This study aimed to investigate the effect of quercetin on atherosclerosis(AS) in apolipoprotein E knockout(ApoE~(-/-))mice and the mechanism underlying the regulation of cholesterol efflux mediated by adenosine triphosphate-binding cassette transporter A1/G1(ABCA1/G1) pathway and neutrophil extracellular traps(NETs) formation. An AS model was established by feeding Apo E~(-/-)mice with a high-fat diet. The mice were divided into a blank control group, a model group, an atorvastatin calcium group, and lowand high-dose quercetin groups. Serum levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDLC), high-density lipoprotein cholesterol(HDL-C), interleukin(IL)-6, tumor necrosis factor-α(TNF-α), and IL-1β were measured using biochemical methods. Biliary cholesterol excretion rate was determined by acute bile duct cannulation. Hepatic pathology and aortic plaque area were observed by hematoxylin-eosin(HE) and oil red O staining. Collagen and elastic fiber changes in plaques were evaluated by Masson and Verhoeff's Van Gieson(VVG) staining. CD3 and CD68 protein expressions in the aortic root and the colocalization of citrullinated histone H3(Cit-H3) and myeloperoxidase(MPO) were detected by immunohistochemistry and immunofluorescence double staining, respectively. ABCA1 and ABCG1 protein expressions in liver and aortic tissues were detected by Western blot. The results showed that in the model group, serum levels of TC, TG, LDL-C, IL-6, TNF-α, and IL-1β were significantly elevated, hepatic lipid deposition was pronounced, aortic plaque area was enlarged, collagen deposition and elastic fiber rupture were aggravated, inflammatory cell infiltration and NET formation in plaques were enhanced, whereas serum HDL-C level,biliary cholesterol excretion rate, and ABCA1 and ABCG1 protein expressions decreased. Following quercetin intervention, all these abnormal indicators were significantly improved, as evidenced by reduced blood lipid and inflammatory cytokine levels, alleviated hepatic lipid deposition, decreased aortic plaque area, stabilized collagen and elastic fiber architecuture in plaques, suppressed inflammatory cell infiltration and NET formation, accelerated biliary cholesterol excretion, and upregulated ABCA1 and ABCG1 protein expressions. The effects of quercetin were dose-dependent, and the high-dose group showed comparable efficacy to atorvastatin calcium. In conclusion, quercetin may effectively attenuate the progression of AS in Apo E~(-/-)mice by upregulating ABCA1/G1-mediated cholesterol efflux, inhibiting NET formation, and alleviating inflammatory responses.

Oral squamous cell carcinoma (OSCC) develops through a continuum of tissue states from chronic inflammation and potentially malignant lesions to invasive cancer, yet the dynamic remodeling of the oral immune microenvironment and its relevance to immunotherapy-associated inflammation remain poorly understood. Here, we integrated single-cell RNA sequencing, spatial transcriptomics, murine immunotherapy datasets, and experimental validation to characterize immune and stromal alterations across healthy mucosa, periodontitis, leukoplakia, and OSCC. This integrated analysis revealed distinct oral immune microenvironment states and identified condition-associated neutrophil programs, including an S100A12-enriched inflammatory state, an S100A14-associated metabolic state in leukoplakia, and tumor-associated neutrophil states in OSCC. Spatial analyses and cell-cell communication modeling further nominated immune-stromal interaction networks involving S100A12+ neutrophils and fibroblast-associated inflammatory signaling. A machine-learning framework identified a nine-gene Neu_S100A12-associated signature that discriminated periodontitis-associated inflammatory states across two retrospective cohorts, with seven concordantly upregulated genes prioritized for biological validation. Multiplex immunofluorescence and an IFN-γ-primed OSCC inflammatory model provided experimental support for a TNF-associated inflammatory phenotype linked to the S100A12 program. Together, these findings establish a cross-sectional multi-omics framework for defining oral immune states and identify S100A12-associated neutrophil programs as candidate mediators of oral inflammation and immunotherapy-related immune perturbation, providing a foundation for future prospective and mechanistic studies.

