Lack of investment for magnetic resonance (MR) fusion systems is an obstacle to deliver targeted prostate biopsies within the prostate cancer diagnostic pathway. We developed a coordinate-based method to support cognitive targeted prostate biopsies and then performed an audit on cancer detection and the location of lesions. In each patient, the prostate is considered as two separate hemiprostates, and each hemiprostate is divided into 4 × 4 × 4 units. Each unit is therefore defined by a three-dimensional coordinate. We prospectively applied our coordinates approach to target 106 prostatic lesions in 93 men. Among 45 (of 106; 42.5%) lesions positive for cancer, 27 lesions (60.0%) harbored clinically significant disease. PSA density was significantly higher in patients with proven cancer (median: 0.264 ng ml⁻²) when compared to the noncancer group (median: 0.145 ng ml⁻²; P = 0.003, Wilcoxon rank-sum test). Lesions with Prostate Imaging-Reporting and Data System (PIRADS) score of 5 were found to have a cancer incidence of 65.2%, while PIRADS 4 and 3 lesions have a lower risk of cancer detection, as expected, at 37.3% and 31.3%, respectively. The probability of a lesion being cancerous in our series significantly decreases as we go from the “apex-to-base” dimension (odds ratio [OR]: 2.62, 95% confidence interval [CI]: 1.55–4.44, P = 0.00034). Our analysis also indicates that the probability of cancer decreases as the prostate volume increases (OR: 1.03, 95% CI: 1.01–1.05, P = 0.00327). Based on this feasibility study, the use of coordinates to guide cognitive targeted prostate biopsies warrants future validation study in additional centers.

Penile fracture (PF) is a surgical emergency. Given its rarity, we queried a national cohort over an 11-year period to study the temporal and demographic variations in presentation, evaluation, and management of patients with PF compared with a cohort of control patients. The National Inpatient Sample was queried between the years 2005 and 2016 for patients with a diagnosis of PF. Appendectomy patients were selected as a control cohort, given the non-discriminatory nature of this disease. Clinical and demographic data of the patients were compared with that of controls. Presenting symptoms, rates of surgical repair, and rates of associated surgical procedures were evaluated in the PF cohort. During the study period, 5802 patients were hospitalized for PF. The annual incidence of PF remained unchanged at 1.0–1.8 cases per 100 000 hospitalizations over the study period. Compared with the control cohort, PF patients were more likely to be younger (38.7 years vs 41.2 years, P ≤ 0.001), have lower rates of comorbidities except erectile dysfunction (1.4% vs 0.1%, P ≤ 0.001), and were more likely of Black race (25.4% vs 6.2%, P ≤ 0.001). Notably, PF patients had significantly higher rates of substance abuse (26.4% vs 18.1%, P ≤ 0.001), despite no difference in the diagnosed psychiatric disorders. PF rarely presented with hematuria (3.5%); however, urethral evaluation was performed in 23.1%, most commonly with cystoscopy (19.2%). PF occurs more commonly in a younger, healthier male population, and among minorities. Importantly, rates of substance abuse appear to be higher in the PF cohort compared with those of controls.

Spermatogonial stem cells (SSCs) have great applications in both reproductive and regenerative medicine. Primates including monkeys are very similar to humans with regard to physiology and pathology. Nevertheless, little is known about the isolation, the characteristics, and the culture of primate SSCs. This study was designed to identify, isolate, and culture monkey SSCs. Immunocytochemistry was used to identify markers for monkey SSCs. Glial cell line-derived neurotrophic factor family receptor alpha-1 (GFRA1)-enriched spermatogonia were isolated from monkeys, namely Macaca fascicularis (M. fascicularis), by two-step enzymatic digestion and magnetic-activated cell sorting, and they were cultured on precoated plates in the conditioned medium. Reverse transcription-polymerase chain reaction (RT-PCR), immunocytochemistry, and RNA sequencing were used to compare phenotype and transcriptomes in GFRA1-enriched spermatogonia between 0 day and 14 days of culture, and xenotransplantation was performed to evaluate the function of GFRA1-enriched spermatogonia. SSCs shared some phenotypes with rodent and human SSCs. GFRA1-enriched spermatogonia with high purity and viability were isolated from M. fascicularis testes. The freshly isolated cells expressed numerous markers for rodent SSCs, and they were cultured for 14 days. The expression of numerous SSC markers was maintained during the cultivation of GFRA1-enriched spermatogonia. RNA sequencing reflected a 97.3% similarity in global gene profiles between 0 day and 14 days of culture. The xenotransplantation assay indicated that the GFRA1-enriched spermatogonia formed colonies and proliferated in vivo in the recipient c-Kit^W/W (W) mutant mice. Collectively, GFRA1-enriched spermatogonia are monkey SSCs phenotypically both in vitro and in vivo. This study suggests that monkey might provide an alternative to human SSCs for basic research and application in human diseases.

