To evaluate the therapeutic efficacy and clinical applicability of the novel P100 extracorporeal shock wave therapy (ESWT) device in the treatment of type IIIB chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). In this randomized, single-blind, sham-controlled trial, 83 patients with type IIIB CP/CPPS were enrolled and randomly assigned to either the P100 treatment group (n = 51) or the control group (n = 32). Patients in the treatment group received four weekly low-intensity ESWT sessions (0.2 mJ/mm²), while the control group received identical procedures with shock transmission blocked. The primary endpoint was the clinical response rate (≥6-point reduction in NIH-CPSI score) at week 4; week 8 outcomes were further analyzed to assess sustained efficacy. Secondary endpoints included IPSS, IIEF-5, and VAS scores. At week 4, the clinical response rate was 78.4

Clear cell renal cell carcinoma (ccRCC) is a common urological malignancy with limited therapeutic options for advanced disease. Aberrant DNA methylation and dysregulated ferroptosis have both been implicated in ccRCC progression, yet the mechanisms connecting these processes remain incompletely defined. Here, we identify ZBTB10 as a suppressor of ccRCC progression that transcriptionally represses GPX4, a central inhibitor of ferroptosis. Mechanistically, ZBTB10 recruits DNMT1 to the GPX4 promoter, thereby increasing promoter methylation and silencing GPX4 expression. We further define a self-regulatory ZBTB10/DNMT1/FBXW4 loop that maintains this epigenetic state. FBXW4 acts as an E3 ubiquitin ligase that promotes DNMT1 degradation and directly ubiquitinates ZBTB10 to reduce its stability. In turn, ZBTB10 recruits DNMT1 to the FBXW4 promoter, increases promoter methylation, and suppresses FBXW4 transcription. This self-regulatory circuit stabilizes both ZBTB10 and DNMT1, sustains low GPX4 expression, and promotes ferroptosis in ccRCC cells, as evidenced by increased lipid peroxidation and reactive oxygen species accumulation. Together, these findings reveal an epigenetic mechanism linking ZBTB10 to ferroptosis in ccRCC and suggest that targeting the ZBTB10/DNMT1/FBXW4/GPX4 axis may provide a therapeutic strategy for limiting ccRCC progression.

114 Background: Currently, the clinical outcomes of poly(ADP-ribose) polymerase (PARP) inhibitors varied widely in metastatic castration-resistant prostate cancer (mCRPC) patients with different HRR gene alterations (HRRalt). It is urgent and necessary to develop a novel biomarker for predicting the clinical efficiency of PARP inhibitors in the mCRPC patients. Tissue-based immunofluorescence (IF) assay for the functional RAD51 foci is emerging as a promising biomarker for assessing homologous recombination deficiency (HRD). However, the predictive value of the RAD51 foci using the IF assay for mCRPC patients following PARP inhibitors remains uncertain. This multicenter real-world study was to evaluate the predictive value of the RAD51 foci in the IF assay in mCRPC patients with HRRalt and not-altered HRR after the PARP inhibitor treatment. Methods: The multicenter real-world study involved 217 consecutive patients who had received the next-generation sequencing (NGS) and PARP inhibitor treatment from three tertiary referral hospitals. RAD51 foci were quantified in formalin-fixed, paraffin-bedded, untreated tumor specimens by IF. We assessed progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. Potential factors influencing PFS and OS were compared between the treatment arms using Cox proportional-hazards models. Prediction models were established to compare their predictive value in PFS and OS. The prostate-specific antigen (PSA) response and the treatment effect across subgroups were also evaluated. Results: RAD51 foci had significantly better predictive efficacy than the BRCA1/2alt and HRRalt, with a significantly higher predictive power in PFS and OS (RAD51: area under the curve [AUC]: PFS: 0.795; OS: 0.765, BRCA1/2alt: AUC: PFS: 0.669; OS: 0.628, HRRalt: AUC: PFS: 0.635; OS: 0.566). In the overall cohort, median PFS and OS were significantly longer in the RAD51-Low group than the RAD51-High group (PFS: 9.0 vs 2.0 mo; hazard ratio [HR] 0.25, 95% confidence interval [CI] 0.18–0.35; p < 0.01; OS: 25.0 vs 11.0 mo; HR 0.34, 95% CI 0.22–0.43; p < 0.01). In the not-altered HRR cohort, the RAD51-Low group also had significantly longer survival than the RAD51-High group (PFS: 6.5 vs 1.0 mo; HR 0.21, 95% CI 0.11–0.40; p < 0.01; OS: 24.0 vs 8.0 mo; HR 0.32, 95% CI 0.17–0.56; p < 0.01). PSA responses were also significantly higher in the RAD51-Low group than the RAD51-High group. Limitations include its retrospective design and small sample size. Conclusions: In mCRPC patients treated with PARP inhibitors, RAD51 foci demonstrates a superior predictive value for clinical outcomes compared to HRRalt and BRCA1/2alt. RAD51 foci also serve as a pivotal biomarker for extending the PARP inhibitor efficacy to not-altered HRR patients. A large-scale prospective randomized controlled trial is needed to confirm these results.

