Clinical and Experimental Medicine最新文献

Foundation Models (FMs) are profoundly transforming the clinical management pathway for liver cancer. Their core value lies in enhancing diagnostic accuracy, enabling personalized therapeutic decision-making, and optimizing clinical efficiency through the integrative analysis of multimodal data, encompassing symptoms, medical histories, imaging findings, and genomic profiles. At the diagnostic level, FMs facilitate risk stratification by analyzing symptom and historical data while leveraging imaging features to aid in the early identification of lesions. Within the therapeutic decision-making domain for liver cancer, intelligent systems such as IDEAL provide critical clinical support by enabling precise hepatic anatomical reconstruction, quantitative assessment of surgical feasibility, and generation of individualized therapeutic recommendations for targeted agents and immunotherapy, thereby serving as essential adjuncts to HCC management. Despite their transformative potential, the clinical deployment of FMs faces significant core challenges: including concerns over model accuracy, reliability, and ethical issues such as data privacy and equitable access. Addressing these challenges requires interdisciplinary efforts focused on domain-specific model fine-tuning, robust ethical frameworks, and standardized regulatory guidelines. This review outlines the evolution and current state of FMs within healthcare, specifically highlighting their substantial application value in the liver cancer therapeutic landscape, and articulates the stage-specific challenges impeding their broader clinical adoption.

Peritoneal metastasis (PM) of solid tumours is a major contributor to cancer-associated mortality and morbidity. The mechanism of PM development encapsulates Paget's hypothesis of seed and soil, whereby cancer cells remotely prepare a pre-metastatic niche in the peritoneal microenvironment to facilitate transcoelomic cancer progression. The bidirectional communication between cancer cells and host mesothelial cells, endothelial cells, leukocytes, adipocytes, and fibroblasts occurs via exosomes. Exosomes are nano-sized extracellular vesicles that carry cargos of proteins, cytokines, and microRNA. Cancer-derived exosomes enable exfoliated tumour cells to resist anoikis, disseminate, adhere, and implant in the peritoneum. This process involves the degradation of the peritoneal glycocalyx, the transformation of peritoneal mesothelial cells into cancer-associated fibroblasts via mesothelial-mesenchymal transition, and metabolic coupling with omental and subperitoneal adipocytes. Exosomes also enhance ascites and peritoneal immunosuppression. Exosomes promote PM development from mesenchymal subtypes of epithelial cancers, which have a predilection for transcoelomic metastasis compared to other molecular subtypes. Mesenchymal subtypes include diffuse gastric cancer, CMS4 colorectal cancer, and high-grade serous ovarian carcinoma. Understanding the oncogenic roles of exosomal cargo offers potential for future research and therapy in PM.

MicroRNAs (miRNAs) are increasingly recognized as pivotal regulators in autoimmune diseases. Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent inflammation, progressive joint destruction, and systemic complications. Although several miRNAs have been implicated in RA, their specific roles and clinical relevance remain unclear. This study aimed to identify and validate differentially expressed miRNAs in peripheral blood mononuclear cells (PBMCs) from patients with RA and evaluate their potential as diagnostic biomarkers. RNA sequencing (RNA-seq) was performed on PBMCs obtained from three RA patients and three healthy controls (HCs) to screen for differentially expressed miRNAs. Three candidate miRNAs were selected for validation and measured using real-time fluorescence quantitative PCR (RT-qPCR) in an independent cohort of 41 RA patients and 41 HCs. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance. A total of 103 differentially expressed miRNAs were identified, with 34 upregulated and 69 downregulated in RA patients compared with HCs. RT-qPCR confirmed that hsa-miR-1276, hsa-miR-4433a-5p, and hsa-miR-409-3p were significantly upregulated in PBMCs of RA patients (P < 0.05), consistent with the sequencing results. Among them, hsa-miR-1276 showed promising diagnostic accuracy, with an area under the ROC curve (AUC) of 0.9726. Hsa-miR-1276 is significantly upregulated in PBMCs of RA patients and demonstrates promising diagnostic potential. These findings suggest that hsa-miR-1276 may serve as a novel biomarker for the diagnosis of RA.

The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, and the accurate, non-invasive assessment of liver fibrosis remains an important clinical challenge. This study aimed to identify ferroptosis biomarkers associated with MASLD-related liver fibrosis progression, explore their potential biological links with MRI-derived parameters, and provide new clues for developing non-invasive diagnostic strategies for ferroptosis. A MASLD-related liver fibrosis model was established using 30 Sprague-Dawley (SD) rats. Hub differentially expressed ferroptosis-related genes (DE-FRGs) were identified through the integration of weighted gene co-expression network analysis (WGCNA), differential expression analysis, and LASSO regression. The role of ferroptosis in MASLD was evaluated using transmission electron microscopy (TEM) and measurements of glutathione (GSH) and Fe²⁺ content. T2*, R2*, and proton density fat fraction (PDFF) were obtained through magnetic resonance imaging (MRI) and were analyzed for correlations with hub DE-FRGs and Fe²⁺ levels. A total of eight hub DE-FRGs were identified: Pck2, Idh2, Nr1d1, Fads1, Sat1, Abhd12, Got1, and Srebf1. Enrichment analyses revealed that these hub DE-FRGs were predominantly implicated in carbohydrate response, amino acid biosynthesis, insulin resistance, and the AMPK signaling pathway. TEM and biochemical markers analyses demonstrated an association between MASLD-related liver fibrosis and ferroptosis. MRI‑derived parameters were significantly correlated with Fe²⁺ levels and the expression of hub DE-FRGs. This study preliminarily identified hub DE-FRGs associated with liver fibrosis in MASLD and their signaling pathways, verified indirect indicators related to ferroptosis, and proposed their potential correlation with MRI-derived parameters.

