Benign prostatic hyperplasia (BPH) is a common urological disease in middle-aged and elderly men. Its incidence increases continuously with age, which significantly affects patients' quality of life and may even be life-threatening. As population aging intensifies, BPH has become an increasingly prominent public health problem. Existing studies suggest that the occurrence and progression of BPH are associated with multiple factors. However, there is currently a lack of systematic and standardized guidance on managing risk factors for BPH in clinical practice. Focusing on existing evidence and integrating clinical experts' opinions, this consensus formulates 20 items recommendations aiming to promote the standardized management of risk factors influencing the occurrence and progression of BPH, in order to delay its age of onset, slow clinical progression, and reduce the disease burden.

5090 Background: In the CHART trial, Rez plus ADT significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) compared with Bic plus ADT in patients (pts) with high-volume mHSPC (Gu et al., Lancet Oncol 2022). Here, we present updated outcomes ~5 years after the enrollment of the last pt. Methods: Pts with high-volume mHSPC and without previous chemotherapy or other localized treatment for PC were eligible to be enrolled. Pts were randomized 1:1 to receive ADT plus either Rez (240 mg) or Bic (50 mg) orally once daily. Final analysis for OS was planned after 325 deaths were reported. Results: Between Jun 28, 2018, and Aug 6, 2020, 654 pts were randomized to receive Rez plus ADT (n=326) or Bic plus ADT (n=328). As of data cutoff (Jun 6, 2025), with a median follow-up of 72.8 months (IQR 69.1-77.4), there were 141 (43.3%) deaths in Rez plus ADT group and 194 (59.1%) in Bic plus ADT group. OS was improved with Rez plus ADT versus Bic plus ADT (median 78.8 months [95% CI 68.3-not reached (NR)] vs 44.8 months [95% CI 37.1-57.4]; HR 0.59 [95% CI 0.47-0.73]; 2-sided p<0.0001). Risk of progression or death in Rez plus ADT group was reduced by 62% compared with Bic plus ADT group (HR 0.38 [95% CI 0.30-0.48]). Other efficacy outcomes also favored Rez plus ADT (Table). Rez plus ADT improved patient-reported quality of life. No new safety signals were observed. Conclusions: Rez plus ADT continued to show meaningful survival benefits with manageable toxicities after long-term follow-up, further supporting Rez plus ADT as frontline treatment for pts with high-volume mHSPC. Clinical trial information: NCT03520478 . Efficacy endpoints. Rez plus ADT (n=326) Bic plus ADT (n=328) HR (95% CI) 2-sided p-value OS, months 78.8 (68.3-NR) 44.8 (37.1-57.4) 0.59 (0.47-0.73) <0.0001 rPFS per investigator, months 81.0 (62.6-NR) 18.5 (14.8-25.7) 0.38 (0.30-0.48) <0.0001 rPFS per investigator (sensitivity analysis # ), months 58.9 (50.10-NE) 18.6 (16.30-22.90) 0.38 (0.31-0.47) <0.0001 Time to PSA progression, months NR (NR-NR) 11.0 (9.2-12.9) 0.21 (0.17-0.27) <0.0001 Time to next skeletal-related event, months 78.8 (58.9-NR) 37.7 (34.3-48.2) 0.63 (0.51-0.78) <0.0001 Time to initiation of new anti-prostate cancer therapy, months 62.4 (46.4-75.6) 15.1 (13.6-18.1) 0.32 (0.26-0.39) <0.0001 Data are median (95% CI) unless otherwise indicated. # New anti-cancer therapy and missing tumor assessments were not considered. PSA, prostate specific antigen.

