Sacituzumab tirumotecan (Sac-TMT) has demonstrated survival benefits over chemotherapy in patients with previously treated metastatic triple-negative breast cancer (mTNBC). However, its economic value under different payment contexts in China remains uncertain.

A state-transition (Markov) model was used to estimate lifetime costs and quality-adjusted life-years (QALYs) for Sac-TMT versus single-agent chemotherapy in second-line and later-line mTNBC. Clinical efficacy was derived from a phase III randomized trial, with survival extrapolated using parametric models. Cost-utility and price threshold analyses were conducted using willingness-to-pay (WTP) thresholds defined as three times the per-capita gross domestic product (GDP) at the national level and in economically underdeveloped regions. Scenarios incorporating patient assistance programs were also evaluated.

Sac-TMT increased QALYs but incurred substantially higher costs, resulting in incremental cost-effectiveness ratios exceeding both national and regional WTP thresholds at the current list price. To achieve cost-effectiveness, the price of Sac-TMT would need to be reduced to 48.3% of the current list price under the national WTP threshold and to 34.9% under the regional threshold. Although patient assistance programs increased the acceptable price range, Sac-TMT remained unlikely to be cost-effective at the list price. The reimbursed price following the 2025 national health insurance negotiation was markedly below these thresholds, suggesting improved economic value under current reimbursement conditions.

Sac-TMT is unlikely to be cost-effective at its current list price for previously treated mTNBC in China. Substantial price reductions and reimbursement strategies may improve its economic value, particularly in economically underdeveloped regions.

Gastric signet-ring cell carcinoma (SRCC) is a rare form of gastric cancer characterized by mucus-rich tumor cells forming a distinctive ring-like appearance and is exceedingly rare in children, accounting for less than 1% of all childhood malignancies. We report a case of a 14-year-old patient who presented with melena, hematemesis, and syncope. Upper gastrointestinal endoscopy revealed an ulcerative mass located in the gastric cardia. Histopathological examination confirmed gastric adenocarcinoma demonstrating signet-ring cell features. The patient underwent laparoscopic-assisted radical proximal gastrectomy, esophagogastric anastomosis, abdominal drainage, and a D2 lymphadenectomy, which includes dissection of both perigastric and second-tier lymph nodes. The final diagnosis was SRCC of the stomach. Postoperative Tumor Node Metastasis (TNM) staging was stage III (T3N0M0). Follow-up indicates that the patient remains in good health and has remained symptom-free for 5 years. Given the rarity of this malignancy and the limited number of pediatric case studies, there is an urgent need to accumulate additional clinical and immunohistochemical data to enhance understanding and improve diagnostic accuracy.

Solid pseudopapillary epithelial neoplasm (SPEN) of the pancreas is a rare, low-grade pancreatic neoplasm that is uncommon in the pediatric population. We present the case of previously healthy 11-year-old girl with a pancreatic mass initially misdiagnosed as a pseudocyst, later confirmed to be a SPEN. This report highlights key clinical and imaging features distinguishing SPEN from pancreatic pseudocysts and underscores the importance of maintaining a broad differential diagnosis when the clinical course is atypical.

Cystic nephroma (CN) is a rare, benign renal tumor often misdiagnosed due to overlapping radiological features with simple renal cysts and malignant cystic neoplasms. CN primarily affects boys and adult females. This study aimed to review the clinical, imaging, and pathological characteristics of CN to improve diagnostic accuracy.

A retrospective analysis was conducted on six confirmed CN cases treated at a single institution (2010-2024). Data included demographics, imaging findings (Bosniak classification), surgical approach, histopathology, and immunohistochemistry (IHC).

The cohort consisted of two males (one pediatric) and four females. Preoperative imaging, revealing multilocular cystic lesions with septal enhancement, led to a high misdiagnosis rate: five cases (83%) were misinterpreted as simple renal cysts (Bosniak II-III). Surgical interventions included partial nephrectomy (n=3), radical nephrectomy (n=1), and nephroureterectomy (n=1). Intraoperative frozen section analysis in one case was instrumental in confirming the CN diagnosis and guiding radical resection. Histopathology showed multilocular cysts lined by hobnail epithelium. IHC confirmed PAX-8 positivity (4/4) and ER/PR expression (3/4 and 2/4, respectively).

