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.

Significant Increase of Sexual Dysfunction in Patients With Renal Failure Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: It has been shown that sexual dysfunction (SD) is highly prevalent among patients with chronic renal failure (CRF), and starting renal replacement therapy may even increase it. However, SD is an infrequently reported problem in these treated patients. AIM: To investigate the prevalence of SD among patients with CRF undergoing renal replacement therapy, by a meta-analysis method. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for all studies assessing sexual function in patients with CRF receiving renal replacement therapy from January 2000 to April 2020. Relative risk (RR) with 95% CIs was used for analysis to assess the risk of SD in patients with CRF receiving renal replacement therapy. The cross-sectional study quality methodology checklist was used for the cross-sectional study. The methodologic quality of the case-control and cohort studies was assessed with the Newcastle-Ottawa Scale. Data were pooled for the random-effect model. Sensitivity analyses were conducted to assess potential bias. The Begg and Egger tests were used for publication bias analysis. OUTCOMES: The prevalence of SD among patients with CRF receiving renal replacement therapy was summarized using pooled RR and 95% CI. RESULTS: This meta-analysis included 3,725 participants from 10 studies. Of these, 737 were patients with CRF receiving renal replacement therapy. The mean age of participants ranged from 32.75 to 56.1 years. Based on the random-effect model, synthesis of results demonstrated that the prevalence of SD was significantly increased among patients with CRF receiving renal replacement therapy in women (RR = 2.07, 95% CI: 1.47-2.91, P = .000; heterogeneity: I2 = 78.7%, P = .000) and in men (RR = 2.95, 95% CI: 2.16-4.02, P = .000; heterogeneity: I2 = 86.1%, P = .000). Estimates of the total effects were generally consistent in the sensitivity analysis. No evidence of publication bias was observed. CLINICAL IMPLICATIONS: Patients with CRF receiving renal replacement therapy had a significantly increased risk of SD, which suggests that clinicians should evaluate sexual function, when managing patients with CRF receiving renal replacement therapy. STRENGTHS AND LIMITATIONS: This is the first study to explore the prevalence of SD among patients with CRF undergoing renal replacement therapy based on all available epidemiologic studies. However, all included studies were an observational design, which may downgrade this evidence. CONCLUSION: The prevalence of SD is significantly increased among patients with CRF receiving renal replacement therapy. More research studies are warranted to clarify the relationship. Luo L, Xiao C, Xiang Q, et al. Significant Increase of Sexual Dysfunction in Patients With Renal Failure Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis. J Sex Med 2020;17:2382-2393.

The m6A methylation regulator-based signature for predicting the prognosis of prostate cancer.

Aim: To construct a survival prediction signature for prostate cancer (PC) based on the RNA N6-methyladenosine (m6A) methylation regulator. Materials & methods: This paper explores the interaction network of differentially expressed m6A RNA methylation regulators in PC by Pearson correlation analysis. Univariate Cox risk regression and LASSO regression analysis were used to construct a predictive signature of PC. Kaplan-Meier survival analysis compared the overall survival of the high- and low-risk groups. Results & Conclusion: We first constructed a prognostic two gene signature for PC based on the m6A RNA methylation regulators MRTTL14 and YTHDF2. The interaction network of m6A RNA methylation regulators in PC was also established.

Low intensity extracorporeal shockwave Therapy shifts PDE5i nonresponders to responders.

To evaluate the efficiency of an energy density of 0.05mj/mm2 of low intensity extracorporeal shockwave therapy (Li-ESWT) on erectile dysfunction (ED) patients. A total of 45 ED patients met the inclusion criteria, including 7 PDE5i responders and 38 nonresponders. All the patients have already been delivered 10000 shockwaves of total seven treatment points twice a week for 4 weeks. Simultaneously, questionnaires of International Index of Erectile Function-Erectile Function (IIEF-EF), Erectile Hard Score (EHS) and Minimal Clinical Important Differences (MCID) were evaluated for the efficiency and safety at 8th and 16th weeks. The changes in the IIEF-EF score by MCID suggested that Li-ESWT treatment was effective in 22 PDE5i nonresponders patients (58%) at 8th week. Then at 16th week the number of patients who were effectively treated increased to 27 (71%). Among PDE5i responders, 5 patients (71%) were effective base on MCID at 16th week. Among PDE5i nonresponders 22 patients (58%) achieved erection hard enough for vaginal penetration and increased to 27 (71%) patients at 16th week (EHS ≥3). Moreover, even 3 patients achieved EHS 4 in PDE5i nonresponders at 16th week. Among PDE5i responders, 4 of 7 patients reached EHS of 4 from EHS 3 at 16th week. Apart from this, Li-ESWT treatment was also effective in 9 patients (24%) in PDE5i nonresponders without follow-up PDE5i. Energy flux density (EFD) of 0.05 of Li-ESWT could improve the erectile function of ED patients with PDE5i response. In addition, EFD of 0.05 of Li-ESWT treatment could turn PDE5i nonresponders to responders.

