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Prostatic stromal tumor of uncertain malignant potential (STUMP), characterized by an atypical, unique stromal proliferation of the prostate, is often difficult to be differentiated from other nonepithelial neoplastic lesions. We present a unique case of recurrent STUMP after transurethral resection of the prostate (TURP) with concurrent prostatic adenocarcinoma. Patients diagnosed with prostatic STUMP should be followed up closely, for it may recur and invade adjacent organs after TURP shortly. Concurrent prostatic adenocarcinoma can be found in STUMP patients, and there may be some potential mechanisms which promote the simultaneous occurrence of the 2 tumors. [ABSTRACT FROM AUTHOR]

Background: The study aims to analyze the epidemiology of preservation fluid (PF) contamination and investigate the impact of PF contamination and possible donor-derived infections(p-DDI) on early postoperative prognosis in kidney transplant (KT) recipients. Methods: A total of 256 PF samples were collected for microbiological evaluation from all KT recipients who received deceased donor donations in our hospital from June 2018 to August 2022. Data on the baseline and clinical characteristics of these PF corresponding to recipients and donors were extracted from the electronic medical record. It mainly included the early postoperative complications and prognosis of KT recipients. Results: From June 2018 to August 2022, 597 kidney transplants were performed in our center, with 260 recipients receiving kidney transplantation from donation after citizens' death. A total of 256 samples of PF were collected, of which 64.5% (165/256) were culture positive, and 24.6% (63/165) of the culture-positive PF were polymicrobial contamination. A total of 238 strains were isolated, of which coagulase-negative staphylococci (CoNS) had the highest proportion of 34.0% (81/238), followed by Klebsiella pneumoniae with 20.6% (49/238) and Escherichia coli with 8.8% (21/238). Recipients with culture-positive PF had a significantly higher incidence of postoperative infection (55.8% vs. 20.9%, P < 0.001) and DGF (38.2% vs. 24.2%, P = 0.023). In addition, the incidence of p-DDI was 12.9% (33/256). CRKP was the most common pathogen causing p-DDI. The recipients who developed p-DDI had a higher rate of graft loss (9.1% vs. 0.4%, P < 0.001), mortality (12.1% vs. 3.1%, P = 0.018), and longer postoperative hospital stay (30 days (19.5–73.5) vs. (22 days (18–32), P < 0.05) compared with recipients who did not develop p-DDI. Conclusions: Culture-positive PF is potentially significant for KT recipients, and p-DDI may increase the risk of poor prognosis for recipients. Prophylactic anti-infective treatment should be actively performed for highly virulent or multidrug-resistant (MDR) pathogens (especially Carbapenem-resistant Klebsiella pneumoniae, CRKP) in PF to avoid the occurrence of p-DDI. [ABSTRACT FROM AUTHOR]

Background: The surgical treatment of horseshoe kidney (HSK) remains a huge challenge because of the complex anatomy and abnormal blood vessel distribution. Therefore, this study aimed to evaluate the surgical technique and outcomes of robot-assisted laparoscopic isthmus division using endoscopic transection equipment (endoscopic linear stapler; Ethicon, ECHELON 60 FLEX™) in the treatment of symptomatic HSK and to conduct a literature review. Materials and Methods: Patients with HSK who underwent robot-assisted laparoscopic isthmus division using endoscopic transection equipment from August 2015 to August 2019 at the First Affiliated Hospital of Anhui Medical University in China were recruited. Isthmus division was conducted using an endoscopic linear stapler. Results: All 10 surgeries were performed successfully. Major organs and large blood vessels were effectively protected. Only 1 patient presented with postoperative perinephric effusion. The mean operative time was 179 minutes, and the mean length of the postoperative hospital stay was 6 days. During the 1- to 5-year follow-up, all patients were cured with mitigated symptoms and improved renal function, except for 1 patient with transitional cell carcinoma who died of multiple metastases 18 months postoperatively. Conclusion: Robot-assisted laparoscopic isthmus division using endoscopic transection equipment is a safe and effective method to manage patients with symptomatic HSK and to help them have few complications and quick recovery. Clinical Trial Registration No: Quick-PJ 2021-03-18. [ABSTRACT FROM AUTHOR]

Background: The VHL-HIF pathway and lipid droplet accumulation are the main characteristics of clear cell renal cell carcinoma (ccRCC). However, the connection between the two features is largely unknown. Methods: We used transcriptional sequencing and TCGA database analysis to identify APOL1 as a novel therapeutic target for ccRCC. The oncogenic functions of APOL1 were investigated by cell proliferation, colony formation, migration and invasion assays in ccRCC cells in vitro and xenografts derived from ccRCC cells in vivo. Oil red O staining and quantification were used to detect lipid droplets. Chromatin immunoprecipitation (ChIP) assays and luciferase reporter assays were carried out to identify HIF-2α bound to the promoter of APOL1 and lncRNA LINC02609. RNA-FISH and luciferase reporter assays were performed to determine that LncRNA LINC02609 functions as a competing endogenous RNA to regulate APOL1 expression by sponging miR-149-5p. Findings: RNA-seq data revealed that HIF2α can regulate APOL1 and lncRNA LINC02609 expression. We also found that HIF-2α can bind to the promoter of APOL1 and lncRNA LINC02609 and transcriptionally regulate their expression directly. We further demonstrated that LncRNA LINC02609 functions as a competing endogenous RNA to regulate APOL1 expression by sponging miR-149-5p in ccRCC. Mechanistically, APOL1-dependent lipid storage is required for endoplasmic reticulum (ER) homeostasis and cell viability and metastasis in ccRCC. We also showed that high APOL1 expression correlated with worse clinical outcomes, and knockdown of APOL1 inhibited tumor cell lipid droplet formation, proliferation, metastasis and xenograft tumor formation abilities. Together, our studies identify that HIF2α can regulate the expression of the lipid metabolism related gene APOL1 by direct and indirect means, which are essential for ccRCC tumorigenesis. Interpretation: Based on the experimental data, in ccRCC, the HIF-2α/LINC02609/APOL1 axis can regulate the expression of APOL1, thus interfering with lipid storage, promoting endoplasmic reticulum homeostasis and regulating tumor progression in ccRCC. Together, our findings provide potential biomarkers and novel therapeutic targets for future studies in ccRCC. [ABSTRACT FROM AUTHOR]

This article explores the role of regulatory T cells (Tregs) in prostate cancer (PCa) and their impact on prognosis and treatment response. The researchers found that Tregs can be divided into two subtypes: TregR, which is associated with a poor prognosis, immunosuppression, and resistance to therapy, and TregP, which has the opposite characteristics. TregR showed higher expression of TGF-β and mutations in the TP53 and PIK3CA genes, which may contribute to therapy resistance. The study suggests that targeting TGF-β and the PI3K-AKT-mTOR pathway may improve treatment outcomes for TregR PCa. [Extracted from the article]

Clear cell renal cell carcinoma (ccRCC) is a heterogeneous tumor with different genetic and molecular alterations. Schemes for ccRCC classification system based on multiomics are urgent, to promote further biological insights. Two hundred and fifty‐five ccRCC patients with paired data of clinical information, transcriptome expression profiles, copy number alterations, DNA methylation, and somatic mutations were collected for identification. Bioinformatic analyses were performed based on our team's recently developed R package "MOVICS." With 10 state‐of‐the‐art algorithms, we identified the multiomics subtypes (MoSs) for ccRCC patients. MoS1 is an immune exhausted subtype, presented the poorest prognosis, and might be caused by an exhausted immune microenvironment, activated hypoxia features, but can benefit from PI3K/AKT inhibitors. MoS2 is an immune "cold" subtype, which represented more mutation of VHL and PBRM1, favorable prognosis, and is more suitable for sunitinib therapy. MoS3 is the immune "hot" subtype, and can benefit from the anti‐PD‐1 immunotherapy. We successfully verified the different molecular features of the three MoSs in external cohorts GSE22541, GSE40435, and GSE53573. Patients that received Nivolumab therapy helped us to confirm that MoS3 is suitable for anti‐PD‐1 therapy. E‐MTAB‐3267 cohort also supported the fact that MoS2 patients can respond more to sunitinib treatment. We also confirm that SETD2 is a tumor suppressor in ccRCC, along with the decreased SETD2 protein level in advanced tumor stage, and knock‐down of SETD2 leads to the promotion of cell proliferation, migration, and invasion. In summary, we provide novel insights into ccRCC molecular subtypes based on robust clustering algorithms via multiomics data, and encourage future precise treatment of ccRCC patients. Highlights: Three molecular subtypes of ccRCC based on multiomics data were identified, with diverse overall survival time, and validated in external cohorts.MoS1 is an immune exhausted subtype, which can benefit from PI3K/AKT inhibitors; MoS2 is an immune "cold" subtype, but is more suitable for sunitinib therapy; MoS3 is an immune "hot" subtype, which can benefit from anti‐PD‐1 immunotherapy.SETD2 is a tumor suppressor in ccRCC, and knock‐down of SETD2 leads to the promotion of cell proliferation, migration, and invasion. [ABSTRACT FROM AUTHOR]

