Conventional endourological techniques, including balloon dilation and endoureterotomy, offer mechanical luminal relief but do not modulate the fibroproliferative cascade that drives restenosis. Paclitaxel-coated balloons, widely validated in vascular and urethral interventions, deliver localized antiproliferative therapy with minimal systemic exposure. Their mechanism-selective drug uptake into the urothelium, submucosa, and muscularis-may theoretically enhance long-term patency after endoscopic management. This review aims to summarize the translational rationale, mechanistic basis, and technical application of paclitaxel- and paclitaxel-dextran-coated balloons for benign ureteral and ureteroenteric strictures, and to contextualize their potential role within contemporary endourology. A narrative, non-systematic synthesis was performed integrating data from preclinical ureteral pharmacokinetic studies, vascular and urethral drug-coated balloons (DCBs) experience, and early human reports in benign ureteral and ureteroenteric strictures. The review emphasizes device characteristics, inflation parameters, drug-tissue interactions, and procedural workflows relevant to translational endourological practice. Experimental models demonstrate time-dependent paclitaxel penetration across ureteral layers and sustained tissue residence. Early clinical experience-including a prospective pilot study and recent case-based observations-indicates that DCB use is technically feasible, exhibits an acceptable safety profile, and may achieve encouraging short-term radiologic patency. Cross-territory evidence from vascular and urethral platforms provides additional mechanistic justification for translational use in the ureter. Paclitaxel-based DCBs represent a technically feasible adjunct with a strong biological rationale for the endourological management of benign ureteral and ureteroenteric strictures. While mechanistic foundations and preliminary clinical signals are promising, rigorous prospective studies are required to define optimal technique, inflation parameters, patient selection, pharmacokinetics, and long-term outcomes before widespread adoption.
As a highly prevalent malignant tumor within the urinary system, bladder cancer (BLCA) is manifested as frequent recurrence and substantial prognostic heterogeneity. The development of BLCA is strongly linked to epigenetic dysregulation. Bromodomain-containing proteins (BRDs)-related genes (BRDRGs) serve as critical regulators across various cancers. However, the expression profiles, prognostic significance, and influence on the tumor immune microenvironment (TIME) of BRDRGs in BLCA remain underexplored. This study aimed to systematically explore the expression and prognostic significance of BRD-related genes in BLCA and to construct a BRD-based prognostic model. Utilizing transcriptomic data within The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) for BLCA, BRDRGs were screened through GeneCards. Consensus clustering was leveraged to define BRD molecular subtypes. Differential expression analysis was implemented to ascertain BRD co-expressed genes, and we intersected them with differentially expressed genes (DEGs) between tumor and normal samples in TCGA-BLCA to obtain differentially expressed BRD genes (DE-BRDRGs). A prognostic risk model was developed utilizing univariate Cox and least absolute shrinkage and selection operator (LASSO) regression, followed by survival analysis, receiver operating characteristic (ROC) evaluation, and nomogram validation. Associations between the model and immune characteristics with immunotherapy response were estimated utilizing Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT), Tumor Immune Dysfunction and Exclusion (TIDE), and pRRophetic analyses. Gene set enrichment analysis (GSEA) was implemented to ascertain functions of key genes. In vitro, the key gene DSP was knocked down utilizing small interfering RNA (siRNA). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot were implemented to verify the effectiveness of knockdown, while Cell Counting Kit-8 (CCK-8) was leveraged to evaluate the proliferation of BLCA cells. In total, 1,572 upregulated genes and 1,111 downregulated genes were ascertained from TCGA-BLCA, with 36 DE-BRDRGs ultimately ascertained through the intersection of BRD co-expressed genes. Seven genes (DSP, DSC2, HSPG2, GJA1, TXNRD1, PCDHGC3, and PEG10) were chosen to formulate the risk model. In TCGA-BLCA, the area under the curve (AUC) values within 1, 2, and 3 years were 0.620, 0.665, and 0.682. In GSE13507, the AUC values within 1, 2, and 3 years were 0.730, 0.655, and 0.664. Marked distinctions were observed between high- and low-risk cohorts regarding immune cell infiltration (e.g., Tregs and CD8+ T cells) and immunotherapy response. GSEA indicated that key genes contributed to the progression of BLCA through pathways like the cell cycle and PI3K-Akt signaling. In vitro experiments denoted that DSP knockdown considerably inhibited the proliferation of BLCA cells, and the knockdown was effective, suggesting its pro-tumorigenic role. This research ascertained seven key BRDRGs and comprehensively analyzed their functions in BLCA. In vitro experimental validation demonstrated that DSP exerts tumor-promoting effects and represents a potential therapeutic target. The established BRD-based prognostic model offers a novel strategy for risk stratification and personalized management of individuals with BLCA.
