Cancer immunotherapy has revolutionized oncology by harnessing the immune system to combat malignant tumors, driving significant advancements in cancer treatment. However, due to the complex interplay between tumor cells and immune cells, many patients fail to achieve durable responses. Mast cells are bone marrow-derived immune cells and a crucial component of the innate immune system. Previously, mast cells were primarily recognized for their roles in allergic and inflammatory responses. In recent years, increasing attention has been directed toward their dual functions in the tumor microenvironment during cancer progression, highlighting the potential of mast cell-targeted strategies in cancer immunotherapy. This review summarized recent advances about the dual role of mast cells in the tumor microenvironment. At the same time, this review further evaluates the translational potential of mast cells as predictive markers and innovative therapeutic targets for cancer immunotherapy. By elucidating these mechanisms, this review aims to bridge the gap between preclinical insights and clinical applications, offering a roadmap for mast cell-centric approaches to overcome resistance and improve outcomes in cancer immunotherapy.

BACKGROUND: Neutrophil extracellular traps (NETs) play a critical role in amplifying intestinal inflammation in ulcerative colitis (UC). Clostridium butyricum (CB) has shown anti-inflammatory effects in gastrointestinal diseases; however, its impact on NETs formation and related molecular mechanisms remains unclear. METHODS: UC was induced in C57BL/6 mice by DSS, followed by CB and/or PMA administration. Colonic injury was assessed by colon length measurement, histopathology, and histological scoring. NETs formation was determined by immunofluorescence staining of Ly6G and citrullinated histone H3 (Cit-H3), and serum myeloperoxidase (MPO)/Cit-H3 levels were quantified by ELISA. In vitro, NETs release was induced in neutrophils by PMA with or without CB supernatant (CBS) administration. RNA-seq and qRT-PCR/Western blot analyses were used to explore underlying signaling pathways. IL-17A knockdown via siRNA was conducted to validate mechanistic involvement. RESULTS: CB significantly alleviated DSS-induced colitis, evidenced by reduced colon shortening, lower colon mass, and improved mucosal architecture. CB markedly suppressed NETs formation in both colonic tissue and serum. Comparative transcriptomics indicated that CBS suppresses NETs formation primarily through modulation of the IL-17 signaling pathway. DSS-induced colitis and PMA stimulation markedly increased the expression of IL-17A, IL-17RA, and p-p65 and elevated pro-inflammatory cytokines (IL-1β and TNF-α), while reducing the anti-inflammatory cytokine IL-10. CB or CBS treatment significantly reversed these pathological changes in both colon tissues and neutrophils. Importantly, IL-17A knockdown significantly reduced PMA-induced activation of the IL-17A/IL-17RA/NF-κB, and CBS treatment further enhanced these inhibitory effects under IL-17A-deficient conditions. CONCLUSION: CB protects against DSS-induced colitis by suppressing IL-17A/IL-17RA/NF-κB-mediated NETs formation in neutrophils. IL-17A knockdown confirmed IL-17A as a critical upstream regulator of NETs, establishing the IL-17A-NETs axis as a central mechanistic target of CB.

Organic luminescent radicals with efficient doublet emission can directly transfer electrons and energy to oxygen, enabling fluorescence-guided photodynamic therapy. However, their water insolubility and unclear oxygen interaction mechanisms limit their application. To address these challenges, we synthesized an amphiphilic organic radical (TTM-2PyPh) that forms self-assembled water-soluble nanoparticles (TTM-2PyPh_SA@NPs) with deep-red emission, serving as Type-I/II photosensitizers. Quantum chemistry calculations confirm an efficient electron transfer process between the radicals and oxygen. These nanoparticles self-assemble in vivo, target tumors, and produce reactive oxygen species more effectively than core-shell nanoparticles (TTM-2Py_CS@NPs), chlorin e6, and methylene blue. Additionally, TTM-2PyPh_SA@NPs demonstrate superior tumor eradication in vivo. This work advances the development of novel water-soluble radical-based photosensitizers for enhanced photodynamic therapy.

