miR-199b-5p-DDR1-ERK signalling axis suppresses prostate cancer metastasis via inhibiting epithelial-mesenchymal transition.

BACKGROUND: The investigation of underlying mechanism and the exploitation of novel therapies for metastatic prostate cancer (PCa) are still urgently needed. miR-199b-5p has been suggested to function as tumour suppressor in various human cancers. However, the clinical significance and role of miR-199b-5p in PCa remain unclear. METHODS: The current study sought to investigate the expression status of miR-199b-5p in PCa and the involved molecular mechanisms in PCa metastasis by using bioinformatics analyses, loss-and gain-of-functions and rescue experiments in vitro and in vivo. RESULTS: We demonstrated that miR-199b-5p was significantly downregulated in metastatic PCa tissues and cells when compared with the normal prostate tissue, the localised disease, the weakly metastatic and androgen-dependent PCa cell and the normal prostate epithelial cell. We also found that miR-199b-5p drastically suppressed PCa cell proliferation, migration and invasion in vitro and inhibited xenografts tumour growth and metastasis in vivo. Mechanistically, our results showed that miR-199b-5p could inhibit discoidin domain receptor tyrosine kinase 1 (DDR1) expression by directly targeting its 3'-UTR, thereby hindering epithelial-mesenchymal transition (EMT)-associated traits, which were induced by DDR1 activating ERK signalling pathway. Moreover, PCa patients with low miR-199b-5p expression level had a remarkably shorter overall survival than those with high miR-199b-5p level, indicating an association of miR-199b-5p loss with poor prognosis in patients with PCa. Furthermore, DDR1 was upregulated in PCa, and significantly correlated with high Gleason score, advanced pathological stage, tumour metastasis and shorter overall survival. CONCLUSIONS: Our study, for the first time, provide evidence of a tumour-suppressive function of miR-199b-5p in the invasion and metastasis of PCa, supporting the translational exploitation of miR-199b-5p-based therapeutic approaches for PCa metastases. Also, the miR-199b-5p-DDR1-ERK signalling axis identified in this study represents a novel mechanism of regulating EMT in PCa metastases.

A PSCA/PGRN-NF-κB-Integrin-α4 Axis Promotes Prostate Cancer Cell Adhesion to Bone Marrow Endothelium and Enhances Metastatic Potential.

Distant metastasis, predominantly to bone, is the leading cause of morbidity and mortality in prostate cancer. However, the mechanisms underlying prostate cancer metastases remain unknown. Prostate cancer cells exhibited discrete adhesion to bone marrow endothelial cells (BMEC), resulting in osteotropic metastasis. Prior data showed an increased metastatic propensity of prostate stem cell antigen (PSCA)-positive prostate cancer cells. The current study sought to characterize the roles of PSCA in the adhesion of prostate cancer cells to BMECs. Cell adhesion was assessed using the adhesion assay and transendothelial migration. The expression and regulation of integrins were evaluated by qRT-PCR, Western blot, promoter-luciferase activity, and chromatin immunoprecipitation (ChIP). Functionally, the potential interacting partners of PSCA in prostate cancer cells were identified by coimmunoprecipitation and mass spectrometry (MS) analysis. The association of PSCA expression with bone metastasis was further analyzed in an in vivo model and prostate cancer patients. We found that overexpression of PSCA enhanced the adhesion capability of prostate cancer cells to BMECs through upregulating integrin-α4 expression, concurrent with transcriptionally activated NF-κB. Growth factor progranulin (PGRN) was identified as a potential interacting partner of PSCA in prostate cancer cells. Functional studies showed that downregulation of PGRN and PSCA with siRNAs in prostate cancer cells significantly suppressed the integrin-α4 expression and the adhesion to BMECs in vitro, respectively, which were restorable by exogenous PGRN. Importantly, PSCA depletion significantly reduced tumors' presence in the bone of a mouse model. Furthermore, PSCA expression is elevated in prostate cancer tissue, and significantly associated with increased Gleason score, advanced stage, bone metastasis, and poor prognosis in prostate cancer patients. We conclude that PSCA/PGRN promoted the adhesion of prostate cancer cells to BMECs through NF-κB/integrin-α4 pathways, to facilitate metastases. IMPLICATIONS: The findings presented here suggest PSCA/PGRN as a potential therapeutic target for prostate cancer metastases, especially for bone metastasis.

