Nomograms for predicting clinically significant prostate cancer in men with PI-RADS-3 biparametric magnetic resonance imaging.

This study aimed to construct nomograms for predicting the likelihood of clinically significant prostate cancer (csPCa) in patients with lesions rated as Prostate Imaging Reporting and Data System (PI-RADS) 3 on biparametric magnetic resonance imaging (bpMRI). We retrospectively analyzed a cohort of 457 patients from the Peking Union Medical College Hospital (January 2017-July 2021) to develop the model and externally validated it with a cohort of 238 patients from the Second Hospital of Tianjin Medical University (September 2017-September 2021). Univariate and multivariate logistic regression analyses identified significant predictors of csPCa, defined by tumor volumes ≥ 0.5 cm3, Gleason score ≥ 7, or presence of extracapsular extension. Diagnostic performance for the peripheral zone (PZ) and transitional zone (TZ) was compared using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Through univariate and multivariate logistic regression analyses, we identified age, prostate-specific antigen (PSA), and prostate volume (PV) as predictors of csPCa for the PZ, and age, serum-free to total PSA ratio (f/t PSA), and PSA density (PSAD) for the TZ. The nomograms demonstrated robust discriminative ability, with an area under the ROC curve (AUC) of 0.819 for PZ and 0.804 for TZ. The external validation corroborated the model's high predictive accuracy (AUC of 0.831 for PZ and 0.773 for TZ). Calibration curves indicated excellent agreement between predicted and observed outcomes, and DCA underscored the nomogram's clinical utility for both PZ and TZ. Overall, the nomograms offer high predictive accuracy for csPCa at initial biopsy, potentially reducing unnecessary biopsies in clinical settings.

The association between plant-based diet and erectile function in Chinese young healthy men: A population-based study.

The study was designed and conducted to evaluate the plant-based diet status and its association with erectile function (EF) in Chinese young healthy men. From July 2018 to May 2020, 116 objectively proved physically and psychologically healthy men were selected. Clinical questionnaires, detailed physical examinations and blood tests were all assessed. An overall plant-based diet index (PDI) and a healthful plant-based diet index (hPDI) were developed from each participant to measure plant-based diet quantitatively. The EF was measured by both the International Index of Erectile Function-5 (IIEF-5) and the surrogated measures of endothelial function, peripheral levels of nitric oxide (NO) and E-selectin. In subjects, the mean PDI and hPDI were 53.8 ± 8.2 and 54.7 ± 8.9 respectively. Results of multivariate analysis showed that both PDI and hPDI were negatively associated with BMI (all p < .05), but had no relationships with NO, E-selectin, TT levels and IIEF-5 scores (all p > .05). In a subgroup of male population, Chinese young healthy men, the plant-based diet, measured by PDI and hPDI, was not related to erectile function. The population can adhere to plant-based diet to keep healthy without concerns of negative influence on erectile function.

Progress in studies on pathological changes and future treatment strategies of obesity-associated female stress urinary incontinence: a narrative review.

With the increasing prevalence of obesity worldwide, obesity-related female stress urinary incontinence (FSUI) has become a key health problem. Recent studies indicated that FSUI is primarily caused by obesity-related pathological changes, such as fat droplet deposition, and results in pelvic floor nerve, vascular, and urethral striated muscle injury. Meanwhile, treatments for obesity-associated FSUI (OA-FSUI) have garnered much attention. Although existing OA-FSUI management strategies, including weight loss, pelvic floor muscle exercise, and urethral sling operation, could play a role in symptomatic relief; they cannot reverse the pathological changes in OA-FSUI. The continued exploration of safe and reliable treatments has led to regenerative therapy becoming a particularly promising area of researches. Specifically, micro-energy, such as low-intensity pulsed ultrasound (LIPUS), low-intensity extracorporeal shock wave therapy (Li-ESWT), and pulsed electromagnetic field (PEMF), have been shown to restore the underlying pathological changes of OA-FSUI, which might be related by regulation endogenous stem cells (ESCs) to restore urine control function ultimately in animal experiments. Therefore, ESCs may be a target for repairing pathological changes of OA-FSUI. The aim of this review was to summarize the OA-FSUI-related pathogenesis, current treatments, and to discuss potential therapeutic options. In particular, this review is focused on the effects and related mechanisms of micro-energy therapy for OA-FSUI to provide a reference for future basically and clinical researches.