Prostate cancer is the predominant malignancy in males, with bone metastasis representing a defining characteristic of its progression. Bone tissue involvement significantly deteriorates patient quality of life and incurs substantial healthcare expenditure. Emerging evidence suggests a potential link between cuproptosis and tumor biology, thereby identifying cuproptosis-related genes (CRGs) as promising biomarkers for bone metastatic prostate cancer (BMPC). Consequently, this bioinformatics study aimed to identify specific biomarkers and establish a robust diagnostic model. To conduct this study, we downloaded publicly available datasets on prostate cancer bone metastasis from the Gene Expression Omnibus (GEO) database and integrated them after a rigorous standardization process to address batch effects. Following differential expression analysis to identify the upregulated and downregulated genes, comprehensive functional annotation was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and immune infiltration profile analyses were performed. Multidimensional analysis identified 24 cuproptosis-related differentially expressed genes (CRDEGs). Based on 23 of these CRDEGs, a support vector machine (SVM) diagnostic model was created and further optimized using the least absolute shrinkage and selection operator (LASSO) regression, ultimately focusing on 13 key genes. The predictive accuracy of the model was validated using a receiver operating characteristic curve analysis. To elucidate the molecular interactions, protein-protein interaction (PPI) networks and GeneMANIA prediction results were analyzed, along with regulatory network analysis to identify potential therapeutic targets. In total, 3,401 differentially expressed genes (DEGs) (1,744 upregulated and 1,657 downregulated genes) were identified. Among them, 24 CRDEGs were closely linked to copper metabolism and likely influenced tumor cell survival and migration, including Metallothionein 1M (MT1M), Heat Shock Protein Family D (Hsp60) Member 1 (HSPD1), and Glutathione Peroxidase 4 (GPX4). GO and KEGG enrichment highlighted processes, such as "response to copper ion" and "copper ion detoxification", implicating these genes in prostate cancer bone metastasis. The diagnostic model, constructed via SVM using 13 key genes selected by LASSO regression, exhibited excellent discriminatory ability, with an area under the curve (AUC) of 0.97. PPI analysis revealed dense interactions among the key genes, which was corroborated by GeneMANIA predictions. Exploration of the regulatory network revealed upstream transcription factors (TFs) and downstream pathways that may serve as therapeutic targets for BMPC. This bioinformatics study identified cuproptosis-related biomarkers and established a high-performance diagnostic model specifically targeting BMPC, despite limitations in sample size and experimental validation. These findings suggested potential molecular mechanisms underlying the pathogenesis of bone metastases in prostate cancer and provided a computational foundation for the development of early detection strategies and targeted therapeutic interventions. Future research should focus on increasing cohort sizes and integrating in vitro and in vivo experiments to further confirm the potential clinical implications of the identified biomarkers.
Lactylation, a metabolic-driven post-translational modification, plays a critical role in tumor microenvironment (TME) remodeling. Lactylation modifies histones and non-histone proteins to regulate gene expression and cell signaling, and recent studies have linked it to immune evasion and tumor progression in bladder cancer (BLCA). However, the prognostic value of lactylation-related genes (LRGs) and their underlying immunoregulatory mechanisms in BLCA have yet to be elucidated. This study aims to establish a lactylation-based molecular classification for BLCA and to construct a robust machine learning prognostic model, thereby clarifying the immunoregulatory role of lactylation and its clinical implications. We integrated multi-center transcriptomic datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Unsupervised consensus clustering was employed to identify lactylation-associated molecular subtypes. Innovatively, we developed an ensemble machine learning framework using 107 combinations of 10 distinct algorithms to establish an optimal prognostic model, incorporating a SHapley Additive exPlanations (SHAP) analysis to interpret core gene contributions. We further evaluated the association between the model, the TME landscape, immune checkpoints, and drug sensitivity. We identified two molecular subtypes with distinct survival outcomes based on 40 differentially expressed LRGs. The final 12-gene prognostic model-constructed using a combination of random survival forest (RSF) and Ridge regression-demonstrated superior predictive performance across multiple cohorts [with its concordance index (C-index) and area under the curve (AUC) values significantly exceeding those of existing models]. The SHAP analysis identified five core contributors, including PTGIS and SRP68. Immunological characterization revealed that the high-risk group exhibited a paradoxical combination of high immune infiltration (including activated CD4+ T cells, activated B cells, natural killer cells, macrophages, and dendritic cells) and high immune suppression, characterized by upregulated checkpoints [e.g., CD274/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4)] and elevated Tumor Immune Dysfunction and Exclusion (TIDE) scores, suggesting significant immune evasion potential. Conversely, this group showed enhanced sensitivity to conventional chemotherapeutics such as cisplatin and gemcitabine. This study established a robust, lactylation-based prognostic tool for BLCA and provided mechanistic insights into how lactylation shapes the immunosuppressive microenvironment, offering a scientific basis for precision immunotherapy and chemotherapy strategies.