Purpose: With the heterogeneous genetic background, prognosis prediction and therapeutic targets for testicular germ cell tumors (TGCTs) are still unclear. We defined the tumor immune microenvironment activation status (TIMEAS). Methods: We collected a total of 314 TGCT patients from four cohorts, including a 48-case microarray. A nonnegative matrix factorization algorithm was applied to identify the "immune factor", derived the top 150 weighted genes to divide patients into immune and non-immune classes, and further separated the immune class into activated and exhausted subgroups by nearest template prediction. Tumor mutant burden, gene mutation, and copy number alteration were compared with our recently developed package "MOVICS". A random forest algorithm was performed to establish a prediction model with fewer genes. Immunohistochemistry staining was performed to identify TIMEAS in the microarray. Results: We constructed the TIMEAS in the TCGA-TGCT cohort and further validated it in the GSE3218 and GSE99420 cohorts. The immune class contained the activated status of T-lymphocytes, B-lymphocytes, and macrophages, while Treg cells and the WNT/TGFβ signature were more activated in the immune-suppressed subgroup. Patients in the immune-exhausted subgroup had the worst prognosis, and 22.9% of patients in the immune-activated subgroup had KRAS mutations, which might stimulate the response of the immune system and lead to a favorable prognosis. The immune-exhausted group benefited more from chemotherapy, while the immune-activated subgroup responded well to anti-PD-1/PD-L1 therapy. FSCN1 was validated as the target of the immune-exhausted microenvironment by immunohistochemistry. Conclusion: TIMEAS classification can separate TGCT patients; patients in the immune-activated subgroup could benefit more from anti-PD-L1 immunotherapy, and those in the immune-exhausted subgroup are more suitable for chemotherapy. [ABSTRACT FROM AUTHOR]

Resveratrol (Res) is a non-flavonoid polyphenol compound with biological pleiotropic properties, but low bioavailability limits its application value. Here, we synthesized a new Res derivative ((E)-5-(dimethylamino)-2-(4-methoxystyryl)phenol), and attempted to determine the function of Res derivative combined with radial extracorporeal shock wave therapy (rESWT) in chronic nonbacterial prostatitis (CNP). CNP model rats were constructed by subcutaneous administration of prostatein suspension (15 mg/ml), followed by rESWT treatment alone or in associated with Res or Res derivatives. In this study, inflammatory cell infiltration and tissue fibrosis in the prostate tissues of CNP rats were significantly deteriorated, which was effectively abolished by rESWT treatment alone or in combination with Res or Res derivative. The expression of interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), nerve growth factor (NGF), and nuclear factor kappa-B (NF-κB) were increased, while silent information regulator 1 (SIRT1) expression was suppressed in the prostate tissues of CNP rats, which were then rescued by rESWT treatment alone or in associated with Res or Res derivative. Importantly, compared with Res derivative treatment alone or rESWT combined with Res treatment, combination treatment with rESWT and Res derivative was more effective in alleviating inflammation and fibrosis, in reducing IL-1β, TNF-α, NGF, and SIRT1 expression, and in facilitating SIRT1 expression. Overall, rESWT combined with Res derivative treatment improved CNP in rat by reducing inflammation and fibrosis, which attributed to regulate the expression of SIRT1 and NF-κB. Thus, this work provides a theoretical basis for rESWT combined with Res derivative in the clinical treatment of CNP. [ABSTRACT FROM AUTHOR]

Purpose: To determine the risk factors for postoperative fever after retrograde intrarenal surgery (RIRS) in patients with negative preoperative urine culture (UC), and to establish a nomogram for predicting postoperative fever based on these risk factors. Methods: This study collected 322 patients with negative UC who received RIRS at the First Affiliated Hospital of Anhui Medical University from March 2019 to May 2022. The study population was divided into a fever group and a non-fever group. The risk factors of postoperative fever were determined by univariate and multivariate logistic regression analyses, and a nomogram was established. The nomogram was evaluated in terms of differentiation, calibration, and clinical practicability. Results: In this study, 47 (14.6%) patients developed a fever after surgery. Multivariate logistic regression analysis showed that for patients with negative preoperative urine culture, urinary leucocyte esterase (P = 0.005), operative time (P = 0.019), and intraoperative hypotension (P = 0.028) were independent risk factors of postoperative fever, and a nomogram was constructed according to the above variables. The area under the curve (AUC) calculated by receiver operating characteristic (ROC) analysis was 0.807 (95% CI 0.739–0.876), indicating good discrimination. The calibration curves showed good consistency, and the clinical decision curve analysis (DCA) showed the clinical applicability of the model. Conclusions: For patients with negative preoperative urine culture, urine leukocyte esterase, operative time, and intraoperative hypotension are independent risk factors of postoperative fever. The new nomogram can better assess the risk of infection in patients with negative UC after RIRS. [ABSTRACT FROM AUTHOR]

Objective: To introduce a wireless high‐definition endoscopic system (WHES) and compare it with a Storz high‐definition (HD) system for image resolution, colour resolution, weight, and costs. Materials and Methods: The WHES incorporated a portable light‐emitting diode light source and a wireless camera module, which can be compatible with different types of endoscopes. Images were wirelessly transmitted to a monitor or mobile platform such as smartphone through a receiver. The International Standards Organization 12233 resolution chart image was used for the comparison of image resolution and Munsell Colour Checker Chart for colour resolution. In all, 38 endourologists used a Likert questionnaire to blindly evaluate cystoscopic images from a patient with haematuria. The surgical team was asked about the overall performance of the WHES in 20 laparoscopic adrenalectomies using a unvalidated subjective survey. Results: There was no difference in image resolution between the two systems (5.82 vs 5.89 line pairs/mm). Without lens and respective light sources, there were better purple (ΔE = 21.48 vs 28.73), blue (ΔE = 34.88 vs 38.6) and red colour resolution (ΔE = 29.01 vs 35.45) for the WHES camera (P < 0.05), but orange (ΔE = 43.45 vs 36.52) and yellow (ΔE = 52.7 vs 35.93) resolutions were better for the Storz HD camera (P < 0.05). Comparing the WHES to a Storz laparoscopic system, the Storz system still had better resolution of orange and yellow, while the resolution of purple, blue, and red was similar for the two systems. The expert comments on resolution, brightness, and colour for cystoscopy were not statistically different, but the ergonomics score for the WHES was higher (3.7 vs 3.33, P = 0.038). The overall cost of the WHES was $23 000–25 000 compared with $45 000–50 000 for a Storz system. There were 100% general satisfaction for the WHES in the survey. Conclusion: We developed a new WHES that provides the same resolution images as a Storz laparoscopic system and acceptable colour resolution with the advantages of wireless connection, small volume, low cost, portability, and high‐speed wireless transmission. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) has a high metastatic rate, and its incidence and mortality are still rising. The aim of this study was to identify the key tumor-infiltrating immune cells (TIICs) affecting the distant metastasis and prognosis of patients with ccRCC and to construct a relevant prognostic panel to predict immunotherapy response. Based on ccRCC bulk RNA sequencing data, resting mast cells (RMCs) were screened and verified using the CIBERSORT algorithm, survival analysis, and expression analysis. Distant metastasis-associated genes were identified using single-cell RNA sequencing data. Subsequently, a three-gene (CFB, PPP1R18, and TOM1L1) panel with superior distant metastatic and prognostic performance was established and validated, which stratified patients into high- and low-risk groups. The high-risk group exhibited lower infiltration of RMCs, higher tumor mutation burden (TMB), and worse prognosis. Therapeutically, the high-risk group was more sensitive to anti-PD-1 and anti-CTLA-4 immunotherapy, whereas the low-risk group displayed a better response to anti-PD-L1 immunotherapy. Furthermore, two immune clusters revealing distinct immune, clinical, and prognosis heterogeneity were distinguished. Immunohistochemistry of ccRCC samples verified the expression patterns of the three key genes. Collectively, the prognostic panel based on RMCs is able to predict distant metastasis and immunotherapy response in patients with ccRCC, providing new insight for the treatment of advanced ccRCC. [ABSTRACT FROM AUTHOR]

Dear Editor, Prostate cancer (PCa) is forecasted to be second death-related cancer worldwide.[1] PCa stem cells (PCSCs) are slow-cycling cells that participate in the carcinogenesis, progression and therapeutic resistance of PCa. In silico validation of a new classifier, PCSCGier, for predicting recurrence-free survival in prostate cancer patients: Evidence from multiple datasets Here, we correlated PCSCs-related genes (PCSCGs) with PCa patients' recurrence-free survival (RFS) and established a PCSC-related gene-based classifier (termed PCSCG SB ier sb ). Besides, we found that FAM129A was lower expressed in the stem cell enriched C4-2 cell group, and the lower expression of this gene was correlated with unfavorable prognosis of PCa patients (HR < 1, log-rank I p i -value <.05). [Extracted from the article]