Phosphodiesterase Type 5 Inhibitors and Risk of Skin Cancers in Men: A Meta-Analysis and Trial Sequential Analysis Involving 7,479,852 Subjects.

PURPOSE: We conducted a systematic review and meta-analysis to quantify the association between phosphodiesterase type 5 inhibitors (PDE5Is) use and skin cancers and we also examined whether down-expression of the PDE5A gene was related to worse prognosis for malignant melanoma (MM) patients. MATERIALS AND METHODS: The PubMed, Cochrane Library, Web of Science, EMBASE, and ClinicalTrails.gov databases were searched. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the association between PDE5Is use and risk of skin cancers. Cumulative meta-analysis and trial sequential analysis (TSA) were also conducted. Survival outcomes were analyzed online. RESULTS: After pooling all 8 eligible studies comprising 7,479,852 subjects, we found that PDE5Is use was significantly associated with slightly increased risk of developing MM (OR: 1.13, 95% CI: 1.05 to 1.21, I²=67.1%), basal cell carcinoma (OR: 1.16, 95% CI: 1.13 to 1.19, I²=49.6%), and squamous cell carcinoma (OR: 1.07, 95% CI: 1.01 to 1.13, I²=0.0%). Totally, PDE5Is increased the risk of developing skin cancers (OR: 1.13, 95% CI: 1.09 to 1.17, I²=70.8%). TSA results showed that the sample size was enough to reach a positive conclusion. CONCLUSIONS: The use of PDE5Is may be slightly associated with increased risk of developing skin cancers. There should be a balance between drug benefits and potential safety issues. However, the pooled results should be considered tentative until confounding factors such as sun exposure and lifestyle are well-controlled in further studies.

The association between anogenital distance and benign prostatic hyperplasia related lower urinary tract symptoms in Chinese aging men.

PURPOSE: We conducted the study to investigate the relationship between anogenital distance (AGD) and benign prostatic hyperplasia (BPH) related lower urinary tract symptoms (LUTS). METHODS: From May 2018 to January 2020, 220 subjects: 110 men with BPH-related LUTS (BPH-LUTS group) and 110 men without any urination complaints (control group) were selected. Clinical questionnaires, detailed physical examinations, including AGDas (distance between the anus and posterior base of the scrotum) and AGDap (distance between the anus and upper penis) measurements, and blood tests were all assessed. RESULTS: The two groups were similar in terms of basic features (P > 0.05). The AGDap and AGDas in the control group were significantly shorter than the BPH-LUTS group (P < 0.001). Adjusted multivariate analyses showed that AGDas was significantly related to International Prostate Symptom Score (IPSS), post-voiding residual volume (PVR), total prostate volume (TPV) and maximum urine flow rate (Qmax) (P = 0.002, P = 0.009, P = 0.001, P = 0.028, respectively). However, the associations between AGDap and IPSS score, PVR, TPV, Qmax and total testosterone (TT) were all negligible (P > 0.05 for all). The associations between TT and BPH-LUTS related evaluations were also negligible (P > 0.05 for all). Furthermore, the study revealed that the AGDas cut-off values for mild, moderate, and severe symptom (based on IPSS score) in BPH-LUTS cases were 27.4 mm and 46.8 mm [area under curve (AUC): 0.802 and AUC: 0.779, respectively], respectively. CONCLUSION: Longer AGDas was related to more severe BPH related symptoms. It may be useful to consider AGD as a marker for BPH-LUTS. Further well-designed studies are remained to be done to explore the intriguing problem.

