Translational andrology and urology最新文献

Background and objective: As more clinicians adopt alternatives to radical cystectomy (RC) for Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC), understanding how these approaches are applied in practice is essential. To explore global treatment trends, we analyzed regional surveys on BCG-unresponsive NMIBC management.

Methods: A structured literature review identified four published provider-based surveys, along with a fifth, unpublished survey conducted by our team in collaboration with Romanian colleagues. These included an international survey (January-May 2019) of 508 physicians from eight countries (Europe, Japan, and China); a 2022 U.S. national survey (n=259); and a regional Arab survey (October-November 2023; n=106 across 14 countries). Additional national surveys were conducted in Saudi Arabia (n=19; April-May 2024) and Romania (n=216; May-June 2025). Responses were grouped by key questions and analyzed using descriptive statistics.

Key content and findings: For treating BCG-unresponsive disease, urologists in the U.S. and Saudi Arabia mainly followed guidelines from the American Urological Association (AUA). Romanian urologists, by contrast, primarily adhered to European Association of Urology (EAU) guidelines. Across Arab countries, practices reflected a mix of recommendations from the EAU, AUA/Society of Urologic Oncology (SUO), and the National Comprehensive Cancer Network (NCCN). Treatment approaches for BCG-unresponsive disease varied widely across regions. Intravesical chemotherapy was most frequently used in the U.S. and China, whereas RC was the preferred option in Romania and many Arab countries. In Japan, clinicians favored watchful waiting, resection, and surveillance, with limited use of RC. European physicians similarly leaned toward conservative strategies, mirroring Japanese urologist approach. Preferences for intravesical chemotherapy agents differed by region: gemcitabine (Gem) was commonly used in the US and Arab countries; epirubicin and doxorubicin were favored in China; mitomycin C (MMC) was preferred in Europe. While most urologists were familiar with gemcitabine/docetaxel (Gem/Doce), its actual use in clinical practice remained limited. Barriers to intravesical chemotherapy use in this setting were mainly due to unclear clinical guidelines. Notably, at the time of the surveys, newly Food and Drug Administration (FDA)-approved therapies like nadofaragene and pembrolizumab were rarely used.

Conclusions: Global practice patterns for BCG-unresponsive disease vary widely across regions, highlighting the need for a more unified, consensus-driven approach to the use of evolving bladder-sparing therapies and clinical guidelines.

Background: Metabolomics has proven to be a useful science for obtaining biomarkers in prostate cancer. In this work, urine samples were analyzed by nuclear magnetic resonance (NMR) spectroscopy to identify potential urinary biomarkers associated with biochemical recurrence in prostate cancer.

Methods: Urine samples were obtained from patients undergoing transrectal prostate biopsy after prostate massage. Patients were classified as with or without biochemical recurrence after having received prostate cancer treatment. All spectra were acquired using a Bruker Avance III DRX 600 spectrometer. Univariate and multivariate analysis were performed with metabolites and clinical variables to predict tumor presence.

Results: Data were collected from 70 patients treated for prostate cancer, 16 of whom developed biochemical recurrence within 5 years following treatment, with an average time to diagnosed recurrence of 25.68±15.39 months. After establishing a predictive model with the 25 most influential metabolites in Partial Least Squares Discriminant Analysis (PLS-DA analysis), a predictive model of biochemical recurrence was obtained with an area under the curve of 0.95, a sensitivity of 80%, specificity of 98%, positive predictive value (PPV) of 92% and a negative predictive value (NPV) of 96%. Metabolites derived from amino acid metabolism and glycolysis featured most predominantly in this model.

Conclusions: The metabolic profile in urine can be used to construct a model with good discrimination for predicting the development of biochemical recurrence. The molecules highlighted herein frequently belong to amino acid metabolism and glycolysis.

Background: The global incidence of kidney stones (KS) has increased markedly, affecting approximately 9% of the world's population. The well-established role of high fat diet (HFD) in promoting metabolic disorders through mechanisms such as chronic inflammation and gut dysbiosis, combined with clinical observations from lithogenic dietary patterns like the ketogenic diet, suggests that HFD may represent a significant yet underexplored risk factor for KS formation. This study aimed to explore the association between HFD and KS.

Methods: This cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey (NHANES) 2007-2020. Questionnaire and interview data were used to obtain information on HFD and the history of KS. Univariate and multivariate logistic regression analyses were conducted to explore the association between HFD and KS.

Results: A total of 31,059 participants were included in the study, with a 9.7% (3,003/31,059) prevalence of KS. Regression analysis demonstrated that HFD was associated with a significantly increased risk of KS [odds ratio (OR) =1.23, 95% confidence interval (CI): 1.06-1.42, P=0.008]. This association persisted after adjustment for potential confounders. Furthermore, subgroup analyses identified no significant effect modifications.