OBJECTIVES:Lasers show promising application in partial nephrectomy due to their excellent hemostatic effect. This study aimed to evaluate the suction effect of the novel laser operating handle on the smoke generated by a 980-nm diode laser (DL) and a 532-nm potassium-titanyl-phosphate (KTP) green laser (GL) in laparoscopic partial nephrectomy (LPN) and to analyse the surgical smoke generated by the laser treatment. METHODS:Fresh porcine kidneys were purchased from a slaughterhouse. Electrocoagulation knife (EK), ultrasonic knife (UK), DL, and GL were utilised in LPN. The operation time and the composition and concentration of the surgical smoke were recorded. HE staining was performed to observe the degree of thermal damage. RESULTS:In terms of smoke generation, the 532-nm KTP laser results in the largest amount of smoke. The surgical field of DL-LPN was adequately improved with the aid of the instrument with the novel handle. The thickness of the coagulation layer, which ranged from thick to thin, was DL, GL, EK, and UK. The coagulation of EK, UK, DL, and GL was 0.35 ± 0.08 mm, 0.52 ± 0.08 mm, 4.16 ± 0.21 mm, and 1.55 ± 0.21 mm, respectively. For formaldehyde, total volatile organic compounds (TVOC), and carbon monoxide (CO), there was a marked reduction after the application of the aspirator. For the DL group, the Formaldehyde TVOC and CO were 4.95 ± 0.48 mg/m3 and 1.69 ± 0.46 mg/m3, 8.34 ± 0.72 mg/m3 and 1.11 ± 0.33 mg/m3, 124.14 ± 9.58 PPM and 23.71 ± 3.9 PPM, respectively. CONCLUSIONS:As shown in the present study, though a large amount of harmful smoke was generated during laser-assisted laparoscopic partial nephrectomy (LALPN), the novel laser handle can be sucked effectively and provides a clear surgical field. As to the harmful gases released, an effective protective mask is needed.

The rehabilitation of erectile function post-radical prostatectomy remains a great challenge in clinical practice. We aimed to develop a novel rat model suitable for investigating erectile dysfunction (ED) following nerve-sparing radical prostatectomy (NSRP) and to validate its applicability. Thirty-two male Sprague-Dawley rats were randomly assigned to undergo either a novel NSRP modeling procedure or sham surgery. The surgical protocol for the NSRP group included identification and dissection of the major pelvic ganglia and cavernous nerve, prostatectomy, and reconstruction of the lower urinary tract. Mean arterial pressure (MAP) and intracavernous pressure (ICP) were assessed at 1 and 2 weeks postoperatively. Subsequently, the penis tissues were collected for histopathological analyses. The results showed that rats in the NSRP group exhibited significantly lower maximum ICP/MAP ratios (0.39 ± 0.17 vs 0.77 ± 0.08, P < 0.0001) and areas under the ICP curve (2090.13 ± 1050.15 vs 4326.08 ± 1042.08, P = 0.0001) compared to the sham-operated group at 1 week postoperatively. By 2 weeks postoperatively, the NSRP group showed a significant improvement in both the maximum ICP/MAP ratio (0.73 ± 0.09 vs 0.39 ± 0.17, P < 0.0001) and the area under the ICP curve (3654.40 ± 679.28 vs 2090.13 ± 1050.15, P = 0.005) compared to the 1-week post-NSRP group. However, the area under the ICP curve in the NSRP group remained significantly lower than that in the sham-operated group at 2 weeks postoperatively (3654.40 ± 679.28 vs 5259.10 ± 951.48, P = 0.003). Similarly, histological staining suggested that smooth muscle atrophy and collagen deposition in the penis gradually improved over time post-NSRP. However, significant differences in the ratio of smooth muscle to collagen remained between the NSRP and sham-operated groups at 2 weeks postoperatively (0.22 ± 0.03 vs 0.27 ± 0.05, P = 0.011). In conclusion, this study established a novel rat model for investigating post-NSRP ED and validated its utility through erectile function monitoring and histological analysis. Further promising preclinical studies using this model are necessary to explore underlying mechanisms and evaluate the efficacy of treatments for post-NSRP ED.

