Background:Significant clinical variations exist in the definitions of acute/active vs. chronic/stable Peyronie's disease (PD), limiting treatment options. To determine whether penile pain should inform PD treatment timing, we analyzed the association between baseline penile pain levels and treatment efficacy using data from the IMPRESS (Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies) I/II studies of collagenase clostridium histolyticum (CCH). Methods:A post hoc analysis of pooled data from 2 phase 3 randomized double-blind trials of CCH in PD (IMPRESS I, NCT01221597; IMPRESS II, NCT01221623) was conducted. CCH-treated participants were stratified by baseline penile pain levels using investigator-assessed and patient-reported measures. A subgroup analysis stratified participants with Any Pain by disease duration. Results:At total of 364 CCH-treated men were included. Mean penile curvature improvements at week 52 were similar across all 4 investigator-assessed and patient-reported penile pain measures (35.0-36.7% improvement for the No Pain group vs. 32.2-33.9% improvement for the Any Pain group, P=0.14-0.65). Among those experiencing Any Pain, no statistical differences were observed in men with shorter (12-18 months; 21.8-34.8% improvement) vs. longer (>18 months; 31.4-36.8% improvement, P=0.20-0.95) disease durations. Conclusions:Men with PD who were treated with CCH experienced similar curvature improvements regardless of baseline pain status or disease duration among those who experienced any pain. Findings support the literature that demonstrate similar efficacy when treating men with active vs. stable disease, suggesting that ongoing pain is not a contraindication to CCH therapy.
Background:Erectile dysfunction (ED) and premature ejaculation (PE) frequently co-occur, presenting a significant clinical challenge in male health. However, existing research remains fragmented, lacking a systematic overview of the field's developmental trajectory, knowledge structure, and future trends. This study aims to systematically map the research landscape of ED/PE comorbidity over the past two decades [2005-2025] using bibliometric methods, revealing its evolutionary pathways, research hotspots, collaborative networks, and emerging frontiers. Methods:Based on the Web of Science Core Collection (WoSCC) database, 1,089 ED/PE comorbidity-related publications were retrieved and analyzed. Tools including VOSviewer, CiteSpace, and Bibliometrix were employed for quantitative analysis and visualization of countries, institutions, authors, journals, keywords, and citation networks. Results:Findings indicate: (I) annual publication volume exhibits exponential growth, with pivotal inflection points occurring in 2008 and 2021. (II) China leads in publication output, whereas Italy and the United States dominate academic influence and international collaboration. (III) Research themes evolved through three phases: epidemiology and disease definition [2005-2013], combination therapies and mechanism exploration [2014-2020], and diversified integrated interventions [2021-2025]. (IV) Cognitive behavioral therapy, pathophysiological mechanisms, and emerging physical therapies represent current frontiers, whereas patient psychological counseling and endocrine regulation remain relatively peripheral. Conclusions:This study presents the first knowledge map of ED/PE comorbidity research, revealing a clear trajectory from isolated disease perspectives toward integrated comorbidity models. Future research should deepen exploration of "neuro-vascular-psychological" integrated mechanisms, strengthen high-quality clinical trials, and address current research gaps to advance clinical practice to precision.
Background and Objective:Varicoceles, defined as an abnormal dilation of the pampiniform venous plexus within the scrotum, are considered the most common surgically correctable cause of male infertility. Yet, it remains unclear exactly how to best select patients for the procedure and how the different surgical methods compare in practice. While prior reviews have established the general benefits of varicocelectomy, there is a clinical need to synthesize recent data on emerging molecular markers like sperm DNA fragmentation, alongside conventional parameters and final reproductive outcomes. The objective of this review is to evaluate the effects of varicocele repair on overall semen quality and male fertility outcomes, while comparing the safety and efficacy of different surgical approaches. Methods:A literature search was conducted across the PubMed and Embase databases for English-language clinical trials published between January 2010 and April 2026. Studies were eligible if they evaluated adult men undergoing varicocelectomy and reported quantitative postoperative data on semen parameters, pregnancy rates, or surgical complications. The extracted data were qualitatively synthesized to provide a broad clinical overview of treatment efficacy. Key Content and Findings:A total of 24 core clinical trials were included in the primary analysis. The synthesized evidence demonstrates that varicocelectomy significantly improves conventional semen parameters and reduces molecular damage. Microsurgical techniques consistently outperformed laparoscopic and open methods, offering the highest spontaneous pregnancy rates and the lowest incidence of complications. The literature reveals ongoing inconsistencies regarding the optimal management of subclinical contralateral varicoceles, with varying reproductive outcomes reported across different cohorts. Conclusions:Varicocelectomy is an effective method for treating male infertility, leading to improved semen quality and increased chances of natural conception. Microsurgical varicocelectomy remains the method of choice due to its highest efficacy and lowest complication rate. Current literature is still limited by varied methodologies and inconsistent reporting of long-term reproductive outcomes. Debate also continues regarding the exact extent of surgery needed in bilateral or subclinical cases. Future trials should use standard outcome measures and group patients by specific baseline characteristics to help tailor treatments to individual patients.
