surgery with primary IOL implantation (mean follow-up 8.19 years). The model was externally validated in an independent cohort of 72 patients with a mean follow-up of 7.83 years. METHODS: Preoperative and postoperative ocular biometric parameters were collected. Risk factors for postoperative high myopia were analyzed using Cox proportional hazards regression, which served as the basis for model construction. The predictive performance of the model was rigorously evaluated for discrimination and calibration. Discriminative ability was quantified using Harrell's C-index and the area under the receiver operating characteristic curve (AUC). Model calibration was assessed via calibration plots by comparing predicted probabilities with actual observed outcomes. Internal validation was performed using a bootstrapping method (500 iterations) to ensure model stability and adjust for potential overfitting. RESULTS: An initial postoperative refraction of <+0.75D, and a higher IOL Power to Axial length Ratio (IOL/AL ratio) were identified as significant risk factors for the development of postoperative high myopia. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. The predictive model demonstrated robust performance, achieving a C-index of 0.711 (internal validation C-index: 0.713). The area under the receiver operating characteristic curve (AUC) values for predicting high myopia at 5 and 10 years were 0.858 and 0.745, respectively. Furthermore, calibration curves demonstrated excellent agreement between the predicted and observed outcomes throughout the follow-up period. In external validation, the model achieved a C-index of 0.825, 5-year AUC of 0.833, and 10-year AUC of 0.713. CONCLUSIONS: Our analysis established that initial postoperative refraction <+0.75D, and an elevated IOL/AL ratio are key determinants of high myopia risk following surgery. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. This predictive framework provides clinicians with a practical tool to optimize preoperative IOL selection and identify high-risk infants who require vigilant myopia prevention and balanced amblyopia management.

Humans↗

PubMed2026

Multiomics Integration Identifies a Molecular Subtype of Intrahepatic Cholangiocarcinoma With Enhanced Benefit From Adjuvant Therapy.

Intrahepatic cholangiocarcinoma (iCCA) is a molecularly heterogeneous liver cancer with a poor prognosis. Improved stratification is needed to guide postoperative therapy. In this study, we applied integrative multiomics analysis to classify iCCA and identify biomarkers predictive of adjuvant treatment benefit. Using publicly available datasets (including whole exome sequencing, RNA sequencing, proteomics, and phosphoproteomics from FU-iCCA cohort and a transcriptomic cohort GSE244807), we defined 3 robust molecular subtypes of iCCA. These subtypes exhibited distinct genomic alterations, pathway activation, and immune microenvironments, with significant differences in overall survival (OS). Through protein-protein interaction network analysis and consensus feature selection using 10 clustering algorithms, we prioritized 8 marker genes distinguishing the subtypes. A Cox proportional-hazards model constructed from these markers stratified patients into high- and low-risk groups. High-risk iCCA, characterized by elevated expression of markers such as CLDN18, MUC1, and MUC5AC, had significantly worse OS in the absence of adjuvant therapy. Notably, in an independent validation of 174 patients with iCCA who underwent resection (single-center cohort), high expression of any of these 3 markers were associated with markedly prolonged OS in patients who received adjuvant chemotherapy or chemoembolization, compared with those who did not. In contrast, marker-negative patients showed no clear benefit from adjuvant therapy. In conclusion, our multiomics approach identified a high-risk, mucin-enriched subtype of iCCA. CLDN18, MUC1, and MUC5AC emerge as candidate predictive biomarkers for adjuvant chemotherapy benefit in iCCA, warranting prospective validation to improve personalized postoperative management.

Humans↗

PubMed2025

In vitro activity of contezolid and other comparators against clinical Staphylococcus and Enterococcus: a multicenter study in China.

OBJECTIVE: To evaluate the in vitro activity of contezolid against clinical Staphylococcus and Enterococcus isolates from across China, and compare its performance with linezolid and other key agents. METHODS: A total of 2510 non-duplicate Gram-positive cocci isolates were collected from 70 hospitals in seven Chinese regions. Minimum inhibitory concentrations (MICs) were determined using broth microdilution (BMD) per CLSI guidelines. MIC50/90 values, susceptibility rates, cumulative MIC curves and MIC distribution agreement between contezolid and linezolid were assessed. Linezolid-resistant isolates and contezolid-resistant isolates-defined as those based on CLSI 2025 linezolid breakpoints-underwent whole-genome sequencing and comprehensive screening for known oxazolidinone resistance determinants, including acquired resistance genes, 23S rRNA mutations and amino acid substitutions in ribosomal proteins L3, L4 and L22. RESULTS: Contezolid exhibited potent in vitro activity, with >99% of isolates inhibited at ≤4 mg/L and showed lower MIC50/90 than linezolid, with a consistently left-shifted cumulative MIC distribution. Cohen's kappa analysis supporting enhanced activity of contezolid. Notably, we report for the first time clinical isolates with contezolid MICs up to 16 mg/L. Whole-genome analysis of 14 linezolid-resistant isolates (including five resistant to contezolid) revealed universal presence of optrA, cfr, fexA and other resistance genes, alongside domain V 23S rRNA mutations and substitutions in ribosomal proteins L3 and L4, supporting a shared genetic basis and potential cross-resistance between the two agents. CONCLUSIONS: Contezolid demonstrated potent and consistent activity against drug-resistant Gram-positive cocci, supporting its potential as a therapeutic alternative to linezolid. Further studies are needed to confirm resistance mechanisms and clinical utility.

Microbial Sensitivity Tests↗