RAB25/GCN1 Signaling Promotes ER Stress to Mediate Alcohol-associated Liver Disease Progression.

Background/aims: Endoplasmic reticulum (ER) stress in hepatocytes plays a causative role in alcohol-associated liver disease (ALD). The incomplete inhibition of ER stress by targeting canonical ER stress sensor proteins suggests the existence of noncanonical ER stress pathways in ALD pathology. This study aimed to delineate the role of RAB25 in ALD and its regulatory mechanism in noncanonical ER stress pathways.

Phase separation of ERCC6L2-CtIP regulates the extent of DNA end resection.

The ataxia telangiectasia mutated (ATM) kinase orchestrates the early stages of DNA double-strand break repair by promoting hyperphosphorylation of CtIP, a key step in the initiation of DNA end resection. However, the regulatory mechanisms controlling resection extent remain incompletely understood. Here we identify ERCC6L2 as a key regulator of DNA end resection in response to ATM inhibition.

Efficacy and safety of induction immunotherapy plus chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: a meta-analysis.

Background: Locally advanced nasopharyngeal carcinoma (LA-NPC) has a heterogeneous prognosis, with approximately one-fourth of patients experiencing poor outcomes. Studies have explored the application of induction chemoimmunotherapy followed by chemoradiotherapy, but its efficacy was controversial.

Methods: The protocol was registered in the Prospective Register of Systematic Reviews (PROSPERO, CRD42024619387).

RNF217-KEAP1-NRF2 feedback loop confers therapeutic resistance by inhibiting ferroptosis in esophageal squamous cell carcinoma.

Resistance to chemoradiotherapy is a crucial factor limiting the efficacy of therapy and prognosis of esophageal cancer. It is necessary to elucidate the key genes and regulatory mechanisms responsible for therapeutic resistance in esophageal squamous cell carcinoma (ESCC). In this study, we found a relationship between ferroptosis and therapeutic sensitivity in ESCC and identified the ring finger protein 217 (RNF217) as a new regulator of ferroptosis associated with resistance to chemoradiotherapy in ESCC.

Development and validation of a nomogram for predicting overall survival in patients with primary central nervous system germ cell tumors.

Background: Primary central nervous system (CNS) germ cell tumors (GCTs) are common neoplasms in the CNS of pediatric and adolescent patients. This study aimed to identify prognostic factors associated with CNS GCTs and establish an effective nomogram for predicting overall survival (OS) in patients with CNS GCTs.

Methods: The development cohort including 1166 CNS GCTs patients was selected from Surveillance, Epidemiology, and End Results (SEER) program between 2000 and 2021.

Childhood Obesity Raises GDM Risk Through Adult Obesity: Evidence From Lifecourse Mendelian Randomization Study.

Background: The relationship between childhood and adulthood obesity and the risk of gestational diabetes mellitus (GDM) remains unclear. To clarify the independent and joint effects of childhood and adulthood body size on GDM risk, and explore inflammation's role.

Methods: Using female-specific UK Biobank genome-wide association study data, genetic instruments for childhood/adult body size ("thinner," "about average," "plumper") and C-reactive protein (CRP) were identified.

Nonlinear Associations of Depression and Stigma With Subclinical Hikikomori in Cancer Survivors.

Background: Cancer survivors often experience depression and stigma associated with chronic diseases, which may increase the risk of subclinical hikikomori.

Aims: This study examined the prevalence of subclinical hikikomori and its nonlinear associations with depression and stigma among cancer patients.

Methods: A cross-sectional survey was conducted among 1951 cancer survivors.

Target volume delineation of the neck for radiotherapy in nasopharyngeal carcinoma: CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas.

The Chinese Society for Therapeutic Radiology Oncology, the Chinese Anti-Cancer Association, the Chinese Society of Clinical Oncology, the Head and Neck Cancer International Group, the European Society for Radiotherapy and Oncology, and the American Society for Radiation Oncology collaboratively developed evidence-based guidelines and a comprehensive contouring atlas for neck target volume delineation in nasopharyngeal carcinoma. These guidelines address five key challenges in modern radiotherapy practice: margin design of clinical target volume; nodal target volume delineation after induction chemotherapy; delineation of equivocal nodes evident on imaging; low-risk clinical target volume delineation based on regional stepwise extension patterns; and modifications for anatomical boundaries of lymphatic areas. Developed through a rigorous systematic review and expert appraisal process by a panel of 50 international, multidisciplinary members from 17 countries and regions, these guidelines incorporate the latest advances in nasopharyngeal carcinoma diagnosis and treatment.

Primary target volume delineation for radiotherapy in nasopharyngeal carcinoma: CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas.