Background:Male infertility accounts for nearly half of infertility cases, with abnormal semen quality being a major cause. Pentoxifylline (PTX), a methylxanthine derivative with antioxidant and anti-inflammatory properties, has been proposed to improve semen parameters, but evidence remains inconsistent. This systematic review and meta-analysis aimed to assess the efficacy and safety of oral PTX supplementation compared with placebo in improving semen parameters and reproductive hormone profiles in infertile men. Methods:PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from inception to July 2025. Randomized controlled trials (RCTs) comparing oral PTX with placebo in infertile men were included. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Primary outcomes included semen parameters (sperm concentration, total motility, morphology, semen volume). Secondary outcomes comprised serum hormones [testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH)]. Data were pooled calculating mean difference (MD) with 95% confidence intervals (CIs). Results:Five RCTs involving 455 participants were included. PTX dosages ranged from 800 to 1,200 mg/day, with treatment durations of 3 to 6 months. PTX supplementation correlated with increased total sperm motility (MD =10.44, 95% CI: 3.57-17.30) and normal morphology (MD =3.86, 95% CI: 1.01-6.71). Sperm concentration transiently improved at 3 months but did not differ significantly from placebo at 6 months. No significant differences were observed in testosterone (MD =0.22, 95% CI: -0.23 to 0.67) or FSH (MD =-1.51, 95% CI: -4.16 to 1.14) levels, whereas LH decreased marginally (MD =-0.97, 95% CI: -1.45 to -0.49). Reported adverse events were predominantly mild and gastrointestinal. Conclusions:PTX supplementation appears to enhance sperm motility and morphology in infertile men with a favorable safety profile. Its effects on sperm concentration and reproductive hormones are less consistent, and evidence on ultimate clinical effectiveness regarding pregnancy and live birth rates remains unproven. Larger, high-quality trials with reproductive endpoints are needed to clarify its clinical role.
Ureteroplasty using autologous grafts or flaps has emerged as an important reconstructive option for complex proximal or mid-ureteral strictures. Among available tissues, vesical mucosa may be a promising graft material because it is covered by urothelium, readily available, and well adapted to the urinary environment. This study aimed to present our surgical technique and perioperative outcomes of robot-assisted vesical mucosal graft (VMG) ureteroplasty for a mid-ureteral stricture. A 36-year-old woman with progressive left hydronephrosis was admitted to our hospital after failed prior endourological management. Preoperative antegrade and retrograde pyelography demonstrated an approximately 5-cm stricture in the left mid-ureter. In addition, the patient was scheduled to undergo dental implantation, making oral mucosal graft harvest less desirable. Robot-assisted VMG ureteroplasty was therefore performed. The procedure consisted of four main steps: identification of the ureter and longitudinal incision of the stricture segment; harvesting and ex vivo tailoring of the VMG; double-J stent placement and ventral onlay anastomosis; and mesenteric fat wrapping of the graft with closure of the bladder incision. During graft preparation, the serosal and muscular layers were removed, and the submucosal tissue was carefully thinned while preserving the lamina propria as much as possible. A previously reported "two-point" fixation technique was used to stabilize the VMG during anastomosis, and indocyanine green was administered intravenously to confirm satisfactory perfusion before suturing. The procedure was completed successfully in 146 minutes, with an estimated blood loss of 10 mL. Postoperative hospital stay was 5 days, and no perioperative complications occurred. During 6 months of follow-up, the patient remained asymptomatic, renal function was stable, and computed tomography showed improvement of hydronephrosis. In conclusion, robot-assisted VMG ureteroplasty appears to be a safe and feasible option for selected patients with mid-ureteral stricture. Larger series and longer follow-up are needed to further validate this technique.