Objective This study aims to develop and validate a comprehensive scoring system based on anatomical and clinical parameters to predict surgery duration, operative blood loss, and urinary control in patients undergoing laparoscopic radical prostatectomy (LRP). Methods This retrospective analysis included 361 patients with prostate cancer who underwent surgery performed by Xudong Yao. The study evaluated the correlation of variables such as height/weight ratio (HWR), prostate/pelvis ratio (PPR), retzius space (RS) size, intravesical prostatic protrusion (IPP), and prostate volume (PV). Based on these factors, the RRRIV scoring system was developed. The correlation between these variables and key outcomes (surgery duration, operative blood loss, and urinary function recovery) was then assessed in relation to the RRRIV score. Results Correlation analysis revealed significant positive associations between the RRRIV score and operative time (95% CI = 0.229(0.129-0.325), p < 0.001), operative blood loss (95% CI = 0.305(0.209-0.386), p < 0.001), and recovery of urinary function (95% CI = 0.381(0.289-0.466), p < 0.001). Furthermore, intergroup comparison showed that the medium and high-risk groups had significantly greater intraoperative blood loss, longer operative duration, and delayed recovery of urinary continence compared to the low-risk group. For the primary outcomes, the model demonstrated good discrimination, with an area under the curve ≥0.6. Conclusions The RRRIV scoring system provides a reliable method for predicting surgery duration, intraoperative blood loss, and recovery of urinary function in LRP, aiding surgeons in making more informed decisions during preoperative planning and patient discussions.

Objective Recurrence is not rare for high-risk non-muscle invasive bladder cancer (HR-NMIBC) after bacillus Calmette-Guérin (BCG) immunotherapy. We aimed to introduce disitamab vedotin (DV) to BCG and evaluate its efficacy. Methods Consecutive BCG-naïve patients with HER2-expressing HR-NMIBC receiving transurethral resection followed by BCG alone or combined with intravenous DV (BCG + DV) were enrolled in this retrospective study. Relationship with recurrence-free survival (RFS) was analyzed using log-rank and Cox regression analyses. Given the differences in baseline patient characteristics, propensity score matching (PSM) was also implemented to address the heterogeneity. Results A total of 117 patients with a median follow-up of 19 months were finally evaluated (BCG: 85, BCG + DV: 32). Compared with BCG group, BCG + DV group had significantly higher proportions of multifocal lesions (81.2%/57.6%), HER2 2+/3+ tumors (87.6%/51.8%), very-high-risk (VHR) disease (31.3%/14.1%) and tumor residue after initial resection (40.6%/21.2%). The 3-month complete response rates of BCG + DV and BCG groups were 100% and 91.8%, respectively (p = 0.187). BCG + DV yielded superior RFS (1-year: 92.3%, 2-year: 86.5%) versus BCG (1-year: 80.0%, 2-year: 64.6%; p = 0.041), and this advantage was pronounced in HER2 2+/3+, VHR and residual disease subgroups. Independent risk factors of recurrence after BCG monotherapy included large tumor, HER2 2+/3+ and residual disease. Combination treatment emerged as the strongest predictor of improved RFS for the entire cohort. After PSM, BCG + DV still rendered significantly better RFS in both entire matched cohort and aforementioned subgroups. Conclusion Addition of DV to BCG provided favorable early response and superior intermediate-term RFS for BCG-naïve HER2-expressing HR-NMIBC, highlighting its prospect in HR-NMIBC management.