The Chinese Society for Therapeutic Radiology Oncology, the Chinese Anti-Cancer Association, the Chinese Society of Clinical Oncology, Head and Neck Cancer International Group, the European Society for Radiotherapy and Oncology, and the American Society for Radiation Oncology jointly developed evidence-based guidelines and a contouring atlas for primary target volume delineation for radiotherapy in nasopharyngeal carcinoma. The guidelines systematically address three crucial challenges: margin design of clinical target volumes; target volume delineation after induction chemotherapy; and low-risk clinical target volume delineation based on local stepwise extension patterns. Based on a comprehensive systematic review and critical appraisal by an international multidisciplinary panel of 50 nasopharyngeal carcinoma specialists from 17 countries and regions, these guidelines are in keeping with advances in nasopharyngeal carcinoma diagnosis and treatment, embodying contemporary treatment concepts, and elaborating on the differences in practice.

Pre-treatment S-index as a promising prognostic indicator of treatment response and survival in patients with synchronous colorectal liver metastases: A retrospective multi-center study.

Background: Patients with synchronous colorectal cancer liver metastasis (CRLM) often face sub-optimal outcomes from systemic therapy or resection. This study investigates the prognostic value of the pre-treatment S-index, a reliable non-invasive marker for liver fibrosis, for outcomes in synchronous CRLM patients.

Methods: This study included two populations of patients with synchronous CRLM: one population undergoing resection and another population receiving systemic therapy for unresectable CRLM.

Ligustilide Suppresses Macrophage-Mediated Intestinal Inflammation and Restores Gut Barrier via EGR1-ADAM17-TNF-α Pathway in Colitis Mice.

Ulcerative colitis is a chronic nonspecific intestinal inflammatory disease, which usually occurs in the rectal and colonic mucosa and submucosa. Ligustilide, a major component derived from (Oliv.) Diels, exerts anti-inflammation effect.

Efficacy and safety of utidelone in pretreated patients with metastatic breast cancer in China: a multicenter, real-world study.

Background: Utidelone (UTD1), a genetically engineered epothilone derivative, has been approved in China for use in combination with capecitabine in treating metastatic breast cancer (MBC) patients previously treated with anthracyclines or taxanes.

Objectives: To evaluate the real-world efficacy and safety of UTD1 in Chinese patients with MBC and to explore potential predictors of therapeutic effectiveness.

Design: A multicenter, retrospective, real-world study.

YRDC is a Prognostic-Related Biomarker Correlated With Immune Infiltration and Drug Sensitivity in Pan-Cancer.

Background: YRDC has emerged as a potential biomarker in cancer, yet its prognostic value, oncogenic mechanisms, role in immune infiltration, and anticancer drugs efficacy in pan-cancer remained poorly understood.

Aims: This study aimed to comprehensively investigate YRDC's role in pan-cancer and to explore the potential effects of YRDC on the immune infiltration pattern and anticancer drug sensitivity.

Methods And Results: Based on bioinformatics analysis of multi-omics data, we firstly demonstrated that YRDC was markedly overexpressed and associated with worse prognosis in various tumors.

Health literacy model integrating health education, health behaviors, self-rated health, and socioeconomic status in the Chinese population.

Health literacy is crucial for influencing health behaviors and outcomes; however, its development in China has been hindered by the lack of effective measurement tools and conceptual models. This study aimed to evaluate health literacy among Chinese residents using the HLS-Q47 and construct a health literacy model. A cross-sectional survey was conducted in Guangzhou from February to June 2023 involving 4047 participants.

Dysregulated Immune Responses in Sepsis: Insights From Treg-Related Gene Expression.

Introduction: Sepsis, a life-threatening dysregulated immune response to infection, has a high global mortality rate. Tregs play dual roles in sepsis pathogenesis, with their expansion linked to immunosuppression. This study explores Treg dynamics and the novel role of CD82 in sepsis.

Optochemical control of G1 cell cycle by regulating CDK4/6 degradation.

Cancer progression is characterized by dysregulated G1/S phase transition mediated by CDK4/6-dependent Rb protein phosphorylation. Although CDK4/6 degraders show encouraging anti-tumor efficacy, it is highly desired to develop strategies to spatiotemporally control the release of active CDK4/6 degraders to further reduce adverse effects. In this study, we employ an optochemical strategy for CDK4/6 degradation by caging the CRBN ligand with a photoremovable protecting group.

Light-Activated CD36-Targeted Cuproptosis Triggers Metabolic-Immune Synergy for Precision Breast Cancer Therapy.

Breast cancer therapy confronts dual challenges of metabolic plasticity-driven drug resistance and immunosuppression. To address this, we developed DCP-TPP, a therapeutic nanoplatform that integrates dysregulation of copper homeostasis and lipid metabolism for precise breast cancer therapy. Leveraging the overexpression of cluster of differentiation 36 (CD36) in breast cancer cells, DCP-TPP employs fatty acid camouflage (PCM) to deliver disulfiram (DSF) and photothermal CuBiS to cancer cells and features triphenylphosphonium (TPP) modification for targeted mitochondrial drug delivery.

TIPs: Tooth instance and pulp segmentation based on hierarchical extraction and fusion of anatomical priors from cone-beam CT.