This study aimed to evaluate the therapeutic effect of IR-61, a novel mitochondrial heptamethine cyanine dye with antioxidant effects, on diabetes mellitus-induced erectile dysfunction (DMED). Eight-week-old male Sprague–Dawley rats were intraperitoneally injected with streptozotocin (STZ) to induce type 1 diabetes. Eight weeks after STZ injection, all rats were divided into three groups: the control group, DM group, and DM + IR-61 group. In the DM + IR-61 group, the rats were administered IR-61 (1.6 mg kg⁻¹) twice a week by intravenous injection. At week 13, erectile function was evaluated by determining the ratio of the maximal intracavernous pressure to mean arterial pressure, and the penises were then harvested for fluorescent imaging, transmission electron microscopy, histological examinations, and Western blot analysis. Whole-body imaging suggested that IR-61 was highly accumulated in the penis after intravenous injection. IR-61 treatment significantly improved the maximal ICP of diabetic rats. Additionally, IR-61 ameliorated diabetes-induced inflammation, apoptosis, and phenotypic transition of corpus cavernosum smooth muscle cells (CCSMCs) in penile tissue. IR-61 also attenuated mitochondrial damage, reduced reactive oxygen species production in the corpus cavernosum and upregulated sirtuin1 (SIRT1), sirtuin3 (SIRT3), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase expression in penile tissue. In conclusion, IR-61 represents a potential therapeutic option for DMED by protecting the mitochondria of CCSMCs, which may be mediated by activation of the SIRT1, SIRT3, and Nrf2 pathways.

Accumulating evidence supports the significance of aberrant alternative splicing (AS) events in cancer; however, genome-wide profiling of progression-free survival (PFS)-related AS events in testicular germ cell tumors (TGCT) has not been reported. Here, we analyzed high-throughput RNA-sequencing data and percent-spliced-in values for 150 patients with TGCT. Using univariate and multivariate Cox regression analysis and a least absolute shrinkage and selection operator method, we identified the top 15 AS events most closely associated with disease progression. A risk-associated AS score (ASS) for the 15 AS events was calculated for each patient. ASS, pathological stage, and T stage were significantly associated with disease progression by univariate analysis, but only ASS and pathological stage remained significant by multivariate analysis. The ability of these variables to predict 5-year progression was assessed using receiver operating characteristic curve analysis. ASS had stronger predictive value than a combination of age, pathological stage, and T stage (area under the curve = 0.899 and 0.715, respectively). Furthermore, Kaplan–Meier analysis of patients with low and high ASS demonstrated that high ASS was associated with significantly worse PFS than low ASS (P = 1.46 × 10⁻⁷). We also analyzed the biological functions of the PFS-related AS-related genes and found enrichment in pathways associated with DNA repair and modification. Finally, we identified a regulatory network of splicing factors with expression levels that correlated significantly with AS events in TGCT. Collectively, this study identifies a novel method for risk stratification of patients and provides insight into the molecular events underlying TGCT.

The inhibition of 5-α reductase type 2 (SRD5A2) by finasteride is commonly used for the management of urinary obstruction resulting from benign prostatic enlargement (BPE). Certain BPE patients showing no SRD5A2 protein expression are resistant to finasteride therapy. Our previous work showed that methylated cytosine-phosphate-guanine (CpG) islands in the SRD5A2 gene might account for the absence or reduction of SRD5A2 protein expression. Here, we found that the expression of the SRD5A2 protein was variable and that weak expression of the SRD5A2 protein (scored 0–100) occurred in 10.0% (4/40) of benign adult prostates. We showed that the expression of SRD5A2 was negatively correlated with DNA methyltransferase 1 (DNMT1) expression. In vitro SRD5A2-negative BPH-1 cells were resistant to finasteride treatment, and SRD5A2 was re-expressed in BPH-1 cells when SRD5A2 was demethylated by 5-Aza-2'-deoxycytidine (5-Aza-CdR) or N-phthalyl-L-tryptophan (RG108). Furthermore, we determined the exact methylation ratios of CpG dinucleotides in a CpG island of SRD5A2 through MassArray quantitative methylation analysis. Ten methylated CpG dinucleotides, including four CpG dinucleotides in the promoter and six CpG dinucleotides in the first exon, were found in a CpG island located from −400 bp to +600 bp in SRD5A2, which might lead to the silencing of SRD5A2 and the absence or reduction of SRD5A2 protein expression. Finasteride cannot exert a therapeutic effect on patients lacking SRD5A2, which may partially account for the resistance to finasteride observed in certain BPE patients.