Background: It is well-established that biochemical recurrence is detrimental to prostate cancer (PCa). In the present study, we explored the mechanisms underlying PCa progression. Methods: Five cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases were used to perform gene set variation analysis (GSVA) between nonrecurrent and recurrent PCa patients. We obtained the intersection of pathway enrichment results and extracted the corresponding gene list. LASSO Cox regression analysis was used to identify recurrence-free survival (RFS)-related significant genes and establish an RFS prediction gene signature and nomogram. MTT and colony formation assays were conducted to validate our findings. Results: The E2F signaling pathway was activated in recurrent PCa patients compared to nonrecurrent patients. We established an E2F-related gene signature for RFS prediction based on the four identified E2F-related genes (CDKN2C, CDKN3, RACGAP1, and RRM2) using LASSO Cox regression in the Memorial Sloan Kettering Cancer Center (MSKCC) cohort. The risk score of each patient in MSKCC was calculated based on the expression levels of CDKN2C, CDKN3, RACGAP1, and RRM2. PCa patients with low-risk scores exhibited higher RFS than those with high-risk scores. Receiver operating characteristic (ROC) curve analysis validated the good performance and prognostic accuracy of the E2F-related gene signature, which was validated in the TCGA-prostate adenocarcinoma (TCGA-PRAD) cohort. Compared to patients with low Gleason scores and early T stages, PCa patients with high Gleason scores and advanced T stages had high-risk scores. Moreover, the E2F-related gene signature-based nomogram yielded good performance in RFS prediction. Functional experiments further confirmed these results. Conclusions: The E2F signaling pathway is associated with biochemical recurrence in PCa. Our established E2F-related gene signature and nomogram yielded good accuracy in predicting the biochemical recurrence in PCa. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma (ACC) is a malignancy of the endocrine system. We collected clinical and pathological features, genomic mutations, DNA methylation profiles, and mRNA, lncRNA, microRNA, and somatic mutations in ACC patients from the TCGA, GSE19750, GSE33371, and GSE49278 cohorts. Based on the MOVICS algorithm, the patients were divided into ACC1-3 subtypes by comprehensive multi-omics data analysis. We found that immune-related pathways were more activated, and drug metabolism pathways were enriched in ACC1 subtype patients. Furthermore, ACC1 patients were sensitive to PD-1 immunotherapy and had the lowest sensitivity to chemotherapeutic drugs. Patients with the ACC2 subtype had the worst survival prognosis and the highest tumor-mutation rate. Meanwhile, cell-cycle-related pathways, amino-acid-synthesis pathways, and immunosuppressive cells were enriched in ACC2 patients. Steroid and cholesterol biosynthetic pathways were enriched in patients with the ACC3 subtype. DNA-repair-related pathways were enriched in subtypes ACC2 and ACC3. The sensitivity of the ACC2 subtype to cisplatin, doxorubicin, gemcitabine, and etoposide was better than that of the other two subtypes. For 5-fluorouracil, there was no significant difference in sensitivity to paclitaxel between the three groups. A comprehensive analysis of multi-omics data will provide new clues for the prognosis and treatment of patients with ACC. [ABSTRACT FROM AUTHOR]

Background: The incidence of prostate cancer (PCa) increases with age, and age and tumor microenvironment (TME) have important roles in the development of PCa, while the underlying mechanisms have not been fully elucidated. Materials and method: The Cancer Genome Atlas‐Prostate Adenocarcinoma (TCGA‐PRAD) RNA‐Seq, the Surveillance, Epidemiology, and End Results (SEER‐PRAD), and ESTIMATE data were downloaded, and the clinical information of PRAD patients in our cohort was collected. The associations among age, TME, and PCa were analyzed. The age‐ and TME‐related risk score (ATRS) of each TCGA‐PRAD sample was calculated based on the identified age‐ and TME‐related differentially expressed genes (DEGs), and the correlation of ATRS with immune‐related characteristics of PCa patients was analyzed, and the ATRS‐based overall survival (OS)‐predicting nomogram was also established. Results: Age was correlated with OS, PSA level, tumor stage, T stage, N stage, Gleason score, nerve invasion of PCa, and age was positively correlated with stromal, immune, and ESTIMATE scores. The compositions of immune cells of TCGA‐PRAD patients altered with age. Nine age‐ and TME‐related prognostic DEGs were identified, and the ATRS of each TCGA‐PRAD patient was calculated based on the identified nine DEGs. The ATRS was associated with the expression of immune checkpoints and intratumoral cytolytic activity, and the ATRS‐based nomogram performed well in predicting the outcomes of PCa patients. Conclusions: Age and TME had crucial roles in PCa, and the ATRS gene signature was associated with the immune‐related characteristics of PCa patients, which showed good performance in predicting OS of PCa patients. [ABSTRACT FROM AUTHOR]

Background: Rezvilutamide, a novel androgen-receptor inhibitor with low blood-brain barrier penetration, has shown potent antitumour activity against metastatic castration-resistant prostate cancer. In this study, we aimed to evaluate the efficacy and safety of rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy (ADT) for high-volume, metastatic, hormone-sensitive prostate cancer.Methods: CHART is a randomised, open-label, phase 3 study done at 72 hospitals in China, Poland, Czech Republic, and Bulgaria. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had high-volume metastatic, hormone-sensitive prostate cancer. Previous chemotherapy or other localised treatment for prostate cancer were not allowed. Patients were randomly assigned (1:1) to receive ADT plus either rezvilutamide (240 mg) or bicalutamide (50 mg) orally once daily. Randomisation was done via an interactive response technology system (block size of four) and stratified according to ECOG performance status and presence of visceral metastasis (excluding lymph nodes). Herein, we present the results of the preplanned interim analyses for the two co-primary endpoints of radiographic progression-free survival assessed by a blinded independent review committee and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study medication. This study is ongoing, but is closed to recruitment. This trial is registered with ClinicalTrials.gov, NCT03520478.Findings: Between June 28, 2018, and Aug 6, 2020, 792 patients were screened and 654 patients were randomly assigned to receive rezvilutamide plus ADT (n=326) or bicalutamide plus ADT (n=328). At the preplanned interim analysis for radiographic progression-free survival (data cutoff May 16, 2021), the median follow-up duration was 21·2 months (IQR 16·6-25·8). Rezvilutamide significantly improved radiographic progression-free survival compared with bicalutamide (median radiographic progression-free survival not reached [95% CI not reached-not reached] vs 25·1 months [95% CI 15·7-not reached]; hazard ratio [HR] 0·44 [95% CI 0·33-0·58]; p<0·0001). At the preplanned interim analysis for overall survival (data cutoff Feb 28, 2022), the median follow-up duration was 29·3 months (IQR 21·0-33·3). Rezvilutamide significantly improved overall survival compared with bicalutamide (HR 0·58 [95% CI 0·44-0·77]; p=0·0001; median overall survival was not reached [95% CI not reached-not reached] vs not reached [36·2-not reached]). The most common grade 3 or worse adverse events of any cause in the safety population were hypertension (26 [8%] of 323 patients in the rezvilutamide group vs 24 [7%] of 324 patients in the bicalutamide group), hypertriglyceridaemia (24 [7%] vs seven [2%]), increased weight (20 [6%] vs 12 [4%]), anaemia (12 [4%] vs 16 [5%]), and hypokalaemia (11 [3%] vs four [1%]). Serious adverse events were reported in 90 (28%) of 323 patients in the rezvilutamide group and 69 (21%) of 324 patients in the bicalutamide group. No treatment-related deaths occurred in patients in the rezvilutamide group; one treatment-related death of unknown specific cause (<1%) occurred in the bicalutamide group.Interpretation: In the two interim analyses, rezvilutamide plus ADT significantly improved radiographic progression-free survival and overall survival compared with bicalutamide plus ADT in patients with high-volume, metastatic, hormone-sensitive prostate cancer, with a tolerable safety profile.Funding: Jiangsu Hengrui Pharmaceuticals. [ABSTRACT FROM AUTHOR]

To identify factors that could influence the treatment outcomes of low‐intensity extracorporeal shock wave therapy (Li‐ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)‐like symptoms and establish a predictive model based on these factors to precisely screen individuals who might be more suitable for Li‐ESWT. This study enrolled 84 patients with CP/CPPS‐like symptoms who received Li‐ESWT. Patients were divided into an effective group and an ineffective group based on the reduction of their National Institutes of Health Chronic Prostatitis Symptom Index (NIH‐CPSI). A nomogram was established based on logistic regression analyses. Then, receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA) were used to evaluate the nomogram. Univariate and multivariate logistic regression analysis showed that a higher NIH‐CPSI score, a habit of holding urine, alcohol consumption, and urination soon after intercourse were independent predictors of Li‐ESWT efficacy (p < 0.05). The nomogram constructed based on these four indicators and the added age effectively predicted the probability of Li‐ESWT effectiveness for CP/CPPS‐like symptoms (0.809 [95% CI: 0.717–0.901]; Hosmer–Lemeshow: p = 0.936). This study established a predictive model for the efficacy of Li‐ESWT in treating CP/CPPS‐like symptoms patients and help improve the management of CP/CPPS‐like symptoms. [ABSTRACT FROM AUTHOR]