Identification and verification of hub microRNAs in varicocele rats through high-throughput sequencing and bioinformatics analysis.

Varicocele (VC) is the most common treatable cause of infertility, but it is difficult to distinguish fertile from infertile VC populations because the pathogenesis is unclear. In order to study the related mechanism of VC causing male sterility, we made VC rats model by surgery, analyzed the rat epididymal sperm, and use the transcriptome sequencing compared all the miRNA expression differences in testicular tissue between VC rats, surgical treatment rats and control rats. The differentially expressed miRNAs (DEMs) of testicular tissue were also screened by the edgeR package in R software. We found that rno-miR-210-3p, rno-miR-6316, rno-miR-190a-5p and rno-miR-135b-5p were key miRNAs for VC and they were all up-regulated in VC samples and they are enriched in regulation of immune system process (GO:0002683), innate immune system (R-RNO-168,249) and apoptotic signaling pathway (GO:0097190). We hypothesize that negative regulation of immune system and apoptosis play an important role in the occurrence and development of VC, and it is induced the abnormal expression of target genes (such as Kitlg, Cxcl12) may involve in the development of VC associated infertility. Four key miRNAs, rno-miR-210-3p, rno-miR-6316, rno-miR-190a-5p and rno-miR-135b-5p, as well as their target genes are critical in VC, which could have attractive applications to provide new biomarkers for VC.

Development and Validation of a Nomogram to Predict Lymph Node Metastasis in Patients With T1 High-Grade Urothelial Carcinoma of the Bladder.

PURPOSE: This study aims to develop and validate a nomogram to predict lymph node (LN) metastasis preoperatively in patients with T1 high-grade urothelial carcinoma. METHODS: We retrospectively evaluated the data of 2,689 patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC) and bilateral lymphadenectomy in two medical centers. Eventually, 412 patients with T1 high-grade urothelial carcinoma were enrolled in the primary cohort to develop a prognostic nomogram designed to predict LN status. An independent validation cohort (containing 783 consecutive patients during the same period) was subjected to validate the predicting model. Binary regression analysis was used to develop the predicting nomogram. We assessed the performance of the nomogram concerning its clinical usefulness, calibration, and discrimination. RESULTS: Overall, 69 (16.75%), and 135 (17.24%) patients had LN metastasis in the primary cohort and external validation cohort, respectively. The final nomogram included information on tumor number, tumor size, lymphovascular invasion (LVI), fibrinogen, and monocyte-to-lymphocyte ratio (MLR). The nomogram showed good predictive accuracy and calibration with a concordance index in the primary cohort of 0.853. The application of the nomogram in the external validation cohort still gave good discrimination (C-index, 0.845) and good calibration. The analysis of the decision curve shows that the nomogram has clinical application value. CONCLUSION: The nomogram that incorporated the tumor number, tumor size, LVI, fibrinogen, and MLR showed favorable predictive accuracy for LN metastasis. It may be conveniently used to predict LN metastasis in patients with T1 high-grade urothelial carcinoma and be helpful in guiding treatment decisions.

The Prevalence and Prognostic Role of PD-L1 in Upper Tract Urothelial Carcinoma Patients Underwent Radical Nephroureterectomy: A Systematic Review and Meta-Analysis.