Hypersensitivity reactions (HSRs) to oxaliplatin occur in 7-25% of patients and pose a significant clinical challenge, particularly for individuals who otherwise benefit from oxaliplatin-based therapy. Although evidence supporting its efficacy remains limited, drug desensitisation protocols (DDPs) involving stepwise dose escalation have been adopted in clinical practice. This study describes the experience of a tertiary cancer centre with oxaliplatin desensitisation, focusing on recurrence of HSRs and treatment completion rates. A retrospective observational study was conducted at a comprehensive cancer centre between October 2019 and January 2024. Clinicopathological characteristics and oncological outcomes were examined for patients with gastrointestinal malignancies who received oxaliplatin-based chemotherapy using a DDP. Sixty-six patients underwent oxaliplatin desensitisation (median age 60 years; 55% female). Most had colorectal cancer (CRC) (n = 35, 53%) or upper gastrointestinal malignancies (n = 26, 39%); 85% (n = 56) were treated with palliative intent. The median number of oxaliplatin cycles prior to the first HSR was six (range 1-26). CAPOX (53%) and FOLFOX (42%) were the most common regimens associated with HSRs. Patients received a median of three cycles within the DDP (range 1-19). Most (76%) remained on their original systemic anti-cancer therapy without premature treatment modification. Sixteen patients (24%) experienced a recurrent HSR; however, 55 patients (83%) successfully completed their intended treatment. Outcomes during the desensitisation period included: no evidence of disease in eight patients (seven treated in the adjuvant setting), treatment response in 26 patients, and disease progression in 32 patients. Oxaliplatin desensitisation is feasible and enables most patients to continue systemic therapy, with low rates of treatment discontinuation and acceptable oncological outcomes. This approach should be considered for eligible patients who experience oxaliplatin-related HSRs to maintain access to effective chemotherapy.

To develop and validate a routine indicator-based multimarker panel for fungal infection (FI) diagnosis and prognosis prediction. A retrospective cohort of 134 patients (63 FI, 71 non-FI) was stratified randomly into a training set (n = 75) and validation set (n = 59). Differential indicators were screened via non-parametric tests and univariate logistic regression, with LASSO regression verifying core variables. Four machine learning algorithms (logistic regression, SVM, GNB, LightGBM) were compared via 5-fold cross-validation. The model with the best performance was validated in the validation set. Six core indicators (hsCRP, BNP, PT%, D-Dimer, IL-17, PCT) were selected. The logistic regression algorithm was finally selected for modeling because of its optimal efficacy in the training set. The logistic-based model in validation set showed better performance than others. The diagnostic AUC was 0.845, sensitivity was 80.00%, specificity was 72.41%. The prognostic AUC was 0.767, sensitivity was 72.41% and specificity was 90.00%, outperforming single indicators. The logistic regression-derived multimarker panel integrates inflammatory, coagulation, and cardiac biomarkers, offering a reliable, accessible tool for FI diagnosis and prognostic stratification, especially in resource-limited settings.

The introduction of vonoprazan has markedly enhanced the effectiveness of the first-line Helicobacter pylori (H. pylori) eradication regimens. This study aimed to compare the effectiveness of vonoprazan-amoxicillin based dual therapy with that of quadruple therapy as second-line treatments, while also investigating potential clinical predictors of therapeutic success. From January 2023 to June 2025, we retrospectively analyzed clinical data from H. pylori-infected patients who received second-line treatment with either: vonoprazan-amoxicillin dual therapy (VA) or VA based quadruple therapy (VAMB; vonoprazan, amoxicillin, minocycline, and colloidal bismuth pectin). The eradication status was evaluated by ^13/14C-urease breath test four weeks after treatment completion. Adverse events and medication compliance were systematically documented during follow-up. The study included 241 patients, with 107 receiving VA dual therapy and 134 undergoing VAMB quadruple therapy. Eradication rates were comparable between groups: 90.7% (VA) versus 92.5% (VAMB) by modified intention-to-treat (mITT) analysis, and 91.4% versus 93.7% by per-protocol (PP) analysis (all p > 0.05). Notably, the VA regimen demonstrated significantly fewer adverse events (8.4% vs 17.9%, p = 0.033). Both treatment arms maintained excellent medication adherence. Compared to the vonoprazan-amoxicillin-minocycline-bismuth (VAMB) quadruple regimen, vonoprazan-amoxicillin (VA) dual therapy achieved comparable eradication efficacy with a more favorable safety profile in second-line H. pylori treatment, representing a simplified yet effective rescue therapy option.