Bladder cancer (BLCA) is a clinically complex malignancy characterized by high heterogeneity and recurrence, posing significant challenges for patient management. Growing evidence implicates dysregulated RNA processing, a crucial layer of gene expression control, as a key driver of BLCA pathogenesis and progression, highlighting its potential as a therapeutic vulnerability. This study aims to identify novel molecular subtypes based on RNA processing-related genes (RPRGs) and construct a robust prognostic risk model to improve survival prediction and personalize treatment strategies, particularly in the context of the immune landscape and immunotherapy response. We analyzed BLCA data from The Cancer Genome Atlas (TCGA) (training cohort, N=394) and Gene Expression Omnibus (GEO) (validation cohort, GSE32894, N=224). Using RPRGs from the Molecular Signatures Database (MSigDB), we identified prognostic genes via univariate Cox regression and performed molecular subtyping with the non-negative matrix factorization (NMF) algorithm. A prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression ("glmnet" package), and its performance was validated using receiver operating characteristic (ROC) analysis (timeROC). Immune infiltration was assessed via single-sample gene set enrichment analysis (ssGSEA), ESTIMATE, and CIBERSORT, while functional enrichment was analyzed using GSEA and clusterProfiler. Drug sensitivity was predicted using the CellMiner and DGIdb databases, along with the "pRRophetic" package. Using RPRGs, we stratified BLCA into two molecular subtypes and developed an 8-gene prognostic model via LASSO Cox regression. The model effectively stratified patients into high-risk (poor prognosis) and low-risk (favorable prognosis) groups in both TCGA and GEO cohorts [area under the curve (AUC) >0.71]. High-risk group displayed immunosuppressive traits [e.g., elevated Tumor Immune Dysfunction and Exclusion (TIDE) score, M2 macrophage enrichment] and reduced immunotherapy response, while low-risk group showed elevated tumor mutation burden (TMB) and CD8+ T cell infiltration. Functional enrichment revealed extracellular matrix pathways in high-risk cases, and drug sensitivity profiling identified signature gene-chemotherapy associations. Based on RPRGs, this study establishes a novel risk model that effectively stratifies BLCA patients, not only predicting prognosis but also revealing its close association with the tumor microenvironment and immunotherapy response, providing a new tool for personalized treatment.
Single-port (SP) robotic platforms have expanded the landscape of minimally invasive urologic surgery by enabling complex renal and upper-tract procedures through a single access point. Their design and ergonomics offer potential advantages in confined anatomical spaces and have driven growing clinical adoption in oncologic kidney surgery. This review aims to summarize current evidence supporting SP approaches for radical nephrectomy (RN), partial nephrectomy (PN), and radical nephroureterectomy (RNU), with emphasis on perioperative performance, access strategies, and emerging patient-selection frameworks. A focused PubMed search was performed to identify studies evaluating SP approaches for RN, PN, and RNU. Eligible publications included clinical studies of any design, Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL)-phase evaluations, multi-institutional cohorts, case series, learning-curve analyses, and technical reports. SP-PN represents the most mature application of the platform, with multicenter cohorts and IDEAL-phase studies demonstrating perioperative and early oncologic outcomes comparable to multiport (MP)-PN. Retroperitoneal SP-PN, particularly using the low anterior access (LAA) technique, is associated with reduced postoperative pain, lower opioid requirements, and shorter hospitalization, which supports outpatient pathways in appropriately selected patients. SP-RN likewise shows perioperative safety comparable to MP approaches, with increasing preference for retroperitoneal access because this reduces external arm interference and improves exposure of the renal hilum. Single-port robotic-assisted radical nephroureterectomy (SP-RANU) remains in earlier stages of clinical adoption but demonstrates a consistent perioperative profile across institutions, and intracorporeal bladder cuff excision is feasible in most published series. Across all procedures, the current evidence is largely derived from early institutional experience with variability in cohort size, surgeon volume, and duration of follow-up. Comparative studies evaluating long-term oncologic outcomes remain limited. SP robotic surgery has become a validated and increasingly refined platform in renal and upper-tract oncology. SP-PN demonstrates perioperative and early oncologic equivalence to MP-PN, with distinct advantages in postoperative recovery. SP-RN and SP-RANU show promising early outcomes; however, larger comparative studies are required to determine long-term oncologic performance and optimal patient selection.
The 2025 World Health Organization (WHO) Guideline for the Prevention, Diagnosis, and Treatment of Infertility represents the first comprehensive global framework integrating male and female contributors to infertility within a unified public health strategy. This commentary examines the male-relevant components of the guideline from the perspective of reproductive biology and translational andrology. The WHO guideline mandates a parallel evaluation of both partners and structures male assessment around the medical history, a focused physical examination and semen analysis as a triage tool. While pragmatic and globally applicable, semen analysis remains a descriptive rather than a mechanistic test, underscoring the need for a deeper investigation into sperm chromatin integrity, epigenetics and molecular function. The guideline's conservative treatment recommendations - limited to clinical varicocele repair and antioxidant therapy - reflect Population, Intervention, Comparison, Outcome prioritization, the GRADE methodology and an emphasis on pregnancy and live-birth outcomes, as well as considerations of equity and feasibility across diverse health systems. By embedding male reproductive health within a global infertility approach, the guideline promotes structured evaluation, early specialist referral and reproductive equity, while highlighting critical gaps in mechanistic understanding that must inform future research and clinical innovation.
