Miconazole attenuates LPS-induced lung inflammation by modulating alveolar macrophage polarization via promoting lipid metabolic reprogramming.

Objective: Pulmonary inflammation is closely associated with macrophage polarization and lipid metabolic reprogramming. Miconazole (MCZ), traditionally used as an antifungal agent, exhibits emerging anti-inflammatory potential, yet its underlying mechanisms remain unclear.

Methods: A mouse model of lipopolysaccharide (LPS)-induced lung inflammation was employed to evaluate MCZ's anti-inflammatory efficacy.

Multigene germline and somatic testing for epithelial ovarian cancer in China.

This study investigated BRCA1/2 and homologous recombination repair (HR) pathway gene variants in Chinese epithelial ovarian cancer (EOC) patients. Germline and somatic variants in 21 HR-related genes were analyzed in 229 patients using a 21-gene ovarian panel and in 141 patients using a 508-gene pan-cancer panel. BRCA1, BRCA2, and HR-related gene mutation rates were 17.

Identification of constitutional MLH1 methylation in MLH1-deficient colorectal cancer.

Background: Constitutional MLH1 methylation (epimutation), a poorly recognized mechanism for Lynch syndrome (LS), is usually overlooked due to current screening strategies that rely on tumor MLH1 methylation as an indication of sporadic mismatch repair-deficient (dMMR) colorectal cancer (CRC). We aimed to assess the frequency and clinicopathological characteristics of constitutional MLH1 methylation among dMMR CRC cases with tumor MLH1 methylation.

Methods: We conducted a retrospective study on two independent cohorts: a discovery cohort of 48 MLH1-deficient CRC cases (2017-2021) and a validation cohort of 159 consecutive CRC cases (2022-2024).

Prevalence of Atypical and Subclonal p53 Immunohistochemistry Expression in Mismatch Repair Deficient and/or POLE-Mutant Endometrial Carcinomas with TP53 Mutation.

p53 Immunohistochemistry (IHC) is a reliable surrogate for determining TP53 mutation status in endometrial carcinomas (ECs). However, the correlation of p53 IHC patterns and TP53 mutation characteristics in mismatch repair deficiency (MMRd) and/or POLE-mutant ECs was not comprehensively investigated. In this study, we identified 4 p53 expression patterns in 40 MMRd and/or POLE-mutant ECs with TP53 mutations.

Rescuing dendritic cell interstitial motility sustains antitumour immunity.

The dendritic cell (DC)-initiated and sustained cancer immunity cycle is indispensable for effective endogenous and therapeutically mobilized antitumour T cell responses. This necessitates the continuous migration of antigen-carrying DCs from the tumour microenvironment (TME) to the tumour draining lymph nodes (tdLNs). Here, through longitudinal analysis of human and mouse tumours, we observed a progressive decrease in migratory conventional DCs (mig-cDCs) in the tdLNs during tumour progression.

Malignant mesothelioma with a novel germline frameshift mutation treated with dual immune checkpoint inhibitors: A case report.

Germline pathogenic mutation of the gene is a common molecular event in malignant mesothelioma (MM). A patient with a positive family history of tenacious peritoneal effusions presented with hydropneumothorax and suffered from recurrent pleural and peritoneal effusions since. Tuberculosis (TB) was assumed by preceding clinicians who prescribed futile anti-TB regimens.

Molecular profiling reveals the malignant potential in solid pseudopapillary neoplasms of the pancreas.

Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare tumor primarily affecting middle-aged women, typically characterized by indolent behavior but occasionally demonstrating malignant potential through invasive growth and metastasis. To elucidate the molecular mechanisms driving this heterogeneity, a multi-omics approach was applied to analyze paired metastatic lesions, primary tumors, and normal pancreatic tissues. Methylation profiling via the Illumina Infinium Methylation EPIC BeadChip identified 2425 differentially methylated positions (DMPs) in metastatic versus primary lesions, with 798 DMPs conserved across both lesion types.

WFDC3 identified as a prognostic and immune biomarker in pancreatic cancer.

