Prostate adenocarcinoma (PCa) is the most common cause of death due to malignancy among men, and bone metastasis is the leading cause of mortality in patients with PCa. Therefore, identifying the causes and molecular mechanism of bone metastasis is important for early detection, diagnosis and personalized therapy. In this study, we systematically analyzed molecular correlates of bone metastasis by bioinformatics analysis. A total of 12 differentially expressed microRNAs (miRNAs) and 102 differentially expressed genes were identified. Five miRNAs had prognostic significance in biochemical recurrence‐free survival (miR‐636, miR‐491‐5p, miR‐199b‐5p, miR‐199b‐3p, miR‐28‐3p). The differentially expressed genes were significantly enriched in extracellular matrix, cell‐substrate adhesion, collagen and integrin. Seven hub genes (VCAN, COL3A1, COL1A1, APOE, COL1A2, SDC1, THY1) with worse biochemical recurrence‐free survival and one hub gene (MMP9) with worse overall survival were detected. miR‐636, a novel oncogene, was found to be up‐regulated in bone metastatic PCa tissues and also predominately up‐regulated in human PCa cell lines. miR‐636 promoted cellular invasion and migration, and may promote bone metastasis via targeting MBNL2, TNS1 and STAB1. In conclusion, we have successfully defined molecular signatures of bone metastasis in PCa.

This meta-analysis combined data from 10 observational studies with the aim of investigating whether polycystic ovary syndrome (PCOS) is a risk factor for female sexual dysfunction (FSD). The pooled results revealed that the prevalence of FSD in women with PCOS seems comparable to healthy controls. ABSTRACTThe 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: I 2 = 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: I 2 = 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.

Prostate cancer (PCa) is the second cause of death due to malignancy among men, and metastasis is the leading cause of mortality in patients with PCa. MicroRNAs (miRNAs) play important regulatory roles in tumor development and metastasis. Here, we identified 13 miRNAs related to PCa metastasis by bioinformatics analysis. Moreover, we found that miR-671-5p was increased in metastatic PCa tissues, and its high expression indicated poor prognosis of PCa. MiR-671-5p could facilitate PCa cells proliferation, migration, and invasion in vitro and vivo. We confirmed that miR-671-5p directly bound to the 3’ untranslated regions of NFIA mRNA, and NFIA directly bound to the CRYAB promoter. High expression of NFIA and CRYAB negatively correlated with the advanced clinicopathological characteristics and metastasis status of PCa patients. Our study demonstrated that miR-671-5p promoted PCa development and metastasis by suppressing NFIA/ CRYAB axis.

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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.

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.

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.

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: I  2 = 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: I  2 = 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.