Background:Long non-coding RNA (lncRNA) X inactive-specific transcript (XIST) is linked to tumor metastasis; however, research on its role in renal cancer (RC) is limited. This study investigated the function and underlying mechanism of XIST in RC. Methods:After transforming growth factor beta (TGF-β) stimulation of 786-O and Caki-1 cells, morphological changes were assessed by microscopy, and XIST expression was quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). XIST-microRNA-141-3p (miR-141-3p) and miR-141-3p-zinc-finger E-box binding protein 1 (ZEB1) interactions were validated by dual-luciferase reporter assays. Cells were then transfected with small interfering (si)-XIST alone or combined with miR-141-3p inhibitor, followed by analyses of: (I) XIST and miR-141-3p expression; (II) cellular morphology; (III) proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay]; (IV) apoptosis (flow cytometry); (V) epithelial-mesenchymal transition (EMT) markers (N-cadherin, Vimentin, and Snail) and E-cadherin (western blot/immunofluorescence); and (VI) migration and invasion (Transwell assays). ZEB1-mediated rescue of miR-141-3p mimic effects was similarly examined. Results:TGF-β triggered EMT in RC cells and elevated XIST expression. XIST knockdown suppressed proliferation, EMT, migration, and invasion, while promoting apoptosis in TGF-β-stimulated cells. Mechanistically, XIST sponged miR-141-3p, and miR-141-3p inhibition partially rescued the phenotypic effects of XIST silencing. Additionally, ZEB1 was identified as a miR-141-3p target, and ZEB1 overexpression reversed the miR-141-3p mimic-mediated suppression of TGF-β-induced malignant behaviors. Conclusions:These findings establish the XIST/miR-141-3p/ZEB1 axis as a regulator of TGF-β-driven proliferation and metastasis in RC in vitro.
Background:Pathological risk stratification of prostate cancer (PCa) guides treatment decisions. Preoperative noninvasive assessment of PCa risk stratification holds promise for reducing unnecessary invasive biopsies. Elevated levels of iron and fat, along with metabolic disorders in PCa significantly correlate with tumor proliferation and aggressiveness, yet its predictive value in risk stratification remains unclear. We aimed to noninvasively measure fat content as well as iron deposition of PCa lesions by multiparametric magnetic resonance imaging (mpMRI) and investigate their effectiveness in predicting PCa risk. Methods:We prospectively collected patients suspected of PCa with preoperative MRI from 2019 to 2022, and ultimately included 109 pathologically confirmed PCa patients. The Gleason score (GS) and International Society of Urological Pathology grade group (ISUP GG) were determined by two uropathologists who evaluated independently and reached a consensus. Patients were stratified based on the ISUP GG, with 42 in the pathological low-risk (PL) group (ISUP GG ≤2; 69.9±6.08 years), 67 in the pathological high-risk (PH) group (ISUP GG ≥3; 71.82±5.86 years). We also collected clinical, pathologic, and imaging data from the patients. Based on the variables screened by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, an improved fusion (IF) model was established and visualized with a nomogram plot. The conventional fusion (CF) model was constructed by removing the non-conventional image variables in the IF model. Model performance was evaluated using 10-fold cross-validation, receiver operating characteristic (ROC) analysis, DeLong test, and decision curve analysis (DCA). P<0.05 was considered statistically significant. Results:Significant differences were observed in the prostate-specific antigen (PSA), prostate volume (PV), Prostate Imaging Reporting and Data System (PI-RADS) scores, fat fraction (FF), T2*, and average apparent diffusion coefficient (ADC) values of the lesions between the two groups. These variables were selected to construct the IF model. The CF model was developed by removing FF and T2* values. The IF model demonstrated higher accuracy than the CF model [IF model: sensitivity =0.952, specificity =0.761, area under the curve (AUC) =0.920; CF model: sensitivity =0.762, specificity =0.761, AUC =0.819; DeLong test: P=0.002, <0.05]. Conclusions:mpMRI‑derived FF and T2* values were significantly associated with ISUP GG in PCa. Intergrating FF and T2* values with ADC, PI-RADS, PSA and PV may predict pathological risk classification more effectively.
