[Clinical characteristics and treatment strategies of prostatic mucinous adenocarcinoma: A report of 10 cases and literature review].

OBJECTIVE: To investigate the clinical characteristics and treatment strategies of prostatic mucinous adenocarcinoma (PMAC). METHODS: We retrospectively analyzed the clinical data on 10 cases of PMAC treated in the First Affiliated Hospital of Nanjing Medical University from January 2014 to June 2018. The patients were aged 51－79 (65 ± 14) years, with a medium PSA level of 89 (14.63－128.05) µg/L and Gleason scores of 3 + 3 in 1 case, 3 + 4 in 2, 4 + 3 in 1 and 8 in 6 cases preoperatively, 1 treated by robot-assisted radical prostatectomy and the other 9 by laparoscopic radical prostatectomy. We conducted pelvic cavity lymph node dissection for all the patients and analyzed their prognosis and survival. RESULTS: Operations were successfully completed in all the cases. Pathological examination revealed 2 cases of mucinous adenocarcinoma with signet ring cell carcinoma in the 10 PMAC patients, 2 at stage ≤T2b, 5 at stage ≥T2c, 3 positive at pelvic lymph node dissection and 5 positive at the incision margin. The patients were followed up for 6－48 (median 26) months. Four of the patients were found with biochemical recurrence within 2 years after operation and treated by androgen-deprivation therapy, radiotherapy and chemotherapy, which reduced the PSA level to <1.0 µg/ml in all the 4 cases. CONCLUSIONS: PMAC has a good prognosis. Radical surgery is recommended for moderate and low-risk PMAC and the patients with postoperative biochemical recurrence can benefit from comprehensive treatment of total androgen blockade.

[Updated reproductive toxicology of polybrominated diphenyl ether].

Since 1970, polybrominated diphenyl ether (PBDE) has been widely used as additive flame retardants in everyday consumer products, including polyurethane foam and electronic products like mattresses and upholstered furniture. Thermoplastics, mixed in polymers, do not chemically bond with plastics, textiles, etc., and therefore can be separated from the product into the environment. Because of its high lipophilicity, accumulation, degradation-resistance and biochemical toxicity, PBDE can invade the human body in a variety of ways and is toxic to multiple systems in the human body. PBDE affects the male reproductive system in many aspects, as by causing sperm quality decline, epididymis, seminal vesicle and prostate dysplasia, sperm head deformity, and decreased levels of testosterone and other reproductive hormones. PBDE also affects male reproductive function from the genetic aspect, as by altering the sperm DNA methylation level, inducing sperm chromatin damage, etc. Some environmental factors, such as high-fat diet and indoor dust increase, can indirectly promote the reproductive toxicity of PBDE. This article reviews the impacts of PBDE on exposed populations and the animal reproductive system and the latest research progress at home and abroad.

Di-n-butyl phthalate epigenetically induces reproductive toxicity via the PTEN/AKT pathway.

Di-n-butyl phthalate (DBP) is a kind of ubiquitous chemical linked to hormonal disruptions that affects male reproductive system. However, the mechanism of DBP-induced germ cells toxicity remains unclear. Here, we demonstrate that DBP induces reduction of proliferation, increase of apoptosis and DNA damage dependent on the PTEN/AKT pathway. Mechanistically, DBP decreases PTEN promoter methylation and increases its transcriptional activity, leading to increased PTEN expression. Notably, DNMT3b is confirmed as a target of miR-29b and miR-29b-mediated status of PTEN methylation is involved in the effects of DBP treatment. Meanwhile, DBP decreases AKT pathway expression via increasing PTEN expression. In addition, the fact that DBP decreases the sperm number and the percentage of motile and progressive sperm is associated with downregulated AKT pathway and sperm flagellum-related genes. Collectively, these findings indicate that DBP induces aberrant PTEN demethylation, leading to inhibition of the AKT pathway, which contributes to the reproductive toxicity.

[Glans-preserving surgery for superficial penile squamous cell carcinoma ≥2 cm in diameter].