Excessive activation of the estrogen receptor (ER) drives proliferation, progression, and the formation of breast cancer stem cells (CSCs) in ER-positive breast cancer. Estrogenic endocrine disrupting compounds (EDCs) found in plastics, water, and food are also able to bind to the ER. Thus, we hypothesized that estrogenic EDCs mimic estrogen (E2) in the pathogenesis of breast cancer by promoting their survival and proliferation. Three estrogenic EDCs routinely found in human biosamples were selected for analysis: bisphenol-A (BPA), diethyl-hexyl phthalate (DEHP), and alpha-zeranol (αZAL). We assessed proliferation, transcriptional reprogramming, and CSC formation in breast cancer cell lines. E2, BPA, and αZAL significantly increased cell proliferation in ER-positive, but not ER-negative cell lines. This was reversed after administration of the ER-antagonist, ICI 182,780. BPA and αZAL upregulated estrogen target genes (PGR, TFF1) and increased levels of cell-cycle protein. RNA sequencing analysis revealed that BPA and αZAL altered expression of genes related to cell division, DNA repair, and estrogen signaling, with a substantial transcriptional overlap between EDCs and estrogen treatments. Additionally, BPA and αZAL increased the proportion of CSCs, defined as the CD24/CD44 expressing subpopulation. Overall, these data indicate that BPA and αZAL act as functional estrogen mimics in breast cancer cells, activating canonical estrogen signaling pathways and promoting stem-like characteristics. Notably, this study provides the first transcriptomic and stem-associated characterization of αZAL in ER-positive breast cancer cells, revealing a robust estrogenic mode of action. This work provides mechanistic insight into how environmental EDCs may influence ER-positive breast cancer biology.

BACKGROUND: As overall survival improves in metastatic hormone-sensitive prostate cancer (mHSPC), non-cancer causes of death are increasingly relevant. METHODS: We conducted a real-world multicenter study of patients diagnosed with mHSPC treated with ADT alone or in combination. Causes of death before progression to castration-resistant prostate cancer (CRPC) were classified as cancer- or non-cancer-related. Deaths were classified as non-cancer-related if they occurred in the absence of cancer progression. RESULTS: Among 565 patients, 35 (6.2%) died from non-cancer-related causes without disease progression, mainly infections (34%) and cardiovascular events (20%). CONCLUSIONS: Non-cancer mortality represents a meaningful proportion of deaths in mHSPC, supporting systematic cardiovascular risk evaluation and infection-prevention strategies.

BACKGROUND: Hypofractionated salvage radiotherapy is increasingly used for biochemical recurrence of prostate cancer post-prostatectomy, yet its toxicity profile remains underexplored. This study evaluates the incidence, timing, and resolution of treatment-related toxicities in this setting. METHODS: A retrospective cohort study of 403 men receiving hypofractionated salvage radiotherapy (62.5 Gy in 25 fractions) from 2017 to 2024 was conducted. Toxicities, categorized as genitourinary (hematuria, urinary incontinence, frequency, dysuria) or gastrointestinal (rectal bleeding, diarrhea, proctitis, nausea), were graded (1-3) using CTCAE-based criteria. Outcomes included any-time incidence, Kaplan-Meier time-to-first-event estimates (12- and 24-month cumulative incidence), and first-onset timing. Episode-level analyses merged events ≤ 30 days apart, assessing resolution and intervention. RESULTS: Median follow-up was 18.2 months. Any-grade genitourinary and gastrointestinal toxicities occurred in 34.2% and 24.6% of patients, respectively (24-month incidence: genitourinary 40.4%; gastrointestinal 28.9%). Grade 2+ toxicities were less frequent (genitourinary 9.7%; gastrointestinal 7.7%), with Grade 3+ rare (genitourinary 1.7%; gastrointestinal 0.7%). In terms of patient-level ever-event incidences, common symptoms included urinary incontinence (20.3%), rectal bleeding (19.9%), and hematuria (13.9%). Urinary toxicities predominantly onset at 6-12 months, whereas rectal bleeding and hematuria emerged later (≥ 12 months). Approximately two-thirds of Grade 2+ episodes resolved (e.g., urinary incontinence, 66.7%; rectal bleeding, 69.2%), with median resolution times of 3.0-8.4 months. CONCLUSION: With a median follow-up of 18.2 months, hypofractionated salvage radiotherapy demonstrates favorable short-to-intermediate term tolerability, with infrequent severe toxicities. Vigilant monitoring for late-onset rectal bleeding and hematuria is recommended during the 6-24 months after treatment to optimize patient management. Longer follow-up is required to confirm long-term safety.