Background: Several studies investigating the role of PD-L1 in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU) to predict prognosis had been published and great controversy existed among them. We, therefore, in the meta-analysis, reported the association between PD-L1 and survival in UTUC patients who underwent RNU. Methods: We searched the PubMed, Cochrane Library, EMBASE, and Web of Science by April 1, 2020. Hazard ratio (HR) and odds ratio (OR) were adopted to evaluate relationships between PD-L1 and survival outcomes, and tumor features, respectively. We formulated clinical questions and organized following the PICOS strategy. Results: Eight retrospective studies incorporating 1406 patients were included. The pooled positive rate of PD-L1 in UTUC patients was 21.0% (95% CI = 13.0-30.0%, I 2 = 95.3%). Furthermore, higher PD-L1 in tumor tissues was related to shorter cancer-specific survival (CSS) in radically resected UTUC patients (HR = 1.63, 95% CI = 1.17-2.26, I 2 = 0.0%), but was not associated with overall survival (OS) (HR = 1.49, 95% CI = 0.76-2.91, I 2 = 74.9%). Subgroup analyses indicated associations between higher PD-L1 and shorter CSS in both Caucasus (HR = 1.72, 95% CI = 1.02-2.92, I 2 = 0.0%) and Asian (HR = 1.57, 95% CI = 1.03-2.39, I 2 = 23.1%) UTUC patients. Furthermore, PD-L1 was related to tumor grade of UTUC (High vs. Low, OR = 3.56, 95% CI = 1.82-6.97, P = 0.000) and invasive depth (pT3+pT4+pT2 vs. pT1+pTa/pTis, OR = 2.53, 95% CI = 1.07-5.96, P = 0.001). In the cumulative meta-analysis, results indicated that the 95% CIs narrowed as the pooled results gradually moved near the null. Conclusions: PD-L1 overexpression was related to worse survival outcomes in UTUC patients after RNU. It may be useful to incorporate PD-L1 into prognostic tools to select appropriate treatment strategies for UTUC. PD-L1 can also be clinically used for survival anticipation, risk stratification, and patient counseling. However, the pooled findings should be considered tentative until ascertained by more researches.

Relationship between aryl hydrocarbon receptor and spermatogenic dysfunction in male patients with varicocele.

The main purpose of this project is to verify whether there is a difference in the expression of aryl hydrocarbon receptor (AhR) between varicocele (VC) and normal male semen, and determine whether there is a connection with the parameters of semen analysis. The risk factors of infertility in patients with VC were also studied. Semen samples were collected for semen analysis and Western blot. Logistic regression was used to investigate the risk factors associated with infertility in patients with VC. Men with VC had lower AhR expression compared to healthy men; correlation analysis results showed that: AhR expression in patients with VC group was significantly positively correlated with sperm concentration and sperm motility; significantly negatively correlated with the diameter of spermatic veins during Valsalva and the percentage of abnormal sperm morphology; the research results of related risk factors show that the risk of infertility of patients with grade III is 1.67 times that of patients with grades I and II. For each unit of abnormal sperm morphology, the risk of infertility increases 1.04 times. Sperm concentration, total sperm viability and each unit the expression of AhR protein decreases the risk of infertility by 3%, 9% and 11% respectively.

The association between acquired premature ejaculation and metabolic syndrome in young Chinese men.

We conducted the study to investigate the association between metabolic syndrome (MetS) and acquired premature ejaculation (APE). From January 2017 to December 2019, 1,000 subjects, 500 men with APE (APE group) and 500 men without APE (control group), were selected. Self-estimated intravaginal ejaculatory latency time (IELT) and Premature Ejaculation Diagnostic Tool (PEDT) were recorded from each participant to evaluate APE. Detailed physical examinations, body composition analysis and blood tests were all assessed. The neck circumference, waist circumference, visceral fat rating, fat mass, fasting blood glucose (FBG) and highly sensitive C-reactive protein (hs-CRP) in the APE group were significantly higher than the control group (p < .05 for all). Furthermore, the APE population had a higher prevalence of MetS than the control group (49.4% versus 35.6%, p = .000). Consistent results could also be observed in terms of the number of MetS components and each component of the MetS (both p < .05). Moreover, both the prevalence of APE and the severity of PE increased significantly as the number of MetS components increased. Finally, in the multivariate analysis, we found that both MetS and hs-CRP were independent risk factors for APE (both p < .01). The results indicated that APE was related to MetS but not its components.

Association between 5-hydroxytryptamine transporter gene-linked promoter region polymorphism and the susceptibility of lifelong premature ejaculation: a meta-analysis involving 1,604 subjects.