Is polycystic ovary syndrome associated with risk of female sexual dysfunction? A systematic review and meta-analysis.

The aim of this study was to evaluate whether polycystic ovary syndrome (PCOS) is a risk factor for female sexual dysfunction (FSD) by conducting a systematic review and meta-analysis. The databases PubMed, EMBASE and the Cochrane Library were searched for relevant studies. The association between PCOS and risk of FSD was assessed by relative risk or standard mean differences with 95% confidence interval. The protocol for this meta-analysis is available from PROSPERO (CRD42018102247). Overall, 2626 participants (mean age 25-36 years) were included from 10 studies (five cross-sectional and five case-control studies), 1163 of whom were women with PCOS. The pooled results from eight included studies providing the number of cases revealed no significant association between PCOS and increased risk of FSD (RR = 1.09, 95% CI 0.9 to 1.32; heterogeneity: I2 = 11.0%). The combined overall standard mean difference from five studies reporting Female Sexual Function Index (FSFI) scores showed that patients with PCOS had similar values in total FSFI scores compared with healthy controls (standard mean difference = -0.03, 95% CI -0.12 to 0.05; heterogeneity: I2 = 0.0%). Sensitivity analyses yielded similar results. This meta-analysis suggests no direct association between PCOS and risk of FSD. Well-controlled trials with large sample sizes, however, are needed to validate this evidence.

Parkinson's Disease Is Associated with Risk of Sexual Dysfunction in Men but Not in Women: A Systematic Review and Meta-Analysis.

BACKGROUND: Mounting evidence has emerged suggesting that patients with Parkinson's disease (PD) are susceptible to sexual dysfunction (SD). AIM: To better clarify the relationship between PD and SD. METHODS: PubMed, Embase, Cochrane Library database, and PsychINFO database were systematically searched for pertinent studies evaluating sexual function in the patients with PD. This systematic review and meta-analysis have been registered on PROSPERO (ID: CRD42018108714; http://www.crd.york.ac.uk/PROSPERO). OUTCOMES: The association between PD and SD was assessed using relative risk (RR) with 95% CI. The quality of evidence was ranked by the GRADE profiler. RESULTS: 11 observational studies met the predefined criteria for inclusion, enrolling 30,150 subjects from both the PD group and healthy control group (mean age 54.6-75.1 years). Synthesis results revealed that PD was associated with an elevated risk of SD in males (7 studies; 1.79; 95% CI = 1.26-2.54, P = .001; heterogeneity: I2 = 73.2%, P < .001). However, when restricted to female subjects, the combined RR from 3 eligible studies suggested a lack of significant association between PD and SD (RR = 1.3, 95% CI = 0.64-2.61, P = .469; heterogeneity: I2 = 80.0%, P = .007). The GRADE profiler indicated the overall quality of the evidence was low in studies including males and very low in studies including females. CLINICAL IMPLICATIONS: The current meta-analysis indicated that men with PD were more likely to experience SD than those without PD. In female subjects, however, PD seemed to not be associated with a high prevalence of SD compared with healthy controls. Based on these findings, patients with PD should be routinely assessed for sexual functioning, especially males. STRENGTHS & LIMITATIONS: This is the first systematic review and meta-analysis of the association between PD and the risks of SD in both males and females. However, substantial heterogeneities were detected across the included studies. CONCLUSION: A hazardous effect of PD for developing SD was detected in men but not in women. As a result, sexual function assessment and appropriate therapy are recommended for men with PD in clinical practice. Zhao S, Wang J, Xie Q, et al. Parkinson's Disease Is Associated with Risk of Sexual Dysfunction in Men but Not in Women: A Systematic Review and Meta-Analysis J Sex Med 2019;16:434-446.