Mesenchymal stem cell-derived exosomes ameliorate erection by reducing oxidative stress damage of corpus cavernosum in a rat model of artery injury.

Erectile dysfunction (ED) is a common ageing male's disease, and vascular ED accounts for the largest proportion of all types of ED. One of the mechanisms of vascular ED in the clinic is arterial insufficiency, which mainly caused by atherosclerosis, trauma and surgical. Moreover, oxidative stress damage after tissue ischemia usually aggravated the progress of ED. As a new way of acellular therapy, mesenchymal stem cell-derived exosomes (MSC-Exos) have great potential in ED treatment. In the current study, we have explored the mechanism of MSC-Exos therapy in a rat model of internal iliac artery injury-induced ED. Compared with intracavernous (IC) injection of phosphate-buffered saline after artery injury, of note, we observed that both mesenchymal stem cells (MSCs) and MSC-Exos through IC injection could improve the erectile function to varying degrees. More specifically, IC injection MSC-Exos could promote cavernous sinus endothelial formation, reduce the organization oxidative stress damage, and improve the nitric oxide synthase and smooth muscle content in the corpus cavernosum. With similar potency compared with the stem cell therapy and other unique advantages, IC injection of MSC- Exos could be an effective treatment to ameliorate erectile function in a rat model of arterial injury.

SPTLC1 inhibits cell growth via modulating Akt/FOXO1 pathway in renal cell carcinoma cells.

Serine palmitoyltransferase long chain-1 (SPTLC1), which is the rate-limiting enzyme for sphingolipid biosynthesis, has been indicated to be essential for carcinoma cell survival and proliferation in recent, but its role in the regulation of renal cell carcinoma (RCC) remains unknown. In the present study, we found that SPTLC1 expression was significantly decreased in RCC tissues compared to non-tumor tissues, and low SPTLC1 expression was associated with poor overall survival of RCC patients. In addition, our results revealed that forced expression of SPTLC1 could significantly inhibit cell growth in vitro and in vivo via, at least in part, modulating Akt/FOXO1 signaling pathway, thus representing a novel role of SPTLC1 in the regulation of tumor growth in RCC for the first time.

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.

Gout is associated with elevated risk of erectile dysfunction: a systematic review and meta-analysis.

Previous studies investigating the risk of erectile dysfunction (ED) among patients with gout have produced inconsistent evidence. Therefore, the aim of this meta-analysis was to investigate the relationship between gout and the risk of ED. The Embase, Medline, Scopus, Web of Science and Cochrane Library databases were searched for all studies assessing the risk of ED in patients with gout. Relative risks (RR) and corresponding 95% confidence intervals (CI) were adopted to estimate the association between gout and the risk of ED. Sensitivity analyses were applied to evaluate the robustness of results. Overall, 355,761 participants were included from 8 studies (3 cross-sectional and 5 cohort studies). Of these, 85,067 were patients with gout. Synthesis results showed patients with gout had a 1.2-fold higher risk of ED than individual without gout (RR 1.20, 95% CI 1.10-1.31, P < 0.001). The results of sensitivity analysis are consistent with the trend of synthesis results. The present meta-analysis revealed that the risk of ED in patients with gout was dramatically increased when compared with the general population, which suggests that clinicians should assess erectile function when treating an individual who suffers from gout.

Serum Neuroendocrine Markers Predict Therapy Outcome of Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis.

PURPOSE: To evaluate whether serum neuroendocrine markers could effectively predict treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: The PubMed, Cochrane Library and Embase databases were sought to identify eligible studies concerning serum neuroendocrine markers and the prognosis of post-treatment mCRPC from inception to April 2018. The association between serum neuroendocrine markers, that is, chromogranin A (CgA) and neurone-specific enolase (NSE), levels and the prognosis of post-treatment mCRPC were summarized using a random-effects model and hazard ratio (HR) with 95% CI Sensitivity analyses were conducted to assess potential bias. RESULTS: A total of 234 participants are included in this meta-analysis (mean age = 71.3 years) from 6 studies. The pooled results show that higher markers' levels at baseline in patients were associated with unfavorable overall survival (OS; univariate analysis: HR 3.775, 95% CI 1.469-9.698, p = 0.006; multivariate analysis: HR 3.838, 95% CI 1.774-8.304, p = 0.001), and a similar situation was observed in progression-free survival (PFS; univariate analysis: HR 2.785, 95% CI 1.315-5.898, p = 0.007; multivariate analysis: HR 1.266, 95% CI 1.017-1.577, p = 0.035). Estimates of the total effects were generally consistent in the sensitivity analysis. Publication bias was observed when performing the univariate analysis of PFS, and we have the explanation accordingly. CONCLUSIONS: The results of this pooled analysis confirm serum neuroendocrine markers could be the effective predictor of treatment outcome in patients with mCRPC. In addition, a combination of CgA and NSE is more valuable to predict worse OS. Further randomized case-control trials are required to validate this relationship.