The relationship between 5-hydroxytryptamine transporter-linked promoter region (5-HTTLPR) gene and lifelong premature ejaculation (LPE) risk was discussed widely for the last few years, which was still controversial and remained to be explored. We performed the meta-analysis with 8 reliable research, which were searched in the following databases: PubMed, Embase and Cochrane Library. We also performed random and fixed effects models to evaluate the odds ratios (ORs) and 95% confidence intervals respectively. By pooling all included studies, we found that SS genotype of 5-HTTLPR polymorphism was linked with significantly higher PE risk in Caucasian population (OR =0.635, 95% CI: 0.417-0.958, I2=0.311, P=0.035), and S-allele of 5-HTTLPR polymorphism increased the risk of LPE significantly in Asian population (OR =0.656, 95% CI: 0.539-0.799, I2=0.435, P<0.001). However, no significant was observed between 5-HTTLPR gene polymorphism and LPE risk in overall studies. Further studies were anticipated to be done.

Can the combination of biparametric magnetic resonance imaging and PSA-related indicators predict the prostate biopsy outcome?

To assess the value of biparametric magnetic resonance imaging (bpMRI) for detecting and ruling out prostate cancer in patients with elevated prostate-specific antigen (PSA). The basic information and bpMRI images of enrolled patients who took transperineal template saturate biopsy were retrospectively collected for analysis. Based on our results, we found that free/total PSA, and PI-RADS score were independent risk factors of PCa (p < .05), the PSA density, PI-RADS score were the independent risk factors of csPCa (p < .05). PI-RADS score threshold of 3 could achieve the highest Yonder index for predicting PCa, and PI-RADS score threshold of 4 could achieve the highest Yonder index for predicting csPCa. Therefore, we draw a conclusion that PI-RADSv2 score-based bpMRI could diminish the unnecessary prostate biopsies in patients with elevated PSA when combined with other PSA-related indicators.

Identification of an immune-related long non-coding RNA signature and nomogram as prognostic target for muscle-invasive bladder cancer.

To identify an immune-related prognostic signature based on long non-coding RNAs (lncRNAs) and find immunotherapeutic targets for bladder urothelial carcinoma, we downloaded RNA-sequencing data from The Cancer Genome Atlas (TCGA) dataset. Functional enrichment analysis demonstrated bladder urothelial carcinoma was related to immune-related functions. We obtained 332 immune-related genes and 262 lncRNAs targeting immune-related genes. We constructed a signature based on eight lncRNAs in training cohort. Patients were classified as high-risk and low-risk according to signature risk score. High-risk patients had poor overall survival compared with low-risk patients (P < 0.001). Multivariate Cox regression suggested the signature was an independent prognostic indicator. The findings were further validated in testing, entire TCGA and external validation cohorts. Gene set enrichment analysis indicated significant enrichment of immune-related phenotype in high-risk group. Immunohistochemistry and online analyses validated the functions of 4 key immune-related genes (LIG1, TBX1, CTSG and CXCL12) in bladder urothelial carcinoma. Nomogram proved to be a good classifier for muscle-invasive bladder cancer through combining the signature. In conclusion, our immune-related prognostic signature and nomogram provided prognostic indicators and potential immunotherapeutic targets for muscle-invasive bladder cancer.

The prevalence and prognostic and clinicopathological value of PD-L1 and PD-L2 in renal cell carcinoma patients: a systematic review and meta-analysis involving 3,389 patients.