BACKGROUND: Local recurrence after definitive radiotherapy for prostate cancer (PCa) remains a challenging clinical problem. Salvage irreversible electroporation (sIRE) is a non-thermal focal ablation approach with limited published evidence in the radiorecurrent setting. We report safety and early oncologic outcomes of sIRE for these patients. METHODS: We performed a retrospective review of consecutive patients undergoing sIRE at a single institution (December 2023 to June 2025). Inclusion required biopsy-confirmed intraprostatic recurrence and PSMA PET demonstrating no metastatic disease. Outcomes included perioperative morbidity, early PSA response, and post-treatment prostate MRI findings. RESULTS: Eighteen patients underwent sIRE. Mean age was 73.78 ± 7.0 years. Seventeen patients were discharged on the day of surgery. Postoperative urinary morbidity included urinary tract infection in 3 patients (16.7%), urinary retention requiring limited TURP in 2 (11.1%), and new bothersome storage lower urinary tract symptoms requiring treatment in 2 (11.1%). Mean PSA decreased from 5.37 ± 2.09 ng/mL pre-IRE to 1.61 ± 1.57 ng/mL at approximately 3 months, and 2.17 ± 1.92 ng/mL at approximately 6 months. Twelve patients underwent post-IRE prostate MRI; results included post-treatment change, or ablation defect, or susceptibility artifact in most patients. One patient underwent repeat PSMA PET for a rising PSA and was found to have a PSMA-avid lung lesion consistent with metastatic disease. CONCLUSIONS: Salvage IRE for radiorecurrent prostate cancer has generally manageable short-term urinary morbidity and encouraging early PSA responses, with limited utility of post-treatment MRI. A longer follow-up is needed to define durability and optimal selection.

Tertiary lymphoid structures (TLSs) are key components of the tumor immune microenvironment and show prognostic relevance in many cancers. However, their genetic association with lung adenocarcinoma (LUAD) is still lacking. This study aims to construct a TLS-related prognostic model through an integrated multi-omics strategy and to elucidate relevant immunogenetic mechanisms. TLS-related genes (TRGs) showing genetically supported associations with LUAD were identified using Mendelian randomization (MR). A TRG-based model was established using machine learning (ML), with its accuracy assessed through a nomogram. Downstream analyses were performed, including immune microenvironment, tumor mutational burden (TMB), pathway enrichment, drug sensitivity profiling, and single-cell RNA sequencing (scRNA-seq). The expression of TRGs was confirmed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The prognostic model we built using the best algorithm showed strong prognostic value (1-, 3-, and 5-year AUCs > 0.75). Individuals classified in the high-risk (H-R) cohort exhibited markedly poorer outcomes (p < 0.001). Incorporation of the risk model into the nomogram improved its predictive accuracy compared with the model without this variable (AUC = 0.769 for risk score). TMB analysis suggested a higher TMB in the H-R group, which may predict a worse prognosis. Drugs targeting the PI3K-AKT-mTOR and cell cycle pathways showed higher efficacy in the H-R group. According to enrichment results, TRGs were mainly involved in immune activation and cell cycle regulation, suggesting that these genes may regulate LUAD prognosis through PI3K-AKT-mTOR and cell cycle pathways. The scRNA-seq analysis showed that the 10 TRGs were predominantly localized within T/NK and myeloid cell clusters, indicating their potential involvement in modulating local immune responses. The differential expression patterns of these genes across multiple cell lines were validated using RT-qPCR. In summary, this comprehensive model highlights the significance of TRGs in LUAD, providing a new paradigm for immunogenetic risk evaluation and personalized therapy.

