Cytotoxicity of nonylphenol on spermatogonial stem cells via phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway

BACKGROUND With continuous advancement of industrial society,environmental pollution has become more and more serious.There has been an increase in infertility caused by environmental factors.Nonylphenol(NP)is a stable degradation product widely used in daily life and production and has been proven to affect male fertility.However,the underlying mechanisms therein are unclear.Thus,it is necessary to study the effect and mechanism of NP on spermatogonial stem cells(SSCs).AIM To investigate the cytotoxic effect of NP on SSCs via the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway.METHODS SSCs were treated with NP at 0,10,20 or 30μmol.MTT assay was performed to evaluate the effect of NP on the proliferation of SSCs.Flow cytometry was conducted to measure SSC apoptosis.The expression of Bad,Bcl-2,cytochrome-c,pro-Caspase 9,SOX-2,OCT-4,Nanog,Nanos3,Stra8,Scp3,GFRα1,CD90,VASA,Nanos2,KIT,PLZF and PI3K/AKT/mTOR-related proteins was observed by western blot,and the mRNA expression of SOX-2,OCT-4 and Nanog was detected by quantitative reverse transcription polymerase chain reaction.RESULTS Compared with untreated cells(0μmol NP),SSCs treated with NP at all concentrations showed a decrease in cell proliferation and expression of Bcl-2,Nanog,OCT-4,SOX-2,Nanos3,Stra8,Scp3,GFRα1,CD90,VASA,Nanos2,KIT,and PLZF(P<0.05),whereas the expression of Bad,cytochrome-c,and pro-Caspase 9 increased significantly(P<0.05).We further examined the PI3K/AKT/mTOR pathway and found that the phosphorylation of PI3K,AKT,mTORC1,and S6K was significantly decreased by NP at all concentrations compared to that in untreated SSCs(P<0.05).NP exerted the greatest effect at 30μmol among all NP concentrations.CONCLUSION NP attenuated the proliferation,differentiation and stemness maintenance of SSCs while promoting apoptosis and oxidative stress.The associated mechanism may be related to the PI3K/AKT/mTOR pathway.

Circumcision with ＂no-flip Shang Ring＂ and ＂Dorsal Slit＂ methods for adult males： a single-centered, prospective, clinical study

This paper was aimed to compare the clinical effectiveness and safety of adult male circumcision using the Shang RingTM （SR） with the no-flip technique compared with Dorsal Slit （DS） surgical method, A single-centered, prospective study was conducted at the West China Hospital, where patients were circumcised using the no-flip SR （n = 408） or the DS （n = 94） procedure. The adverse events （AEs） and satisfaction were recorded for both groups, and ring-removal time and percentage of delayed removals were recorded for the SR group. Finally, complete follow-up data were collected for 76.1% of patients （SR： n = 306; DS： n = 76）. The average ring-removal time for the SR group was 17.62 ± 6.30 days. The operation time （P 〈 0.001）, pain scores during the procedure （P 〈 0.001） and at 24 h postoperatively （P 〈 0.001）, bleeding （P = 0.001）, infection （P = 0.034）, and satisfaction with penile appearance （P 〈 0.001） in the SR group were superior to those in the DS group. After two postoperative weeks, the percentage of patients with edema in the SR group （P = 0.029） was higher but no differences were found at 4 weeks （P = 0, 185） between the two groups. In conclusions, the no-flip SR method was found to be superior to the DS method for its short operation time （〈5 min）, involving less pain, bleeding, infection, and resulting in a satisfactory appearance. However, the time for recovery from edema took longer, and patients may wear device for 2-3 weeks after the procedure.

Androgen-deprivation therapy alone versus combined with radiation therapy or chemotherapy For nonlocalized prostate cancer： a systematic review and meta-analysis

In this paper, we reviewed the long-term survival outcomes, safety, and quality-of-life of androgen-deprivation therapy （ADT） alone versus combined with radiation therapy （RT） or chemotherapy for locally advanced and metastatic prostate cancer （PCa）. A literature search was performed using OvidSP. Randomized controlled trials （RCTs） that met the following criteria were included： including locally advanced or metastatic PCa, comparing ADT alone versus combined with any treatment method and reporting quantitative data of disease control or survival outcomes. Finally, eight RCTs met the inclusion criteria. Among these, three compared ADT versus ADT plus RT （n = 2344） and one compared ADT versus ADT plus docetaxel-estramustine （n = 413） in locally advanced PCa; two compared ADT versus ADT plus docetaxel （n = 1175） and two compared ADT versus ADT plus estramustine （n = 114） in metastatic PCa. For locally advanced PCa, the addition of RT to long-term ADT can improve the outcomes of survival and tumor control with fully acceptable adverse effects. Specially, the pooled odds ratio （OR） of overall survival （OS） was 1.43 （95% confidence interval 1.20-1.71） when compared ADT plus RT with ADT alone （P 〈 0.0001）. For metastatic hormonally sensitive PCa, the concurrent use of docetaxel plus ADT was effective and safe （pooled OR of OS： 1.29 [1.01-1.65]： P = 0.04）. In all, long-term ADT plus RT and long-term ADT plus docetaxel should be considered as proper treatment option in locally advanced and metastatic hormonally sensitive PCa, respectively. The major limitation for the paper was that only eight RCTs were available.