In this study, we develop a stacked ensemble model that utilizes cell-free DNA (cfDNA) fragmentomics for the early detection of esophageal squamous cell carcinoma (ESCC). This model incorporates four distinct fragmentomics features derived from whole-genome sequencing (WGS) and advanced machine learning algorithms for robust analysis. It is validated across both an independent validation cohort and an external cohort to ensure its generalizability and effectiveness. Notably, the model maintains its robustness in low-coverage sequencing environments, demonstrating its potentials in clinical settings with limited sequencing resources. With its remarkable sensitivity and specificity, this approach promises to significantly improve the early diagnosis and management of ESCC. This study represents a substantial step forward in the application of cfDNA fragmentomics in cancer diagnostics, emphasizing the need for further research to fully establish its clinical efficacy.

Patient-derived organoids (PDOs) represent a promising approach for replicating the characteristics of original tumors and facilitating drug testing for personalized treatments across diverse cancer types. However, clinical evidence regarding their application to esophageal cancer remains limited. This study aims to evaluate the efficacy of implementing PDOs in clinical practice to benefit patients with esophageal squamous cell carcinoma (ESCC). Fresh surgical biopsies were obtained from patients with esophageal cancer for the establishment of PDOs. These PDOs were subsequently characterized through histological analysis. A customized drug panel, based on standard-of-care chemotherapy regimens, was applied to the PDOs. The resulting drug sensitivity profiles were then correlated with the clinical responses observed in individual patients undergoing actual treatment. A total of 34 PDOs were successfully established with a 61.8% success rate. The classification method based on chemotherapy sensitivity closely corresponded to clinical responses. The paclitaxel plus cisplatin (TP)-sensitive group demonstrated significantly longer progression-free survival (PFS) compared to the resistant groups, Hazard ratio (HR), 5.12; 95% confidence intervals (CI 0.58–44.71; p < 0.05), thus illustrating the potential of this approach for guiding personalized treatment strategies. Organoid biobanks were established across multiple institutes to facilitate PDOs-based functional precision medicine. The findings demonstrate that this framework offers robust predictive value in clinical settings, enhances precision therapeutics, and advances drug discovery for esophageal cancer.

Objective: To compare the complication rates, nutritional status, and physical state between esophageal cancer (EC) patients managed by nasogastric tube (NGT) feeding versus those managed by oral nutritional supplementation (ONS) during chemoradiotherapy. Methods: EC patients undergoing chemoradiotherapy managed by nonintravenous nutritional support in our institute were retrospectively recruited and divided into an NGT group and an ONS group based on the nutritional support method. The main outcomes, including complications, nutritional status, and physical state, were compared between groups. Results: The baseline characteristics of EC patients were comparable. There were no significant differences in the incidence of treatment interruption (13.04% vs. 14.71%, P = 0.82), death (2.17% vs. 0.00%, P = 0.84), or esophageal fistula (2.17% vs. 1.47%, P = 1.00) between the NGT group and ONS group. Body weight loss and decrease in albumin level were significantly lower in the NGT group than in the ONS group (both P < 0.05). EC patients in the NGT group had significantly lower Nutritional Risk Screening 2002 (NRS2002) and Patient-Generated Subjective Global Assessment (PG-SGA) scores and significantly higher Karnofsky Performance Status (KPS) scores than patients in the ONS group (all P < 0.05). The rates of grade > 2 esophagitis (10.00% vs. 27.59%, P = 0.03) and grade > 2 bone marrow suppression (10.00% vs. 32.76%, P = 0.01) were significantly lower in the NGT group than in the ONS group. There were no significant differences in the incidence of infection and upper gastrointestinal disorders or therapeutic efficacy between groups (all P > 0.05). Conclusions: EN through NGT feeding leads to significantly better nutritional status and physical state in EC patients during chemoradiotherapy than EN via ONS. NGT may also prevent myelosuppression and esophagitis..

Bosworth ankle fracture-dislocation is rare, known to be an irreducible type of ankle injury, with a high incidence of complication. We present two cases of even rarer variants of Bosworth ankle fracture-dislocation. The first case is a type of supination external rotation adduction, and the second case is a type of supination external rotation adduction. These types have not been described before. In both of the cases we failed to achieve close reduction, and therefore proceeded with emergency surgeries, with open reduction and internal fixation. Both of the cases were performed with a postero-lateral approach to reduce the dislocations, and fix the fractures successfully. Unfortunately in one of the cases, acute compartment syndrome developed post-surgically. However, both cases showed good functional outcomes.

KRAS mutations are major drivers of human cancers, yet how distinct mutations rewire protein interactions and metabolic pathways to promote tumorigenesis remains poorly understood. To address this, we systematically mapped the protein interaction networks of wild-type KRAS and three high-frequency oncogenic mutants (G12C, G12D, and G12V) using TurboID proximity labeling coupled with quantitative proteomics. Bioinformatic analysis revealed mutant-specific binding partners and metabolic pathway alterations, including significant enrichment in insulin signaling, reactive oxygen species regulation, and glucose/lipid metabolism. These changes collectively drive tumor proliferation and immune evasion. Comparative analysis identified shared interactome shifts across all mutants: reduced binding to LZTR1, an adaptor for KRAS degradation, and enhanced recruitment of LAMTOR1, a regulator of mTORC1-mediated growth signaling. Our multi-dimensional profiling establishes the first comprehensive map of KRAS-mutant interactomes and links specific mutations to metabolic reprogramming. These findings provide mechanistic insights into KRAS-driven malignancy and highlight LZTR1 and LAMTOR1 as potential therapeutic targets. The study further lays a foundation for developing mutation-specific strategies to counteract KRAS oncogenic signaling.