The present study reports a series of 17 melanocytic tumours harbouring activating fusions of MET, which encodes a key receptor tyrosine kinase (RTK) implicated in mitogen-activated protein kinase (MAPK) signalling. Tumours were diagnosed as Spitz naevus (n=12, 71%) or melanocytoma (n=5, 29%). No cases of melanoma were identified. Three histopathological patterns emerged. The first, 'plexiform maturing fascicles' (n=7), was characterised by spindle-shaped melanocytes arranged in superficial fascicles maturing into smaller rounded nests embedded in desmoplasia. The second, 'Reed-like' (n=6), featured spindled or epithelioid melanocytes at the dermoepidermal junction with epidermal hyperplasia and scattered melanophages. The third, 'BAP1-inactivated melanocytoma-like' (n=2), showed predominantly intradermal epithelioid melanocytes with pleomorphism and a brisk inflammatory infiltrate. Two cases could not be classified in these pattern categories. Cases classified as melanocytomas more frequently exhibited cellular atypia; for example, prominent nucleoli or giant atypical melanocytes. Moreover, TRIM4::MET fusion genes were identified as a recurring initiating genomic alteration, and tumours with this fusion gene (n=5) showed distinctive features: predominantly intradermal nodular growth, fibromyxoid stroma, intercellular clefting, and nested melanocytes. MET fusion kinases represent targetable genetic alterations, with potential therapeutic implications in melanomas. Recognising these three histopathological patterns provides critical insights for diagnosis and targeted ancillary testing.

There are two main margins in histopathological assessment of colorectal resections for primary adenocarcinoma: non-peritonealised and longitudinal margins (proximal and distal). The Royal College of Pathologists of Australasia (RCPA) recommends microscopic examination of longitudinal margins only if tumour extends within 30 mm macroscopically, unless aggressive features are present. We evaluated the utility of microscopic longitudinal margin assessment by auditing colorectal resections presented at the Royal Prince Alfred Hospital (RPAH) multidisciplinary meetings (between July 2023 and June 2025) and surveying Australasian Gastrointestinal Pathology Society (AGPS) members on sampling practices. A total of 308 specimens were identified, of which all underwent routine longitudinal margin sampling. Findings were present in 2.27% (n=7) of margin sections, including five neoplastic and two non-neoplastic abnormalities. Neoplastic findings included adenocarcinoma (n=2), sessile serrated lesion (n=1), low-grade dysplasia (n=1), and Paget disease (n=1). Both adenocarcinomas were macroscopically identified and margin status was not altered by microscopy. Regarding the survey, there were 82 participants; 89% reported routine universal longitudinal margin sampling and 91% donut sampling. Most participants believed routine microscopic examination of margins rarely yields diagnostic information (91% for longitudinal margins; 68% for donuts). A targeted approach to selective sampling could reduce costs, workload, and environmental impact without compromising patient care.

The detection of pulmonary nodules has increased considerably with the widespread use of chest-computed tomography and the development of low-dose CT lung cancer screening. The pulmonary nodule represents a major diagnostic challenge, requiring rigorous evaluation in order to distinguish benign from malignant lesions while limiting unnecessary invasive investigations. Analysis relies on precise morphological characterization (density, size, margins), assessment of persistence and growth over time, and integration of the clinical context. The Fleischner Society guidelines and the protocols derived from organized screening programs now form the basis of standardized management. This article provides a detailed review of the radiological criteria, decision-making algorithms, and the role of transthoracic needle biopsy in the management of pulmonary nodules.

Bladder cancer remains a leading cause of cancer-related mortality in the United States, with most cases classified as conventional urothelial carcinoma. However, a substantial subset of patients presents with aggressive variant histologies, including sarcomatoid, plasmacytoid, and micropapillary subtypes. These variants are associated with early dissemination, treatment resistance, and limited evidence to guide subtype specific management. Despite their clinical relevance, progress in mechanistic understanding and therapeutic development has been hindered due to rarity, underrepresentation in clinical trials, and a research focus on conventional disease. A key impediment is the lack of translational model systems that maintain variant defining morphology, lineage programs, and tumor microenvironmental interactions. Recent advances in translational modeling technologies now provide new opportunities to interrogate the unique biology of variant subtype bladder cancers. In this review, we highlight key preclinical models commonly used in bladder cancer research, including patient-derived xenografts, humanized models, syngeneic systems, genetically engineered mouse models, organoids, and ex vivo explants, and highlight emerging applications in variant histologies. We also discuss innovative and integrative platforms, including hybrid experimental systems and computational approaches, that are beginning to overcome barriers imposed by tumor rarity and heterogeneity. Collectively, these evolving model systems will enable more faithful representation of variant subtype biology, tumor-microenvironment interactions, and therapeutic vulnerabilities, and provide a framework for developing subtype-specific, precision treatment strategies.