Background: The incidence of early‐onset prostate cancer (PCa) has increased significantly over the past few decades. It is necessary to develop a prognostic nomogram for the prediction of overall survival (OS) in early‐onset PCa patients. Methods: A total of 23,730 early‐onset PCa patients (younger than 55 years old) between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled for the current study, and randomly separated into the training cohort and the validation cohort. 361 eligible early‐onset PCa patients from The Cancer Genome Atlas‐Prostate Adenocarcinoma (TCGA‐PRAD) cohort were obtained as the external validation cohort. Independent predictors were selected by univariate and multivariate Cox regression analysis, and a prognostic nomogram was constructed for 1‐, 3‐, and 5‐year OS. The accurate and discriminative abilities of the nomogram were evaluated by the concordance index (C‐index), receiver operating characteristic curve (ROC), calibration plot, net reclassification index (NRI), and integrated discrimination improvement (IDI). Results: Multivariate Cox analysis showed that race, marital status, TNM stage, prostate‐specific antigen, Gleason score, and surgery were significantly associated with poor prognosis of PCa. A nomogram consisting of these variables was established, which had higher C‐indexes than the TNM system (training cohort: 0.831 vs. 0.746, validation cohort: 0.817 vs. 0.752). Better AUCs of the nomogram than the TNM system at 1, 3, and 5 years were found in both the training cohort and the validation cohort. The 3‐year and 5‐year AUCs of the nomogram in the TCGA‐PRAD cohort were 0.723 and 0.679, respectively. The calibration diagram, NRI, and IDI also showed promising prognostic value in OS. Conclusions: We developed an effective prognostic nomogram for OS prediction in early‐onset PCa patients, which will further assist both the precise clinical treatment and the assessment of long‐term outcomes. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to establish and validate a coagulation feature-based nomogram to predict recurrence-free survival in prostate cancer patients. Methods: The study included 168 prostate cancer patients who had received radical prostatectomy between 2012 and 2018. Kaplan-Meier plot and log-rank analysis were used to screen recurrence-free survival-related features. The nomogram was established by combining the significant coagulation features with clinicopathological characteristics by using Cox regression analysis. The accuracy and clinical significance of the nomogram model were assessed by the receiver operating characteristic curve, Kaplan-Meier plot, and calibration plot. We explored the correlation between coagulation pathway activity and patient prognosis in public datasets by using gene set variation analysis (GSVA). Results: The results suggested that patients classified by the nomogram into the high-risk subgroup showed unfavorable prognoses compared with those in the low-risk subgroup in both the training (log-rank p < 0.0001) and validation (log-rank p = 0.0004) cohorts. The nomogram model exhibited high discriminative accuracy in the training cohort (1-year area under the curve [AUC] of 0.74 and 3-year AUC of 0.69), which was confirmed in the internal validation cohort (C-index = 0.651). The calibration plots confirmed good concordance for the prediction of recurrence-free survival at 1 and 3 years. Subgroup analyses confirmed the utility of this model in different clinicopathological subgroups. Finally, GSVA suggested that patients with higher coagulation pathway scores mostly had unfavorable prognoses compared to those with lower scores, a result consistent with the findings above. Conclusions: We developed a practical nomogram model for predicting recurrence-free survival in prostate cancer patients. This model may offer clinicians prognostic assessments and facilitate personalized treatment. [ABSTRACT FROM AUTHOR]

Objective. To assess the safety and efficacy of the application of self-made non-inflating suspension technique in video endoscopic inguinal lymph node dissection (ILND). Methods. We collected 8 patients with penile carcinoma who underwent noninflating video-endoscopic ILND in the Department of Urology, the First Affiliated Hospital of Anhui Medical University, from May 2019 to March 2021. Then, surgical duration, blood loss, drainage tube indwelling time, hospital stay, number of dissected lymph nodes, and complications in the patients were analyzed. Results. All patients (n = 8) finished the surgery successfully, with an average surgical duration of 125 (105-145) minutes, blood loss of 41 (25-50) mL, indwelling time of drainage tube of 7 (5-12) days, and a hospital stay of 14.8 (9-21) days. Additionally, 8.8 (3-14) left side and 7.3 (2-17) right side lymph nodes were dissected on average. Complications occurred in 3 patients during a perioperative period. The patients were followed up for 6-24 months, and none suffered recurrence or metastasis. Conclusion. The efficacy of noninflating video-endoscopic ILND is good. Patients who have undergone the surgery not only have few postoperative complications but also have a good prognosis, suggesting the safety and availability of the clinical application. [ABSTRACT FROM AUTHOR]

During the development of urinary stone disease, the formation of tiny crystals that adhere to the renal tubular epithelium induces epithelial cell damage. This damage and repair of the epithelium is associated with the establishment of more crystal adhesion sites, which in turn stimulates further crystal adhesion and, eventually, stone formation. Deposited crystals typically cause changes in epithelial cell gene expression, such as transcriptome changes and alternative splicing events. Although considered important for regulating gene expression, alternative splicing has not been reported in studies related to kidney stones. To date, whether alternative splicing events are involved in the regulation of stone formation and whether crystallographic cell interactions are regulated by alternative splicing at the transcriptional level have remained unknown. Therefore, we conducted RNA sequencing and alternative splicing-related bioassays by modeling the in vitro stone environment. Many alternative splicing events were associated with crystallographic cell interactions. Moreover, these events regulated transcription and significantly affected the capacity of crystals to adhere to renal tubular epithelial cells and regulate apoptosis. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most frequent malignancy in male urogenital system around worldwide. We performed molecular subtyping and prognostic assessment based on consensus genes in patients with PCa. Five cohorts containing 1,046 PCa patients with RNA expression profiles and recorded clinical follow-up information were included. Univariate, multivariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression were used to select prognostic genes and establish the signature. Immunohistochemistry staining, cell proliferation, migration and invasion assays were used to assess the biological functions of key genes. Thirty-nine intersecting consensus prognostic genes from five independent cohorts were identified. Subsequently, an eleven-consensus-gene classifier was established. In addition, multivariate Cox regression analyses showed that the classifier served as an independent indicator of recurrence-free survival in three of the five cohorts. Combined receiver operating characteristic (ROC) analysis achieved synthesized effects by combining the classifier with clinicopathological features in four of five cohorts. SRD5A2 inhibits cell proliferation, while ITGA11 promotes cell migration and invasion, possibly through the PI3K/AKT signaling pathway. To conclude, we established and validated an eleven-consensus-gene classifier, which may add prognostic value to the currently available staging system. By analysis of gene expression profiles of prostate cancer patients from multiple platforms, an eleven-consensus-gene classifier is constructed to provide a robust tool for the prediction of recurrence-free survival. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles (IONPs)-based contrast agents are widely used for T2-weighted magnetic resonance imaging (MRI) in clinical diagnosis, highlighting the necessity and importance to evaluate their potential systematic toxicities. Although a few previous studies have documented the toxicity concerns of IONPs to major organs, limited data are available on the potential reproductive toxicity caused by IONPs, especially when administrated via intravenous injection to mimic clinical use of MRI contrast agents. Our study aimed to determine whether exposure to IONPs would affect male reproductive system and cause other related health concerns in ICR mice. The mice were intravenously injected with different concentrations IONPs once followed by routine toxicity tests of major organs and a series of reproductive function-related analyses at different timepoints. As a result, most of the contrast agents were captured by reticuloendothelial system (RES) organs such as liver and spleen, while IONPs have not presented adverse effects on the normal function of these major organs. In contrast, although IONPs were not able to enter testis through the blood testicular barrier (BTB), and they have not obviously impaired the overall testicular function or altered the serum sex hormones levels, IONPs exposure could damage Sertoli cells in BTB especially at a relative high concentration. Moreover, IONPs administration led to a short-term reduction in the quantity and quality of sperms in a dose-dependent manner, which might be attributed to the increase of oxidative stress and apoptotic activity in epididymis. However, the semen parameters have gradually returned to the normal range within 14 days after the initial injection of IONPs. Collectively, these results demonstrated that IONPs could cause reversible damage to the reproductive system of male mice without affecting the main organs, providing new guidance for the clinical application of IONPs as T2-MRI contrast agents. [ABSTRACT FROM AUTHOR]

This study was carried out to demonstrate the prognostic value of CD274 (PD-L1 promoter gene) methylation in bladder cancer patients. UCSC Xena database was searched for relevant information on PD-L1 (CD274) methylation and PD-L1 mRNA expression in bladder cancer. 407 bladder patients were included in our analyses. Multivariate analysis revealed that PD-L1 methylation was an independent predictor for OS (P = 0.037). Moreover, PD-L1 methylation might be a prognostic biomarker for immunotherapy response. However, PD-L1 methylation and PD-L1 mRNA expression was not statistically associated with chemotherapy response. In conclusion, PD-L1 methylation was an independent prognostic factor for bladder cancer patients. [ABSTRACT FROM AUTHOR]

The present work aims to evaluate the clinical efficacy and safety of low‐intensity extracorporeal shock wave therapy (Li‐ESWT) on patients with prostatitis‐like symptoms (PLS). Patients with PLS were recruited and received four‐week Li‐ESWT (once per week), which was conducted at a frequency of 3 Hz with a preferred energy flow density of 0.25 mJ/mm2. The scores of the National Institute of Health Chronic Prostatitis Symptoms Index (NIH‐CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF‐5), and Visual Analogue Scale (VAS) were recorded to assess the remission of disease in the 0, 1st, 2nd, 3rd, 4th, 5th, 8th and 16th weeks. A decrease of the NIH‐CPSI score ≥6 was regarded as the effectiveness standard of Li‐ESWT. Among 91 enrolled patients, the scores of all validated questionnaires presented significant improvements in the 4th week (p <.05) compared with that in baseline, except for IIEF‐5. The treatment effective rates in the 1st, 2nd, 3rd, 4th, 5th, 8th and 16th weeks were 28.57%, 38.46%, 47.25%, 51.65%, 57.30%, 68.18% and 69.44%, respectively. No pronounced undesirable side effect has occurred. Li‐ESWT is effective and safe in treating PLS. The efficacy can be maintained within three months. [ABSTRACT FROM AUTHOR]