Background:In recent years, perioperative-sequential therapies have arisen for muscle-invasive bladder cancer (MIBC) treatment strategies. We are able to select more variable regimens for bladder cancer patients. This study aims to compare clinical outcomes in patients with MIBC who underwent robot-assisted radical cystectomy (RARC) followed by adjuvant nivolumab versus those who did not receive it. Methods:This retrospective single-center study included 60 patients with MIBC who underwent RARC between January 2017 and September 2025. Thirty patients who received adjuvant nivolumab (Nivo group), and 30 patients who did not (no-Nivo group). Disease-free survival (DFS), cancer-specific survival (CSS), and immune-related adverse events (irAEs) were evaluated. Survival analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression models. Inverse probability of treatment weighting was used to adjust for baseline characteristics. Results:Median DFS was significantly longer in the Nivo compared with no-Nivo group [26.0 vs. 9.4 months, respectively; adjusted hazard ratio (aHR): 0.44; 95% confidence interval (CI): 0.22-0.88; P=0.02]. However, CSS did not differ significantly between them (aHR: 0.40; 95% CI: 0.14-1.10; P=0.08). Multivariable analysis identified ≥ pT3, pN+, and absence of nivolumab therapy as independent risk factors for poor DFS. Notably, pN+ remained a significant predictor of shorter DFS even in patients receiving nivolumab (aHR: 4.22; 95% CI: 1.19-15.1). irAEs occurred in 36.6% of patients in the Nivo group, with 13.3% experiencing grade ≥3 events, and three patients discontinued treatment due to toxicity. Conclusions:Adjuvant nivolumab significantly improved DFS in patients with high-risk MIBC in real-world practice; however, patients with pN+ remained at high risk for recurrence despite nivolumab, suggesting the need for more intensive therapeutic strategies in this subgroup.
Background:Bladder cancer (BC) remains a prevalent malignant tumor of the urinary system with high morbidity and mortality rates. Despite advances in therapeutic strategies, the underlying molecular mechanisms driving BC progression are not fully understood, necessitating the identification of novel biomarkers and therapeutic targets. Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a critical player in tumor suppression. However, the specific roles of ferroptosis-related genes and their regulatory mechanisms in BC progression require further elucidation. The study aimed to analyze ferroptosis-related genes and their regulatory mechanisms in BC progression. Methods:This study integrated bioinformatics analysis with experimental validation. Differentially expressed genes (DEGs) between BC and normal tissues were identified using The Cancer Genome Atlas (TCGA) and GSE13507 datasets. These DEGs were intersected with ferroptosis-related genes to screen potential candidates. Weighted gene co-expression network analysis (WGCNA) was employed to identify hub modules associated with BC phenotypes, followed by least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) algorithms to pinpoint key genes. Ubiquitination-related databases were utilized to predict upstream regulators. In vitro and in vivo experiments, including co-immunoprecipitation (Co-IP), ubiquitination assays, functional assays (proliferation, apoptosis, and ferroptosis markers), and xenograft mouse model assay, were conducted to validate the molecular mechanisms and biological functions. Results:Through integrated analysis, 84 ferroptosis-related DEGs were identified. WGCNA and machine learning algorithms further screened and identified collagen type XIV alpha 1 chain (COL14A1) as a critical hub gene. Functional enrichment analysis indicated that these genes were primarily involved in extracellular matrix organization and cell division. Mechanistically, COL14A1 was predicted and validated as a substrate of the deubiquitinase ubiquitin specific peptidase 5 (USP5). USP5 was found to be upregulated in BC cells and interacted with COL14A1 to inhibit its ubiquitination, thereby stabilizing its protein expression. Functional experiments demonstrated that USP5 knockdown significantly promoted COL14A1 degradation, leading to suppressed cell proliferation, induced apoptosis, and increased accumulation of reactive oxygen species (ROS), malondialdehyde (MDA), and Fe2+, while decreasing glutathione (GSH) levels. Crucially, the effects induced by USP5 silencing were effectively reversed by COL14A1 overexpression. In vivo studies further confirmed that USP5 knockdown inhibited tumor growth and reduced COL14A1 expression. Conclusions:This study unveiled a novel USP5/COL14A1 regulatory axis that promotes BC progression by inhibiting ferroptosis and apoptosis. These findings highlight USP5 and COL14A1 as promising therapeutic targets.