Background:Renal cell carcinoma (RCC) progression is closely linked to dysregulation of the ubiquitin-proteasome system, particularly aberrant ubiquitination processes governing protein degradation and cell cycle control. As a pivotal E3 ubiquitin ligase, COP1 mediates substrate-specific ubiquitination to regulate protein stability. However, its functional role in RCC remains poorly characterized. This study investigates how COP1 drives RCC malignancy and explores its underlying molecular mechanisms. Methods:We analyzed the expression of COP1 in RCC cells and its relationship with patient overall survival (OS) in databases. The CCK-8 assay was used to detect the effect of COP1 on the proliferation of RCC cells, while the Transwell assay was used to assess the impact of COP1 on the migration and invasion of RCC cells. We employed mass spectrometry, co-immunoprecipitation, Western blot, and RT-qPCR to explore the target proteins that interact with COP1 and their interaction modes. After inducing with ferroptosis inducers, we measured the effect of COP1 on lipid ROS levels in RCC cells. Finally, we validated the role of COP1 in RCC using in vivo experiments. Results:COP1 was significantly correlated with poor patient prognosis. Functional studies demonstrated that COP1 overexpression markedly increased RCC cell proliferation by 65% (786-O) and 58% (ACHN) (p < 0.001) and enhanced migration/invasion (p < 0.01), while COP1 knockdown suppressed these malignant phenotypes by 40-50%. Mechanistically, COP1 directly bound ACSL4 and promoted its K48-linked ubiquitination, reducing ACSL4 protein stability by 70% (p < 0.001) and suppressing ferroptosis, as evidenced by decreased lipid ROS levels (p < 0.01) and reversal of ferroptosis inhibition by ferrostatin-1. In vivo, COP1 overexpression accelerated tumor growth in xenograft models, with a 2.5-fold increase in tumor volume compared to controls (p < 0.001), accompanied by reduced ACSL4 expression and elevated Ki67 proliferation index. These effects were further amplified by the ferroptosis inhibitor ferrostatin-1, underscoring COP1's role in driving tumor progression through ferroptosis suppression. Conclusion:Our study establishes COP1 as a critical driver of RCC progression by suppressing ferroptosis through ubiquitin-mediated degradation of ACSL4, thereby providing a novel theoretical foundation for targeted therapeutic strategies in RCC.

Lymphatic metastasis is recognized as the leading manner of metastasis in bladder cancer (BLCa), but hematogenous metastasis accounts for a majority of cancer-associated deaths. The past two decades have witnessed tremendous attention in long non-coding RNAs (lncRNAs), which are a new hope for the development of targeted drug therapy for metastatic cancers; however, the underlying mechanism of lncRNAs involved in BLCa hematogenous metastasis remains to be elucidated. Here, we identified BLCa-associated transcript 3 (BLACAT3), a lncRNA, which was aberrantly upregulated in BLCa and corelated with poor prognosis of patients with muscle-invasive bladder cancer. Methodologically, m6A epitranscriptomic microarray, RNA sequencing and mass spectrometry (MS) were used to screen the key molecules of the regulatory axis. Functional assays, animal models and clinical samples were used to explore the roles of BLACAT3 in BLCa in vitro and in vivo. Mechanistically, m6A modification contributes to BLACAT3 upregulation by stabilizing RNA structure. BLACAT3 recruits YBX3 to shuttle into the nucleus, synergistically enhances NCF2 transcription, and promotes BLCa angiogenesis and hematogenous metastasis by activating downstream NF-κB signaling. Our findings will develop prognosis prediction tools for BLCa patients and discover novel therapeutic biological targets for metastatic BLCa.

The association between prostate cancer (PCa) and environmental heavy metal exposure is recognized, but molecular mechanisms for mixed metal effects remain unclear. This study employed bioinformatics and NHANES data analysis (logistic regression, dose-response, correlation) to investigate the relationship between blood lead, cadmium, mercury, and mixed metals with self-reported PCa. Significant associations were found. Weighted Quantile Sum (WQS) and quantitative g-computation (qgcomp) analyses confirmed synergistic effects of the metal mixture. Comparative Toxicogenomics Database (CTD) screening identified CNOT3 as a key response gene to lead/mercury. Functional enrichment analysis implicated CNOT3 in cancer pathways. TCGA data validated CNOT3 overexpression in PCa and its prognostic value. Critically, in vitro and in vivo experiments established CNOT3 as a novel oncogene, with its knockdown significantly inhibiting tumor growth (p < 0.001). This study is the first to demonstrate that mixed heavy metal exposure synergistically increases PCa risk and identifies CNOT3 as a biologically significant biomarker and therapeutic target in heavy metal-related PCa development.