The whey acidic protein four-disulfide core (WFDC) family comprises key modulators of tumor initiation and progression, offering significant potential for diagnostic, prognostic, and therapeutic applications. However, the specific role of WFDCs in the oncogenesis of pancreatic cancer (pancreatic adenocarcinoma [PAAD]) remains incompletely understood. To address this, we conducted an initial investigation using comprehensive bioinformatic analyses to evaluate WFDCs expression patterns across multiple tumor types, with a focus on PAAD.

Cytologic DNA methylation for managing minimally abnormal cervical cancer screening results.

Objectives: To explore the role of a DNA methylation assay for managing minimally abnormal cervical cancer screening results in a prospective cohort undergoing opportunistic cervical cancer screening.

Methods: In the cohort of the METHY2 and METHY3 screening studies of women undergoing opportunistic cervical cancer screening, cervical cytology samples were sent for high-risk human papillomavirus (hrHPV) DNA assays, cytologic pathology and methylation assays of PAX1/JAM3 (CISCER). This study evaluated the discriminative power of CISCER in managing women with minimally abnormal cervical cancer screening results for CIN3+.

Successful cryoablation for a phosphaturic mesenchymal tumor in the maxilla causing tumor-induced osteomalacia: a case report.

Background: A 35-year-old man was diagnosed with tumor-induced osteomalacia (TIO) caused by a phosphaturic mesenchymal tumor (PMT) in the right maxilla. The patient underwent CT-guided cryoablation at our institution, which successfully eradicated the tumor while preserving the pulpal vitality of adjacent teeth. We describe the clinical history, physical examination findings, laboratory tests, functional imaging, and follow-up protocol for evaluating treatment outcomes.

The triage role of cytological DNA methylation in women with non-16/18, specifically genotyping high-risk HPV infection.

Objectives: To evaluate cytological DNA methylation testing methods for risk stratification in women with non-16/18 HPV, focusing on high-risk HPV (hrHPV) genotyping.

Methods: This study compared the triage performance of liquid-based cytology (LBC) testing, hrHPV genotyping, and PAX1/JAM3 gene methylation (CISCER) testing. The absolute risks of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), grade 3 or worse (CIN3+), and colposcopy referral rates were calculated.

Labor-Efficient Pathological Auxiliary Diagnostic Model for Primary and Metastatic Tumor Tissue Detection in Pancreatic Ductal Adenocarcinoma.

Accurate histopathological evaluation of pancreatic ductal adenocarcinoma (PDAC), including primary tumor lesions and lymph node metastases, is critical for prognostic evaluation and personalized therapeutic strategies. Distinct from other solid tumors, PDAC presents unique diagnostic challenges owing to its extensive desmoplasia, unclear tumor boundary, and difficulty in differentiating from chronic pancreatitis. These characteristics not only complicate pathological diagnosis but also hinder the acquisition of pixel-level annotations required for training computational pathology models.

A patient with Eradheim-Chester disease presenting with progressive cystic lung lesions and confirmed pulmonary artery hypertension: a case report.

Background: Erdheim-Chester disease (ECD), a rare type of non-Langerhans cell histiocytosis, was classified as a haematopoietic tumour by the World Health Organization (WHO) in 2016. It involves multiple systems and is challenging to diagnose due to its broad spectrum of clinical manifestations. The pulmonary manifestations of ECD lack specificity.

Intrinsic subtype and immunity score in identification of triple-negative breast cancer at low risk.

Introduction: Triple-negative breast cancer (TNBC) is group of heterogeneity caner. Despite majority of them had the unfavorable prognosis, a subset of patients who do not receive chemotherapy exhibit a good prognosis. Biomarkers are required to recognize these group of pateints and improve the current therapeutic strategies for them.

In situ construction of MOF derived CoNC anchored on N-doped carbon xerogel sphere as efficient bifunctional ORR/OER electrocatalyst for Zn-air batteries.

Electrocatalytic materials with dual functions of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) have received increasing attention in the field of zinc-air batteries (ZABs) research. In this study, bifunctional CoNC@NCXS catalysts were prepared by anchoring Co and N co-doped CoNC on N-doped carbon xerogel sphere (NCXS) based on the spatially confined domain effect and in-situ doping technique. CoNC@NCXS exhibited excellent ORR/OER activity in alkaline electrolytes with the ORR onset potential of 0.