Transcription factor activating enhancer binding protein 4 (TFAP4) has been indicated to be correlated with the progression of various human malignancies. However, the effect and regulatory mechanism of TFAP4 in prostate cancer (PC) remain unclear. The protein and mRNA expression were detected by western blotting and RT-qPCR. TFAP4 was overexpressed or knocked down in PC cells. The viability, invasion and migration of PC cells were analyzed by CCK-8, Transwell and wound healing assays. The colony formation was also determined. TFAP4 expression was upregulated in PC patients and cells; high TFAP4 expression predicted poor prognosis, and was associated with a range of clinicopathological features, including metastasis, clinical stage and Gleason score. Moreover, overexpression of TFAP4 promoted cell viability, migration, and invasion in vitro, whereas knockdown of TFAP4 revealed the opposite results. TFAP4 also positively regulated forkhead box K1 (FOXK1) expression. In addition, overexpression of FOXK1 reversed the effects of TFAP4 knockdown on PC cells. These findings clarified the biologic significance of TFAP4 in PC progression and revealed an association between TFAP4 and FOXK1, thus providing a new potential target for clinical therapy of PC. [ABSTRACT FROM AUTHOR]

Background: Eukaryotic initiation factor 3a (EIF3A), a "reader" protein for RNA methylation, has been found to be involved in promoting tumorigenesis in a variety of cancers. The impact of EIF3A in clear cell renal cell carcinoma (ccRCC) has yet to be reported. This study aimed to identify the prognostic value of EIF3A in ccRCC and investigate the relationship between EIF3A expression and immune infiltration. Methods: We collected 29 m6A-related mRNA data and clinicopathological parameters from The Cancer Genome Atlas (TCGA) database. Logistic regression analyses were used to analyse the correlation between EIF3A expression and clinical characteristics. Immunohistochemistry (IHC) was applied to examine EIF3A levels in normal and ccRCC tissues. Univariate and multivariate analyses were conducted to recognize independent factors associated with overall survival (OS) and disease-free survival (DFS). The nomogram aimed to predict the 1-, 3- and 5-year survival probabilities. Gene set enrichment analysis (GSEA) was carried out to determine the potential functions and related signalling pathways of EIF3A expression. To investigate EIF3A of coexpressed genes, we used LinkedOmics, and the results were subjected to enrichment analysis. Simultaneously, LinkedOmics and STRING datasets were used to identify EIF3A coexpressed genes that were visualized via Cytoscape. Finally, we evaluated whether EIF3A expression correlated with the infiltration of immune cells and the expression of marker genes in ccRCC by Tumour Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). Result: EIF3A expression was significantly different between ccRCC tissues and normal tissues. EIF3A expression was correlated with poor prognostic clinicopathological factors, and K–M analyses revealed that low EIF3A expression was correlated with a poor prognosis. The results of univariate and multivariate analyses proved that EIF3A was a prognostic factor in ccRCC patients. GSEA results indicated that EIF3A high expression was enriched in the renal cell carcinoma pathway. EIF3A expression was significantly positively correlated with B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, and dendritic cells. Furthermore, EIF3A expression was associated with most marker genes of immune cells. Conclusions: EIF3A could serve as a potential biomarker for prognostic and diagnostic stratification of ccRCC and is related to immune cell infiltrates. [ABSTRACT FROM AUTHOR]

Background: Eukaryotic initiation factor 3a (EIF3A), a “reader” protein for RNA methylation, has been found to be involved in promoting tumorigenesis in a variety of cancers. The impact of EIF3A in clear cell renal cell carcinoma (ccRCC) has yet to be reported. This study aimed to identify the prognostic value of EIF3A in ccRCC and investigate the relationship between EIF3A expression and immune infiltration. Methods: We collected 29 m6A-related mRNA data and clinicopathological parameters from The Cancer Genome Atlas (TCGA) database. Logistic regression analyses were used to analyse the correlation between EIF3A expression and clinical characteristics. Immunohistochemistry (IHC) was applied to examine EIF3A levels in normal and ccRCC tissues. Univariate and multivariate analyses were conducted to recognize independent factors associated with overall survival (OS) and disease-free survival (DFS). The nomogram aimed to predict the 1-, 3- and 5-year survival probabilities. Gene set enrichment analysis (GSEA) was carried out to determine the potential functions and related signalling pathways of EIF3A expression. To investigate EIF3A of coexpressed genes, we used LinkedOmics, and the results were subjected to enrichment analysis. Simultaneously, LinkedOmics and STRING datasets were used to identify EIF3A coexpressed genes that were visualized via Cytoscape. Finally, we evaluated whether EIF3A expression correlated with the infiltration of immune cells and the expression of marker genes in ccRCC by Tumour Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). Result: EIF3A expression was significantly different between ccRCC tissues and normal tissues. EIF3A expression was correlated with poor prognostic clinicopathological factors, and K–M analyses revealed that low EIF3A expression was correlated with a poor prognosis. The results of univariate and multivariate analyses proved that EIF3A was a prognostic factor in ccRCC patients. GSEA results indicated that EIF3A high expression was enriched in the renal cell carcinoma pathway. EIF3A expression was significantly positively correlated with B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, and dendritic cells. Furthermore, EIF3A expression was associated with most marker genes of immune cells. Conclusions: EIF3A could serve as a potential biomarker for prognostic and diagnostic stratification of ccRCC and is related to immune cell infiltrates. [ABSTRACT FROM AUTHOR]

Background. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) refers to a common disorder with unclear etiology and unsatisfactory treatment, which reduces the male's quality of life. Objective. To examine the effects of genetic polymorphisms of IFNG, IFNGR1, and androgen receptor (AR) on CP/CPPS. Methods. The single nucleotide polymorphisms (SNPs) of IFNG, IFNGR1, and AR were genotyped with the improved multiplex ligation detection reaction. The GTEx, RegulomeDB, HaploReg, and 3DSNP databases were adopted to predict the regulatory functions of the genotyped SNPs. The correlation between SNPs and CP/CPPS was analyzed with the χ 2 test, logistic regression, and two genetic models (codominant and log-additive models). The nomogram was built to predict the risk of CP/CPPS occurrence. Results. On the whole, 130 CP/CPPS patients and 125 healthy controls were recruited in the study, and 18 SNPs of IFNG, IFNGR1, and AR were genotyped. The results of functional annotation indicated that the 18 genotyped SNPs might have regulatory effects in the whole blood. The rs144488434 was correlated with the elevated CP/CPPS risk (odds ratio (OR): 2.40, 95% confidence interval (CI): 1.12-5.13, χ 2 = 5.37 , and P = 0.021) by the χ 2 test. In the built genetic models, rs10457655 was correlated with the elevated National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores (codominant model: GA/GG: crude mean difference MD = 0.98 , 95% CI: -1.71-3.67 and AA/GG: crude MD = 9.10 , 95% CI: 0.58-17.62, P = 0.10). In subgroup analysis, rs2069718 was correlated with the elevated CP/CPPS risk (log-additive model: crude OR = 2.18 , 95% CI: 1.03-4.64, and P = 0.034) in patients ≥ 35 years. The nomogram integrating age, rs2069718, rs10457655, and rs144488434 showed good performance to predict the risk of CP/CPPS. Conclusions. Genetic polymorphisms of IFNG, IFNGR1, and AR might act as the genetic factors for CP/CPPS susceptibility, which deserved further explorations. [ABSTRACT FROM AUTHOR]

Background and Objective. Selenoprotein P (SEPP1) is the major selenoprotein in plasma. Previous studies have demonstrated that SEPP1 expression was reduced in human prostate and colon tumors. Nowadays, studies concerning SEPP1 gene polymorphisms and cancer susceptibility have been extensively investigated, whereas results from these studies remain debatable rather than conclusive. Thus, we performed the present meta-analysis to comprehensively assess the association between two common polymorphisms (rs3877899 and rs7579) in SEPP1 and cancer susceptibility. Method. We search the PubMed, Embase, Google Scholar, and Wanfang (China) databases (up to December 1, 2020) to identify all eligible publications. The pooled odds ratio (OR) correspondence with 95% confidence interval (CI) was calculated to evaluate the associations. Results. Finally, nine eligible studies with 7,157 cases and 6,440 controls and five studies with 2,278 cases and 2,821 controls were enrolled in rs3877899 and rs7579 polymorphisms, individually. However, a null significant association was detected between the two polymorphisms in SEPP1 and susceptibility to colorectal, breast, and prostate cancer in all comparison models. Subsequently, subgroup analysis based on tumor type, no significant association was identified for prostate, breast, and colorectal cancer. In addition, when the stratification analyses were conducted by the source of control, HWE status, and ethnicity, yet no significant association was found. Conclusions. The current meta-analysis shows that SEPP1 rs3877899 and rs7579 polymorphisms may not be associated with susceptibility to colon cancer, breast cancer, and prostate cancer, and further well-designed studies with a larger sample size are warranted to validate our findings. [ABSTRACT FROM AUTHOR]