It is well established that ALKBH5 plays a crucial role in the malignant progression of various types of tumors. However, its role in clear cell renal cell carcinoma (ccRCC) and the underlying regulatory mechanisms remain unclear. In this study, we employed a range of techniques, including protein blotting, real-time quantitative PCR, silver staining, mass spectrometry, co-immunoprecipitation (Co-IP), GST-pull down, and immunofluorescence, to investigate the functions of ALKBH5 in ccRCC and elucidate the specific mechanisms involved. Our results demonstrated that ALKBH5 expression was significantly upregulated in ccRCC. In vitro experiments revealed that ALKBH5 promoted tumor proliferation, invasion, migration, and stemness. In vivo, ALKBH5 was shown to enhance tumor growth and lung metastasis. Mechanistically, our studies suggest that ALKBH5 accelerates the malignant progression of ccRCC by binding to heterogeneous nuclear ribonucleoprotein D-like (HNRNPDL), facilitating the nuclear translocation of MEK, ERK, and p38, and activating downstream targets such as c-Myc and PCNA.

Background Aldolase B (ALDOB), functioning as a glycolytic enzyme, exhibits a controversial role in malignancies and demonstrates dual potential as both a tumor suppressor and cancer-promoting enzyme. Nevertheless, it is still uncertain if there is a relationship between ALDOB levels, prognosis, and tumor-infiltrating lymphocytes in clear cell renal cell carcinoma (ccRCC). Objective This study aims to investigate the prognostic significance of ALDOB in ccRCC and its potential association with clinicopathological features and tumor immune microenvironment. By integrating multi-database bioinformatics analysis and experimental validation, we seek to elucidate the role of ALDOB in ccRCC progression and its potential as a predictive biomarker. Methods To ascertain the potential link between ALDOB level, clinical parameters, and overall survival (OS) in individuals with ccRCC, we employed diverse databases, which include The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), the Human Protein Atlas (HPA) and The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN). Furthermore, an in-depth analysis of the link between tumor-infiltrating immune cells (TIIC) and ALDOB was carried out using the TIMER database. Immunohistochemistry (IHC) was applied to identify the ALDOB level in a tissue microarray. Results The expression of ALDOB demonstrated a strong association with pathologic T stage, pathologic N stage, pathologic M stage, histologic grade, and gender. Decreased ALDOB level was linked to unfavorable disease-specific survival (DSS), progress free interval (PFI), and OS outcomes (p < 0.001). Subsequently, a marked link was observed between ALDOB level and a heightened presence of infiltrating Treg, Th17 cells, and neutrophils in ccRCC. IHC showed that the ALDOB level in ccRCC samples was notably diminished relative to that in the adjacent normal tissues. Conclusions As a prospective predictive indicator for individuals with ccRCC, reduced ALDOB level exhibited strong correlations with clinical characteristics, unfavorable outcomes, and immune infiltration in individuals with ccRCC.

This study aims to compare and evaluate the clinical efficacy of laparoscopic capsule-preserving resection (LCPR) and laparoscopic partial nephrectomy (LPN) in the treatment of renal angiomyolipoma (RAML). Multivariate regression analysis was employed to identify patient characteristics that are most suited for LCPR. We retrospectively analyzed the clinical data of 209 patients diagnosed with RAML and treated surgically at our hospital between January 2010 and December 2023. The patients were divided into two groups: 102 in the LCPR group and 109 in the LPN group. Preoperative factors (e.g., age, sex, glomerular filtration rate (GFR), and tumor location), intraoperative factors (e.g., ischemia time and blood loss), and postoperative outcomes (e.g., extubation time, hospitalization duration, and renal function) were recorded. Chi-square tests, independent sample t-tests, and rank-sum tests were applied where appropriate. Logistic regression analysis was used to identify patient characteristics associated with suitability for LCPR. No significant differences were observed in the preoperative baseline characteristics (age, sex, or tumor size) between the two groups (P > 0.05). All surgeries in the LCPR group were successfully completed, and no patients required conversion to open surgery. The average operation time was 118.56 ± 44.49 min, the warm ischemia time was 17.40 ± 7.51 min, and the intraoperative blood loss was 197.35 ± 282.64 ml, all of which were significantly lower than in the LPN group (P < 0.05). The incidence of postoperative complications in the LCPR group was 21.6