Accurate instance segmentation of tooth and pulp from cone-beam computed tomography (CBCT) images is essential but highly challenging due to the pulp's small structures and indistinct boundaries. To address these critical challenges, we propose TIPs designed for Tooth Instance and Pulp segmentation. TIPs initially employs a backbone model to segment a binary mask of the tooth from CBCT images, which is then utilized to derive position prior of the tooth and shape prior of the pulp.

Baseline tumor burden predicts the efficacy of first-line chemoimmunotherapy in patients with advanced non-small cell lung cancer: results from 2 phase 3 randomized placebo-controlled trials.

Background: Baseline tumor burden (TB), measured radiographically, has emerged as a potential biomarker for stratifying survival outcomes with immune checkpoint inhibitors (ICI) across solid tumors. However, the predictive value for ICI plus chemotherapy (chemoimmunotherapy) in NSCLC has not been confirmed with large cohorts that include a chemotherapy-only control group.

Methods: This post hoc analysis utilized data from ORIENT-11 trial, a phase III, randomized clinical trial of advanced NSCLC patients who were administered with either chemoimmunotherapy or chemotherapy alone.

Comparison of Outcomes Between Ablation and Lobectomy in Stage IA Non-Small Cell Lung Cancer: A Retrospective Multicenter Study.

Background And Objective: Image-guided thermal ablation (IGTA) has been increasingly used in patients with stage IA non-small cell lung cancer (NSCLC) without surgical contraindications, but its long-term outcomes compared to lobectomy remain unknown. This study aims to evaluate the long-term outcomes of IGTA versus lobectomy and explore which patients may benefit most from ablation.

Methods: After propensity score matching, a total of 290 patients with stage IA NSCLC between 2015 and 2023 were included.

Dosimetric and Clinical Effects of Polyethylene Glycol Gel in Radical Concurrent Chemoradiotherapy for Cervical Cancer: A Phase III Prospective Multicenter Randomized Controlled Trial.

Purpose: This study evaluated the safety and efficacy of PEG hydrogels in reducing rectal radiation dose and complication during cervical cancer radical concurrent chemoradiotherapy.

Methods And Design: This phase 3, randomized, parallel-controlled trial (NCT05690906) conducted across nine centers in China (July 2022-January 2025). Participants were randomized 1:1 to receive a 10 mL PEG hydrogel injection (experimental group) or no injection (control group) after 50.

Deep learning-based prediction of axillary pathological complete response in patients with breast cancer using longitudinal multiregional ultrasound.

Background: Noninvasive biomarkers that capture the longitudinal multiregional tumour burden in patients with breast cancer may improve the assessment of residual nodal disease and guide axillary surgery. Additionally, a significant barrier to the clinical translation of the current data-driven deep learning model is the lack of interpretability. This study aims to develop and validate an information shared-private (iShape) model to predict axillary pathological complete response in patients with axillary lymph node (ALN)-positive breast cancer receiving neoadjuvant therapy (NAT) by learning common and specific image representations from longitudinal primary tumour and ALN ultrasound images.

Pharmacokinetics, safety, and efficacy of mixed formulation of fosrolapitant and palonosetron (HR20013) in combination with dexamethasone in patients with solid tumors scheduled for highly emetogenic cisplatin-based chemotherapy: a phase I trial.

Background: This phase I trial aimed to assess the pharmacokinetics (PK), safety, and preliminary efficacy of a single dose of HR20013 (mixed formulation of fosrolapitant and palonosetron) plus dexamethasone in patients with malignant solid tumors.

Methods: Solid tumor patients who were naive to cisplatin-based chemotherapy and scheduled to receive the single-day cisplatin-based chemotherapy were enrolled. Patients would receive a single intravenous infusion of HR20013 (Day 1) before cisplatin-based chemotherapy, alongside oral dexamethasone (Day 1, 12 mg, once a day; Day 2-4, 3.

Adjuvant icotinib for resected EGFR-mutated stage II-IIIA non-small-cell lung cancer (ICTAN, GASTO1002): a randomized comparison study.

The efficacy, safety and ideal treatment duration of an adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for patients with resected EGFR-mutated non-small-cell lung cancer (NSCLC) were not known until 2014, when this study was initiated. In this phase 3 ICTAN trial (GASTO1002, NCT01996098), patients with completely resected, EGFR-mutated, stage II-IIIA NSCLC after adjuvant chemotherapy were assigned in a 1:1:1 ratio to receive icotinib (125 mg, three times daily) for 12 months, to receive icotinib for 6 months, or to undergo observation. The primary endpoint was disease-free survival (DFS).

Dynamic Prognostic Models for Colorectal Cancer With Liver Metastases.

Importance: Current prognostic models for colorectal liver metastases (CRLM) primarily incorporate clinicopathologic features assessed at a single time point, resulting in a static risk assessment for individuals. Given that tumor progression is a dynamic process, especially for patients with CRLM, and patients' data are continuously collected during the follow-up visits, dynamic prediction is a natural model for risk assessments via reflecting the latest prognosis, whenever new marker measurements are available.

Objective: To develop CRLM prognostic models and a clinical web-based tool to facilitate dynamic predictions.