Postprostatectomy erectile dysfunction (pPED) remains a current problem despite improvements in surgical techniques. Vacuum therapy is clinically confirmed as a type of pPED rehabilitation. However, its underlying mechanisms are incompletely understood. Recently, autophagy and apoptosis were extensively studied in erectile dysfunction resulting from diabetes, senescence, and androgen deprivation but not in the context of pPED and vacuum therapy. Therefore, this study was designed to investigate the roles of autophagy and apoptosis in pPED and vacuum therapy. Twenty-four adult male Sprague–Dawley rats were randomly divided into three groups: the control group, bilateral cavernous nerve crush (BCNC) group, and BCNC + vacuum group. After 4 weeks of treatment, intracavernosal pressure was used to evaluate erectile function. Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry were used to measure the molecular expression. TdT-mediated dUTP nick-end labeling staining was used to assess apoptosis. Transmission electron microscopy was used to observe autophagosomes. After treatment, compared with those of the BCNC group, erectile function and cavernosal hypoxia had statistically significantly improved (P < 0.05). Apoptosis and the relative protein expression of B-cell lymphoma-2-associated X and cleaved Caspase3 were decreased (P < 0.05). Autophagy-related molecules such as phosphorylated unc-51-like autophagy-activating kinase 1 (Ser757) and p62 were decreased. Beclin1, microtubule-associated protein 1 light chain 3 A/B, and autophagosomes were increased (P < 0.05). Besides, the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway, as a negative regulator of autophagy to some degree, was inhibited. This study revealed that vacuum therapy ameliorated pPED in BCNC rats by inhibiting apoptosis and activating autophagy.

Diabetes mellitus (DM) is known to cause reproductive impairment. In men, it has been linked to altered sperm quality and testicular damage. Oxidative stress (OS) plays a pivotal role in the development of DM complications. Glutathione (GSH) is a part of a nonenzymatic antioxidant defense system that protects lipid, protein, and nucleic acids from oxidative damage. However, the protective effects of exogenous GSH on the male reproductive system have not been comprehensively examined. This study determined the impact of GSH supplementation in ameliorating the adverse effect of type 1 DM on sperm quality and the seminiferous tubules of diabetic C57BL/6NTac mice. GSH at the doses of 15 mg kg⁻¹ and 30 mg kg⁻¹ was given intraperitoneally to mice weekly for 6 consecutive weeks. The mice were then weighed, euthanized, and had their reproductive organs excised. The diabetic (D Group) showed significant impairment of sperm quality and testicular histology compared with the nondiabetic (ND Group). Diameters of the seminiferous lumen in diabetic mice treated with 15 mg kg⁻¹ GSH (DGSH15) were decreased compared with the D Group. Sperm motility was also significantly increased in the DGSH15 Group. Improvement in testicular morphology might be an early indication of the protective roles played by the exogenous GSH in protecting sperm quality from effects of untreated type 1 DM or diabetic complications. Further investigation using different doses and different routes of GSH is necessary to confirm this suggestion.

Dozens of genes are associated with idiopathic hypogonadotropic hypogonadism (IHH) and an oligogenic etiology has been suggested. However, the associated genes may account for only approximately 50% cases. In addition, a genomic systematic pedigree analysis is still lacking. Here, we conducted whole exome sequencing (WES) on 18 unrelated men affected by IHH and their corresponding parents. Notably, one reported and 10 novel variants in eight known IHH causative genes (AXL, CCDC141, CHD7, DMXL2, FGFR1, PNPLA6, POLR3A, and PROKR2), nine variants in nine recently reported candidate genes (DCAF17, DCC, EGF, IGSF10, NOTCH1, PDE3A, RELN, SLIT2, and TRAPPC9), and four variants in four novel candidate genes for IHH (CCDC88C, CDON, GADL1, and SPRED3) were identified in 77.8% (14/18) of IHH cases. Among them, eight (8/18, 44.4%) cases carried more than one variant in IHH-related genes, supporting the oligogenic model. Interestingly, we found that those variants tended to be maternally inherited (maternal with n = 17 vs paternal with n = 7; P = 0.028). Our further retrospective investigation of published reports replicated the maternal bias (maternal with n = 46 vs paternal with n = 28; P = 0.024). Our study extended a variant spectrum for IHH and provided the first evidence that women are probably more tolerant to variants of IHH-related genes than men.