Conclusions: Our study revealed a positive association between HFD and the increasing risk of KS. However, larger prospective clinical studies are still needed to verify the conclusions.

Background: Renal cell carcinoma (RCC), a frequently diagnosed tumor type, serves as the focus of our investigation into the functional role of the alanine serine cysteine transporter 2 (ASCT2) gene and its potential molecular mechanisms. This study elucidates ASCT2's function in the pathogenesis of RCC and its underlying molecular mechanisms.

Methods: Individuals diagnosed with RCC were collected from Gaoxin Branch of the First Affiliated Hospital of Nanchang University. Quantitative polymerase chain reaction (qPCR), fluorescence immunostaining, proteomic blotting analysis, and gene overexpression were employed to elucidate the contribution of ASCT2 in sustaining the malignant phenotype of RCC and to dissect its influence on the pyroptosis.

Results: ASCT2 RCC specimens exhibited reduced messenger ribonucleic acid (mRNA) and protein expression levels. Overall survival rates and recurrence-free intervals with high expression of ASCT2 in individuals diagnosed with RCC were higher than those of ASCT2 low expression. ASCT2 gene overexpression inhibited cellular proliferation kinetics and migratory capacity, while suppressing 5-ethynyl-2'-deoxyuridine (EdU) incorporation in vitro. ASCT2 gene inhibition increased cellular proliferation and motility rate, and promoted EdU-labelled cells within the cultured system. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) agonist simultaneously counteracted the influences of ASCT2 siRNA (si-ASCT2) on NLRP3-GSDMD protein complex expressions and cellular proliferation in an in vitro system. NLRP3 inhibitor reversed the impact of ASCT2 on NLRP3/GSDMD protein expressions and in an in vitro cellular proliferation assay. NLRP3 inhibitor increased ASCT2-mediated impacts on migration rate and EdU-positive cells in cultured cell system. NLRP3 agonist reduced the effects of si-ASCT2 on cellular migratory capacity and EdU incorporation in the cultured system.

Conclusions: This research focuses on ASCT2's role in RCC, and specifically examines ASCT2-mediated modulation of the NLRP3 inflammasome and pyroptosis. ASCT2 knockdown in RCC cells inhibited proliferation and migration, while overexpression of ASCT2 thereby enhanced pyroptosis, providing a new model for RCC pathogenesis and treatment.

Background: Musashi 2 (MSI2) exhibits oncogenic effects in various solid tumors. However, its mechanism of action in kidney renal clear cell carcinoma (KIRC) remains unclear. Our study objective is to explore the expression of MSI2 in KIRC and its relationship with the tumor microenvironment (TME).

Methods: We analyzed MSI2 expression at the messenger ribonucleic acid (mRNA) and protein levels using the TIMER2.0 and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) databases, respectively. We also validated the expression and role of MSI2 in renal cells in cell-based experiments and examined the relationship between MSI2 expression and prognosis and the immune microenvironment. Furthermore, we performed an enrichment analysis and constructed regulatory networks for MSI2 to explore its functions and regulatory mechanisms. Finally, we conducted single-cell RNA sequencing (scRNA-seq) to identify key cells in KIRC and a pseudotemporal analysis to investigate their differentiation trajectories.

Results: While MSI2 and its mRNA are typically upregulated in other cancers, they are downregulated in KIRC. A Kaplan-Meier (KM) analysis showed that KIRC patients with high MSI2 expression exhibited improved survival rates. MSI2 was mainly expressed in renal tubules in normal renal tissue and not in KIRC cells. Knocking down MSI2 promoted KIRC cell proliferation, invasion, and migration in vitro, and there was a correlation between MSI2 expression and immune cells and checkpoints. The scRNA-seq analysis indicated that T cells are key players in KIRC. A dynamic MSI2 expression pattern was observed during T-cell differentiation, showing an upward trend in the medium term before leveling off.

Conclusions: Our results suggest that MSI2 plays an antitumor role in KIRC by regulating T-cell function. They also indicate that MSI2 is involved in hydrogen ion secretion in renal tubular epithelial cells and that it may be a differentiation and maturation marker in these cells.

Background and objective: Phosphodiesterase-5 inhibitors (PDE5i) remain the first-line treatment for erectile dysfunction (ED). However, nearly 30% of ED patients exhibit inadequate responses or intolerable side effects. Emerging evidence indicates that mitochondrial dysfunction, characterized by bioenergetic failure, oxidative stress, and apoptosis, plays a pivotal role in the pathogenesis of ED.

