Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

Objectives: To elucidate the underlying mechanisms of macrophage-mediated inflammation and tissue injury in diabetic foot ulcer (DFU).

Methods: Skin tissue samples were collected from patients with DFU and with non-DFU. A total of 79 272 high-quality cell transcriptomes were obtained using single-cell RNA sequencing. An unbiased clustering approach was employed to identify cell subpopulations. Seurat functions were used to identify differentially expressed genes between DFU and non-DFU groups, and gene ontology (GO) enrichment analysis was used to reveal gene function. Furthermore, cell-cell communication network construction and ligand-receptor interaction analysis were performed to reveal the mechanisms underlying cellular interactions and signaling regulation in the DFU microenvironment from multiple perspectives.

Results: The results revealed a significant expansion of myeloid cells in DFU tissues, alongside a marked reduction in structural cells such as endothelial cells, epithelial cells, and smooth muscle cells. Major cell types underwent functional reprogramming, characterized by immune activation and impaired tissue remodeling. Specifically, macrophages in DFU skin tissues exhibited a shift toward a pro-inflammatory M1 phenotype, with upregulation of genes associated with inflammation and oxidative stress. Cell communication analysis further demonstrated that M1 macrophages served as both primary signal receivers and influencers in the COMPLEMENT pathway mediated communication network, and as key signal senders and mediators in the secreted phosphoprotein 1 (SPP1) pathway mediated communication network, actively shaping the inflammatory microenvironment. Key ligand-receptor interactions driving macrophage signaling were identified, including C3-(ITGAM+ITGB2) and SPP1-CD44.

Conclusions: This study establishes a comprehensive single-cell atlas of DFU, revealing the role of macrophage-driven cellular networks in chronic inflammation and impaired healing. These findings may offer potential novel therapeutic targets for DFU treatment.

Patients with metastatic castration-resistant prostate cancer (mCRPC) face poor prognoses due to tumor heterogeneity and drug resistance. Antibody-drug conjugates (ADCs) have been under development for over two decades for mCRPC treatment. Several clinical trials have demonstrated promising antitumor activity and acceptable safety profiles for ADCs in this setting. Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 and DXC008 (both dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, an international multicenter phase Ⅲ clinical trial (NCT06925737) for mCRPC has been initiated in May 2025 for evaluating B7-H3-targeted ADC ifinatamab deruxtecan. This review summarizes recent advances in ADCs targeting key antigens in mCRPC (including PSMA, B7-H3, STEAP1, TROP2, SLC44A4, and others) and explores combination strategies, offering insights to inform the clinical management of mCRPC.

Tophaceous wound represent a severe complication of end-stage gout, characterized by the deposition of monosodium urate (MSU) crystals leading to localized tissue ischemia, chronic inflammation, and non-healing ulcers. The pathological mechanism involves the formation of MSU crystals under persistent hyperuricemia, inflammatory encapsulation, and mechanical compression of the vascular system due to tophus enlarge-ment, ultimately resulting in chronic non-healing ulcers. This article consolidates current evidence to outline an integrated management strategy for such wounds, combining systemic metabolic control with localized interventions. Effective treatment depends on maintaining serum uric acid levels below 300 μmol/L through urate-lowering agents, including conventional drugs and novel urate transporter 1 inhibitors such as AR882, complemented by anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs and glucocorticoids to alleviate pain and reduce inflammation. Topical agents and advanced dressings are utilized to support healing and manage exudate. Debridement, which encompasses sharp, ultrasonic, and micro-techniques, is essential for removing necrotic tissue and MSU deposits, with efficacy assessed via local uric acid monitoring. Surgical reconstructions, including skin flap grafting and tendon or ligament reconstruction, are indicated for significant tissue loss or functional impairment. Long-term management emphasizes continuous metabolic control, personalized rehabilitation, and lifestyle modification. The comprehensive treatment of tophaceous wounds requires multidisciplinary collaboration to balance local repair and systemic regulation for improved prognosis. Future research directions include gene therapy to regulate purine metabolism and artificial intelligence-assisted personalized treatment plans, to achieve precision medicine for tophaceous wounds.

The clinical data of 10 patients with pathologically confirmed primary hepatic neuroendocrine neoplasms (PHNENs) were retrospectively analyzed. The cohort included 8 males and 2 females, with a median age of 63 years. None presented with carcinoid syndrome. Three cases were detected incidentally during health check-ups, 2 presented with painless jaundice, and 5 reported abdominal distension or pain (1 with concurrent jaundice). Elevated tumor markers included carbohydrate antigen 19-9 in 4 cases, alpha-fetoprotein in 2 cases, and neuron-specific enolase in 1 case. All patients underwent surgical resection, including hepatectomy and hilar cholangiocarcinoma resection, combining with resection and reconstruction of right hepatic artery, resection of liver metastases and pancreaticoduodenectomy according to the extent of tumor invasion.Preoperative imaging failed to diagnose neuroendocrine neoplasms in all cases. Final pathological diagnoses were neuroendocrine tumor (NET) G2 in 5 cases, NET G3 in 1 case, and neuroendocrine carcinoma (NEC) in 4 cases. During the follow-up, 4 patients died and 6 survived. The study demonstrates that PHNENs lack specific clinical or imaging features, and the diagnosis relies on pathological examination after excluding metastatic disease. Radical resection remains the primary treatment, with prognosis varying significantly by tumor grade.