Psychogenic erectile dysfunction (pED) is closely associated with psychological factors such as anxiety and interpersonal distress. Psychological interventions aimed at enhancing self-efficacy in patients with pED can effectively improve erectile function and overall quality of life. This study examines the potential mediating associations of social support and anxiety in the relationship between intimate relationship quality and self-efficacy among patients with pED, providing theoretical guidance for intervention development. This study was a cross-sectional study conducted at a single tertiary hospital. A total of 210 patients with pED who were treated at the Andrology Outpatient Clinic of a tertiary Grade-A hospital in Nanjing from April 2024 to March 2025 were selected as the study subjects. Tools included the International Index of Erectile Function-5 (IIEF-5), the Quality of Relationship Inventory (QRI), the Social Support Rating Scale (SSRS), the Generalized Anxiety Disorder-7 scale (GAD-7), and the General Self-Efficacy Scale (GSES). Structural equation modeling (SEM) with Bootstrap analysis was utilized to explore the relationships among these variables. The mean scores for intimate relationships, social support, anxiety, and self-efficacy were 32.28±7.88, 34.73±6.28, 6.79±4.92, and 23.72±5.33, respectively. Intimate relationships were significantly and positively correlated with social support (r=0.336, P<0.01) and self-efficacy (r=0.260, P<0.01), while showing a significant negative correlation with anxiety (r=-0.313, P<0.01). SEM analysis further indicated potential mediation effects of social support and anxiety on the relationship between intimate relationships and self-efficacy. The total indirect effect accounted for 51.52% (effect size: 0.321) of the total effect. Specifically, the indirect effects mediated through social support, anxiety, and the serial pathway accounted for 24.56%, 18.30%, and 8.51% of the total effect, respectively. Intimate relationship quality demonstrated both direct and indirect associations with self-efficacy in patients with pED, mediated by social support and anxiety. Consequently, psychological interventions targeting the enhancement of relationship quality, the utilization of social support, and the alleviation of anxiety may help improve self-efficacy in this population.
Clear cell renal cell carcinoma (ccRCC) exhibits significant molecular heterogeneity, which limits the benefit of immunotherapy and underscores the urgent need for robust predictive biomarkers. The highly aggressive sarcomatoid phenotype, with its distinct treatment responses, provides a promising biological foundation for model development. This study aimed to develop and validate a machine-learning-based multi-omics score derived from sarcomatoid-associated genes [sarcomatoid-associated renal cell carcinoma score (SARS)] for prognostic stratification and prediction of therapeutic efficacy across different treatment modalities in advanced ccRCC. A machine learning ensemble algorithm was applied to sarcomatoid-associated genes to develop the SARS. The model stratification power was validated for overall survival (OS) and progression-free survival (PFS) across IMmotion151, CheckMate025, and JAVELIN Renal 101 trials. Multi-omics analyses, including single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and metabolic flux inference, were used to decipher the associated tumor biology, tumor microenvironment (TME), and metabolic reprogramming. The SARS model robustly stratified OS and PFS in both the training and external validation cohorts. SARS effectively stratified patients into SARS-high and SARS-low groups across all cohorts for both OS and PFS, and stratified the efficacy of monotherapy and combination therapy. Multi-omics characterization revealed that SARS-high tumors exhibited enhanced proliferative capacity, metabolism reprogramming, and an immunosuppressive TME. We further identified DRAP1 as a core gene within the SARS signature. Spatial transcriptomics confirmed DRAP1's specific overexpression in malignant regions, and single-cell analyses indicated its critical role in intercellular communication and early tumor progression. The SARS model serves as a powerful and integrative biomarker for prognostic stratification and therapeutic guidance in advanced ccRCC. DRAP1 is a potential novel therapeutic target, while further studies are needed to elucidate its underlying mechanisms.
Bladder cancer (BC) is the sixth most common cancer in men and one of the top 10 cancers in terms of the global cancer burden. Despite the rapid development and widespread application of photodynamic therapy (PDT) in BC research, a comprehensive analysis and bibliometric evaluation of the development trends in this field have yet to be conducted. This study aims to quantify and visualize the research output, major contributors, intellectual structure, and emerging frontiers in photodynamic therapy for bladder cancer research from 2000 to 2025. Articles on PDT in BC published from 2000 to 2025 were retrieved from the Web of Science Core Collection (WoSCC) database. A bibliometric analysis was performed using VOSviewer, CiteSpace, Python, and the R package "bibliometrix". A total of 595 articles from 42 countries were included in the analysis, of which the majority originated from China and the United States. The number of publications related to PDT in BC continues to increase annually. The National University of Singapore, the University of Leuven, the German National Cancer Center, and the University of Coimbra in Portugal were the main research institutions with the highest publication volumes. Photodiagnosis and Photodynamic Therapy was the leading journal in this research area, while The Journal of Urology was the most frequently co-cited publication. A total of 106 authors contributed to these articles, of whom, Fernandes and Olivo contributed the highest number of publications, and Dougherty was the most commonly co-cited author. The main research topics in this field included the development and optimization of novel photosensitizers, combination therapy strategies, and the integration of photodynamic diagnosis and therapy. Further, the core keywords representing emerging research hotspots included "hypericin", "5-aminolevulinic acid", "protoporphyrin IX", "photosensitizer", "nanoparticles", and "immunotherapy". A bibliometric analysis was conducted to examine research on PDT in BC from 2000 to 2025. The investigation identified key trends, collaborative networks, and central research themes, including the application of hypericin and the integration of immunotherapy. While China and the United States were the leading contributors in terms of publication output, international collaborative efforts remained relatively limited. The findings underscore a notable evolution in the field, characterized by a focus on photosensitizer optimization and the development of novel therapeutic strategies. Emerging research directions notably include advancements in nanotechnology, immunotherapeutic approaches, and combination treatment regimens. In summary, this analysis provides a comprehensive mapping of the current knowledge landscape, offering valuable insights to guide future research initiatives in this domain.