The article by Pae et al., titled "LHRH Antagonists Restore Serum Testosterone Faster Than LHRH Agonists in Prostate Cancer Patients After Radiotherapy," provides valuable insights into the differential effects of LHRH antagonists and agonists on testosterone recovery in prostate cancer patients undergoing androgen deprivation therapy. While the study highlights the statistically significant accelerated recovery of testosterone with LHRH antagonists, several limitations warrant further discussion. Notably, the study does not adequately address the variability in the duration and formulations of LHRH agents (e.g., 1-month, 3-month, and 6-month formulations), which may influence recovery times. Existing evidence suggests that long-acting formulations are associated with prolonged recovery, raising questions about whether the observed differences are due to pharmacological properties or formulation duration. The clinical relevance of faster testosterone recovery remains uncertain, as the study does not evaluate its impact on patient-reported outcomes such as quality of life, sexual function, or metabolic health. Future research should focus on stratifying analyses by formulation type and duration and assessing the clinical implications of testosterone recovery on patient-centered outcomes to enhance the applicability of these findings to clinical practice.

INTRODUCTION: Hematoxylin & Eosin (H&E) stained slides are the gold standard for cancer diagnosis but are subject to labor-intensive review and inter-observer variability. Whole-slide imaging (WSI) and digital pathology are reshaping this landscape, enabling remote diagnosis, quantitative analysis, and integration with clinical and molecular data for precision medicine. The complexity of cancer diagnosis highlights the need for sophisticated analytical tools capable of extracting multidimensional information from tissue sections. AREAS COVERED: Technological and computational advances driving the integration of artificial intelligence (AI) and digital pathology. The transition from classical machine-learning to deep learning models that automatically learn hierarchical representations from raw WSIs. Convolutional neural networks, transformers and foundational computational pathology models. Tasks such as biomarker prediction and prognostic modeling. Emerging research on multimodal AI systems that are integrating histology images with text data to improve clinical relevance. Challenges related to data sharing and privacy, generalizability, and the implementation of these approaches in real-world clinical settings. Primary keywords used for screening included 'cancer diagnosis,' 'artificial intelligence,' 'digital pathology,' 'regulation,' 'clinical implementation,' 'foundational models,' 'adoption of AI in pathology,' etc and relevant articles from Pubmed and/or company newsletters were used and cited accordingly. EXPERT OPINION: Digital pathology and AI are transforming cancer diagnosis and evaluation. We expect that AI will be increasingly embedded in routine pathology practice to enhance diagnostic accuracy, improve efficiency, advance biological discovery, and perform tasks out of reach of conventional microscopy, thus advancing precision oncology.

BACKGROUND: Cancer therapy-related cardiac dysfunction (CTRCD) is among the most important adverse effects of treatment of childhood cancer. In the EARLY study (Early detection of acute and early-onset cARdiovascuLar toxicity in children with cancer using a multiparametric approach), cardiac function in children treated for cancer was monitored during and shortly after treatment, using advanced echocardiography, electrocardiography, and cardiac magnetic resonance (CMR) techniques. METHODS: In this prospective pilot study, 100 children newly diagnosed with childhood cancer receiving anthracyclines as part of their cancer treatment were included. A subgroup of 30 children was included in the CMR sub-study. Echocardiography, electrocardiography, and CMR were performed before (T0), three and a half months after (T1), and one year after (T2) start of anthracycline treatment. In this article, we focus on the methodological aspects of the EARLY study, including patient enrollment and characteristics of the study cohort, as well as the feasibility of advanced echocardiography. CURRENT STATUS: The last patient was included in August 2022. Follow-up for the last patient was finalized in August 2023. Follow-up was completed by 92% of the total study population and 97% of the CMR sub-study. CONCLUSIONS: Protocol adherence was high (92%-97%) and a full collection of data on each included individual was achieved. Advanced echocardiography, i.e., 4D ejection fraction and global longitudinal strain, was feasible in 76% and 69% of measurements, respectively. Cardiac outcomes during and shortly after treatment, as well as associations with known risk factors for CTRCD, such as anthracycline dose, dose of radiotherapy involving the heart, childhood cancer disease profile, age at diagnosis and sex will be reported in a future publication. The feasibility of the study allows for future insight into the correlation between early-onset CTRCD and heart failure during long-term follow-up of childhood cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NL-OMON22737.