BACKGROUND:Chemotherapy-induced peripheral neuropathy (CIPN) is a common and serious side effect of paclitaxel-based chemotherapy, with limited therapeutic options that often prove ineffective. Photobiomodulation (PBM), a non-invasive therapeutic approach utilizing near-infrared light, has shown promise in fostering nerve regeneration and modulating inflammatory responses. This study aimed to assess both the therapeutic efficacy and the underlying molecular mechanisms of PBM in a preclinical model of CIPN. METHODS:The effects of 808 nm near-infrared PBM were evaluated in both in vivo and in vitro CIPN models. A murine CIPN model was developed and subjected to three weeks of continuous PBM treatment. Behavioral assessments, intraepidermal nerve fiber (IENF) density analysis, and mitochondrial ultrastructural evaluations were performed in the in vivo experiments. For in vitro investigations, N2a neuroblastoma cells and normal human astrocytes (NHA) were exposed to albumin-bound paclitaxel (nab-paclitaxel), with or without PBM therapy. Cellular assays were conducted to evaluate cell viability, inflammatory cytokine secretion, oxidative stress levels, mitochondrial functionality, and apoptosis. RESULTS:PBM significantly ameliorated mechanical and cold hypersensitivity in CIPN mice, restored IENF density, preserved mitochondrial ultrastructure, and reduced oxidative tissue damage. In addition, PBM enhanced neuronal cell proliferation, reduces the expression of pro-inflammatory cytokines, attenuated oxidative stress, stabilized mitochondrial membrane potential, increased ATP production, and inhibited paclitaxel-induced apoptosis through regulation of the mitochondrial pathway. CONCLUSIONS:Near-infrared PBM effectively mitigates CIPN by promoting neural repair, suppressing neuroinflammation and oxidative stress, and preserving mitochondrial function. These findings highlight PBM as a potential non-pharmacological therapeutic option for CIPN management and suggest that further clinical investigations are warranted.

This study aimed to evaluate the effects and potential mechanisms of gastric mucosal ablation (GMA) using a 450-nm blue laser on weight loss and metabolic outcomes. Male Sprague-Dawley rats were fed a 45

Hexylaminoacetylpropionic acid (HAL), a third-generation photosensitizer prodrug, exhibits targeted accumulation within tumor tissues and microbial biofilms. This review outlines advances in HAL-based drug delivery systems and their expanding use in various diseases, including oncology, antimicrobial therapy, and dermatologic diseases. Clinically, HAL has proven instrumental in enhancing diagnostic accuracy for bladder cancer by facilitating more complete surgical resections, while also demonstrating therapeutic efficacy against actinic keratosis and cervical intraepithelial neoplasia. These clinical advantages are complemented by novel nanocarrier systems that optimize drug delivery that improve patient tolerability. Recent findings point to an underappreciated the interplay between HAL-induced metabolic changes in tumours and anti-tumour immune responses, in which HAL-induced metabolic changes in tumours and anti-tumour immune responses, in which HAL-induced induces cell apoptosis through mitochondrial membrane permeabilization and the nuclear translocation of AIF, and enhances the efficacy of immune checkpoint blockade of key regulatory proteins reshape the tumour microenvironment and enhance immunogenicity. Thus, HAL is a candidate for combination with immune checkpoint inhibitors. However, challenges such as shallow light penetration (<2 mm) and the need for long-term safety validation limit its broader clinical utility. We propose three convergent strategies to address these limitations: (i) reactive oxygen species-responsive nanocarriers for targeted delivery in hypoxic environments, (ii) biomarker-guided combinatorial regimens, and (iii) data-driven treatment personalisation using patient-specific biomarkers. Together, these advances establish a translational framework for HAL as a platform in next-generation metabolism-targeted photomedicine.