Background:In clear cell renal cell carcinoma (ccRCC), mast cell activation and angiogenesis are crucial for disease progression, with interactions occurring between these processes. The involvement of mast cell-related angiogenic characteristics in ccRCC is not yet fully elucidated. To address this gap, this study aims to clarify the biological role and prognostic significance of mast cell-mediated angiogenesis in ccRCC, and to examine its links to the tumor microenvironment and disease progression. Methods:We utilized bioinformatics techniques to integrate and analyze single-cell and bulk transcriptomics data. We developed prognostic models using ten classical machine learning algorithms and conducted intergroup differential gene extraction, functional pathway enrichment, immune infiltration, and somatic mutation analyses. Finally, the expression levels of the model genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Results:TNF-α signaling is significantly upregulated in mast cells within the ccRCC microenvironment, shaping an immunosuppressive microenvironment through receptor-ligand interactions such as SPP1-CD44 and CLEC2C-KLRB1. We developed a mast cell-associated angiogenesis score that demonstrates satisfactory accuracy in assessing prognosis for ccRCC patients. Patients in the high-risk group exhibited activation of oncogenic signaling pathways including JAK-STAT3, accompanied by immunosuppressive status and elevated genomic instability. Furthermore, we identified the core oncogene TIMP1 and the protective gene EMCN. Conclusions:Mast cell-associated angiogenesis features aid in prognostic assessment for ccRCC patients, with TIMP1 and EMCN representing potential therapeutic targets.
Background:Early-onset cancers, often referred to as cancers that occur in those who are less than 50 years old, are indicated to be more prevalent over past decades. Significantly, early-onset genitourinary cancers could cause more burden for individuals. Asia, home to 60% of the world's population, is undergoing a unique epidemiological transition that makes it a critical model for non-communicable disease (NCD) research. We aimed to demonstrate the incidence, burden, prediction, and risk factors of early-onset bladder cancers (EOBCa), kidney cancers (EOKCa), and prostate cancers (EOPCa) to cast light on early-onset genitourinary tumor prevention and management. Methods:We analyzed data from the Global Burden of Disease Study 2023, sourced from the Global Health Data Exchange (GHDx), covering 48 Asian countries (1990-2023). Age-standardized incidence, mortality, and disability-adjusted life-year (DALY) rates were calculated using population denominators from the United Nations. Temporal trends were quantified using the Estimated Annual Percentage Change (EAPC), with 95% uncertainty intervals (UIs) and P values derived from log-linear regression. Bayesian age-period-cohort (BAPC) modeling projected 2024-2035 incidence. Socio-demographic index (SDI) stratification and sex- and age-specific analyses were performed. Results:We found that (I) in Asia, the incidence of EOBCa [EAPC =-0.96 (95% UI: -1.15 to -0.76)] decreased from 1990 to 2023, while EOKCa [EAPC =1.40 (95% UI: 1.22-1.58)] and EOPCa [EAPC =1.50 (95% UI: 1.31-1.68)] rates increased, with EOPCa projected to continue rising; (II) the spectrum of early-onset genitourinary cancers varied across different SDI levels and countries, while EOKCa had the highest burden among the three cancer types in most regions; (III) males suffered higher risks of incidence and mortality, as well as the increasing trends for early-onset genitourinary cancers than females; (IV) tobacco was the common risk factor for these three early-onset cancers and had shown a continued upward trend between 1990 and 2023. Conclusions:(I) The declining incidence of EOBCa may reflect improved drinking water quality, whereas rising EOKCa and EOPCa incidence is likely driven by greater screening awareness, advances in imaging and biomarker-based detection, and possible overdiagnosis; (II) the increase in EOKCa may also be linked to dietary westernization; (III) the faster decline in disease burden in high-SDI regions likely results from better access to advanced treatments; (IV) early-onset genitourinary cancers exhibit substantial heterogeneity within Asia, and public health strategies should therefore be tailored to the specific epidemiologic profiles of individual countries; (V) sex differences remain evident and may involve hormone-related modulation of carcinogen metabolism; (VI) although early-onset patients are generally healthier, they still face psychological stress, fertility concerns, treatment-related sequelae, and recurrence risk. Notably, cause-specific mortality appears higher in early-onset than late-onset cases, underscoring the need for tailored public health strategies, early screening, and timely intervention.