Background: Due to limited data on the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and the suboptimal therapeutic effect, the development of new and effective treatment modalities was needed urgently. Low‐intensity extracorporeal shock wave therapy (Li‐ESWT) has been reported for the treatment of CP/CPPS. However, the underlying mechanism remains to be elucidated. Objective: To interrogated the efficacy and the mechanism of Li‐ESWT in the treatment of CP/CPPS. Materials and Methods: According to different treatments, RWPE‐1 cells (human prostate epithelial cells) were randomly divided into three groups: control group, LPS (lipopolysaccharide) group, or Li‐ESWT group (LPS‐induced RWPE‐1 managed by Li‐ESWT). Following the Li‐ESWT treatment, the levels of oxidative stress were assayed. We then established a rat model of experimental autoimmune prostatitis (EAP) by injecting prostatic protein homogenate mixed with complete Freund's adjuvant. The Sprague‐Dawley rats were randomly divided into the control group, EAP group, or Li‐ESWT group. Von Frey Filament was used to quantify pelvic hyperalgesia in the rats. Prostates tissues from each group were collected for immunohistochemistry, oxidation stress, and Western blot analysis. Results: Histological analysis showed reduced inflammation and expression of cytokines (TNF‐α, IL‐1β, IL‐6, COX‐2, SP) in prostate tissues from the Li‐ESWT group compared with those from the EAP group (all p < 0.05). Similarly, there was reduced pelvic pain and allergic symptoms in the Li‐ESWT group compared with the EAP group (all p < 0.05). Besides, Li‐ESWT treatment could decrease oxidative stress in the prostate and in RWPE‐1 cells, respectively (both p < 0.05). Moreover, the Li‐ESWT upregulated the expression of CAT through the inhibition of phosphorylation of AKT/FOXO1 signaling pathway. Discussion and Conclusions: Li‐ESWT may reduce inflammation, oxidative stress, and pain in rats with autoimmunity‐induced prostatitis via the PI3 K/AKT/FOXO1 pathway. It implies that Li‐ESWT can present a potential therapeutic option for the treatment of CP/CPPS. [ABSTRACT FROM AUTHOR]

(E and F) Barplots revealed that LRisk group in TCGA-BLCA cohort might be more sensitive to immune checkpoint blockade; such finding was also consistent with another prostate cancer cohort in which patients who could respond to anti-CTLA4 had lower IRGPI. Additionally, we stratified 16 patients with prostate cancer who received anti-CTLA4 therapy; a remarkably higher number of patients in LRisk group (50%) responded to anti-CTLA4 treatment than HRisk (12.5%) (Figure 3F). Numerous prognostic signatures to bladder cancer (BCa) have been reported, but many of them limited to either nonmuscle-invasive (NMIBC) or muscle-invasive BCa (MIBC), and inherent technical biases across platforms impeded clinical application. An R package " I BCaller i " (https://github.com/xlucpu/BCaller) was used to calculate an immune-related genes pair index (IRGPI) from single-sample perspective using transcriptome profiles for bladder cancer. [Extracted from the article]

Renal cell carcinoma (RCC) is one of the most frequently occurring tumors worldwide. Herein, we established a microRNA (miRNA) predicting signature to assess the prognosis of papillary-type RCC (PRCC) patients. miR-1293, miR-34a, miR-551b, miR-937, miR-299, and miR-3199-2 were used in building the overall survival (OS)-related signature, whereas miR-7156, miR-211, and miR-301b were used to construct the formula of recurrence-free survival (RFS) with the help of LASSO Cox regression analysis. The Kaplan–Meier and receiver operating characteristic curves indicated good discrimination and efficiency of the two signatures. Functional annotation for the downstream genes of the OS/RFS-related miRNAs exposed the potential mechanisms of PRCC. Notably, the multivariate analyses suggested that the two signatures were independent risk factors for PRCC patients and had better prognostic capacity than any other classifier. In addition, the nomogram indicated synthesis effects and showed better predictive performance than clinicopathologic features and our signatures. We validated the OS and RFS prediction formulas in clinical samples and met our expectations. Finally, we established two novel miRNA-based OS and RFS predicting signatures for PRCC, which are reliable tools for assessing the prognosis of PRCC patients. [ABSTRACT FROM AUTHOR]

RNA binding proteins (RBPs) dysregulation is involved in the processes of various tumors. However, the roles of RBPs in clear cell renal cell carcinoma (ccRCC) remain poorly understand. In present study, we first performed consensus clustering and identified two clusters, of which cluster 2 was closely correlated with the malignancy of ccRCC. Differentially expressed RBPs between normal and tumor tissues were obtained, comprising 71 up-regulated and 44 down-regulated ones. Then, ten hub genes were selected and validated using The Human Protein Atlas database and receiver operating characteristic curves, showing good diagnostic value for cancers. Besides, we identified ten RBPs with the most useful prognostic values, and were used to construct a risk score model. The model could be used to stratify patients with different prognosis and phenotype distributions. The model showed good performance and can be used as a complementation for clinical factors to guide clinical practice in the future. [ABSTRACT FROM AUTHOR]

Prostatic calculi (PCal) are commonly present with prostate disease; we aim to map the incidence and associated clinical risk factors of PCal in Han Chinese. We retrospectively selected men who sought a medical check-up in 2018. Basic clinical items, including age, weight, height, prostate specific antigen (PSA), uric acid (UA), fasting blood glucose (FBG), urinalysis results, and transabdominal prostate ultrasound, were recorded. Univariate and logistic regression analyses were performed to evaluate whether these factors were associated with the presence of PCal. We recorded the parameters of laboratory tests and clinical information from 14,427 men; men with PCal comprised 51.65% of the total group and 76.61% of the subgroup of benign prostate hyperplasia (BPH) patients. All the enrolled parameters showed meaningful differences, but the logistic regression analysis only indicated significant effects related to age (OR = 1.044, 95% CI = 1.040–1.047, and p <.001), body mass index (BMI) (OR = 1.035, 95% CI = 1.022–1.048, and p <.001), UA (OR = 0.999, 95% CI = 0.999–1.000, and p =.029), BPH (OR = 2.923, 95% CI = 2.678–3.191, and p <.001), and prostate cysts (OR = 0.609, 95% CI = 0.471–0.788, and p <.001). The odds ratio of the predicted combined model is 1.068. PCal was detected in 51.65% of men among healthy Han Chinese and in 76.61% of BPH patients. Age, BMI, UA, BPH, and prostate cysts were independent risk factors for the presence of PCal. [ABSTRACT FROM AUTHOR]

Objectives: Patients with autosomal dominant polycystic kidney disease (ADPKD) showed relatively high incidence of urinary stones. Enlarged kidneys occupied by cysts could make the stone-removal surgery relatively difficult. This study aimed to compare the efficacy and safety of retroperitoneal laparoscopic ureterolithotomy (RPLU), flexible ureteroscopic lithotripsy (FURL) and percutaneous nephrolithotomy (PCNL) in the ADPKD patients with upper urinary stones. Methods: In this study, 45 patients with ADPKD who underwent RPLU, FURL and PCNL procedures were evaluated. Demographic and serum parameters, stone features, outcomes and complications were analyzed. Results: 45 patients were included in the present study, 13 received RPLU, 21 received FURL, and 11 received PCNL. There were no significant differences in demographic and serum parameters between the three groups. Stone-free rates of the three approaches are 100%, 85.7% and 90.9%, respectively. Patients who underwent FURL had shorter mean operative time and postoperative hospital stay. Compared to RPLU and PCNL, FURL resulted in fewer complications, but the difference is statistically non-significant. Conclusions: RPLU, FURL and PCNL are commonly used surgical methods to solve upper urinary calculi in ADPKD patients and could achieve satisfactory stone clearance. Among them, FURL showed a relative high safety and faster recovery. [ABSTRACT FROM AUTHOR]

E3 ubiquitin ligase gene, WWP2, is associated with acute kidney injury (AKI). This research was conducted to explore the role of WWP2 in AKI. AKI cell model was produced in human renal proximal tubular epithelial cell line (HK‐2) by ischemia‐reperfusion (IR) injury. CCK8 and flow cytometry assay were performed to explore the influence of WWP2 overexpression on cell proliferation and apoptosis of IR‐induced HK‐2 cells. Quantitative real‐time PCR and immunoblotting (IB) were performed to assess the gene and protein expression. Then, the influence of WWP2 on p53 ubiquitylation and degradation was estimated by immunoprecipitation assay. Our data indicated that WWP2 was down‐regulated and p53 was up‐regulated in IR‐induced HK‐2 cells. WWP2 overexpression promoted proliferation and inhibited apoptosis of IR‐induced HK‐2 cells. And WWP2 interacted with p53 and regulated p53 ubiquitylation and degradation. Furthermore, the influence of WWP2 on cell proliferation and apoptosis was rescued by MG132 (proteasome inhibitor) treatment. In conclusion, our work described for the first time the role of WWP2 in AKI, showing that WWP2 ameliorated AKI by mediating p53 ubiquitylation and degradation. Moreover, the study offers some important insights into the occurrence of AKI and WWP2 may be a novel target of AKI treatment. Significance of the study: Our data elaborates that WWP2 has protective effect against AKI by mediating p53 ubiquitylation and degradation. Thus, WWP2 might be a therapeutic target for AKI. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of tamsulosin combined with dapoxetine in the treatment of type IIIB chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) that is complicated by premature ejaculation (PE), a total of 251 CP/CPPS patients with PE were recruited from nine hospitals across China and were randomly divided into two groups: one received tamsulosin as a control, and the other received a combination therapy of tamsulosin and dapoxetine. Follow‐up was conducted at four time points, and indicators describing CP/CPPS and PE were compared between the two groups. In all, 223 patients were followed up at least once, and 114 patients completed all of the treatment process. The combination group showed more improvement in the symptoms of both PE and CP/CPPS, including thrust number (50.5 vs. 45), premature ejaculation profile score (11.39 vs. 6.96), intravaginal ejaculation latency time (5.95 min vs. 2.63 min) and the National Institutes of Health Chronic Prostatitis Symptom Index (7.44 vs. 11.81) in comparison with the tamsulosin group. In conclusion, for CP/CPPS patients with PE, tamsulosin combined with dapoxetine provided better therapeutic efficacy in the treatment of not only PE symptoms but also CP/CPPS indicators in comparison with tamsulosin monotherapy. [ABSTRACT FROM AUTHOR]