The prognostic value of these pathological morphology alterations induced by neoadjuvant therapy in high-risk prostate cancer (PCa) patients is still unclear. Hence, this study retrospectively reviewed the data of 124 patients with high-risk PCa who underwent neoadjuvant therapy followed by radical prostatectomy (RP), and aimed to explore the prognostic value of pathological morphology alterations. Data from 124 patients with high-risk PCa who underwent neoadjuvant therapy followed by RP were retrospectively reviewed. Pathological morphology alterations observed in RP specimens were independently recorded by two uropathologists, and the primary endpoint was biochemical progression-free survival (bPFS). Cox regression analyses were performed to explore independent predictors of bPFS, and a nomogram was developed. The C-index, calibration curves and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. Among 124 patients, 66 patients (53.2

BACKGROUND:Clear cell Renal cell carcinoma (ccRCC) represents the most common malignant tumor of the kidney. Metallothionein 2A (MT2A) is abnormally expressed in various cancers, but its functional role and underlying mechanism in RCC remain to be elucidated. METHODS:The expression of MT2A in RCC and its adjacent tissues was analyzed using the public TCGA and GEO databases. The effects of MT2A on cell proliferation, migration and invasion were investigated by using CCK-8, Transwell, and wound healing assays. Potential downstream targets and pathways were screened by transcriptomic and metabolomic sequencing. The regulatory mechanisms were further validated via qRT-PCR, Western blotting, ChIP, immunohistochemistry, luciferase reporter assays, and CUT&Tag. Moreover, the in vivo function of MT2A was investigated using a nude mouse xenograft tumor model. RESULTS:MT2A was significantly upregulated in ccRCC and correlated with clinical stage and overall survival. MT2A enhanced ccRCC metastatic potential and epithelial-mesenchymal transition, with a moderate, late-onset effect on cell proliferation, via the TFAP2A/YAP axis. MT2A was shown to enhance lactic acid accumulation and H3K18 lactylation. Further studies confirmed that MT2A contributed to TFAP2A transcription via HBO1-mediated H3K18 lactylation. Consistently, MT2A knockdown in vivo enhanced the tumor-suppressing effect of sorafenib. CONCLUSIONS:MT2A could promote the malignant progression of ccRCC through the TFAP2A/YAP axis, which is controlled by HBO1-mediated H3K18 lactylation. Targeting MT2A effectively inhibits tumor growth and enhances the efficacy of sorafenib, providing a novel potential therapeutic target for ccRCC.

793 Background: Interim results of the randomized phase II trial of neoadjuvant tislelizumab +/- oral APL-1202 (nitroxoline) revealed promising pathological complete response (pCR) rates and met prespecified thresholds for study expansion (ASCO GU 2024). Here, we report the final primary endpoint analysis of this trial. Methods: Patients with cT2-T4aN0M0 urothelial cancer of the bladder based on local assessment, planned for radical cystectomy (RC), and ineligible for or refusing cisplatin-based chemotherapy were eligible. Patients were randomly assigned to APL-1202 plus tislelizumab (A+T) or tislelizumab (T), stratified by PD-L1 expression. Neoadjuvant tislelizumab was administered q3weeks for 3 cycles and APL1202 was administered orally tid. The primary endpoint was centrally assessed (pCR, pT0N0) rate and secondary endpoints included central pathologic response (PaR, < ypT2N0) rate and safety. Results: A total of 103 patients were enrolled; 28 patients declined RC after neoadjuvant treatment (A+T=16, T=12). Consequently, 75 patients remained in the efficacy analysis set (EAS); RC was completed after A+T in 42/43 patients and after T in 31/32 patients. The pCR and PaR results in the EAS are presented in the table. On retrospective central pathology review of baseline TURBT specimens, a large subset of patients were determined to be ineligible due to