Prostatic hyperplasia is a common condition among aging males characterized by excessive prostate cell proliferation, and while it is a benign process, it involves significant metabolic reprogramming and immune infiltration-features typically associated with malignant tumors. This study aimed to elucidate the interaction network between the PIEZO channels and genes related to glycometabolic reprogramming and mitochondrial oxidative phosphorylation (OXPHOS), highlighting their roles in the progression of prostatic hyperplasia. Gene expression datasets from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed genes (DEGs) associated with prostatic hyperplasia. Glycolysis- and OXPHOS-related pathways were obtained from the Molecular Signatures Database (MSigDB). Advanced bioinformatics methods, including differential expression analysis, functional enrichment analysis, immune infiltration analysis, and machine learning models, were employed to explore PIEZO interactions. A competitive endogenous RNA (ceRNA) network and a biomarker-based diagnostic nomogram were constructed and validated across multiple datasets. A total of 4,617 DEGs were identified, among which 122 were glycolysis- and OXPHOS-related genes. The Spearman correlation analysis revealed 84 genes significantly associated with PIEZO1 and PIEZO2 expression. The functional enrichment analysis demonstrated that these PIEZO-related genes regulate critical processes, including ATP production, mitochondrial function, and glycolysis. The immune infiltration analysis revealed associations between PIEZO biomarkers and altered immune cell profiles. Machine learning models identified PGM2 and GFPT1 as robust diagnostic biomarkers with strong predictive performance [area under the curve (AUC) >0.75]. The ceRNA network revealed complex regulatory interactions involving PIEZO genes, biomarkers, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), underscoring their potential roles in disease pathogenesis. This study provides a comprehensive bioinformatics framework linking PIEZO channels to glycometabolic reprogramming and OXPHOS dysregulation in prostatic hyperplasia. The identified biomarkers and regulatory networks offer novel insights into the molecular mechanisms underlying disease progression and potential therapeutic targets.
Urothelial carcinoma (UC) is a common malignancy with poor prognosis in refractory or metastatic stages. While platinum-based chemotherapy and PD-1 inhibitors have improved outcomes for some, the benefits are limited. Disitamab Vedotin (RC48), an HER2-targeted antibody-drug conjugate, combined with PD-1 inhibitors, has shown promising antitumor activity in advanced UC. This study aims to evaluate the clinical efficacy and safety of RC48 combined with PD-1 inhibitors in previously treated UC patients using real-world data. This single-center, retrospective real-world study included 29 patients with mUC who had received prior treatment and were treated with RC48 plus a PD-1 inhibitor between October 2021 and April 2025. Treatment efficacy was assessed according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Treatment-related adverse events (TRAEs) were recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Subgroup analyses were conducted based on age, Eastern Cooperative Oncology Group (ECOG) performance status, tumor human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) status, number of metastatic sites, and programmed cell death ligand 1 (PD-L1) expression. Among 29 included patients, the median age was 67 years, and 69.0% were male. HER2 IHC showed 2+ expression in 51.7% of patients and 3+ expression in 20.7%. The vast majority of patients (93.1%) received ≥4 treatment cycles. The ORR was 34.5%, with a DCR of 96.6%. Disease progression occurred in only 1 patient (3.4%). Median PFS was 14.22 months. In an exploratory preliminary analysis with limited sample size, patients aged ≥65 years, ECOG performance status 0, and HER2 IHC 3+ numerically demonstrated longer PFS. The OS endpoint had not been reached at data cutoff; preliminary survival differences were observed in patients with ≤2 metastatic sites. Regarding safety, TRAEs occurred in 82.8% of patients, primarily peripheral neuropathy (48.28%), anemia (17.24%), and leukopenia (10.34%). Grade ≥3 TRAEs were reported in 6.9% of patients, with no treatment-related deaths recorded. Most adverse events were manageable through dose adjustments or supportive care. This retrospective real-world study provides preliminary evidence that RC48 combined with PD-1 inhibitors may offer encouraging antitumor activity and a manageable safety profile in relapsed or refractory mUC, with a median PFS of 14.22 months and a high DCR observed in this cohort. Given the exploratory nature of this analysis and the study's limitations, including the small sample size, single-center design, and lack of a control arm, these findings should be interpreted with caution. Larger prospective studies are warranted to validate these results.
Reports on the discrimination of benign prostatic hyperplasia (BPH) are rare. This study investigated the related factors and constructed a model to discriminate the risk of BPH, and also performed an in-depth analysis on key indicators. The data were collected from the National Health and Nutrition Examination Survey (NHANES) database. The logistic regression analysis was conducted on differential variables between the BPH and non-BPH groups to explore the independent factors of BPH. Then a nomogram discrimination model was constructed and validated, followed by discriminative performance assessment through receiver operating characteristic (ROC) curves, calibration curve, and decision curve analysis (DCA). Further, we deeply analyzed the action mode of core indicators by SHapley Additive exPlanations (SHAP), interaction effect, and subgroup analyses. A total of 4,151 participants were included, with 820 having BPH. The logistic regression results showed that age, race, smoking, alcoholic drinks, waist circumference (WC), g-tocopherol, and free prostate-specific antigen (PSA) were independently related to BPH. A nomogram constructed by the seven factors had a great discriminative performance on BPH both in training sets and validation sets, and can obtain a favorable clinical net benefit. Within the discrimination model, age, PSA, and WC were the more core influencing factors, and they can jointly amplify the risk of BPH. The effect of g-tocopherol was regulated by these background factors. This study identified key factors and constructed a useful tool for discriminating BPH, and also revealed the action mode of core factors. It provides a scientific basis for risk discrimination and key mechanism analysis of BPH.