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.

ß-arrestin1-medieated inhibition of FOXO3a contributes to prostate cancer cell growth in vitro and in vivo.

Recently, ß-arrestin1 has been indicated as a prostate cancer promoter through promoting cell proliferation and epithelial to mesenchymal transition, but its underlying mechanism remains unclear. Here, our data revealed that ß-arrestin1 could promote cell growth through inhibiting the transcriptional activity and expression of FOXO3a in prostate cancer cells in vitro and in vivo. We found that ß-arrestin1 could promote the cell and tumor growth of prostate cancer, and ß-arrestin1 expression represented a negative correlation with FOXO3a expression but not FOXO1 expression in prostate cancer cell lines and tissues. In addition, forced expression of ß-arrestin1 induced a significant decrease of FOXO3a expression but had no clear effect on FOXO1 expression. Mechanistically, ß-arrestin1 could interact with FOXO3a and MDM2, respectively, and promote the interaction between FOXO3a and MDM2, whereas it had no obvious interaction with FOXO1. Furthermore, ß-arrestin1 could inhibit the transcriptional activity of FOXO3a via Akt and ERK1/2 pathways. Together, our results revealed a novel mechanism for ß-arrestin1 in the regulation of the prostate cancer procession through inhibiting FOXO3a.

Association Between Multiple Sclerosis and Risk of Female Sexual Dysfunction: A Systematic Review and Meta-Analysis.

INTRODUCTION: It has been reported that multiple sclerosis (MS) would increase the susceptibility to female sexual dysfunction (FSD). AIM: To assess whether MS was a risk factor for FSD through a comprehensive literature review and meta-analysis. METHODS: MEDLINE (PubMed), Embase, Cochrane Library, and PsychINFO databases were systematically searched for all studies reporting sexual function in women with MS. The protocol for this meta-analysis is available from PROSPERO (CRD42018094392). MAIN OUTCOME MEASURES: The association between MS and risk of FSD was summarized using relative risk or standard mean differences with 95% CI. Subgroup and sensitivity analyses were conducted to detect potential bias. RESULTS: Overall, 1,485 women participants (the mean age ranged from 29.15 to 45.89 years) were included from 9 studies (4 cross-sectional and 5 case-control studies); 826 of them were patients with MS, with a mean disease duration from 2.7 to 16.51 years. Synthesis of results revealed that MS was significantly associated with an increased risk of FSD (relative risk 1.87, 95% CI 1.25-2.78, P = .002; heterogeneity: I2 = 89.0%, P < .001). Women with MS had significantly lower values in total Female Sexual Function Index scores as compared with healthy controls (standard mean differences -2.41,95% CI -3.87 to -0.96, P = .017; heterogeneity: I2 = 97.2%, P = .001). The grading of recommendations assessment, development, and evaluation-relevant outcomes revealed that the absolute effect of MS on FSD was 434 more per 1000 (from 125 more to 888 more); and the overall quality of the evidence was judged as low. CLINICAL IMPLICATIONS: The present meta-analysis indicates that women patients with MS have a significant elevated risk of sexual dysfunction, which should raise awareness of the potential association between MS and FSD by both neurologists and urologists. STRENGTHS & LIMITATIONS: This the first study to summarize all available evidence for combining the odds on the association between MS and the risk of developing FSD. However, all the included studies were observational design, which may downgrade this evidence. CONCLUSION: Results of this meta-analysis revealed a potential hazardous effect of MS for developing FSD. High-quality stringently controlled studies with large sample size are still warranted to validate this relationship. Zhao S, Wang J, Liu Y, et al. Association Between Multiple Sclerosis and Risk of Female Sexual Dysfunction: A Systematic Review and Meta-analysis. J Sex Med;15:1716-1727.