CN as a rare benign renal tumor, preoperative differentiation of CN, particularly from benign simple renal cyst, remains difficult. Surgical excision with pathological verification is critical. Intraoperative frozen section analysis aids in determining the surgical approach (nephron-sparing vs. radical resection) for patients with lesions that are difficult to distinguish as benign or malignant prior to surgery. Pathological hallmarks and supporting IHC (PAX-8, ER/PR) remain the diagnostic gold standard.

The presence of malignant heterologous elements and malignant transformation of the epithelial component in phyllodes tumor (PT) is infrequent. The co-existence of both features within a single malignant PT is exceptionally rare and poorly documented. We report a unique case of a 57-year-old female with a malignant PT exhibiting both low-grade ductal carcinoma in situ (DCIS) and heterologous chondrosarcomatous differentiation. This case underscores the diagnostic challenges and therapeutic considerations for this complex tumor entity, highlighting the critical importance of extensive histopathological sampling.

Chitinase-3-like protein 1 (CHI3L1) is a key driver of glioblastoma (GBM) progression and an emerging therapeutic target. Building on the CHI3L1 inhibitor 11 g, we optimised the scaffold through medicinal chemistry to assess structure-property relationships and improve pharmacokinetics. Using microscale thermophoresis (MST) and computational studies, we validated 10p, which exhibits a CHI3L1 binding affinity (K_d) of 13.22 µM. Notably, 10p overcomes previous developability hurdles by achieving a kinetic solubility of 758 µM, a five-fold improvement over 11 g. It further demonstrates high metabolic stability across species and no hERG inhibition. In 3D GBM spheroid models, 10p significantly reduced tumour viability, mass, and migration, exceeding the efficacy of prior analogues. Collectively, these findings establish 10p as a CHI3L1 inhibitor with a superior pharmacokinetic profile and robust functional activity, marking it as a promising candidate for further GBM drug development.

We report the case of a 25-year-old woman with a history of acute lymphoblastic leukemia who developed progressive dyspnea and fever following allogeneic hematopoietic stem cell transplantation.

Despite broad-spectrum empirical antimicrobial therapy, the patient's clinical condition worsened. Comprehensive diagnostic evaluation revealed human coronavirus OC43 (HCoV-OC43) as the causative pathogen. Histopathological examination of lung tissue confirmed viral pneumonia. Treatment with nirmatrelvir/ritonavir (Paxlovid) was initiated. The patient demonstrated rapid clinical improvement, with complete radiological resolution within 3 months.

This case highlights the potential therapeutic role of nirmatrelvir/ritonavir in managing severe HCoV-OC43 pneumonia in patients who are immunocompromised.

Mitophagy is essential for cancer formation and invasion, but its role in colorectal cancer (CRC) remains unclear. We obtained sequencing data and mitophagy-related genes (MP-RGs) from public databases. Differential expression analysis and weighted gene coexpression network analysis (WGCNA) identified mitophagy-related differentially expressed genes (DE-MPGs). Mendelian randomization (MR) analysis identified candidate genes with genetically supported causal relevance to CRC. Biomarkers were identified using machine learning, receiver operating characteristic (ROC) analysis and expression studies. Single-cell RNA sequencing (scRNA-seq) analyzed biomarker expression profiles in various CRC cell types. Quantitative PCR (qPCR) validated biomarker expression in clinical CRC samples. 147 DE-MPGs were identified. MR analysis revealed seven genes with potential causal contributions to CRC susceptibility. Three genes, SGCE (IVW: OR = 1.00041, p = 0.011), ATP8B2 (IVW: OR = 0.99920, p = 0.042), and RANGAP1 (IVW: OR = 0.99861, p = 0.002), were selected as biomarkers. Immune microenvironment and checkpoint differences were observed between CRC and controls. Biomarker expression varied among cell types. qPCR showed decreased SGCE and ATP8B2 and increased RANGAP1 in CRC. SGCE, ATP8B2, and RANGAP1 can serve as mitophagy-related biomarkers with genetically supported causal relevance to CRC, providing new insights for CRC diagnosis and therapy.