BACKGROUND: The research of the prognostic and clinicopathologic values of programmed cell death ligand 1/2 (PD-L1/2) in renal cell carcinoma (RCC) patients has been mired by a dearth of studies and considerable controversy. We thus conducted a systematic review and meta-analysis to report the prevalence and prognostic and clinicopathological value of programmed cell death ligand 1 (PD-L1) and programmed cell death-legend 2 (PD-L2) in RCC patients. METHODS: The PubMed, Cochrane Library, EMBASE databases were searched to find human studies limited to English language literature published through October 1, 2019. Using random or fixed effects models, hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated to explore the prognostic value of PD-Ls expression, while odds ratios (ORs) and 95% CIs were evaluated to investigate clinicopathological parameters. The protocol of the study was registered in PROSPERO (CRD42019135199). RESULTS: After pooling all 16 eligible studies comprising 3,389 patients, we found that the overall prevalence of PD-L1 and PD-L2 in RCC patients was 27% and 39%, respectively. Furthermore, PD-L1 over-expression was a strong negative predictor for overall survival (OS), disease-free survival/progression-free survival (DFS/PFS), and cancer-specific survival (CSS) in renal cell carcinoma patients (HR =2.86, 95% CI: 1.83-4.47, P<0.001; HR =2.64, 95% CI: 1.99-3.52, P<0.001; HR =2.78, 95% CI: 2.17-3.56, P<0.001). Meanwhile, PD-L2 over-expression was only a weak negative predictor for CSS (HR =1.66, 95% CI: 1.05-2.65, P<0.05). Subgroup analysis showed that Caucasians had worse OS (HR =3.60, 95% CI: 1.77-7.33, P<0.001), PFS (HR =3.56, 95% CI: 2.44-5.18, P<0.001), and CSS (HR =3.13, 95% CI: 2.37-4.14, P<0.001) than Asians. PD-L1 was a strong indicator for worse prognosis (P<0.05 for all), while PD-L2 over-expression was only associated with sarcomatoid features (presence vs. absence, OR =1.80, 95% CI: 1.13-2.86, P=0.014). Notably, PD-L1 overexpression was more prevalent in women (male vs. female, OR =0.68, 95% CI: 0.51-0.90, P=0.006). CONCLUSIONS: Higher PD-L1 expression is more closely associated with poor prognosis and more advanced clinicopathological features in RCC patients than PD-L2, especially in women and Caucasian patients. PD-L2 was a weak negative predictor of poor CSS of RCC and was not a prompt for the metastasis of RCC.

Is dynamic contrast enhancement still necessary in multiparametric magnetic resonance for diagnosis of prostate cancer: a systematic review and meta-analysis.

BACKGROUND: The purpose of this study is to systematically review the literatures assessing the value of dynamic contrast enhancement (DCE) in the multiparametric magnetic resonance imaging (mpMRI) for the diagnosis of prostate cancer (PCa). METHODS: We searched Embase, PubMed and Web of science until January 2019 to extract articles exploring the possibilities whether the pre-biopsy biparametric magnetic resonance imaging (bpMRI) can replace the position of mpMRI in the diagnosis of PCa. The sensitivity and specificity of bpMRI were all included. The study quality was assessed by QUADAS-2. Bivariate random effects meta-analyses and a hierarchical summary receiver operating characteristic plot were performed for further study through Revman 5 and Stata12. RESULTS: After searching, we acquired 752 articles among which 45 studies with 5,217 participants were eligible for inclusion. The positive likelihood ratio for the detection of PCa was 2.40 (95% CI: 1.50-3.80) and the negative likelihood ratio was 0.31 (95% CI: 0.18-0.53). The sensitivity and specificity were 0.77 (95% CI: 0.73-0.81) and 0.81 (95% CI: 0.76-0.85) respectively. Based on our result, pooled specificity demonstrated little difference between bpMRI and mpMRI [bpMRI, 0.81 (95% CI, 0.76-0.85); mpMRI, 0.82 (95% CI, 0.72-0.88); P=0.169]. The sensitivity, however, indicated a significant difference between these two groups [bpMRI, 0.77 (95% CI, 0.73-0.81); mpMRI, 0.84 (95% CI, 0.78-0.89); P=0.001]. CONCLUSIONS: bpMRI with high b-value is a sensitive tool for diagnosing PCa. Consistent results were found in multiple subgroup analysis.