Elucidating Mechanisms of Long-Term Gasoline Vehicle Exhaust Exposure-Induced Erectile Dysfunction in a Rat Model.

INTRODUCTION: Exposure to air pollution poses a risk for morbidity in multiple diseases. However, the role of ambient air pollutant emissions in public sexual health is just beginning to be understood and remains controversial. AIM: We have determined to elucidate the specific role of gasoline vehicle exhaust (VE), a crucial source and toxicant of air pollution, in the penile erectile function via a rat model. METHODS: 40 male Sprague Dawley rats, 12 weeks of age, were used in this experiment. Except for the control group (10 rats), rats were equally exposed to VE for total 2 hours, 4 hours, and 6 hours daily for 3 months consecutively. During each VE exposure periods, particulate matter (PM) mass concentrations of PM1, PM2.5, and PM10 were 1.43 ± 0.036, 1.45 ± 0.033, and 1.47 ± 0.037 mg/m3, respectively. MAIN OUTCOME MEASURE: Erectile function, pulmonary function, serum inflammatory factors, and histologic examinations of the lung and penile tissues were evaluated. RESULTS: Our study indicates that in vivo, 4-hour, and 6-hour daily exposure to VE causes significant reduction of erectile function, as judged by intracavernous pressure measurement. Meanwhile, we have observed that the 4-hour and 6-hour VE exposure rats exhibited remarkable increased levels of serum inflammatory factors, decreased total lung capacity and chord compliance, thickened alveoli septum, destroyed alveoli, pulmonary fibrosis, as well as down-regulation of the messenger RNA and protein expression of endothelial and neuronal nitric oxide synthase in the penile tissue when compared with normal control rats. CLINICAL IMPLICATIONS: We speculated that the underlying mechanisms of VE inducing erectile dysfunction could be attributed to systemic inflammation, pulmonary dysfunction, and the reduction of nitric oxide synthase activity in the corpus cavernosum. STRENGTH & LIMITATIONS: For the first time, our study revealed the deleterious effect of VE on penile erection in vivo. However, the VE exposure model might not entirely mimic the natural condition of ambient air pollution. CONCLUSION: Our results raise concerns about the potential role played by long-term exposure to gasoline VE in the development of erectile dysfunction. Zhao S, Wang J, Xie Q, et al. Elucidating Mechanisms of Long-Term Gasoline Vehicle Exhaust Exposure-Induced Erectile Dysfunction in a Rat Model. J Sex Med 2019;16:155-167.

Association between epilepsy and risk of sexual dysfunction: A meta-analysis.

PURPOSE: Sexual functioning is an important factor influencing quality of life. Mounting evidence suggests that both male and female patients with epilepsy (PWE) have an increased risk of developing sexual dysfunction (SD). The aim of this meta-analysis was to quantify the association between epilepsy and the risk of SD. METHODS: PubMed, Embase, and Cochrane Library database were systematically searched to identify the pertinent studies focusing on the association between epilepsy and SD. Relative risk (RR) for SD with 95% confidence interval (CI) was calculated. The overall quality of the evidence was generated by applying the GRADE-profiler. This meta-analysis was registered on the PROSPERO (ID: CRD42018103572, http://www.crd.york.ac.uk/PROSPERO). RESULTS: Nine studies (3 cross-sectional, 5 case-control, and 1 cohort) were included in this meta-analysis, for a total of 1556 subjects and 599 cases of epilepsy. Synthetic results demonstrated that epilepsy was associated with an increased risk of female SD (6 studies, pooled RR = 2.69, 95%CI: 1.48-4.89, P = 0.001; heterogeneity: I2 = 88.9%, P < 0.001) as well as male SD (3 studies, pooled RR = 4.85, 95%CI: 2.01-11.7, P < 0.001; heterogeneity: I2 = 74.2%, P = 0.021). The GRADE-profiler showed that the rate of events of SD on average in the PWE and the controls were 383/659 (58.1%) and 168/1017 (16.5%), respectively. The quality of evidence across outcomes was MODERATE. CONCLUSIONS: Epilepsy is significantly associated with an increased risk of SD in both sexes. These findings suggest that both clinicians and patients should recognize that epilepsy has a potential hazardous effect on sexual functioning.