197 Background: Our previous research confirmed that for metastatic castration-resistant prostate cancer (mCRPC) patients with DNA damage repair (DDR) deficiency who have developed resistance to prior abiraterone, the combination of olaparib and abiraterone improves survival compared to olaparib monotherapy. However, further research is needed to identify subgroups who may benefit from olaparib alone or in combination with abiraterone, and to pinpoint risk factors significantly associated with poor prognosis in these patients. This study aims to explore the value of androgen receptor (AR) variant and androgen receptor activity (AR-A) at the transcriptomic level in evaluating the prognosis of mCRPC patients treated with olaparib alone or in combination with abiraterone. Methods: This study included 142 mCRPC patients who underwent targeted next-generation sequencing. Among them, 73 patients received olaparib monotherapy, while 69 patients received combined therapy. Bulk transcriptome sequencing was performed for 62 patients. Kaplan-Meier analysis was employed to evaluate patients' progression-free survival (PFS) and overall survival (OS). The AR-A score was calculated through a weighted linear sum of nine typical AR transcriptional target genes. Results: The combination of olaparib and abiraterone significantly improved PSA response and survival (PFS and OS) compared to olaparib monotherapy. Among mCRPC patients receiving olaparib monotherapy, those without AR pathogenic variant (AR-PV) had superior PFS and OS compared to those with AR-PV (median PFS: 5 months vs 3 months; median OS: 23 months vs 17 months). At the transcriptome level, for mCRPC patients receiving combined therapy, the average AR-A group exhibited better PFS and OS compared to the lower AR-A group (median PFS: 7 months vs 3 months; median OS: 17 months vs 10 months). Conclusions: For mCRPC patients treated with olaparib monotherapy, the absence of AR-PV can obtain better survival benefits. For patients treated with combined therapy, the average AR-A indicates a better survival benefit. For mCRPC patients with AR-PV or lower AR-A score, large-scale prospective randomized controlled clinical trials are needed to further explore therapy strategies that can improve their prognosis.

AbstractBackgroundIn a multi‐institutional clinical study, we assessed the prognostic significance of a novel indicator preoperative peripheral blood immune (PBIS) scores that combined ratios of preoperative lymphocyte, monocyte, and neutrophil of renal cell carcinoma (RCC) patients undergoing laparoscopic nephrectomy.MethodsBetween January 2014 and December 2019, 438 patients with RCC were retrospectively analyzed in three centers. We used X‐tile software to obtain the optimum cut‐off values for neutrophils, monocytes, and lymphocytes to classify the patients. To assess the relationship between PBIS score and overall survival (OS), and cancer‐specific survival (CSS) in patients with RCC by Kaplan–Meier survival curves and Cox regression analyses. In addition, predictive OS and CSS nomograms were constructed. The discriminative ability of nomogram and predictive performance accuracy were verified with consistency index (C‐index), calibration curves, receiver operating curve (ROC) curves, decision curve analysis (DCA) curves, and time‐dependent ROC curves.ResultsThe optimum cutoff values for monocytes, lymphocytes, and neutrophils were 0.46, 1.01, and 4.50, respectively. We divided patients into four subgroups according to PBIS scores, which were significantly associated with M‐stage (p = 0.008), T‐stage (p < 0.001), N‐stage (p = 0.006), and AJCC stage (p < 0.001). Multivariate Cox regression analysis revealed that RCC patients with lower PBIS scores showed a worse postoperative prognosis and served as an independent predictor of OS (p = 0.002) and CSS (p < 0.001). Ultimately, the nomograms based on PBIS scores demonstrated excellent predictive performance for OS (C‐index: 0.770) and CSS (C‐index: 0.828) through the analysis of calibration curves, ROC curves, DCA curves, and time‐dependent ROC curves.ConclusionPBIS score served as novel and effective predictor to accurately predict OS and CSS in patients with RCC receiving laparoscopic nephrectomy.