Do testosterone supplements enhance response to phosphodiesterase 5 inhibitors in men with erectile dysfunction and hypogonadism: a systematic review and meta-analysis.

BACKGROUND: Combining testosterone and phosphodiesterase 5 inhibitors (PDE5-Is) has become increasingly common in the treatment of men with erectile dysfunction (ED) and low testosterone levels, but combination therapy involving PDE5-Is and testosterone is highly debated, with strong reasons for and against argued by the various opinion leaders. PDE5-Is can be given prior to, alongside or after the commencement of any testosterone replacement therapy. Meanwhile, combination of PDE5-Is and testosterone is reported to better increase testosterone levels and thus improve International Index of Erectile Function (IIEF) score in hypogonadal men. The objective of this meta-analysis was to assess whether testosterone therapy (TTh) can possibly enhance the reaction to PDE5-Is in men with ED and hypogonadism. METHODS: Relevant studies and available data were extensively collected form Medline, Embase, and Cochrane Library databases until June 2019. We calculated standard mean differences (SMDs) with their 95% confidence intervals (CIs) for IIEF including IIEF-5 and IIEF-EFD. Trial sequential analysis (TSA) was performed to explore whether the sample size of the accumulated evidence is sufficient. RESULTS: There were 8 studies including 913 patients. The pooled SMD of erectile function (EF) component change was 0.663 [(0.299 to 1.027); P<0.0001], which concluded that combination therapy (TTh plus PDE5-Is) is superior to PDE5-Is monotherapy group. We also conducted a subgroup analysis according to trial follow-up, baseline serum total testosterone, baseline EF score and PDE5-Is type, which may explain for the underlying source of heterogeneity in part. The frequency of adverse events and change in PSA levels did not differ between the 2 groups. None of the patients experienced an increase in the prostate specific antigen (PSA) level above 4 ng/mL. Hematocrit increased significantly more in the testosterone group than in the placebo group but not greater than 0.54. CONCLUSIONS: In summary, the present results confirm that combination therapy is effective and safe. TTh can enhance the reaction to PDE5-Is in men with ED and hypogonadism, but this effect also depends on the specific diagnosis and initial response to PDE5-Is. Most patients with adverse events during treatment are mild, and have a stable overall safety of combination therapy.

Identification and verification of key genes in varicocele rats through high-throughput sequencing and bioinformatics analysis.

Varicocele (VC) is the most common treatable cause of infertility, but it is difficult to distinguish fertile from infertile VC populations because the pathogenesis is unclear. In order to study the related mechanism of VC causing male sterility, we made VC rat model by surgery, analysed the rat epididymal spermatozoa and used the transcriptome sequencing to compare all the mRNA expression differences in testicular tissue between VC rats and control rats. The differentially expressed genes (DEGs) of testicular tissue were also screened by the limma package in R software (version 3.6.1). The 273 DEGs were identified from the four profile data sets including 124 up-regulated genes and 149 down-regulated genes in the VC group compared to control group. We found that Sod1, Casp9, Atg7, Casp3 and Sirt1 in module 1 had higher degrees of connectivity in the first 10 hub genes. Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis demonstrated that Sod1, Casp9, Atg7, Casp3 and Sirt1 are enriched in regulation of oxidative stress-induced cell death (GO:1,903,201) and Amyotrophic lateral sclerosis (KEGG:05,014). From the above evidence, we speculate that hypoxia plays an important role in the occurrence and development of VC, and it induced the abnormal expression of autophagy and apoptosis-related proteins may involve in the development of VC-associated infertility. Sod1, Casp9, Atg7, Casp3 and Sirt1 as well as their module are hub genes for VC, which will have attractive applications to provide new treatment targets for VC.

Gene Expression Profiles Identified Novel Urine Biomarkers for Diagnosis and Prognosis of High-Grade Bladder Urothelial Carcinoma.