We herein report the synthesis, and antiproliferative evaluation of a novel series of N(4)-substituted 5,7-dibromoisatin thiosemicarbazones (TSCs). Structure and activity based approach was used to synthesize derivatives: N(4)-pyrrolidinyl (L1), N(4)-piperidinyl (L2), N(4)-morpholinyl (L3), N(4)-methyl (L4), and N(4)-ethyl (L5). The compounds were characterized by elemental analysis, FTIR, ¹H NMR, ¹³C NMR, UV-Vis spectroscopy, HRMS and single crystal X-ray analysis. The antiproliferative activity of the synthesized TSCs was evaluated in a dose-dependent manner against breast (MCF-7, MDA-MB-231), skin (A431), lung (A549, NCI-H460), and prostate (PC3) cancer cell lines. L3 and L5 exhibited enhanced cytotoxicity in the low micromolar range of IC₅₀; 1.16-2.47 µM. Notably, L5 showed superior potency in MCF-7 cells with IC₅₀; 1.16 µM compared to the FDA-approved thiosemicarbazone Triapine with IC₅₀; 4.27 µM, while displaying minimal toxicity toward non-tumorigenic MCF-10a breast epithelial cells with selectivity index > 86.20, consistent with ADMET predictions. Molecular docking and molecular dynamics simulations demonstrated stronger binding affinity and greater complex stability of L5 with PTOV1 compared to the FDA approved drug Lenalidomide, supporting L5 drug likeness and therapeutic potential. Mechanistic investigations through functional assays like crystal violet assays, flow cytometry, immunoblotting, and microscopy revealed that L5 induces G0/G1 cell-cycle arrest, suppresses cell migration, invasion, colony formation, 3D spheroid growth, and promotes apoptotic cell death in MCF-7. Western blot analysis provided direct mechanistic evidence that L5 downregulates PTOV1 expression, leading to reduced phosphorylation of AKT1/2/3 and c-Jun, reduced β-catenin nuclear translocation, and decreased MMP-2 expression. L5 enhanced H2AX phosphorylation, suppressed PARP and BCL-XL levels, and increased active caspase-3 driving L5 induced apoptosis. This study identifies L5 as a potent anticancer agent in breast cancer, acting through modulation of the PTOV1-AKT-β-catenin signaling axis, and highlights PTOV1 as a promising therapeutic target.

Multimodal large language models (LLMs) offer emerging capabilities in medical image interpretation; however, their efficacy in orthopedic oncology remains unverified. This study aimed to evaluate and benchmark the performance of five contemporary LLMs-ChatGPT 5.2, Gemini 3 Flash, MedGemma 4B, Claude Sonnet 4.6, and DeepSeek-VL2-in detecting and characterizing bone lesions on plain radiographs without task-specific fine-tuning.

A retrospective analysis was conducted using 3,746 anonymized images from the Bone Tumor X-ray Radiograph Dataset (BTXRD), comprising normal, benign, and malignant cases. Reference standard annotations were provided directly by the BTXRD dataset. Models were evaluated on two tasks: lesion detection and lesion characterization. Diagnostic performance metrics, including accuracy, precision, sensitivity, specificity, and Cohen's kappa, were calculated and compared with reference-standard annotations.

ChatGPT 5.2 demonstrated the highest overall accuracy (0.803) and specificity among the models (0.916) for lesion detection, although its sensitivity (0.689) was comparatively low. MedGemma 4B showed relatively low performance, with an overall accuracy of 0.677. Claude Sonnet 4.6 and Gemini 3 Flash had the highest sensitivities among the models (0.991 and 0.972, respectively) but low specificities (0.038 and 0.201, respectively), resulting in excessive false positives. In the characterization task, ChatGPT 5.2 consistently achieved the highest performance among the models, with an accuracy of 0.758 and a weighted F1 score of 0.745. DeepSeek-VL2 achieved high specificity but very low sensitivity for malignancy (0.714 and 0.022, respectively). Gemini 3 Flash provided high sensitivity for malignancy (0.711) but low overall accuracy.

Multimodal LLMs demonstrated heterogeneous performance in the evaluation of bone lesions on plain radiographs, with substantial differences across models and tasks. Although some models achieved high accuracy in lesion detection and overall classification, performance was inconsistent across tasks, particularly in identifying malignant lesions and balancing sensitivity and specificity. These findings suggest that, despite their potential, current multimodal LLMs are not yet sufficiently reliable for diagnostic use in orthopedic oncology and should be considered investigational until further development and validation.

Multimodal LLMs currently lack the diagnostic reliability required for bone lesion assessment, often exhibiting excessive false positives or failing to detect malignancy. Although generalist models show promise, expert radiologist oversight remains essential to ensure patient safety and oncologic accuracy in musculoskeletal imaging.