Our aim was to comprehensively investigate the relationship between blood volatile organic compounds (VOCs) and kidney stone prevalence for U.S. adults. In this cross-sectional study, 10,052 participants from the 2007–2020 National Health and Nutrition Examination Survey (NHANES) were included. Multivariate logistic regression model was employed to investigate the association between 9 blood VOCs and kidney stones. We explored the dose–response relationship between blood VOCs and kidney stones using restricted cubic spline (RCS) analysis. Additionally, weighted quantile sum (WQS) regression model was performed to assess the overall association of 9 blood VOCs with kidney stones. Finally, subgroup analyses were conducted to identify the findings in different populations at high prevalence. Logistic regression analysis and dose–response risk curves revealed that blood benzene (aOR = 1.308, 95

The long non-coding RNA X-inactive specific transcript (lncRNA XIST) and MUC1 gene are dysregulated in chronic inflammation and cancer; however, there is no known interaction of their functions. The present studies demonstrate that MUC1-C regulates XIST lncRNA levels by suppressing the RBM15/B, WTAP and METTL3/14 components of the m6A methylation complex that associate with XIST A repeats. MUC1-C also suppresses the YTHDF2-CNOT1 deadenylase complex that recognizes m6A sites and contributes to XIST decay with increases in XIST stability and expression. In support of an auto-regulatory pathway, we show that XIST regulates MUC1-C expression by promoting NF-κB-mediated activation of the MUC1 gene. Of significance, MUC1-C and XIST regulate common genes associated with inflammation and stemness, including (i) miR-21 which is upregulated across pan-cancers, and (ii) TDP-43 which associates with the XIST E repeats. Our results further demonstrate that the MUC1-C/XIST pathway (i) is regulated by TDP-43, (ii) drives stemness-associated genes, and (iii) is necessary for self-renewal capacity. These findings indicate that the MUC1-C/XIST auto-regulatory axis is of importance in cancer progression.

Clear cell renal cell carcinoma (ccRCC), a prevalent malignant tumor, exhibits resistance to chemotherapy, necessitating advanced therapeutic approaches. Sonocatalytic therapy has emerged as a promising non-invasive treatment for solid tumors due to its ability to penetrate deep tissue. Herein, the development of single atomic Au-doped 2D TiO2 nanosheets are presented with oxygen vacancies (Au-SA/Def-TiO2, ASDT) for sonocatalytic treatment of ccRCC. Surface defects on TiO2 nanosheets effectively stabilize Au single atomic sites via the Ti-Au-Ti structure, enhancing catalytic properties and facilitating reactive oxygen species (ROS) generation by reducing energy barriers and improving electron (e(-)) and hole (h(+)) separation. Additionally, ASDT exhibits peroxidase-like activities, further augmenting ROS production, leading to significant inhibition of tumor growth in subcutaneous and orthotopic ccRCC models under ultrasound irradiation. This study underscores the efficacy of defect engineering for stabilizing single atoms to boost ROS production and achieve effective tumor eradication by the enhanced sonocatalytic effect.

The clinical utility of circulating tumor DNA (ctDNA) in hormone-sensitive prostate cancer (HSPC) remains inadequately elucidated. This study presents the largest real-world cohort to conduct a concordance analysis between ctDNA and tissue-based genomic profiling in HSPC patients. The findings reveal diminished ctDNA abundance in cases with low tumor burden and demonstrate an increased concordance rate between ctDNA and tissue along with the progression of disease burden. Notably, a substantial number of exclusive genomic alterations (GAs) were identified either in ctDNA or tissue in high-volume metastatic disease. Integrating tissue and ctDNA analysis identified specific gene alterations (BRCA1, BRCA2, CDK12, TP53, PTEN, or RB1) associated with a shorter time to the progression to castration-resistant prostate cancer (CRPC), with an escalated CRPC risk correlated with cumulative GAs. This multicenter, real-world investigation underscores the complementary role of ctDNA and tissue in detecting clinically pertinent GAs, highlighting their potential integration into clinical practice for advanced prostate cancer management.