Bladder urothelial carcinoma (BC) has been identified as one of the most common malignant neoplasm worldwide. High-grade bladder urothelial carcinoma (HGBC) is aggressive with a high risk of recurrence, progression, metastasis, and poor prognosis. Therefore, HGBC clinical management is still a challenge. We performed the present study to seek new urine biomarkers for HGBC and investigate how they promote HGBC progression and thus affect the prognosis based on large-scale sequencing data. We identified the overlapped differentially expressed genes (DEGs) by combining GSE68020 and The Cancer Genome Atlas (TCGA) datasets. Subsequent receiver operating characteristic (ROC) curves, Kaplan-Meier (KM) curves, and Cox regression were conducted to test the diagnostic and prognostic role of the hub genes. Chi-square test and logistic regression were carried out to analyze the associations between clinicopathologic characteristics and the hub genes. Ultimately, we performed gene set enrichment analysis (GSEA), protein-protein interaction (PPI) networks, and Bayesian networks (BNs) to explore the underlying mechanisms by which ECM1, CRYAB, CGNL1, and GPX3 are involved in tumor progression. Immunohistochemistry based on The Human Protein Atlas and quantitative real-time polymerase chain reaction based on urine samples confirmed the downregulation and diagnostic values of the hub genes in HGBC. In conclusion, our study indicated that CRYAB, CGNL1, ECM1, and GPX3 are potential urine biomarkers of HGBC. These four novel urine biomarkers will have attractive applications to provide new diagnostic methods, prognostic predictors and treatment targets for HGBC, which could improve the prognosis of HGBC patients, if validated by further experiments and larger prospective clinical trials.

The decline in sexual function, psychological disorders (anxiety and depression) and life satisfaction in older men: A cross-sectional study in a hospital-based population.

This study explored the relationships between the decline in sexual function and psychological burdens and life satisfaction in older men with the aim of providing prospective targets for interventions. From January 2016 to January 2019, we selected 1,326 men aged over 50 years old. We adopted the International Index of Erectile Function-5 (IIEF-5), self-estimated intravaginal ejaculatory latency time (IELT), the premature ejaculation diagnostic tool (PEDT), the General Anxiety Disorder-7 (GAD-7), the Patients Health Questionnaire-9 (PHQ-9), the satisfaction with life scale and the control, autonomy, self-realisation and pleasure scale (CASP-19) to measure premature ejaculation, erectile dysfunction and well-being (including, depression, anxiety, and life quality and satisfaction) respectively. The individuals were divided into two main groups: the decline group and the no-decline group. The incidences of erectile dysfunction (ED), premature ejaculation (PE), anxiety and depression in men who reported a decline in sexuality were 73.83% (330/447), 63.98% (286/447), 75.84% (339/447) and 68.46% (306/447) respectively. Men who showed a decline in sexuality had significantly worse psychological and life satisfaction/quality scores than those in the no-decline group (p < .001 for all). When they had PE or ED simultaneously, these differences widened. Significantly worsened psychological status and life quality/satisfaction scores could be observed in patients who had declined sexual desire and declined frequency of sex (p < .001 for both). Under the impact of the decline in sexual function, the younger participants (age < 60) had significantly worsened negative emotions and life quality and satisfaction. Based on the results of the study, we found that the decline in sexuality was associated with depression and anxiety and worse life satisfaction and quality. Clinicians need to pay more attention to psychological status and life satisfaction and quality for those patients affected by a decline in sexuality.

Non Functioning Paraganglioma in the Urinary Bladder: a Case Report.

Paragangliomas are tumors that arise from autonomic nervous system. Non-functioning bladder paraganglioma is rare and usually misdiagnosed. Here we describe a case of a 45-year-old man with primary urinary bladder paraganglioma. The patient had no active signs and symptoms, and histological and immunohistological examinations of a transurethral resection specimen confirmed correct diagnosis. After successful transurethral resection of the tumors, the patient showed no signs of recurrence at one-year follow-up.