Inflammatory Bowel Diseases Were Associated With Risk of Sexual Dysfunction in Both Sexes: A Meta-analysis.

BACKGROUND: An association between inflammatory bowel diseases (IBD) and increased susceptibility to sexual dysfunction (SD) was reported in a number of studies. METHOD: MEDLINE (PubMed), EMBASE, and the Cochrane Library were systematically searched for all relevant studies reporting the sexual function in IBD patients. Relative risk (RR) with a 95% confidence interval (CI) was used to summarize the association between IBD and risk of SD. Subgroup and sensitivity analyses were applied to detect potential bias. RESULTS: Overall, 351,668 male individuals and 1309 female individuals (the mean age ranged from 33.6 years to 52.4 years) were included from 8 studies (of which 4 studies provided the outcomes of both sexes). Synthesis of results revealed that IBD was significantly associated with an elevated risk of SD in male subjects (7 studies, RR = 1.41, 95% CI, 1.09-1.81, P = 0.008; heterogeneity: I2 = 80.2%, P < 0.001) and female subjects (5 studies, RR = 1.76, 95% CI, 1.28-2.42, P < 0.001; heterogeneity: I2 = 69.6%, P = 0.011). Stratified analysis by the mean age of the individuals indicated that patients with IBD with a relatively young age (male: younger than 50 years; female: younger than 40 years) exhibited a significantly increased odds of SD. Sensitivity analyses showed that no single study dominated the overall combined RR. CONCLUSION: Evidence from this meta-analysis revealed that both male and female patients with IBD have a significantly increased risk of SD, which should remind both gastroenterologists and urologists to be aware of the potential hazardous effect of IBD for developing SD.

Risk of secondary rectal cancer and colon cancer after radiotherapy for prostate cancer: a meta-analysis.

PURPOSE: To investigate whether radiotherapy for prostate cancer increases the risk of therapy-related rectal cancer and colon cancer. METHODS: A systematic literature search was carried out using the Medline (PubMed), EMBASE, and the Cochrane Library to identify studies examining the association between radiotherapy for prostate cancer and secondary colorectal cancer (rectal cancer and colon cancer) published before March 19, 2018. The risk of second colorectal cancer after radiotherapy was summarized using unadjusted odds ratio (OR) and adjusted hazard ratio (HR) with their 95% confidence interval (CI). Subgroup and sensitivity analyses were conducted to detect potential bias and heterogeneity. RESULTS: After study selection, 16 reports were retrieved for analysis. When patients received radiotherapy compared with those unexposed to radiation, there was an increased risk of the rectal cancer (OR 1.37, 95%CI 1.01 to 1.85), but not colon cancer. According to adjusted HR, there was an increased risk of the rectal cancer (HR 1.64, 95%CI 1.39 to 1.94), and colon cancer (HR 1.33, 95%CI 1.02 to 1.76). The OR for rectal cancer showed an increased risk with longer latent period (5 years lag time versus 10 years lag time, OR: 1.56 versus 2.22). Brachytherapy had no association with second cancer across all analyses. CONCLUSIONS: Radiotherapy was associated with an increased risk of subsequent rectal cancer compared with patients unexposed to radiation. Colon may be free from the damage of radiation. Brachytherapy had no association with second rectal cancer or colon cancer.

Bone marrow mesenchymal stem cells reduce ureteral stricture formation in a rat model via the paracrine effect of extracellular vesicles.