BACKGROUND: Renal cell carcinoma (RCC) exhibits heterogeneity and variable responses to systemic therapy. Kidney injury molecule-1 (KIM-1) has emerged as a biomarker in RCC, but its prognostic and treatment-response value has not been quantified. This review and meta-analysis evaluated whether baseline KIM-1 predicts survival in RCC and whether post-treatment changes in KIM-1 reflect systemic therapy response. METHODS: A search of PubMed, Embase, and the Cochrane Library was conducted through November 2025. Eligible studies measured serum or plasma KIM-1 in RCC and reported survival or treatment-response outcomes. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled. RESULTS: Eight studies including 3,002 patients met inclusion criteria. High baseline KIM-1 was associated with worse survival (HR 1.44, 95% CI 1.27-1.62) and disease-free survival (HR 1.72, 95% CI 1.45-2.04), with no heterogeneity (I = 0%). Declines in KIM-1 after systemic therapy were associated with improved progression-free survival (HR 0.55, 95% CI 0.32-0.94; I = 71.5%) and improved disease-free survival (HR 0.66, 95% CI 0.50-0.87). CONCLUSIONS: Elevated baseline circulating KIM-1 indicates higher RCC recurrence and mortality risk, while post-treatment declines may reflect therapeutic response. Preliminary evidence suggests KIM-1 prognostic and predictive value for RCC biomarker, though further validation is required due to lower certainty.

Alongside the physical burden of cancer and its treatments, women with gynecologic cancer face substantial psychological and social challenges that strongly shape quality of life. Adaptive coping and timely psychosocial support may facilitate adjustment, adherence, and rehabilitation. To summarize coping strategies used by women with gynecologic cancer and their association with quality of life, and to describe the role of the multidisciplinary care team in delivering psychosocial support. We conducted a systematic search of PubMed, ScienceDirect, Google Scholar, BioMed Central, AKJournals, and ResearchGate for studies published between 2018 and 2025 without language restrictions. The search yielded 1419 records; after screening and full-text assessment, 36 studies were included. We extracted data on coping patterns, psychological outcomes, quality of life, and the contribution of psychosocial care and communication. Adaptive coping - particularly problem solving and seeking social support - was associated with better emotional well-being, lower distress, and higher quality of life. Avoidant coping was linked to higher anxiety, depressive symptoms, and poorer quality of life. Structured psychosocial interventions and consistent, empathic clinician-patient communication reduced tension, strengthened trust, and improved adherence. Integrating psychosocial support into oncologic care for women with genital tumors can enhance adaptive coping and improve quality of life. A patient-centered, interdisciplinary approach should include decision-making support, early assessment of coping and psychological burden, timely referral to appropriate professionals, and continuous development of communication and patient management competencies among providers. Orv Hetil. 2026; 167(18): 691-701.

Corneal endothelial dysfunction is a major cause of global blindness, with an estimated 12.7 million patients awaiting corneal transplantation, and the severe shortage of donor grafts underscores the urgent need for non-surgical therapies. Gene therapy offers a promising alternative, but is hindered by the limitations in existing delivery systems and the scarcity of validated molecular targets capable of reversing core pathophysiology. To address this, we first employed multi-omics analysis and identified FOXO1 as a central and under-explored therapeutic target for corneal endothelial dysfunction. In vivo FOXO1 overexpression effectively improved corneal endothelial function by preserving mitochondria-associated endoplasmic reticulum membrane integrity and mitochondrial Ca homeostasis, yet its therapeutic potential was limited by low transfection efficiency. To overcome this, we engineered an AAV-Foxo1 delivery system using a viscous choline chloride-fructose-based deep eutectic solvent (DES) as the carrier. The DES-AAV-Foxo1 delivery system exhibited good biocompatibility, significantly prolonged anterior chamber retention, and enhanced transfection efficiency in corneal endothelial cells compared to conventional AAV delivery. Animal experiments confirmed that it effectively improved corneal endothelial pump activity and mitigates endothelial dysfunction in type 1 diabetes mellitus and Fuchs endothelial corneal dystrophy mouse models. Our findings demonstrated the therapeutic potential of DES-AAV-Foxo1 delivery system for corneal endothelial disorders.