The present study aimed to determine whether the number of patients with symptomatic benign prostatic hyperplasia (BPH) who preferred surgery decreased during the past 11 years at our center (West China Hospital, Chengdu, China), and whether this change affected the timing of surgery and the physical condition of surgical patients. This retrospective study included 57 557 patients with BPH treated from January 2008 to December 2018. Of these, 5427 patients were treated surgically. Surgical patients were divided into two groups based on the time of treatment (groups 8–13 and groups 13–18). The collected data comprised the percentage of all patients with BPH who underwent surgery, baseline characteristics of surgical patients, rehabilitation time, adverse events, and hospitalization costs. The surgery rates in groups 8–13 and groups 13–18 were 10.5% and 8.5% (P < 0.001), respectively. The two groups did not clinically differ regarding patient age and prostate volume. The rates of acute urinary retention and renal failure decreased from 15.0% to 10.6% (P < 0.001) and from 5.2% to 3.1% (P < 0.001), respectively. In groups 8–13 and groups 13–18, the mean catheterization times were 4.0 ± 1.7 days and 3.3 ± 1.6 days (P < 0.001), respectively, and the mean postoperative hospitalization times were 5.1 ± 2.4 days and 4.2 ± 1.8 days (P < 0.001), respectively. The incidences of unplanned second surgery and death reduced during the study period. The surgery rate decreased over time, which suggests that medication was chosen over surgery. However, the percentage of late complications of BPH also decreased over time, which indicates that the timing of surgery was not delayed.

We performed this study to investigate the diagnostic performance of prostate-specific antigen density (PSAD) in a multicenter cohort of the Chinese Prostate Cancer Consortium. Outpatients with prostate-specific antigen (PSA) levels ≥4.0 ng ml⁻¹ regardless of digital rectal examination (DRE) results or PSA levels <4.0 ng ml⁻¹ and abnormal DRE results were included from 18 large referral hospitals in China. The diagnostic performance of PSAD and the sensitivity and specificity for the diagnosis of prostate cancer (PCa) and high-grade prostate cancer (HGPCa) at different cutoff values were evaluated. A total of 5220 patients were included in the study, and 2014 (38.6%) of them were diagnosed with PCa. In patients with PSA levels ranging from 4.0 to 10.0 ng ml⁻¹, PSAD was associated with PCa and HGPCa in both univariate (odds ratio [OR] = 45.15, P < 0.0001 and OR = 25.38, P < 0.0001, respectively) and multivariate analyses (OR = 52.55, P < 0.0001 and OR = 26.05, P < 0.0001, respectively). The areas under the receiver operating characteristic curves (AUCs) of PSAD in predicting PCa and HGPCa were 0.627 and 0.630, respectively. With the PSAD cutoff of 0.10 ng ml⁻², we obtained a sensitivity of 88.7% for PCa, and nearly all (89.9%) HGPCa cases could be detected and biopsies could be avoided in 20.2% of the patients (359/1776 cases). Among these patients who avoided biopsies, only 30 cases had HGPCa. We recommend 0.10 ng ml⁻² as the proper cutoff value of PSAD, which will obtain a sensitivity of nearly 90% for both PCa and HGPCa. The results of this study should be validated in prospective, population-based multicenter studies.

Obesity is a major worldwide health problem that is related to most chronic diseases, including male infertility. Owing to its wide impact on health, mechanisms underlying obesity-related infertility remain unknown. In this study, we report that mice fed a high-fat diet (HFD) for over 2 months showed reduced fertility rates and increased germ cell apoptosis, seminiferous tubule degeneration, and decreased intratesticular estradiol (E2) and E2-to-testosterone ratio. Interestingly, we also detected a decrease in testicular fatty acid levels, behenic acid (C22:0), and docosahexaenoic acid (DHA, 22:6n-3), which may be related to the production of dysfunctional spermatozoa. Overall, we did not detect any changes in the frequency of seminiferous tubule stages, sperm count, or rate of in vitro capacitation. However, there was an increase in spontaneous and progesterone-induced acrosomal exocytosis (acrosome reaction) in spermatozoa from HFD-fed mice. These data suggest that a decrease in E2 and fatty acid levels influences spermatogenesis and some steps of acrosome biogenesis that will have consequences for fertilization. Thus, our results add new evidence about the adverse effect of obesity in male reproduction and suggest that the acrosomal reaction can also be affected under this condition.