With no effective therapy to prevent or treat ureteral stricture (US), a multifactorial fibrotic disease after iatrogenic injury of the ureter, the need for new therapies is urgent. Mesenchymal stem cells (MSCs) have been widely studied for treating tissue defects and excessive fibrosis, and recent studies established that one of the main therapeutic vectors of MSCs is comprised in their secretome and represented by extracellular vesicles (EVs). Thus, we have determined to explore the specific role of MSCs-derived EVs (MSC-EVs) treatment in a pre-clinical model of US. The results firstly showed that either a bolus dose of MSCs or a bolus dose of MSC-EVs (administration via renal-arterial) significantly ameliorated ureteral fibrosis and recuperated ureter morphological development in a US rat model. We confirmed our observations through MSCs or MSC-EVs treatment alleviated hydronephrosis, less renal dysfunction and blunted transforming growth factor-ß1 induced fibration. Due to MSC-EVs are the equivalent dose of MSCs, and similar curative effects of transplantation of MSCs and MSC-EVs were observed, we speculated the curative effect of MSCs in treating US might on account of the release of EVs through paracrine mechanisms. Our study demonstrated an innovative strategy to counteract ureteral stricture formation in a rat model of US.

Rheumatoid Arthritis and Risk of Sexual Dysfunction: A Systematic Review and Metaanalysis.

OBJECTIVE: It has been reported that there is an association between rheumatoid arthritis (RA) and increased susceptibility to sexual dysfunction (SD). This systematic review and metaanalysis aimed to investigate whether RA was a risk factor for SD. METHODS: MEDLINE (PubMed), EMBASE, and the Cochrane Library were systematically searched for all studies assessing sexual function in patients with RA. The association between RA and risk of SD was summarized using relative risk (RR) with 95% CI. RESULTS: Overall, 44,745 participants (mean age 43.2 yrs) were included from 7 studies (4 cross-sectional and 3 case-control studies). Of these, 6642 were patients with RA, with the mean disease duration from 5.7 years to 12.17 years. The methodological qualities of the included studies were judged as moderate to high. Synthesis of results demonstrated that RA was significantly associated with an increased risk of SD in females (RR 1.73, 95% CI 1.36-2.22, p < 0.001; heterogeneity: I2 60.3%, p = 0.028) as well as in males (RR 1.99, 95% CI 1.64-2.43, p < 0.001). The outcomes related to the Grading of Recommendations Assessment, Development, and Evaluation approach showed that the absolute effect of RA on SD was 10 more per 1000 (6-15 more); the overall quality of evidence was rated as low. CONCLUSION: Evidence from included studies indicates that patients with RA have a significantly increased risk of SD, which suggests that both patients and clinicians should be aware of the potential role of RA in the development of SD.

Comparison of two cannulation methods for assessment of intracavernosal pressure in a rat model.

Intracavernous pressure (ICP) measurement is a well-established technique for assessing the erectile function, which was performed by cannulating either crus or shaft of the penis. However, there are no studies concerning the experimental performance of the two cannulation sites yet. The aim of this study was to compare the measuring outcomes using two different cannulation sites. To validate the capacity of our study, both normal and the castration-induced erectile dysfunction rat models were conducted. Fifty adult male Sprague-Dawley rats were randomized equally into two groups: an intact group and a castration group. Five rats from each group firstly underwent different stimulation parameters to detect the optimal erectile responses. The residual rats in each group were further assigned into two subgroups (n = 10 per subgroup) according to two different cannulation sites (crus or shaft of the corpus cavernosum). The ICP values were compared between groups after different interventions. The optimal parameters for mean maximum ICP were recorded at 2.5V and a frequency of 15 Hz. The rats under the two different cannulation sites tended to show similar ICP values in both the intact and the castration groups. However, the success rate in monitoring ICP was significantly higher in the groups cannulating into the shaft of the penis compared to the crus (100% vs. 70%; P = 0.02). Our data suggested that the method of cannulation into the penile shaft could serve as a better alternative for the ICP measurement in rats.

PSCA promotes prostate cancer proliferation and cell-cycle progression by up-regulating c-Myc.