Skin fibrosis is primarily characterized by excessive fibroblasts proliferation and aberrant extracellular matrix accumulation, leading to pathological conditions such as hypertrophic scars, keloids, and systemic sclerosis. This dynamic and complex process involves intricate interactions among various resident skin cells and inflammatory cells, ultimately resulting in extracellular matrix deposition and even invasive growth. The maintenance of cellular phenotypes and functions relies on dynamic metabolic responses, and cellular signal transduction is closely coupled with metabolic processes. Given that the coupling of cell metabolism and signaling in the skin fibrosis microenvironment plays a critical role in inflammatory responses and fibrotic activation, modulation of these metabolic pathways may offer novel therapeutic strategies for inhibiting or even reversing the progression of skin fibrosis. This review systematically summarizes the metabolic characteristics of various cell types involved in skin fibrosis, with a focus on core metabolic reprogramming mechanisms such as hyperactive glycolysis, dysregulated fatty acid metabolism, cellular metabolic dysfunction and dysregulated mTOR/AMPK signaling. Furthermore, potential intervention strategies targeting these metabolic pathways are explored, thereby providing new research perspectives for the treatment of skin fibrosis.

To enhance medication safety and rational use, a multidisciplinary expert panel from the Yangtze River Delta region-comprising specialists in pharmacy, clinical medicine, healthcare administration, and evidence-based medicine-was convened to develop this consensus through multiple rounds of Delphi consultation. A management system for the off-label use of novel antineoplastic agents was established, incorporating a tiered management process and a regional information sharing platform. Standardized procedures were implemented to regulate the applications, review, documentation, and dynamic adjustment of off-label use. The regional platform centralizes the collection and evaluation of evidence for off-label usage, facilitating consistent and homogeneous manage-ment across healthcare institutions. The tiered management process and information sharing platform established herein are intended to serve as a practical reference for standardizing the management of off-label use of novel antineoplastic agents in medical institutions.

Health management is highly complex due to interactions across multiple levels and factors. System dynamics model (SDM) offers a holistic perspective and a dynamic analytical framework for understanding such complex systems. It has been applied across various domains of health management, including psychological interventions, chronic disease management, rehabilitation, optimization of medical services, and health policy development. By identifying key factors and pathways influencing health behaviors, determining critical targets for interventions, conducting cost-benefit analyses and process optimization, and simulating the long-term effects of health policies, SDM provides quantitative support for decision-making from individual-level interventions to macro-level policies. This article reviews the application of SDM in these four major areas within health management, discusses its advantages and limitations, and serves as a reference for researchers and practitioners aiming to utilize SDM in future studies. The goal is to advance health management toward greater personalization and precision, thereby offering stronger support for health interventions and policy development.

Congenital lower urinary tract obstruction (CLUTO) is a spectrum of fetal malformations caused by anatomical abnormalities of the urethra, characterized by high rates of perinatal complications and mortality. The 2024 joint guideline from the European Association of Urology (EAU) and the European Society for Paediatric Urology (ESPU) introduced systematic revisions to the comprehensive management of CLUTO. Key updates encompass advancements in prenatal and postnatal screening and precise diagnosis, refined fetal prognosis assessment, clearer indications and modality selection for prenatal intervention, optimization of postnatal treatment strategies, and the establishment of a lifelong follow-up framework within an integrated care pathway. This article elucidates these key updates by comparing the 2024 EAU/ESPU guideline with the 2022 European Rare Kidney Disease Reference Network (ERKNet) consensus. It also discusses ongoing controversies and future research directions. The aim is to provide clinicians with the latest evidence-based insights to inform practice, ultimately improving outcomes and quality of life for children with CLUTO.

A middle-aged patient presented with persistent purulent discharge from a scalp incision five years after undergoing craniotomy with artificial dura mater implantation. The wound showed no significant improvement despite a month of systemic antibiotic therapy and local debridement. Subsequent superficial ultrasonography revealed complete separation of the artificial dura mater implant area from the surrounding flap tissue, with a loss of local blood supply. Based on these findings, the artificial dura mater was surgically removed, and a free skin flap transplantation was performed to successfully cover the wound. The wound was well-healed at the 10-month postoperative follow-up.