This study analyzed the trend in semen quality of infertile male patients in Wenzhou, China, based on the data obtained from 38 905 patients during 2008–2016 in The First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). The results showed that only 24.9% of the patients had normal semen quality. For the semen quality of infertile male patients, that of the workers and 40-year-olds was significantly worse than the other occupational and age groups. For all the infertile patients, low semen volume, asthenozoospermia, and teratozoospermia accounted for 8.4%, 50.5%, and 54.1%, respectively. During 2008–2016, the annual mean percentage of fast forward motile spermatozoa, percentage of total forward motile spermatozoa, and percentage of spermatozoa with normal morphology decreased linearly with slopes of −2.11, −2.59, and −0.70, respectively. The proportion of patients with asthenozoospermia and multi-abnormal spermatozoa increased during 2008–2016 with slopes of 4.70 and 4.87, respectively, while for low semen volume, it decreased with a slope of −0.47 in the same time period. The proportion of patients with teratozoospermia increased from 2008 to 2011 and from 2011 to 2016 with slopes of 17.10 and 2.09, respectively. In general, the deteriorating trend of semen quality of infertile male patients in Wenzhou was obvious. Future efforts should be made to reveal the adverse influences on semen quality, such as occupational exposure, environmental quality, and living habits. Furthermore, more pervasive reproduction health education is necessary.

This study aimed to assess the association between psychological disorders and erectile dysfunction (ED) in patients with different degrees of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This was a retrospective study conducted from June 2017 to October 2019 and included 182 outpatients. Patients were interviewed using the Structured Interview on Erectile Dysfunction (SIEDY) for pathogenic quantification. The National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Index of Erectile Function-5 (IIEF-5) were used for the evaluation of CP/CPPS and ED. The Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to assess anxiety symptoms and depressive symptoms. The number of patients with mild CP/CPPS and mild ED, mild CP/CPPS and moderate-to-severe ED, moderate-to-severe CP/CPPS and mild ED, and moderate-to-severe CP/CPPS and moderate-to-severe ED was 69 (37.9%), 36 (19.8%), 35 (19.2%), and 42 (23.1%), respectively. The corresponding PHQ-9 scores of the four groups were 6.22, 7.19, 10.69, and 7.71, respectively. The corresponding GAD-7 scores of the four groups were 5.26, 6.31, 8.77, and 6.36, respectively. Among patients with moderate-to-severe CP/CPPS, the PHQ-9 and GAD-7 scores of the moderate-to-severe ED group were significantly lower than those of the mild ED group (P = 0.007 and P = 0.010, respectively). The prevalence of ED and premature ejaculation (PE) in patients with moderate-to-severe CP/CPPS was significantly higher than that in patients with mild CP/CPPS (P = 0.001 and P = 0.024, respectively). Our findings proved that the severity of ED was negatively associated with psychological symptoms in outpatients with moderate-to-severe CP/CPPS.

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been associated with multiple entities and several types of cancers. They can be assumed as markers of inflammatory imbalance. The objective of this study is to evaluate the NLR and PLR in Peyronie's disease (PD) and to establish a comparison of its values in the acute and chronic stages. We recruited patients with PD from March 2018 to March 2019. The patients enrolled underwent medical and sexual history as well as a physical examination. The values of blood count of each patient were collected both in the acute and chronic stages. Wilcoxon test was used to compare the acute and chronic stage ratios. Kruskal–Wallis test was carried out to evaluate the impact of treatments on the ratios. To identify cutoff values, we used sensibility and specificity tables and receiver operating characteristic (ROC) curves. A total of 120 patients were enrolled. Their mean age was 55.85 (range: 18–77) years and the mean penile curvature was 48.43° (range: 10°–100°). In the acute stage, the mean NLR was 2.35 and the mean PLR was 111.22. These ratios, in the chronic stage, were 1.57 and 100.00, respectively. Statistically significant differences between acute and stable stages for both indices were found (NLR: P< 0.0001; PLR: P= 0.0202). The optimal cutoff for classification in acute or stable stage was 2 for NLR and 102 for PLR. According to our results, with an ordinary blood count, we could have important indications regarding the disease stage of the patient, and consequently on the most appropriate type of therapy to choose.