Methods: This review employed a systematic literature search to comprehensively synthesize evidence on mitochondrial transplantation (MT) and mitochondrial dysfunction in the context of ED. Databases searched included PubMed, Embase, and Web of Science, covering publications from January 1, 2000 to July 1, 2025. Search strategies utilized keywords such as "mitochondrial transplantation", "erectile dysfunction", "mitochondrial dysfunction", "ROS", and "apoptosis", combined with Boolean operators (e.g., "mitochondrial transplantation AND erectile dysfunction" or "mitochondrial dysfunction OR apoptosis AND ED").

Key content and findings: The search initially identified 1,247 abstracts, from which 289 full-text articles were retrieved and evaluated for eligibility, ultimately yielding 58 key references incorporated into this review. This review systematically examines the potential of MT as a novel therapeutic strategy in ED. In preclinical ED models, MT restored adenosine triphosphate (ATP) levels, attenuated reactive oxygen species (ROS) accumulation, inhibited apoptotic signaling, and improved erectile hemodynamics in cavernous smooth muscle cells. Furthermore, we discuss recent advancements in mitochondrial isolation techniques, delivery optimization strategies (including nanocarriers and hydrogels), and immunological safety considerations for both autologous and allogeneic transplantation.

Conclusions: Although clinical translation faces challenges such as scalable production, dosage standardization, and long-term immunocompatibility, MT holds promise as a mechanism-based therapy for refractory ED, offering new insights beyond conventional hemodynamic approaches.

Background: Prostate cancer (PCa) is a common malignancy among men, marked by pronounced clinical and molecular heterogeneity. Metabolic reprogramming and immune evasion are recognized as critical factors in PCa progression; however, the underlying regulatory mechanisms remain insufficiently characterized. This study aimed to elucidate the interaction between metabolic reprogramming and the immune microenvironment in PCa through a multi-omics approach, and to identify key metabolic biomarkers with prognostic significance.

Methods: A multi-omics analytical framework was used, integrating single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) data from publicly available datasets. Following quality control and clustering using Seurat and Signac, cell types were annotated. Key metabolic genes were identified through combined gene activity and chromatin accessibility analyses. Immune cell infiltration was estimated using Cell Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), and functional pathway enrichment was assessed using gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). Furthermore, using The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) cohort, a prognostic nomogram was constructed by integrating ENO1 and CKB expression with clinical parameters [age, pathological tumor stage (T stage), node stage (N stage)] via multivariate Cox regression. Gene expression differences across N stages (N0 vs. N1) were assessed using the Wilcoxon rank-sum test.

Results: Six distinct cell subtypes were delineated, along with enrichment of key metabolic pathways, particularly glycolysis and oxidative phosphorylation associated with tumor progression. The metabolic regulators ENO1 and CKB demonstrated significant involvement in both metabolic reprogramming and modulation of the immune microenvironment. Their expression levels were positively correlated with the infiltration of immune cells, including CD8⁺ T lymphocytes and macrophages. The prognostic nomogram demonstrated that CKB contributed substantially to the total points, indicating strong prognostic relevance. Stratified analysis revealed ENO1 was significantly upregulated in N1 tumors (P<0.01), while CKB was higher in N0 tumors (P<0.05).

Conclusions: ENO1 and CKB serve as clinically meaningful markers-ENO1 indicating metastatic potential and CKB predicting overall prognosis-while also representing promising therapeutic targets. These findings bridge molecular metabolism-immune crosstalk with clinical outcomes, offering novel perspectives for integrating metabolic intervention and immunotherapy in PCa management.

Background: Venous thromboembolism (VTE) is a feared complication in the perioperative period. Patients undergoing urethroplasty are placed in high lithotomy for an extended period, which is known to increase venous stasis, thus possibly increasing VTE risk. Even then, rates of VTE in urethroplasty patients have been shown to be low. We sought to evaluate the applicability of the 2005 Caprini risk assessment module in predicting VTE risk for patients undergoing urethroplasty.

Methods: We performed a retrospective cohort study of patients who underwent urethroplasty at our institution from 2019-2024. Ninety-day perioperative outcomes were collected, and patients who had thromboembolic events were isolated for reporting. Risk factors for VTE were quantified using the 2005 Caprini risk assessment model.

Results: There were 222 patients eligible for inclusion. Overall, the average Caprini risk score was 4.78, which is between high risk (Caprini score 3-4) and highest risk (score 5-6). Of the patients, 37.8% were categorized as high risk and 55% of patients were categorized as highest risk. Despite this, only one patient had a thromboembolic event; he had a Caprini score of 3.

Conclusions: In our cohort, 92.8% of patients were high risk or highest risk for VTE by Caprini risk score, while only a single patient had a thromboembolic event. Although the Caprini score is well accepted for quantifying thromboembolic risk in hospitalized patients, it appears to have limited applicability for patients undergoing urethroplasty, as it overestimates the risk of VTE in this population. Caprini score alone should not be used to guide treatment with chemoprophylaxis in this population.