Bladder urothelial carcinoma (BLCA) is a prevalent malignant tumor within the urinary system. Aspartyl-tRNA Synthetase 2, Mitochondrial (DARS2), a key enzyme involved in mitochondrial protein synthesis, is frequently overexpressed in various cancers and is associated with clinical stage. This study aims to explore the potential of DARS2 as a prognostic biomarker and therapeutic target in BLCA, with the ultimate goal of constructing a prognostic model. Expression profiles of BLCA were obtained from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database, encompassing a total of 431 samples. Differential gene expression between tumor and normal tissues was first analyzed using the "limma" R package. To identify independent prognostic genes, we integrated various statistical and machine learning approaches, including univariate and multivariate Cox proportional hazards analyses, with variable selection performed via Cox proportional hazards regression with least absolute shrinkage and selection operator (LASSO). For the key gene DARS2, its expression differences were further analyzed using the edgeR method, followed by gene set enrichment analysis (GSEA) to explore associated functional pathways. Furthermore, immune cell infiltration was evaluated using multiple algorithms. The role of DARS2 in BLCA progression was systematically investigated by integrating analyses of gene mutations, tumor mutational burden (TMB), and survival outcomes. Finally, a prognostic model was constructed based on DARS2 expression levels and validated using the GSE13507 dataset from the Gene Expression Omnibus (GEO) database. Based on the analytical methods described above, we observed that the expression of DARS2 messenger ribonucleic acid (mRNA) was significantly upregulated in BLCA tissues, and its elevated expression was independently associated with adverse patient prognosis. Immune infiltration analysis revealed that DARS2 expression exhibited a significant negative correlation with major immunologically active cells, such as CD4+ T cells and CD8+ T cells. In terms of genetic mutations, the somatic mutation rate of DARS2 in BLCA was 2.21%, whereas the receptor tyrosine kinase (RTK)/RAS GTPase signaling pathway (RTK-RAS) represented the most frequently mutated oncogenic pathway (72.97%). DARS2 expression showed a moderate positive correlation with TMB, with factors including advanced age, male sex, and higher tumor grade potentially contributing to elevated TMB. Survival analysis further demonstrated that patients with high DARS2 expression had significantly poorer outcomes in overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI). The risk-scoring model constructed based on DARS2 expression indicated that age, metastasis (M) stage, and risk score all served as independent prognostic factors for BLCA. Comprehensive analysis suggests that DARS2 holds promise as a potential independent prognostic biomarker for patient stratification in BLCA and may serve as a viable target for the development of immunotherapeutic strategies.
Kidney cancer represents a significant global health burden, with renal cell carcinoma (RCC) being the predominant form. The treatment landscape for metastatic RCC (mRCC) has evolved significantly. Understanding the current status, trends, and research hotspots in kidney cancer immunotherapy is therefore crucial. This study aimed to systematically clarify the research status, hotspots, and trends in kidney cancer immunotherapy by integrating scattered studies via bibliometric analysis. We retrieved literature from the Web of Science Core Collection [2014-2024] and conducted bibliometric analysis using CiteSpace 5.8.R3, focusing on publications, countries/institutions, authors, co-cited references, and keywords. A total of 5,123 relevant papers were included, showing two phases of growth: steady development [2014-2018] and rapid expansion [2019-2024], with 2020 publications increasing by 50% compared to 2019. The USA, China, and Italy contributed 50% of total studies, while Harvard University and the University of Texas System were leading institutions (inter-institutional collaborations remained weak). Choueiri TK (87 publications) and Motzer RJ (four top co-cited New England Journal of Medicine papers) were core contributors. Dominant keywords included "renal cell carcinoma", "immunotherapy", "sunitinib", and "nivolumab", with "interferon alpha", "tumor-infiltrating lymphocytes", and "dendritic cells" as emerging burst terms. Kidney cancer immunotherapy research has boomed since 2019, driven by the USA, China, and Italy. Core focuses are key agents and mechanisms, while tumor microenvironment-related topics represent future directions.