BACKGROUND: The Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored protein. Increasing evidence has indicated PSCA plays an important role in tumorigenesis. However, its function and the underlying molecular mechanisms in prostate cancer (PCa) are still not fully elucidated. In this study, we aimed to explore the effect of PSCA on cell cycle of PCa cells and its mechanism research. METHODS: Immunohistochemistry, quantitative reverse transcription-PCR (qRT-PCR) and Western blotting were used to quantify PSCA expression pattern in PCa tissues and cell lines. The association of PSCA expression with the biochemical recurrence (BCR)-free survival and overall survival (OS) of PCa patients were analyzed using Kaplan-Meier method. The roles of PSCA in PCa were confirmed based on both in vitro and in vivo systems. RESULTS: Immunohistochemistry results showed that PSCA was upregulated in PCa tissue. PSCA overexpression were significantly associated with high Gleason score (GS) (P = 0.028), positive BCR (P = 0.002), and poor OS (P = 0.032) and high c-Myc expression (P = 0.019). PSCA promoted PCa cell cycle progression and tumor growth via increased c-Myc expression. Additional, PI3K/AKT signaling pathways was involved in PSCA-mediated c-Myc expression and cell proliferation. CONCLUSIONS: PSCA is a novel cell cycle regulator with a key role in mediating c-Myc-induced proliferation. PSCA may be a potential diagnostic marker and therapeutic target for patients with PCa.

Association Between Opioid Use and Risk of Erectile Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: Opioid analgesics have been widely used to relieve chronic pain conditions; however, a connection between opioid analgesic administration and increased susceptibility to erectile dysfunction (ED) has been hypothesized. AIM: To evaluate whether opioid use was a risk factor for ED in a systematic review and meta-analysis. METHODS: The PubMed, Cochrane Library, and Embase databases were searched to identify eligible studies concerning opioid use and risk of ED from inception to April 2017. The association between opioid use and risk of ED was summarized using the relative risk with 95% CI. Sensitivity analyses were conducted to assess potential bias. The Begg and Egger tests were used for publication bias analysis. The GRADE evidence profile tool was used to assess the quality of the evidence. OUTCOMES: The overall combined risk estimates for the effect of opioid use on ED were calculated using a random-effects model. RESULTS: This meta-analysis included 8,829 men (mean age = 41.6 years) from 10 studies, 2,456 of whom received opioid management (duration of intervention = 4 months to 9.5 years). Pooled results demonstrated that the use of opioids was significantly associated with an increased risk of ED (relative risk = 1.96, 95% CI = 1.66-2.32, P < .001). Estimates of the total effects were generally consistent in the sensitivity analysis. No evidence of publication bias was observed. The overall quality of evidence was rated as low. CLINICAL IMPLICATIONS: We found that men with opioid use had a significantly increased prevalence of ED, which suggests that patients and clinicians should be aware of the potential role played by opioid administration in the development of ED. STRENGTHS AND LIMITATIONS: This is the first meta-analysis performed to describe the relation between opioid use and ED risk based on all available epidemiologic studies. However, the direction of causality between opioid use and risk of ED should be interpreted with caution because most included studies used a cross-sectional design. CONCLUSION: Evidence from the included observational studies indicated that men with opioid use had a significantly increased risk of ED. Further randomized controlled trials are still needed to confirm this relation. Zhao S, Deng T, Luo L, et al. Association Between Opioid Use and Risk of Erectile Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2017;14:1209-1219.

PSCA regulates IL-6 expression through p38/NF-κB signaling in prostate cancer.

BACKGROUND: Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. We previously reported that PSCA involved in proliferation and invasion of PCa cells, however, the underlying mechanisms are unknown. In this study, we aimed to explore the regulating role of PSCA gene expression in interleukin-6 (IL-6) autocrine of PCa cells. METHODS: The stable knockdown-PSCA and ectopically overexpressed-PSCA vector were constructed and transfected into human PCa DU145 and PC-3M cells. The effects of PSCA overexpression or knockdown were determined in proliferation, invasion, and metastasis assays. The effect of PSCA on the expression and secretion of IL-6 was evaluated by immunoblotting and ELISA. Subcellular localization and expression pattern of PSCA and IL-6 protein were examined by immunohistochemistry. Its clinical significance was statistically analyzed. RESULTS: The results showed that stable knockdown of PSCA delayed proliferation, migration, and invasion while overexpressing PSCA enhanced the proliferation, migration, and invasion in vitro and the lung metastasis in vivo of PCa cells. Importantly, the PSCA involved in the IL-6 secretion and positively regulated p38/NF-κB/IL-6 signaling, leading to enhanced PCa cell invasion and metastasis. Both the expression of PSCA and IL-6 were significantly associated with poor biochemical recurrence-free survival of patients with PCa. PSCA protein expression showed a prognostic value in overall survival as indicated by Kaplan-Meier analysis. CONCLUSIONS: These results indicate that PSCA regulates the expression and secretion of IL-6 in human PCa cells through p38/NF-κB signaling pathways. PSCA may be a potential diagnostic marker and therapeutic target for PSCA-positive PCa.

