The risks, degree of malignancy and clinical progression of prostate cancer associated with the MDM2 T309G polymorphism： a meta-analysis

To determine the risk, malignant degree and clinical progression of prostate cancer （PCa） associated with mouse double-minute 2 protein （MDM2） T309G variants, a meta-analysis was performed on all eligible published studies. Odds ratios （ORs） with 95% confidence intervals （CIs） were estimated to assess these associations in seven studies that included 5151 cases and 1003 controls. In the overall analysis, the 309G allele was significantly associated with a decreased PCa risk （0R=0.85, 95% CI： 0.74-0.97）; this was also the case for the homozygous comparison （0R--0.72, 95% Ch 0.55-0.95） and the dominant genetic model （0R=0.79, 95% Ch 0.65-0.96）. The 309G allele was also found to be significantly associated with lower degrees of PCa malignancy （0R=0.85, 95% Ch 0.75-0.96） in the overall analysis, as well as in the heterozygous comparison （0R=0.79, 95% Ch 0.65-0.96）, homozygous comparison （0R=0.76, 95% Ch 0.58-0.98） and dominant genetic model （0R=0.81, 95% CI： 0.68-0.96）. Furthermore, grouping analysis showed that the 309G allele in Caucasians was significantly correlated with a decreased PCa risk （0R=0.77, 95% Ch 0.61-0.96）; this was also the case in the homozygous comparison （0R=0.51, 95% Ch 0.31-0.86）. The grouping analysis also showed that the 309G variant in Caucasians was significantly associated with a lower degree of PCa malignancy in all of the genetic models. In addition, we found that the 309G variant in Caucasians was significantly associated with a slower PCa clinical progression in all of the genetic models. In summary, our meta-analysis showed that the MDM2 309G variant was significantly associated with a decreased PCa risk, lower malignant degree and slower clinical progression in Caucasians, but there was no obvious association in the Asian population.

Losartan improves erectile function through suppression of corporal apoptosis and oxidative stress in rats with cavernous nerve injury

This study aimed to investigate the functional and morphological changes in the corpus cavernosum after cavernous nerve(CN)injury or neurectomy and then reveal whether treatment with the angiotensin II Type 1 receptor antagonist losartan would improve erectile function as well as its potential mechanisms.A total of 48 10-week-old Sprague-Dawley male rats,weighing 300-350 g,were randomly divided into the following four groups(n=12 per group):sham operation(Sham)group,bilateral cavernous nerve injury(BOND group,losartaretreated BCNI(BCNI+Losartan)group,and bilateral cavernous neurectomy(Neurectomy)group.Losartan was administered once daily by oral gavage at a dose of 30 mg kg^-1 day^-1 for 4 weeks starting on the day of surgery.The BCNI and the Neurectomy groups exhibited decreases in erectile response and increases in apoptosis and oxidative stress,compared with the Sham group.Treatment with losartan could have a modest effect on erectile function and significantly prevent corporal apoptosis and oxidative stress?The phospho-B-cell lymphoma 2(Bcl-2)-associated death promoter(p-Bad)/Bad and phospho-the protein kinase B(p-AKT)/AKT ratios were substantially lower,while the Bcl-2-associated X protein(Bax)/Bcl-2 ratio,nuclear factor erythroid 2-related factor 2(Nrf2)/Kelch-like ECH-associated protein 1(Keap-1),transforming growth factor-p 1(TGF-pi)and heme oxygenase-1(HO-1)levels,and caspase-3 activity were higher in the BCNI and Neurectomy groups than in the Sham group.After 4 weeks of daily administration with losartan,these expression levels were remarkably attenuated compared with the BCNI group.Taken together,our results suggested that early administration of losartan after CN injury could slightly improve erectile function and significantly reduce corporal apoptosis and oxidative stress by inhibiting the Akt/Bad/Bax/caspase-3 and Nrf2/Keap-1 pathways.

Prostate-derived IL-1βupregulates expression of NMDA receptor in the paraventricular nucleus and shortens ejaculation latency in rats with experimental autoimmune prostatitis

Experimental autoimmune prostatitis(EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid(NMDA)receptors in the paraventricular nucleus(PVN).However,the mechanism has not yet been elucidated.Herein,we screened out the target prostate-derived inflammation cytokines(PDICs)by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid(CSF)between EAP rats and their controls.After identifying the target PDIC,qualified males in initial copulatory behavior testing(CBT)were subjected to implanting tubes onto bilateral PVN.Next,they were randomly divided into four subgroups(EAP-1,EAP-2,Control-1,and Control-2).After 1-week recovery,EAP-1 rats were microinjected with the target PDIC inhibitor,Control-1 rats were microinjected with the target PDIC,while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF(aCSF).Results showed that only interleukin-1β(IL-1β)had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls(P<0.001)and significantly higher protein concentrations in both the serum(P=0.001)and CSF(P<0.001)of the EAP groups compared to the Control groups.Therefore,IL-1βwas identified as the target PDIC which crosses the blood-brain barrier,thereby influencing the central nervous system.Moreover,the EAP-1 subgroup displayed a gradually prolonged ejaculation latency(EL)in the last three CBTs(all P<0.01)and a significantly lower expression of NMDA NR1 subunit in the PVN(P=0.043)compared to the respective control groups after a 10-day central administration of IL-1βinhibitors.However,the Control-1 subgroup showed a gradually shortened EL(P<0.01)and a significantly higher NR1 expression(P=0.004)after homochronous IL-1βadministration.Therefore,we identified IL-1βas the primary PDIC which shortens EL in EAP rats.However,further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1βupregulates NMDA expression.

Microdissection testicular extraction for a patient with transverse testicular ectopia and testicular fusion

Dear Editor, Transverse testicular ectopia （TTE） is a rare condition whereby both testes migrate toward the same hemiscrotum. Most of the cases （65%） are diagnosed intraoperatively during an inguinal hernia repair; only few are diagnosed preoperatively.