Cytoreductive radical prostatectomy (cRP) has emerged as a promising therapeutic approach for low-volume metastatic hormone-sensitive prostate cancer (mHSPC), but the best candidates for cRP are still unknown. This study aims to explore the potential value of 18F-PSMA-1007 PET/CT-derived quantitative volumetric tumor parameters in cRP treatment selection among patients with low-volume mHSPC. A total of 122 patients with primary low-volume mHSPC who underwent 18F-PSMA-1007 PET/CT followed by systemic therapy alone or plus cRP were included. The whole-body PSMA-derived tumor volume (PSMA-TV) was defined as the total volume of whole-body PSMA-avid tumor lesions, and prostate PSMA-TV was defined as the volume of prostate PSMA-avid tumor lesions. Spearman’s correlation was used to analyze the relationships between whole-body PSMA-TV and clinicopathological characteristics. The primary endpoint was progression-free survival (PFS), and Cox regression analyses were performed to explore the independent predictors for PFS. Among 122 patients, 37 (30.32

Objectives: 2'-Hydroxyflavanone (2HF) has been recognized for its antitumor potential in recent years. In the past decade, the role of miRNAs in tumors has been gradually explored. Since natural compounds may regulate miRNA networks, our objective is to investigate the potential effects and mechanisms of 2HF in the treatment of bladder cancer (BCa) by targeting miRNAs. Methods: Cell viability, tube formation, Transwell, western blotting and colony formation assays were used to evaluate the effects of 2HF on the viability and angiogenesis of BCa cells. The expression of miR-99a-5p and mTOR was detected via RT-qPCR and western blotting. A subcutaneous xenograft animal experiment was used to evaluate the tumor inhibition of 2HF in vivo. The binding of miR-99a-5p to mTOR was demonstrated via dual-luciferase reporting and RNA pull-down assays. Results: 2HF inhibited the cell viability, angiogenesis, protein expression of VEGFa and Ki67 in T24 and 253J cells and protein expression of CD31 in HUVEC cells. Also, 2HF induced the upregulation of miR-99a-5p but the downregulation of mTOR expression. Additionally, the inhibitory effect of 2HF on tumor cells can be effectively rescued by silencing miR-99a-5p or overexpressing mTOR in vitro. Moreover, 2HF inhibited tumor growth in nude mice, in which it upregulated miR-99a-5p but suppressed mTOR expression in xenograft tissues. Mechanistically, miR-99a-5p can directly target the mRNA of mTOR by binding to its 3' untranslated region (3'-UTR) and then inhibiting the expression of mTOR. Conclusions: 2HF inhibited BCa cell proliferation and angiogenesis by regulating the miR-99a-5p/mTOR/VEGFa axis, which may provide a novel treatment strategy and molecular mechanism for BCa treatment.

Acne vulgaris is a chronic inflammatory skin disease closely linked to the abnormal colonization and proliferation of Cutibacterium acnes (C. acnes). Photodynamic therapy (PDT) has emerged as an ideal treatment. However, it still faces challenges such as low reactive oxygen species (ROS) production rates with porphyrin-based photosensitizers and low activation efficiency of conventional red light. This study investigated the in vitro and in vivo bactericidal effects of sinoporphyrin sodium (DVDMS) combined with a novel 450 nm blue laser-mediated photodynamic therapy (BL-PDT) on C. acnes, and explored the potential mechanisms, focusing on energy metabolism. In our results, C. acnes showed a time-dependent uptake of DVDMS, and BL-PDT demonstrated an excellent bactericidal effect on C. acnes in vitro by inducing a large amount of ROS production. RNA sequencing and metabolomic analysis revealed that BL-PDT inhibited C. acnes carbon metabolism while initially enhancing respiration; however, both fermentation and respiration were suppressed after 2 h, and ATP declined time-dependently in this process. Ultimately, the combined effects of ROS-induced damage (from DVDMS and enhanced respiration) and ATP depletion led to bacterial death. Similarly, in vivo experiments confirmed the favorable therapeutic efficacy and safety of BL-PDT in a rat model of acne. In conclusion, DVDMS-based BL-PDT may be a safe and effective new treatment against acne. Thus, our results provide compelling evidence for using DVDMS and BL-PDT in acne treatment.