Effect of Testosterone on the Phenotypic Modulation of Corpus Cavernosum Smooth Muscle Cells in a Castrated Rat Model.

OBJECTIVE: To investigate the effect of testosterone (T) on the phenotypic modulation of corpus cavernosum smooth muscle (CCSM) cells in a castrated rat model. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomly divided into 3 groups: control, castration, and castration with T supplementation (castration + T). Erectile function, histologic change, and biochemical markers were assessed for phenotypic modulation of CCSM cells in corporal tissue. Moreover, the primary rat CCSM cells were isolated and examined by Western blot analysis. RESULTS: Our data showed that serum T level, mean weight of the body, erectile function, and smooth muscle-to-collagen ratio were significantly decreased in the castration group compared with those in the control and castration + T groups. The expressions of CCSM cells' phenotypic markers, such as α-smooth muscle actin, calponin, and smooth muscle myosin heavy chain 11, were markedly lower, whereas osteopontin protein expression was significantly higher in castrated rats than in control and castrated + T rats. In addition, the immunofluorescence staining of α-smooth muscle actin and calponin markedly decreased in the primary CCSM cells of the castrated rats compared with the intensity of the control and the castration + T rats. CONCLUSION: CCSM cells undergo phenotype modulation in castrated rats, whereas T reversed the alterations. T may play a key role in the phenotype modulation of CCSM cells.

Corrigendum to "Combination of low-energy shock-wave therapy and bone marrow mesenchymal stem cell transplantation to improve the erectile function of diabetic rats" by Hai-Tao Shan et al.

[This corrects the article DOI: 10.4103/1008-682X.184271.].

A prospective and randomised trial comparing fluoroscopic, total ultrasonographic, and combined guidance for renal access in mini-percutaneous nephrolithotomy.

OBJECTIVE: To compare the safety and efficacy of fluoroscopic guidance (FG), total ultrasonographic guidance (USG), and combined ultrasonographic and fluoroscopic guidance (CG) for percutaneous renal access in mini-percutaneous nephrolithotomy (mini-PCNL). PATIENTS AND METHODS: The present study was conducted between July 2014 and May 2015 as a prospective randomised trial at the First Affiliated Hospital of Guangzhou Medical University. In all, 450 consecutive patients with renal stones of >2 cm were randomised to undergo FG, USG, or CG mini-PCNL (150 patients for each group). The primary endpoints were the stone-free rate (SFR) and blood loss (haemoglobin decrease during the operation and transfusion rate). Secondary endpoints included access failure rate, operating time, and complications. S.T.O.N.E. score was used to document the complexity of the renal stones. The study was registered at http://clinicaltrials.gov/ (NCT02266381). RESULTS: The three groups had similar baseline characteristics. With S.T.O.N.E. scores of 5-6 or 9-13, the SFRs were comparable between the three groups. For S.T.O.N.E. scores of 7-8, FG and CG achieved significantly better SFRs than USG (one-session SFR 85.1% vs 88.5% vs 66.7%, P = 0.006; overall SFR at 3 months postoperatively 89.4% vs 90.2% vs 69.8%, P = 0.002). Multiple-tracts mini-PCNL was used more frequently in the FG and CG groups than in the USG group (20.7% vs 17.1% vs 9.5%, P = 0.028). The mean total radiation exposure time was significantly greater for FG than for CG (47.5 vs 17.9 s, P < 0.001). The USG had zero radiation exposure. There was no significant difference in the haemoglobin decrease, transfusion rate, access failure rate, operating time, nephrostomy drainage time, and hospital stay among the groups. The overall operative complication rates using the Clavien-Dindo grading system were similar between the groups. CONCLUSIONS: Mini-PCNL under USG is as safe and effective as FG or CG in the treatment of simple kidney stones (S.T.O.N.E. scores 5-6) but with no radiation exposure. FG or CG is more effective for patients with S.T.O.N.E. scores of 7-8, where multiple percutaneous tracts may be necessary.