The roof plate-specific spondin (RSPO) family of proteins has critical roles in the tumorigenesis and progression of several carcinomas; however, little is known about their functions in bladder cancer (BLCA). This study aimed to investigate RSPO in terms of their expression levels, prognostic value, and potential mechanisms of action in BLCA. mRNA expression profiles and clinical information of BLCA patients were collected from The Cancer Genome Atlas database. Genetic alteration and DNA methylation data were obtained from cBioPortal and MethHC databases, respectively, and SurvExpress was used to determine the prognostic risk score of each RSPO. R software was used to analyze the expression levels and prognostic roles of RSPOs in BLCA. The effects of RSPO2 overexpression in BLCA cells were detected using MTT, colony formation, and Transwell invasion assays. Gene set enrichment analysis (GSEA) was used to analyze the functions of RSPOs and associated signaling pathways in BLCA. All members of the RSPO family were differentially expressed in BLCA cells compared with normal control cells. Aberrant RSPO expression levels were associated with higher histological stages and worse prognosis. The frequency of genetic alterations in RSPO genes was very high, which was related to a less favorable prognosis. Moreover, the effects of mutations in the RSPO2 gene were reversed using a Wnt/β-catenin inhibitor, IWP-2. In addition, GSEA demonstrated that RSPOs were associated with focal adhesion and immune cell infiltration, which was then confirmed by tumor immune cell infiltration analysis. RSPOs are potential biomarkers for predicting the prognosis of patients with BLCA and may serve as novel therapeutic targets. Moreover, overexpressed RSPO2 promoted BLCA cell growth and invasion through the Wnt/β-catenin pathway. In addition, RSPOs may regulate the progression of BLCA through modulating cell adhesion, focal adhesion, and CD4+ T cell and macrophage infiltration. [ABSTRACT FROM AUTHOR]

Background: Currently, the prognosis of kidney cancer depends mainly on the pathological grade or tumor stage. Clinicians have few effective tools that can personalize and adequately evaluate the prognosis of kidney cancer patients. Methods: A total of 70 481 kidney cancer patients were selected from the Surveillance, Epidemiology, and End Results database, among which patients diagnosed in 2005‐2011 (n = 42 890) were used to establish nomograms for overall survival (OS) and cancer‐specific survival (CSS), and those diagnosed in 2012‐2015 (n = 24 591) were used for external validation. Univariate and multivariate Cox analyses were used to determine independent prognostic factors. Concordance index (C‐index), receiver operating characteristic curve, and calibration curve were used to evaluate the predictive capacity of the nomograms. We further reduced subgroup classification and used propensity score matching to balance clinical informations, and analyzed the effect of other variables on survival. We established a new kidney cancer prognostic score system based on the effect of all available variables on survival. Cox proportional hazard model and Kaplan‐Meier curves were used for survival comparison. Results: Age, gender, marital status, surgery, grade, T stage, and M stage were included as independent risk factors in the nomograms. The favorable area under the curve (AUC) value (for OS, AUC = 0.812‐0.858; and for CSS, AUC = 0.890‐0.921), internal (for OS, C‐index = 0.776; and for CSS, C‐index = 0.856), and external (for OS, C‐index = 0.814‐0.841; and for CSS, C‐index = 0.894‐0.904) validation indicated that the proposed nomograms could accurately predict 1‐, 3‐, and 5‐year OS and CSS of kidney cancer patients. The Aggtrmmns prognostic scoring system based on age, gender, race, marital status, grade, TNM stage, and surgery of kidney cancer patients could stage patients more explicitly than the AJCC staging system. Conclusion: The nomogram and Aggtrmmns scoring system can predict OS and CSS in kidney cancer patients effectively, which may help clinicians personalize prognostic assessments and clinical decisions. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the regulatory mechanism of cancer‐associated fibroblasts (CAFs) exosome in bladder cancer (BC) cell proliferation and invasion. CAFs and normal fibroblasts (NFs) were isolated from tumor tissues and adjacent normal tissues of BC patients, and examined by immunocytochemistry for the expression of fibroblast activation protein alpha (FAP) and α‐smooth muscle actin (α‐SMA). Exosomes were extracted from CAFs and NFs and observed under a transmission electron microscope, and expression of the exosome markers CD9 and CD63 was confirmed by western blotting. The distribution and intensity of fluorescence were observed by confocal laser microscopy to analyze exosomes uptake by BC cell lines T24 or 5367. BC cell proliferation and invasion were detected by MTT and Transwell assays, respectively. LINC00355 levels in CAFs, NFs, CAFs exosome, NFs exosome, and BC cells were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). Results showed that CAFs exosome significantly promoted BC cell proliferation and invasion relative to NFs exosome. LINC00355 expression was significantly elevated in CAFs exosome when compared with that in NFs‐exosome. Up‐regulated LINC00355 expression was observed both in T24 and 5367 cells co‐incubated with CAFs exosome. Exosomes derived from LINC00355 siRNA‐transfected CAFs observably repressed BC cell proliferation and invasion when compared with control siRNA‐CAFs exosome. In conclusion, CAFs exosome–mediated transfer of LINC00355 regulates BC cell proliferation and invasion. Significance of the study. In this study, our data suggest that the exosomes released from CAFs promote BC cell proliferation and invasion. The mechanism of this effect is, at least in part, related to the increased LINC00355. Regulation of LINC00355 expression in exosomes released from CAFs might be a putative therapeutic strategy against the pathogenesis of BC. [ABSTRACT FROM AUTHOR]

Patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) commonly experience learning and memory decline and the underlying pathogenesis remains unclear. Therefore, we aimed to study the effects of CP/CPPS on cognitive function by using a mouse model of experimental autoimmune prostatitis (EAP). Non-obese diabetic mice were immunized subcutaneously by prostate antigen and adjuvant twice and tested for cognitive performance by Morris water maze and novel object recognition test after the EAP induction. Then, dendritic complexity and spine densities were measured by using the Golgi-Cox procedure. Transmission electron microscopy was used to observe the synaptic morphology. In addition, activation of microglia and its association with synapses were also investigated by immunofluorescence staining. Our results showed that EAP induced a notable decrease in the learning and memory ability of mice, simultaneously causing a reduction in dendritic complexity detected by Sholl analysis. Likewise, the spine densities and synaptic proteins including synaptophysin and postsynaptic density protein 95 (PSD95) were significantly decreased in the EAP group. These observations were also accompanied by structural changes in synaptic plasticity. Additionally, EAP mice showed microglial activation in the hippocampus, and these activated microglia further increased contact with synaptic terminals. Taken together, our data are the first to indicate that EAP induces cognitive declines and structural neuroplastic changes in mice, accompanied by microglial activation and microglia-synapse contacts. [ABSTRACT FROM AUTHOR]

IL-1α is closely related to the development and metastasis of cancer, and its polymorphisms have been reported affecting the susceptibility of malignancy tumors, yet the conclusions are controversial. Present an overall meta-analysis was performed to reach more general findings. Relevant literature was searched from Google Scholar, Web of Science, PubMed, EMBASE, CNKI database and Wanfang database, and the association among polymorphism and cancer risk was appraised by counting ORs and 95% CIs of overall and stratification analysis. The date from 15,586 cases and 18,430 controls in 40 publications were enrolled. There is significantly upregulated risk leads by rs3783553 in all genetic models, while the same tendency was found in all cancer types. The results also suggest a high risk of cancer susceptibility in patients carried rs1800587 polymorphism, of which draw out form allelic and homozygote models in overall studies, especially for cervical cancer. However, there are no significant results in analysis of rs17561. In a word, IL1A SNPs play an essential role in upregulating cancer susceptibility, and current analysis provides detail date for further study in the future. [ABSTRACT FROM AUTHOR]

Purposes: To explore the efficacy of circumcision with Chinese Shang Ring (CSR) in the different cohorts so that can obtain the best applicable population and manage complications better.Methods: This study consisted of 657 patients who were circumcised with CSR in our institute between August 2017 and August 2018. All cases were followed up at post-operation for 3 to 15 months. The surgery time (ST), wound healing time (WHT), satisfaction with the appearance of postoperative penis and complications were collected and comparatively analyzed. Multivariate analysis was used to determine the independent risk factors associated with efficacy, which were presented by odd ratios and its 95% confidence index.Results: All cases wore the CSR successfully. The ST and WHT respectively were 5.75 ± 2.27 mins and 21.15 ± 5.05 days. The long-term complications, total complications (TC), satisfaction and successful circumcision (SC) respectively were 5.30%, 11.70%, 97.70% and 94.70%. For TC and SC, there was a difference between phimosis and redundant foreskin (21.30% vs 6.20%, P<0.001 and 89.20% vs 97.8%, P<0.001, respectively). In terms of satisfaction and SC, adolescents were higher than children (98.70% vs 94.70%, P=0.035 and 96.80% vs 90.10%, P=0.024, respectively) but was similar to adults (98.70% vs 100.00%, P=0.071 and 96.80% vs 98.00%, P=0.257, respectively). The degree of pain and the incidence of wound dehiscence in adults was higher than adolescents (P<0.05). The phimosis (OR= 1.47, 95% CI=1.26-1.79, P<0.001) and childhood (OR= 1.13, 95% CI =1.06-1.36, P<0.001) were associated with poor efficacy.Conclusion: The curative effect of circumcision by CSR in adolescents was similar to adults, both higher than that of children. However, adults have more severe pain and a higher probability of wound dehiscence in the later stage than adolescents. So, adolescence is probably the best time to be circumcised with CSR. [ABSTRACT FROM AUTHOR]