Hypospadias is among the most prevalent congenital malformations in male newborns. Despite its clinical significance, the molecular etiology of hypospadias has not extensively characterized. Although environmental exposures, epigenetic dysregulation, and mitochondrial dysfunction have been identified as potential contributing factors, the role of mitochondrial DNA (mtDNA) methylation in the pathogenesis of hypospadias has not been systematically examined. Therefore, this study aimed to investigate the potential involvement of mtDNA methylation in hypospadias and to explore its association with mitochondrial gene expression and oxidative phosphorylation-related pathways. To investigate mtDNA-related epigenetic alterations in hypospadias, an integrated analysis of transcriptomic and methylomic data was conducted. Alongside control specimens, preputial tissue samples were obtained from patients diagnosed with distal, midshaft, and proximal hypospadias. RNA sequencing (RNA-seq) was performed to profile gene expression. Subsequent functional enrichment analyses were conducted to identify the key disturbed biological pathways. Additionally, mtDNA methylation patterns were examined via publicly available methylation datasets, and this was followed by targeted validation with bisulfite pyrosequencing in order to facilitate the quantification of site-specific methylation levels of the selected mitochondrial genes. RNA-seq identified 96 differentially expressed genes (DEGs), of which 87 were upregulated and 9 downregulated. Subsequent functional enrichment analysis indicated that oxidative phosphorylation (OXPHOS)- and reactive oxygen species (ROS)-related pathways were the most significantly affected biological processes. Further analysis of mitochondrial gene transcriptomes revealed broadly similar upregulation patterns across different hypospadias subtypes, with MT-CO1, MT-CO3, MT-RNR2, and MT-ND6 being identified as the commonly dysregulated genes. Methylation analysis of target genes revealed unique epigenetic features in hypospadias tissue: MT-CO1 and MT-RNR2 exhibited significant hypomethylation, MT-ND6 showed hypermethylation, and MT-CO3 demonstrated no significant methylation changes. Notably, this methylation pattern was not significantly different across clinical subtypes, suggesting that it may represent a potentially shared epigenetic feature independent of anatomical classification. Our findings indicate that aberrant mtDNA methylation is associated with altered mitochondrial gene expression and disrupted OXPHOS in hypospadias. This type of epigenetic dysregulation may impair mitochondrial energy metabolism and redox balance, thereby contributing to abnormal urethral development. These results constitute novel evidence linking mitochondrial epigenetic modifications to the pathogenesis of hypospadias and highlights potential of molecular targets in future risk assessment, early diagnosis, and preventive interventions.
Renal cell carcinoma (RCC) is a common and aggressive urological malignancy with a complex tumor microenvironment that may influence systemic inflammation. This review aimed to comprehensively explore the association between the systemic inflammatory response index (SIRI) and prognosis in patients with renal cell carcinoma (RCC) through a systematic review and meta-analysis. Following the PRISMA guidelines, we systematically searched PubMed, Embase, Web of Science, and the Cochrane Library up to September 2025. Studies investigating the predictive value of SIRI [SIRI = (neutrophil count × monocyte count)/lymphocyte count] for overall survival (OS), cancer-specific survival (CSS), or progression-free survival (PFS) in patients with localized and advanced RCC were included. Two researchers independently performed article screening, data extraction, and quality assessment. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were pooled using a random-effects model with Review Manager 5.4.1 software. The I2 metric was applied to assess heterogeneity, and Egger's test, along with the trim-and-fill method, was used to detect and adjust for publication bias. A total of 10 studies involving 5,314 patients were included. Meta-analysisresults showed that a higher SIRI was significantly associated with shorter OS (HR =2.47, 95% CI: 1.85-3.29, P<0.00001), although there was high heterogeneity (I2=76%). Furthermore, a higher SIRI was associated with shorter CSS (HR =3.60, 95% CI: 1.40-9.26, P=0.008) and shorter PFS (HR =1.21, 95% CI: 1.11-1.33, P<0.0001). Sensitivity analyses showed that the results for OS and PFS were robust, but the results for CSS became non-significant after excluding specific studies. The analysis of OS revealed publication bias, but the association remained significant after adjustment for trimming and filling. This study demonstrates that a higher SIRI is a potential predictor of adverse prognosis (including OS, CSS, and PFS) in patients with RCC. As an easily accessible inflammatory marker, SIRI may have important clinical value in the risk stratification of RCC, but the findings still need to be further verified by prospective studies.
White light cystoscopy (WLC), the first-line diagnostic modality for bladder lesions, has inherent limitations in detecting flat lesions and distinguishing low-grade malignancies. Imported probe-based confocal laser endomicroscopy (pCLE) systems address these gaps but are restricted by high costs and limited accessibility. This study aimed to assess the technical feasibility and safety (primary outcomes) of a domestic pCLE system for bladder lesion evaluation, while preliminarily comparing the clinical performance of two fluorescein sodium administration routes and three probe diameters (secondary outcomes) to inform future clinical research. A single-center, prospective single-arm cohort study was conducted at a tertiary hospital, enrolling 10 patients with suspected bladder masses or a history of bladder cancer undergoing cystoscopy. Feasibility was defined as the technical completion rate of pCLE imaging, and safety was evaluated using the Clavien-Dindo classification system for adverse events within 72 hours post-procedure. Patients with negative fluorescein sodium skin tests received either intravesical instillation or intravenous injection. Probes of 1.9, 2.6, and 3.2 mm were tested for imaging quality and maneuverability. Baseline clinical characteristics and histopathological results were collected for descriptive analysis; no inferential statistics for diagnostic accuracy were performed. The technical completion rate was 100%, with no Clavien-Dindo grade ≥ I adverse events observed. Transient yellowish-green urine occurred in all patients who received