Combination of low-energy shock-wave therapy and bone marrow mesenchymal stem cell transplantation to improve the erectile function of diabetic rats.

Stem cell transplantation and low-energy shock-wave therapy (LESWT) have emerged as potential and effective treatment protocols for diabetic erectile dysfunction. During the tracking of transplanted stem cells in diabetic erectile dysfunction models, the number of visible stem cells was rather low and decreased quickly. LESWT could recruit endogenous stem cells to the cavernous body and improve the microenvironment in diabetic cavernous tissue. Thus, we deduced that LESWT might benefit transplanted stem cell survival and improve the effects of stem cell transplantation. In this research, 42 streptozotocin-induced diabetic rats were randomized into four groups: the diabetic group (n = 6), the LESWT group (n = 6), the bone marrow-derived mesenchymal stem cell (BMSC) transplantation group (n = 15), and the combination of LESWT and BMSC transplantation group (n = 15). One and three days after BMSC transplantation, three rats were randomly chosen to observe the survival numbers of BMSCs in the cavernous body. Four weeks after BMSC transplantation, the following parameters were assessed: the surviving number of transplanted BMSCs in the cavernous tissue, erectile function, real-time polymerase chain reaction, and penile immunohistochemical assessment. Our research found that LESWT favored the survival of transplanted BMSCs in the cavernous body, which might be related to increased stromal cell-derived factor-1 expression and the enhancement of angiogenesis in the diabetic cavernous tissue. The combination of LESWT and BMSC transplantation could improve the erectile function of diabetic erectile function rats more effectively than LESWT or BMSC transplantation performed alone.

Effect of 5α-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials.

INTRODUCTION: 5α-Reductase inhibitors (5ARIs) are widely used for the treatment of benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA). AIM: To review all the available data on the effect of 5ARIs on sexual function and assess whether 5ARIs increase the risk of sexual dysfunction. METHODS: A systematic search of the literature was conducted using the Medline, Embase, and Cochrane databases. The search was limited to articles published in English and up to October 2015. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Data were analyzed using Stata 12.0. A fixed- or a random-effects model was used to calculate the overall combined risk estimates. Publication bias was assessed using Begg and Egger tests. MAIN OUTCOME MEASURES: Sexual dysfunction, erectile dysfunction, and decreased libido. RESULTS: After screening 493 articles, 17 randomized controlled trials with 17,494 patients were included. Nine studies evaluated the efficacy of 5ARIs in men with BPH. The other eight reported using 5ARIs in the treatment of men with AGA. The mean age of participants was 60.10 years across all studies. We included 10 trials (6,779 patients) on the efficacy and safety of finasteride, 4 trials (6,222 patients) on the safety and tolerability of dutasteride, and 3 trials (4,493 patients) using finasteride and dutasteride for AGA. The pooled relative risks for sexual dysfunction were 2.56 (95% CI = 1.48-4.42) in men with BPH and 1.21 (95% CI = 0.85-1.72) in men with AGA; those for erectile dysfunction were 1.55 (95% CI = 1.14-2.12) in men with BPH and 0.66 (95% CI = 0.20-2.25) in men with AGA; and those for decreased libido were 1.69 (95% CI = 1.03-2.79) in men with BPH and 1.16 (95% CI = 0.50-2.72) in men with AGA. Estimates of the total effects were generally consistent with the sensitivity analysis. No evidence of publication bias was observed. CONCLUSION: Evidence from the randomized controlled trials suggested that 5ARIs were associated with increased adverse effects on sexual function in men with BPH compared with placebo. However, the association was not statistically significant in men with AGA. Well-designed randomized controlled trials are indicated to study further the mechanism and effects of 5ARIs on sexual function.