Glutaminase 1 (GLS1) drives glutaminolysis to support tumor growth and survival, yet its role in the tumor microenvironment remains poorly understood. Here, we demonstrate that GLS1 promotes angiogenesis in head and neck squamous cell carcinoma (HNSCC) via an exosome-dependent mechanism. In HNSCC xenograft models, genetic silencing of GLS1 or treatment with CB-839 markedly reduces intratumoral angiogenesis. Exosomes from GLS1-deficient cells impair endothelial cell migration and tube formation compared with control exosomes. Proteomic analysis reveals a loss of the pro-angiogenic protein Tenascin C (TNC) in GLS1-deficient exosomes. Mechanistically, loss of GLS1 interferes with USP1-mediated deubiquitination of Caveolin-1 (CAV1), resulting in CAV1 degradation and impaired recruitment of TNC into exosomes. Exosomes deficient in CAV1-TNC complexes subsequently disrupt integrin-dependent FAK-SRC signaling in endothelial cells, inhibiting their angiogenic activity. Collectively, these findings uncover a non-metabolic role of GLS1 in promoting tumor angiogenesis through exosome-mediated CAV1-TNC signaling, suggesting that targeting GLS1 may simultaneously inhibit tumor metabolism and angiogenesis in HNSCC.

A 52-year-old male presented with a 3-month history of dysphagia. Laryngological examination showed a left-sided hypopharyngeal tumor, and biopsy of biopsy the tumor revealed moderately differentiated squamous cell carcinoma (SCC). Computed tomography (CT) and esophagogastroduodenoscopy also revealed a 50 mm mass in the middle thoracic esophagus. Biopsy of the esophageal tumor revealed lymphoepithelial carcinoma (LEC), characterized by lymphoplasmacytic infiltration and atypical immunohistochemical markers: The infiltrated cells were positive for EMA, partially positive for cytokeratin (CK) AE1/AE3, slightly positive for p63, and negative for CK5/6, synaptophysin, chromogranin A, CK7, p40, S100, HMB45, Melan A, and EBER-ISH. The patient underwent chemoradiotherapy (CRT) with 50.4 Gy in 24 fractions and concurrent chemotherapy with cisplatin and 5-fluorouracil. After CRT, both the tumors showed complete resolution on CT and endoscopy. No recurrence has been observed for 17 months. LEC, often associated with Epstein-Barr virus (EBV), is extremely rare in the esophagus. To our knowledge, this is the first reported case of coexistence of esophageal LEC and primary hypopharyngeal SCC, in which complete response was achieved by CRT.

BACKGROUND: Stage III non-small cell lung cancer (NSCLC) presents marked heterogeneity under evolving therapeutic paradigms. Real-world evidence on current treatment practices and outcomes remains limited. OBJECTIVE: The MOOREA study aimed to evaluate real-world molecular testing, treatment patterns, and clinical outcomes of treatment-naïve Chinese patients with stage III NSCLC. PATIENTS AND METHODS: MOOREA is a prospective, multicenter Chinese study enrolling patients with untreated stage III NSCLC (16 July 2019 to 28 February 2022) from 28 hospitals. Patients were consecutively enrolled. The primary endpoint was treatment pattern of cohort 1 (C1; unresectable stage III NSCLC), and the secondary endpoints included molecular testing pattern, progression-free survival (PFS), overall survival (OS) of C1, and treatment pattern of cohort 2 (C2; resectable stage III NSCLC). RESULTS: In total, 486 patients were analyzed (C1: 379; C2: 107). Molecular testing rates were: EGFR (20.0%), ALK (15.0%), and PD-L1 (13.0%). Of the 45.6% (173/379) of individuals in C1 who received chemoradiotherapy (CRT), 53.8% (93/173) underwent consolidation therapy, including 37.6% (35/93) who received immunotherapy (IO). In C2, lobectomy was the main surgical approach (85.8%, 91/106), whereas pneumonectomy was performed on 14.2% of patients (15/106). Adjuvant treatment was planned for 71.4% (75/105) of the patients in C2. For C1, the median follow-up was 27.5 months, with PFS and OS of 12.6 (95% CI: 11.0-14.0) and 33.3 months (95% CI: 29.6-not estimable), respectively. Subgroup analysis showed better OS and PFS for patients receiving CRT with IO consolidation versus CRT only, especially for those who underwent more than six IO consolidation cycles (24-month OS: 79.3% versus 66.4%; PFS: 49.6% versus 24.2%). CONCLUSIONS: MOOREA reveals the real-world management of stage III NSCLC in 20 provinces/cities in mainland China and Hong Kong SAR. Patients with unresectable tumors derived significant benefit from radiotherapy and consolidation after CRT. Substantial disparity persists between actual practice and guideline recommendations, necessitating efforts to enhance adherence to guideline-based care. CLINICAL TRIAL REGISTRATION: NCT04023812.