Background:Though idiopathic urethral strictures are a common form of strictures, little is understood about the pathophysiology leading to their development. This retrospective cohort study sought to analyze the risk of environmental toxins on the development of stricture disease. Methods:Using the Utah Population Database (UPDB), we identified patients with idiopathic urethral strictures born between 1996-2021. Each case was matched 1:1 with controls, based on year of birth and location. Models compared historical air pollution exposure data between the cohorts. Environmental exposures were analyzed in the prenatal period, the first year of life, and the 5 years prior to diagnosis and individual exposures were weighted by the risk of stricture development. Results:We identified 2,048 patients with urethral strictures, diagnosed between 1996 and 2021 and were matched to 1,939 controls for a total cohort of 3,987 men. There was no difference in risk of stricture development for exposure prenatally and within the 5 years prior to diagnosis. The relative risk of cumulative exposures in the first year of life was 1.21 (1.07-1.36, P=0.002) in the development of stricture disease. On univariate analysis, the toxins most associated with stricture development within the first year of life were ethylbenzene, tetrachloroethylene, and molybdenum trioxide. Conclusions:Idiopathic urethral stricture is a common presentation of anterior urethral stricture disease (aUSD) but the mechanism is not well understood. Environmental exposures within the first year of life were associated with an increased risk of the development of a stricture, indicating a potential role within broader inflammatory pathways associated with urethral strictures.
Background:Hydrocelectomy is one of the most commonly performed benign scrotal procedures, but postoperative complications such as hematoma, infection, and wound-related issues remain common.Minimally invasive approaches to hydrocelectomy may reduce perioperative morbidity and healthcare utilization. Minimally invasive approaches may reduce perioperative morbidity and postoperative healthcare utilization. The minimal-incision modified fenestration technique (MIMFeT), performed under local anesthesia, has not been evaluated in a multi-surgeon, real-world setting. We conducted a retrospective cohort study comparing outcomes of MIMFeT vs. standard hydrocelectomy. Methods:We retrospectively reviewed 313 patients who underwent hydrocelectomy [2018-2024]. Patients underwent either MIMFeT or standard hydrocelectomy based on surgeon preference. The primary outcome was 30-day postoperative complications (bleeding, infection, and/or reoperation). Secondary outcomes included unplanned postoperative healthcare utilization and recurrence. Results:Among 313 patients (132 MIMFeT; 181 standard), overall complication rates were lower with MIMFeT (6.1% vs. 13%, P=0.057). Bleeding occurred in 6.1% of standard cases and 0% of MIMFeT cases (P=0.003). Rates of infection and reoperation were similar between groups. Patients undergoing MIMFeT also experienced significantly fewer unplanned postoperative patient contacts, including phone calls, portal messages, and clinic visits (43% vs. 59%, P=0.01). One-year recurrence rates were similar between groups. Conclusions:When compared to standard hydrocelectomy technique, MIMFeT provides comparable efficacy with elimination of bleeding events and reduced postoperative healthcare utilization. These findings support MIMFeT as a particularly advantageous option for patients at elevated bleeding risk and as a scalable, office-based alternative to standard hydrocelectomy that may improve patient outcomes while reducing healthcare resource utilization.
Background:Prostate cancer (PCa) remains a prevalent male malignancy, imposing significant health burdens and socio-economic challenges globally. While early diagnosis is critical for effective intervention, current clinical strategies lack precision in risk stratification and treatment response prediction. This study aimed to identify key machine learning-derived biomarkers for PCa and to comprehensively evaluate the diagnostic, prognostic, and immune-related significance of HOXC4. Methods:In this study, we integrated 258 samples from four Gene Expression Omnibus (GEO) datasets to identify differentially expressed genes (DEGs) between tumor and normal tissues. Robust feature selection was performed using the intersection of least absolute shrinkage and selection operator (LASSO) regression, random forest, and support vector machine recursive feature elimination (SVM-RFE) algorithms. Ten machine learning models were constructed, with the optimal model interpreted using SHapley Additive exPlanations (SHAP) analysis. These findings were further integrated with gene set enrichment analysis (GSEA), CIBERSORT-based immune infiltration analysis, independent external validation in the Memorial Sloan Kettering Cancer Center (MSKCC) cohort, and pan-cancer analysis. Results:A total of 123 DEGs were identified, from which five key feature genes (RAB17, FAM107A, COL9A1, HOXC4, and TRPM4) were selected. Among the ten models, Partial Least Squares (PLS) exhibited superior diagnostic performance, with an area under the receiver operating characteristic curve (AUC) of 0.977. SHAP interpretation highlighted HOXC4 as a positive risk-associated feature and prognostic candidate. High HOXC4 expression was associated with poor progression-free survival (P=0.02), and this prognostic association was further validated in the independent MSKCC cohort. GSEA indicated that HOXC4-high phenotypes were enriched in cellular energy metabolism and protein processing pathways, whereas HOXC4-low phenotypes showed immune-related enrichment patterns. Immune infiltration analysis suggested that high HOXC4 expression was associated with an immunosuppressive tumor microenvironment characterized by increased regulatory T cell and M2 macrophage infiltration. HOXC4 also showed significant correlations with several immune checkpoint molecules, including CD40 and SIGLEC-15. Furthermore, pan-cancer analysis validated the heterogeneous expression patterns of HOXC4 across diverse tumor types. Conclusions:Identified via interpretable machine learning, HOXC4 serves as a promising diagnostic and prognostic biomarker linked to immune suppression and metabolic reprogramming. This study highlights the potential of combining machine learning-driven feature selection with biological validation to optimize personalized management in PCa.