intravenous fluorescein sodium, resolving spontaneously without intervention. The 2.6 mm probe exhibited the best balance of imaging quality and maneuverability, while the 3.2 mm probe had poor maneuverability in narrow anatomical sites. Intravenous injection shortened procedure time but caused mild surgical field interference in 50% of cases during transurethral resection, whereas intravesical instillation had no interference but a longer duration. Pathological results included eight malignant lesions (five high-grade and three low-grade urothelial carcinoma), one benign lesion, and one papillary urothelial neoplasm of low malignant potential (PUNLMP). Distinguishable cellular and tissue features were observed on pCLE imaging across different lesion types. This domestic pCLE system demonstrates favorable technical feasibility and safety in this pilot cohort. Due to the small sample size, no conclusions regarding diagnostic accuracy can be drawn. Larger, multicenter studies are urgently needed to validate these preliminary findings and evaluate the system's diagnostic efficacy in bladder cancer management.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disorder, characterized by progressive cyst formation, kidney enlargement, and eventual loss of kidney function. Tolvaptan, a selective vasopressin V2 receptor antagonist, is the only disease-modifying treatment for ADPKD, demonstrating efficacy in slowing cyst growth and preserving kidney function. However, its efficacy and safety in Chinese patients are not well studied due to limited clinical data and regulatory approval gaps. This study aimed to evaluate the efficacy and safety of tolvaptan in kidney volume and kidney function in Chinese patients with rapidly progressing ADPKD. This single-center, prospective, single-arm study enrolled patients with rapidly progressing ADPKD (Mayo classification types 1C-1E). Participants received tolvaptan at doses tailored to baseline estimated glomerular filtration rate based on serum creatinine (eGFRcr), with follow-up assessments at 3, 6, 9, and 12 months. The primary outcome was the difference between expected and actual height-adjusted total kidney volume (htTKV) growth rates (eHTKV-α - annual change in htTKV), while secondary outcomes included changes in eGFRcr and safety profiles. Statistical analyses included hierarchical clustering to explore comorbidity patterns and their association with outcomes. Among 145 analyzed patients, htTKV growth stabilized over time, with the median annual change decreasing from 16.8% at 3 months to -2.5% at 12 months. The eHTKV-α - annual change in htTKV shifted from -12.6% at 3 months to 7.6% at 12 months, indicating slower kidney growth than predicted. eGFRcr remained stable overall, although subgroups (e.g., females) showed slight declines. Comorbidity clustering revealed that patients with proteinuria and pelviectasis had poorer outcomes. Safety monitoring indicated mild liver enzyme elevations [alanine aminotransferase (ALT) > upper limit of normal (ULN): 6.3% at baseline to 9.1% at 12 months] and minimal hyponatremia, with no severe hepatic toxicity. Tolvaptan effectively slowed kidney volume growth and stabilized kidney function in Chinese patients with rapidly progressing ADPKD. The safety profile was favorable, with no severe adverse events observed. These results support tolvaptan as a viable therapeutic option for Chinese patients with ADPKD.
Continuous renal replacement therapy (CRRT) serves as a cornerstone of supportive care for critically ill patients. The selection of anticoagulation strategies and hemofiltration solutions is pivotal to the safety and efficacy of CRRT. Regional citrate anticoagulation (RCA) has been widely adopted in CRRT practice; however, it is associated with cumbersome operational procedures. Furthermore, traditional high-concentration sodium citrate anticoagulants are associated with an increased risk of metabolic complications. This study compared a novel 18 mmol/L sodium citrate hemofiltration solution with the traditional RCA protocol, with the aim of evaluating the safety, efficacy, and clinical convenience of the novel solution in CRRT for critically ill patients. This retrospective cohort study was conducted on 105 CRRT sessions in the intensive care unit (ICU) of Beijing Electric Power Hospital between July 1 and September 30, 2025. Inclusion criteria were age ≥18 years and use of CRRT with regional citrate anticoagulation (RCA). Exclusion criteria were contraindications to citrate anticoagulation, psychiatric illness, or pregnancy/lactation. Patients were divided into two groups based on the anticoagulation method: sodium citrate hemofiltration solution group (n=53) and traditional regional citrate anticoagulation (tRCA) group (n=52). We collected and compared baseline characteristics, CRRT treatment parameters, post-filter ionized calcium levels, complication rates, and workflow parameters between the two groups. No significant differences were observed between the two groups in terms of gender distribution, comorbidities or disease severity indicators, including Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The sodium citrate hemofiltration solution group demonstrated a significantly longer mean CRRT duration compared to the tRCA group (50.91±13.07 vs. 45.19±10.83 hours; P=0.02). Multivariable Cox regression analysis was performed to adjust for potential confounders; the use of sodium citrate hemofiltration solution remained independently associated with significantly longer filter survival compared with tRCA [adjusted hazard ratio (HR) =0.615, 95% confidence interval (CI): 0.404-0.935, P=0.02]. Post-filter ionized calcium concentrations remained within target ranges (0.2-0.4 mmol/L) across all time points in both groups. The sodium citrate hemofiltration solution group showed lower incidences of citrate accumulation (0% vs. 7.7%, P=0.04) and metabolic alkalosis (3.8% vs.17.3%, P=0.02). The study group showed a higher rate of hypomagnesemia than the tRCA group (9.4% vs. 0%, P=0.02). The sodium citrate hemofiltration solution group required fewer infusion and syringe pumps {2 [interquartile range (IQR), 2-2] vs. 3 (IQR, 3-3), P<0.001} and had a lower hourly bag-change frequency [0.57 (IQR, 0.51-0.59) vs. 1.17 (IQR, 1.15-1.19) bags/hour, P<0.001] compared with the tRCA group. Sodium citrate hemofiltration replacement solution enables effective anticoagulation, prolongs filter lifespan, reduces metabolic complications, and simplifies clinical procedures in critically ill patients undergoing CRRT. These findings support the potential utility of sodium citrate hemofiltration solution in the ICU, though confirmation in prospective trials is warranted.