BACKGROUND: Cancer therapy-related cardiac dysfunction (CTRCD) has become an important clinical issue with advances in cancer treatment and improved patient survival. The Japanese Society of Echocardiography previously published practice guidance in 2020. The present document provides an updated revision reflecting recent developments in cardio-oncology. METHODS: This guidance was developed based on contemporary evidence, including the 2022 European Society of Cardiology cardio-oncology guidelines, recent clinical studies, and advances in echocardiographic and multimodality imaging technologies. RESULTS: Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) are emphasized as essential parameters for diagnosing and monitoring CTRCD. The document provides standardized protocols for echocardiographic evaluation before, during, and after cancer drug therapy, as well as recommendations for long-term surveillance following radiotherapy. It also addresses cardiovascular complications associated with immune checkpoint inhibitors, particularly myocarditis, and highlights the importance of measurement accuracy, quality control, artificial intelligence, and three-dimensional echocardiography in clinical practice. CONCLUSIONS: This updated guidance offers practical and evidence-based recommendations for echocardiographic assessment in cardio-oncology, aiming to facilitate early detection of cardiotoxicity and optimize multidisciplinary management.

Urological cancers exhibit significant sex differences in incidence, treatment response, and prognosis, with males generally showing higher morbidity and mortality. This review systematically summarizes the underlying molecular and clinical mechanisms of these disparities, focusing on sex hormones, chromosome biology, tumor immune microenvironment, and microbiota. Sex hormones modulate key tumor processes including proliferation, apoptosis, non-apoptotic cell death, and DNA repair. Genetic factors such as X chromosome inactivation escape genes and Y chromosome loss also contribute to sex-biased cancer susceptibility. Furthermore, sex-specific differences in the urinary system and gut microbiota influence local immunity and inflammation, thereby affecting tumor progression and therapeutic response. Lifestyle and environmental factors, including smoking, alcohol consumption, and occupational exposures, further exacerbate these disparities. Clinically, sex differences impact the efficacy of immunotherapy and targeted therapies, underscoring the need for sex-informed treatment strategies. Integrating sex as a biological variable in research, clinical practice, and public health policies is essential for advancing precision oncology in urologic cancers.

B-cell lymphoma 6 (BCL6) is an attractive drug target for diffuse large B-cell lymphoma (DLBCL). This study aimed to create a lipid nanoparticle (LNP)-based peptide-proteolysis-targeting chimera (PROTAC), specifically BCL6-PROTAC, to develop effective strategies for treating DLBCL via targeted degradation of the BCL6 protein. Molecular docking, SPR and cellular thermal shift assays revealed that F1324 (Ac-LWYTDIRMSWRVP-OH) is a high-affinity BCL6-binding peptide. PROTAC LNPs were synthesized by modifying F1324 and pomalidomide aptamers onto LNPs via a covalent chemical reaction in a certain proportion. The LNPs were characterized using dynamic light scattering and transmission electron microscopy. The ligand ratio (F1324:pomalidomide) used to verify the optimal BCL6 degradation was 1:5, as determined using western blotting. In vitro and in vivo studies revealed that BCL6-PROTAC significantly inhibited the proliferation of DLBCL cells. Target-specific uptake was used to evaluate the accumulation of BCL6-PROTAC in vivo. Toxicity in normal tissues was detected using H&E staining and serum indices. Overall, we developed a PROTAC that exhibited persistent and excellent BCL6 degradation ability in DLBCL, with an excellent safety profile. Thus, our BCL6 degrader provides a complementary approach to existing clinical‑stage candidates.