Background:Ureteral reimplantation (UR) is the standard treatment for distal ureteral stricture, yet postoperative anastomotic restenosis impairs outcomes, with conventional imaging unable to quantify urinary tract obstruction and dysfunction. This study aimed to explore the clinical value of the modified Whitaker test in ruling out upper urinary tract obstruction and assisting postoperative efficacy evaluation after UR. Methods:A total of 100 patients (105 renal units) who underwent UR from January 2022 to December 2025, with preoperative nephrostomy tube placement and postoperative modified Whitaker test, were prospectively enrolled. Combined standing and supine position examination, gradient perfusion (5~25 mL/min) pressure measurement combined with imaging development classification was used. Patients were classified into three types based on the pyelovesical pressure difference and ureteral peristalsis. Perioperative and follow-up data were collected to evaluate the curative effect. Results:Among patients undergoing modified Whitaker test after UR, 73 cases (69.52%) were Type I, 24 cases (22.86%) Type II, and 8 cases (7.62%) Type III. The median follow-up time was 12.63 (6.92, 25.80) months. The overall surgical efficacy rate was 92.38% (97/105), and the objective efficacy rate was 98.10% (103/105). In the modified Whitaker test, the median intrapelvic pressure was 20.00 (16.00, 25.50) cmH2O, the median intravesical pressure was 14.00 (9.50, 20.00) cmH2O, and the median pressure difference was 5.00 (2.00, 9.00) cmH2O. The unobstructed results of the modified Whitaker test were consistent with successful overall postoperative efficacy in 85.71% (90/105) of renal units and with successful objective postoperative efficacy in 91.43% (96/105) of renal units. All patients successfully completed the modified Whitaker test without any postoperative discomfort. Conclusions:UR the modified Whitaker test exhibits excellent negative predictive performance and favorable consistency with mid-term postoperative follow-up outcomes. It serves as a reliable adjunctive tool for ruling out upper urinary tract obstruction and guiding nephrostomy tube removal after UR.
Background and Objective:Metabolic alterations in chronic diseases such as dyslipidemia, type 2 diabetes mellitus (T2DM), and obesity disrupt hormonal regulation and perpetuate inflammation and oxidative stress across multiple systems, including the reproductive system. Focusing on the physiological functions of glucagon-like peptide-1 (GLP-1) and the organ-wide effects of its analogues, this review clarifies their mechanisms of action and long-term consequences, particularly regarding weight loss, oxidative stress, inflammation, and endothelial dysfunction. Methods:A narrative literature search was performed in PubMed, Science Direct, and Web of Science databases, with the search date set on March 20, 2026 using Medical Subject Headings (MeSH) terms such as GLP-1, GLP-1RA, obesity, male sexual dysfunction, and employing the Boolean operators "AND" and "OR" to retrieve relevant information about metabolic syndrome, body mass index (BMI), male infertility, endothelial dysfunction, hypogonadism and erectile dysfunction (ED). Key Content and Findings:The primary emphasis is on the impact of GLP-1 analogs in obesity, highlighting their potential for treating hypogonadism and ED, and establishing their role as a therapeutic approach that addresses key mechanisms underlying metabolic and reproductive pathology. This review examines how GLP-1 analogue treatment, initially developed for T2DM, is now being extensively repurposed for patients with obesity to address these systemic metabolic disturbances, and also examines its effect on male sexual function, ED hypogonadism, and infertility. Conclusions:Even though these drugs were initially administered to improve metabolic control in patients with T2DM, numerous studies have demonstrated that the beneficial effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) extend beyond glucose and weight control, including positive effects on male sexual and reproductive functions.