Treg cells are crucial for maintaining immune homeostasis in CP/CPPS, but the molecular mechanisms underlying the modulation of the function of Treg in CP/CPPS remain unclear. The main purpose of this study is to investigate the relationship between immunosuppressive function of Treg and the methylation level of Foxp3 promoter in experimental autoimmune prostatitis (EAP) mouse model. EAP model was induced by subcutaneous injecting prostate-steroid-binding protein (PSBP) and complete Freund's adjuvant with NOD mice. Histological analysis revealed that EAP model was successfully induced. The expression of IFN-γ was increased, and TGF-β was decreased in the serum of EAP, respectively. The percentage of Tregs in splenic lymphocyte was increased in EAP. The suppressive ability of Tregs on Teffs was impaired in EAP. The methylation level of Foxp3 promoter was increased, and the expression of Foxp3 was decreased in EAP. By injection AZA which was DNA-methylation inhibitor into EAP mice, prostate inflammation was alleviated, expressions of TGF-β and Foxp3 were increased, and the suppressive function of Tregs was improved in vitro and in vivo. Thus, we concluded that aberrant increased methylation of Foxp3 promoter in Treg cells leads to the impaired suppressive function of Treg cells, exacerbating autoimmune inflammatory injury in EAP. [ABSTRACT FROM AUTHOR]

Objective: To present our experience of combining transperitoneal robot-assisted laparoscopic pyeloplasty (RALP) and concomitant flexible cystoscope lithotomy for ureteropelvic junction obstruction (UPJO) complicated by renal caliceal stones in the same session. Patients and methods: Between October 2014 and November 2017, RALP combined with flexible cystoscope lithotomy was performed in 16 patients with UPJO and ipsilateral renal caliceal stones. Stone location and size were preoperatively assessed. After pyelotomy with appropriate length (about 8–15 mm), a 16F flexible cystoscope through the assistant trocar or robotic trocar was introduced directly into the renal pelvis under laparoscopic vision. Holmium laser lithotripsy and pressure irrigation via a pump were used for caliceal stone removal. Subsequently, robot-assisted laparoscopic pyeloplasty was undergone in a standard fashion. Results: The calculi sizes ranged from 5 to 34 mm (mean 18.6 mm) and an average of 3.4 stones per patient was removed (range 1–8 stones). Complete stone clearance confirmed by postoperative imaging was achieved in all patients. Mean operative time was 204.6 min and estimated blood loss was 55.6 mL. Mean hospital stay was 6.7 days (3–17). The stent was removed after 8 weeks. No major intraoperative or postoperative complications were noted during a mean follow-up of 10.4 months (range 6–27 months). Conclusions: RALP combined with flexible cystoscope lithotomy is safe and effective alternatives for the simultaneous management of UPJO complicated by renal caliceal stones. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa), a severe health burden for males, accounts for the second frequent cancer and fifth tumor specific death cancer around the world. Several studies on tumor‐infiltrating immune cells (TIICs) have shown inconsistent and controversial results to PCa. We downloaded a gene expression matrix and clinical information from TCGA, and CIBERSORT was used to identify the proportion of TIICs. Wilcoxon's Sign Rank Test evaluated different gene expression levels in PCa and normal tissues. Kaplan‐Meier curves were used to evaluate the associations of TIICs and recurrence‐free survival (RFS). Finally, based on the preset P‐value of.05, the distribution of TIICs in 73 PCa tissues and 11 normal tissues was illustrated. Activated CD4+ T cells and M0 macrophages account for a high proportion in PCa tissues, while neutrophils and monocytes were found at a high density in normal tissues. Further results showed that the density of plasma cells, Treg cells and resting mast cells were associated with advanced PCa. Additionally, M2 macrophages affected the RFS of PCa patients, and AR was also involved. In the current study, we first evaluated the immune infiltration among PCa and revealed that M2 macrophages could predict the prognosis of PCa patients. Meanwhile, based on the LASSO regression analysis, we established a novel nomogram to assess the recurrence risk of PCa based on immune cell proportions and clinical features. [ABSTRACT FROM AUTHOR]

This study aims to verify whether the inhibitory effect of Sirtuin 3 (SIRT3) on the formation of renal calcium oxalate crystals was mediated through promoting macrophages (Mϕs) polarization. Identification and quantification of M1 and M2 monocytes were performed using fluorescence‐activated cell sorting analysis. SIRT3 protein level and forkhead box O1 (FOXO1) acetylation level were measured using western blot analysis. Cell apoptosis of HK‐2 was detected by flow cytometry. Mouse kidney tissues were subjected to Von Kossa staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical staining for detection of kidney crystals deposition, apoptosis, and expression of crystal‐related molecules, respectively. The results showed that human peripheral blood monocytes from patients with kidney stone (KS) exhibited decreased M2 monocytes percentage and SIRT3 expression, whereas increased FOXO1 acetylation compared with the normal controls. In vitro assay revealed that SIRT3 overexpression in bone marrow‐derived M0/M1/M2 Mϕs induced M2 polarization and decreased FOXO1 acetylation. Furthermore, FOXO1 knockdown reversed SIRT3‐mediated induction of M2 polarization and inhibition of HK‐2 (human proximal tubular cell line) apoptosis. Further in vivo experiments demonstrated that SIRT3‐overexpressing Mϕs transfusion not only induced M2 polarization, but also alleviated inflammation, apoptosis, and crystals deposition in glyoxylate‐induced KS mice. In conclusion, SIRT3 suppresses formation of renal calcium oxalate crystals through promoting M2 polarization via deacetylating FOXO1. Our findings support the notion that Sirtuin 3 (SIRT3) suppresses renal inflammation, renal apoptosis, and formation of renal calcium oxalate crystals. The protective role of SIRT3 in kidney stone (KS) disease was mediated, at least in part, through promoting the polarization of macrophages (Mϕs) toward the M2 phenotype via deacetylating forkhead box O1 (FOXO1). This study supports the therapeutic possibility of targeted Mϕs‐phenotype shifting from M1 to M2 in KS disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of Serenoa repens among patients with benign prostatic hyperplasia (lower urinary tract symptoms/benign prostatic hyperplasia [LUTS/BPH]) in China.Methods: We conducted a double blind, placebo-controlled study of 354 patients with LUTS/BPH from 19 institutions, to evaluate the efficacy and safety of Serenoa repens. Participants were randomly assigned (1:1) into the Serenoa repens extract (320 mg) or placebo groups for 24 weeks. Primary efficacy parameters were changes in International Prostate Symptom Score and peak urinary flow from baseline to each assessment. Secondary efficacy parameters included improvement of storage symptom and voiding symptom scores, prostate volume, urinary frequency, and total prostate-specific antigen level. Other parameters assessed were quality of life score, a four-item male sexual function questionnaire score, and International Index of Erectile Function score across the consecutive double-blind visits.Results: Statistically significant improvement in the peak urinary flow, International Prostate Symptom Score, scores of storage symptoms and voiding symptoms, quality of life score, four-item male sexual function questionnaire score, and International Index of Erectile Function score were observed in the Serenoa repens extract group compared with those in the placebo group (P <.05). Two (1.18%) of 169 patients in the placebo group and 3 (1.89) of 159 patients in the Serenoa repens extract group experienced 1 or more adverse events.Conclusion: The Serenoa repens extract was effective, safe, well-tolerated, and clinically and statistically superior to placebo in the target LUTS/BPH population. [ABSTRACT FROM AUTHOR]

[Display omitted] Prostate cancer is the most common tumor among men. Although the prognosis for early-stage prostate cancer is good, patients with advanced disease often progress to metastatic castration-resistant prostate cancer (mCRPC), which usually leads to death owing to resistance to existing treatments and lack of long-term effective therapy. In recent years, immunotherapy, especially immune checkpoint inhibitors (ICIs), has made great progress in the treatment of various solid tumors, including prostate cancer. However, the ICIs have only shown modest outcomes in mCRPC compared with other tumors. Previous studies have suggested that the suppressive tumor immune microenvironment (TIME) of prostate cancer leads to poor anti-tumor immune response and tumor resistance to immunotherapy. It has been reported that non-coding RNAs (ncRNAs) are capable of regulating upstream signaling at the transcriptional level, leading to a "cascade of changes" in downstream molecules. As a result, ncRNAs have been identified as an ideal class of molecules for cancer treatment. The discovery of ncRNAs provides a new perspective on TIME regulation in prostate cancer. ncRNAs have been associated with establishing an immunosuppressive microenvironment in prostate cancer through multiple pathways to modulate the immune escape of tumor cells which can promote resistance of prostate cancer to immunotherapy. Targeting these related ncRNAs presents an opportunity to improve the effectiveness of immunotherapy in this patient population. [ABSTRACT FROM AUTHOR]