INTRODUCTION: The aerosol foam formulation of calcipotriol/betamethasone dipropionate (Cal/BD) is an efficacious topical treatment for psoriasis. This study evaluated the efficacy of Cal/BD foam versus ointment in Chinese patients, on the basis of investigator-assessed and patient-reported outcomes (PROs) from a 4-week clinical trial, including post hoc analyses after 2 weeks of treatment. METHODS: A randomized, investigator-blind, active-controlled, parallel-group phase 3 trial was conducted in China. Native Chinese adults (≥ 18 years) with plaque psoriasis involving 2-30% of the body surface area (BSA), with at least mild disease severity according to the Physician's Global Assessment (PGA), and modified Psoriasis Area and Severity Index (mPASI) ≥ 2 were randomized 1:1 to receive either Cal/BD foam or ointment once daily for a 4-week treatment period. Efficacy was assessed at weeks 0, 2, and 4 using mPASI, PGA, BSA, Dermatology Life Quality Index (DLQI), Psoriasis Symptom Inventory (PSI), and Subject's Global Assessment of disease severity (SGA). RESULTS: A total of 302 patients were randomized to each treatment. Both groups had clinically meaningful improvements across all outcome measures from baseline to week 2, with sustained or further improvements at week 4. For Cal/BD foam-treated patients, mean change from baseline in mPASI was -59.87% at week 2 (versus ointment: -54.59%; P = 0.010) and -74.69% at week 4 (versus ointment: -70.22%; P = 0.043). Other investigator-assessed outcomes based on mPASI and PGA showed statistically significant treatment differences favoring Cal/BD foam at week 4. Improvements in PROs (DLQI, PSI, and SGA) were numerically slightly greater with Cal/BD foam than ointment, though not statistically significant. For Cal/BD foam-treated patients, mean change from baseline in DLQI was -3.9 at week 2 (versus ointment: -3.7; P = 0.5012) and -5.5 at week 4 (versus ointment: -5.3; P = 0.5119). CONCLUSIONS: Cal/BD foam showed rapid onset of action with clinically meaningful improvements in signs, symptoms, and quality of life in Chinese patients with plaque psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05919082. Plaque psoriasis is the most common type of psoriasis, a chronic disease affecting the skin and other body systems. Plaques are thick, scaly patches of skin that can be itchy and painful, limiting patients' everyday activities. Plaque psoriasis has a major impact on quality of life, comparable with the impact of other chronic diseases such as cancer and heart disease. Many treatments, such as creams, tablets, and injections, can improve plaque psoriasis, but they do not always work well for everyone. In a clinical trial in China, we tested two treatments-a foam and an ointment-that have the same amount of two active ingredients: calcipotriol (Cal) and betamethasone dipropionate (BD). The goal was to find out if Cal/BD foam, which is the newer treatment, worked as well as Cal/BD ointment in Chinese men and women with plaque psoriasis. The trial participants were randomly distributed into two groups, each with 302 participants. One group applied Cal/BD foam on their plaques and the other group applied Cal/BD ointment, both once daily for 4 weeks. Both groups had meaningful improvements in psoriasis signs and symptoms as well as quality of life already after 2 weeks, with sustained or further improvements after 4 weeks. Overall, the improvements were slightly greater with Cal/BD foam than with Cal/BD ointment.

Avian leukosis virus subgroup J (ALV-J) remains a major threat to poultry health and production, particularly in indigenous chicken populations in China. In this study, a highly pathogenic ALV-J field strain, YN2021, was first isolated from indigenous black-bone chickens in Yunnan Province, China, and its biological characteristics and pathogenicity were systematically evaluated in specific-pathogen-free (SPF) chickens. Infected chickens exhibited significant growth retardation, delayed sexual maturation, and increased mortality, accompanied by pathological lesions consistent with ALV-J. To further assess reproductive performance, egg production and egg weight were recorded. YN2021-infected hens showed a reduction in total egg production (70 vs. 92 eggs; ~23.9% decrease) and a significantly lower mean egg weight (35.2 ± 0.2 g vs. 43.7 ± 0.3 g; P < 0.001) compared to controls. To facilitate mechanistic studies and future control strategies, a full-length infectious clone of YN2021 was constructed using a reverse genetics approach, and a synonymous molecular marker was introduced for viral identification. The rescued recombinant virus exhibited replication kinetics, p27 antigen expression, and biological characteristics in DF-1 cells comparable to those of the parental strain, and the molecular marker remained genetically stable during serial passages. Collectively, these results demonstrate that the ALV-J YN2021 strain exhibits high pathogenicity and negatively affects growth and reproductive performance in chickens. The infectious clone established in this study provides a reliable experimental platform for investigating ALV-J pathogenesis and supports the development of effective control strategies to mitigate production losses in poultry.