Robot-assisted laparoscopic versus open ureteral reimplantation for pediatric vesicoureteral reflux: a systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy and safety of robot-assisted laparoscopic ureteral reimplantation (RALUR) and open ureteral reimplantation (OUR) in treating primary pediatric vesicoureteral reflux (VUR) based on published literature. METHODS: A comprehensive literature search of PubMed, Embase, Cochrane Library, CBM, CNKI and VIP databases was conducted to identify studies comparing the outcomes of RALUR with OUR for treating primary pediatric VUR. The last search was in January 2017. Summarized mean differences (MDs) or odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the differences in outcomes between RALUR and OUR. RESULTS: A total of six studies containing 7122 children with primary VUR were included in this analysis. Significantly longer operation time was needed for RALUR than OUR (MD 66.69 min, 95% CI 41.71-91.67, P < 0.00001), while the RALUR group had significantly fewer days of hospital stay (MD - 17.80 h, 95% CI - 21.18 to - 14.42, P < 0.00001) and postoperative Foley placement (MD - 0.32 days, 95% CI - 0.57 to - 0.07, P = 0.01). No significant differences were found in estimated blood loss during operation, success rate, complications, and postoperative analgesia usage between the two groups. In subgroup analyses, a significantly higher rate of short-term postoperative complications in RALUR was found compared with OUR (OR 3.17, 95% CI 1.72-5.85, P = 0.0002). CONCLUSIONS: Our study indicates that compared with OUR, RALUR is also an effective surgical approach for primary pediatric VUR and could help patients return to society more quickly; however, short-term postoperative complications of RALUR should be considered cautiously.

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.

5-alpha Reductase Inhibitors and risk of male breast cancer: a systematic review and meta-analysis.

OBJECTIVE: To assess the relationship between 5α-reductase inhibitors (5ARIs) and the risk of male breast cancer (MBC). MATERIAL AND METHODS: We systematically searched Medline via PubMed, Embase and the Cochrane Library Central Register up to May 2017 to identify published articles related to 5ARIs and the risk of MBC. RESULTS: Summary effect estimates were calculated by a random-effect model, and tests for multivariable-unadjusted pooled risk ratios (RR) and heterogeneity, as well as the sensitivity analyses were conducted to assess publication bias. All four studies were conducted in a quality assessment according to the Newcastle Ottawa Scale system. The strength of association between 5ARIs and the prevalence of MBC was evaluated by using summarized unadjusted pooled RR with a 95% confidence interval [CI]. Four studies involving 595.776 participants, mean age range from 60 to 73.2 years old, were included in a meta-analysis, which produced a summary unadjusted RR of the risk of MBC for the treatment of 5ARIs of 1.16 (95% CI 0.85-1.58, P=0.36) and the multivariable-adjusted RR is 1.03, (95% CI 0.75-1.41, p=0.86). There was no heterogeneity among included studies (I2=0%, P=0.49). Estimates of total effects were generally consistent with the sensitivity. CONCLUSION: We did not observe a positive association between the use of 5ARIs and MBC. The small number of breast cancer cases exposed to 5ARIs and the lack of na association in our study suggest that the development of breast cancer should not influence the prescribing of 5ARIs therapy.

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.

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 HIV Infection and Prevalence of Erectile Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence of erectile dysfunction (ED) in men positive for HIV has been reported to exceed the baseline of the general population. However, no meta-analysis or conclusive review has investigated whether individuals with HIV infection have a significantly higher prevalence of ED. AIM: To explore the exact association between HIV infection and the prevalence of ED. METHODS: The PubMed, Embase, Medline, and Cochrane Library databases were searched to identify studies concerning the association between HIV infection and the prevalence of ED that were published up to December 2016. Manual searches also were performed. Relative risks and corresponding 95% confidence intervals were used to estimate the strength of association between HIV infection and the prevalence of ED. The methodologic quality of the included cohort studies was assessed through the Newcastle-Ottawa Scale. The cross-sectional study quality methodology checklist was used to assess the quality of cross-sectional studies. Sensitivity analyses were conducted to assess potential bias. This study was conducted according to the guidelines for Meta-Analyses and Systematic Reviews of Observational Studies (MOOSE). OUTCOMES: The strength of association between HIV infection and the prevalence of ED was evaluated using summarized unadjusted pooled relative risks and 95% confidence intervals. RESULTS: Two cohort studies and three cross-sectional studies involving 4,252 participants were included. Mean age of patients ranged from 35.2 to 52 years in the included studies. Based on the random-effects model, analyses of all studies showed that HIV infection was significantly associated with an increased prevalence of ED (relative risk = 2.32, 95% confidence interval = 1.52-3.55, P < .001). There was significant heterogeneity among included studies (I2 = 84%, P < .001). Estimates of total effects were generally consistent with the sensitivity. CLINICAL IMPLICATIONS: Individuals with HIV infection had a significantly increased prevalence of ED, which suggests that ED should be of concern to clinicians when managing men with HIV infection. STRENGTHS AND LIMITATIONS: A strength of this study is that it is the first meta-analysis to explore the relation between HIV infection and the prevalence of ED. A limitation is that all included studies were observational studies, which can induce recall bias or selection bias. CONCLUSION: Evidence from the observational studies suggested that individuals with HIV infection had a significantly increased prevalence of ED despite significant heterogeneity. More research is warranted to clarify the relation between HIV infection and the prevalence of ED. Luo L, Deng T, Zhao S, et al. Association Between HIV Infection and Prevalence of Erectile Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2017;14:1125-1132.