Glucose Metabolic Abnormalities and Their Interaction With Defective Phosphate Homeostasis in Tumor-induced Osteomalacia.

Context: Phosphate homeostasis was compromised in tumor-induced osteomalacia (TIO) due to increased fibroblast growth factor 23 (FGF23) secretion. Nevertheless, the glucose metabolic profile in TIO patients has not been investigated.

Objectives: This work aimed to clarify the glucose metabolic profiles in TIO patients and explore their interaction with impaired phosphate homeostasis.

The clinicopathological and molecular features of primary high-grade neuroendocrine tumour in the breast.

Aims: Nottingham grade for breast cancers, rather than gastro-entero-pancreatic (GEP) grade for neuroendocrine tumours (NETs), is currently applied to primary breast NETs, which need further clarification. High-grade NETs in breast also remain poorly recognised.

Methods And Results: Among 595 breast carcinomas with diffuse synaptophysin (Syn) or chromogranin A (CgA) immunostaining (≥ 90%), 197 eligible cases were selected, including 69 NETs, 123 invasive breast carcinomas of no special type (IBC-NSTs) and five neuroendocrine carcinomas (NECs).

Evaluation of fibroinflammatory activity in thyroid eye disease using [F]AlF-NOTA-FAPI-04 PET/CT: A prospective study.

Purpose: This study evaluates the value of [F]AlF-NOTA-FAPI-04PET/CT in assessing the disease activity of thyroid eye disease (TED).

Methods: Twenty-three TED patients and ten healthy controls were prospectively recruited and underwent [F]AlF-NOTA-FAPI-04 PET/CT scans. TED eyes were classified by Clinical Activity Score (CAS) as active (CAS +) or inactive (CAS-).

scMSI: Accurately inferring the sub-clonal Micro-Satellite status by an integrated deconvolution model on length spectrum.

Microsatellite instability (MSI) is an important genomic biomarker for cancer diagnosis and treatment, and sequencing-based approaches are often applied to identify MSI because of its fastness and efficiency. These approaches, however, may fail to identify MSI on one or more sub-clones for certain cancers with a high degree of heterogeneity, leading to erroneous diagnoses and unsuitable treatments. Besides, the computational cost of identifying sub-clonal MSI can be exponentially increased when multiple sub-clones with different length distributions share MSI status.

Triage performance of DNA methylation for women with high-risk human papillomavirus infection.

Objective: DNA methylation is a promising biomarker for cervical cancer screening. This study aimed to validate the triage performance of cytological DNA methylation for detecting cervical intraepithelial neoplasia of grade 3 or worse (CIN3+) in women with high-risk human papillomavirus (hrHPV) infection from a large prospective cohort undergoing opportunistic screening in China (METHY3).

Methods: The triage performance for detecting CIN3+ lesions was compared between HPV16/18 genotyping, a liquid-based cytology (LBC) test, and the PAX1 and JAM3 methylation (PAX1m/JAM3m) test according to cervical pathologic outcomes.

Bronchial salivary gland-type mucinous adenocarcinoma harboring a GNAS mutation: a novel lung cancer entity? A case report.

We report a case of a 65-year-old man with a 1.0-cm mass in the left main bronchus, exhibiting overlapping morphological, immunohistochemical, and genetic features with both pancreatic intraductal papillary mucinous neoplasm (IPMN) with associated invasive carcinoma and salivary gland IPMN. Based on its close proximity to the bronchial submucosal glands and the expression of NKX3.

Nervonic acid triggered ovarian inflammation by inducing mitochondrial oxidative stress to activate NLRP3/ IL-1β pathway.

Introduction: Metabolic syndrome is a serious public health concern across the globe. However, the typical metabolites and mechanisms underlying the decreased fertility related to metabolic syndrome is still elusive.

Objectives: The aim of the present study was to explore the typical metabolites and mechanisms underlying the decreased fertility related with metabolic syndrome.