OBJECTIVE: To explore the feasibility of glans-preserving surgery (GPS) in the treatment of superficial penile squamous cell carcinoma (PSCC) with the lesion diameter of ≥2 cm. METHODS: We retrospectively analyzed the clinical data on 69 cases of superficial PSCC (≤T1aN0) treated by GPS (n = 36) or radical surgery (total or partial penectomy, n = 33) from July 2007 to July 2017. RESULTS: The mean tumor diameter and depth of invasion were 3.16 (2.0－6.0) cm and 0.89 (0.5－2.0) cm in the GPS group and 3.56 (2.0－6.0) cm and 1.89 (0.6－4.0) cm respectively in the radical surgery group. The patients were followed up for 10－102 (mean 42) months, during which, 5 patients in the GPS group developed local recurrence at 40 days and 2, 4, 7 and 9 months postoperatively, again underwent gansectomy, partial penectomy or GPS, and experienced no more recurrence during the follow-up of 54, 34, 39, 66 and 70 months. No local recurrence was observed in the radical surgery group, and none of the 69 patients experienced lymph node metastasis or died during the follow-up. CONCLUSIONS: GPS is safe and efficient for the treatment of superficial PSCC with the lesion diameter of ≥2 cm.

Sulforaphane attenuates di-N-butylphthalate-induced reproductive damage in pubertal mice: Involvement of the Nrf2-antioxidant system.

di-N-butylphthalate (DBP) is a ubiquitous environmental pollutant used for plastic coating and in the cosmetics industry. It has toxic effects on body health, especially the male reproductive system. Here, we investigated the effects of DBP on the male reproductive system of pubertal mice and explored the protective role of sulforaphane (SFN). The results showed that DBP significantly reduced the anogenital distance, testicular weight, sperm count and motility, and plasma and testicular testosterone levels and significantly increased the oxidative stress, sperm abnormalities, and testicular cell apoptosis. SFN supplementation ameliorated these effects. After DBP stimulation, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1 and NQO1. Upregulation of Nrf2 by SFN reduced the DBP-mediated intracellular oxidative toxicity and also increased testosterone secretion and spermatogenesis, which were decreased by DBP. These findings indicate that SFN can attenuate DBP-induced reproductive damage in pubertal mice via Nrf2-associated pathways.

Multivariate model for predicting semen cryopreservation outcomes in a human sperm bank.

Semen cryopreservation is widely used in assisted reproductive technologies, but it reduces sperm quality dramatically. The aim of this study was to develop a model using basal semen quality to predict the outcome of postthaw semen parameters and improve the efficiency of cryopreservation in a human sperm bank. Basal semen parameters of 180 samples were evaluated in the first stage, and a multiple logistic regression analysis involving a backward elimination selection procedure was applied to select independent predictors. After a comprehensive analysis of all results, we developed a new model to assess the freezability of sperm. Progressive motility (PR), straight-line velocity (VSL) and average path velocity (VAP) were included in our model. A greater area under the receiver operating characteristic curve was obtained in our model when compared with other indicators. In the second stage of our study, samples that satisfied the new model were selected to undergo freeze-thawing. Compared with the first stage, the rate of good freezability was increased significantly (94% vs 67%, P = 0.003). By determining basal semen quality, we have developed a new model to improve the efficiency of cryopreservation in a human sperm bank.

Enolase1 (ENO1) and glucose-6-phosphate isomerase (GPI) are good markers to predict human sperm freezability.

Sperm cryopreservation is a method to preserve sperm samples for a long period. However, the fertility of sperm decreases markedly after freezing and thawing in a certain amount of samples. The aim of the present study was to find useful and reliable predictive biomarkers of the capacity to withstand the freeze-thawing process in human ejaculates. Previous researches have shown that enolase1 (ENO1) and glucose-6-phosphate isomerase (GPI) are closely related to spermatozoa quality. We chose the two proteins as probable markers of sperm freezing capacity. Ejaculate samples were separated into good freezability ejaculates (GFE) and poor freezability ejaculates (PFE) according to progressive motility of the sperm after thawing. Before starting cryopreservation protocols, the two proteins from each group were compared using western blot analysis and immunofluorescence. Results showed that normalized content of ENO1 (P<0.05) and GPI (P<0.01) were both significantly higher in GFE than in PFE. The association of ENO1 and GPI with postthaw sperm viability and motility was confirmed using Pearson's linear correlation. In conclusion, ENO1 and GPI can be used as markers of human sperm freezability before starting the cryopreservation procedure.

The role of mitochondrial aconitate (ACO2) in human sperm motility.

Deficiencies in tricarboxylic acid (TCA) cycle enzymes have been shown to cause a wide spectrum of human diseases, including malignancies and neurological and cardiac diseases. In mammalian spermatozoa mitochondria, the TCA cycle is known to be a crucial metabolic pathway that contributes to produce ATP. There is little known about the role and mechanism of mitochondrial aconitase (ACO2), which is an important regulatory enzyme of the TCA cycle, in asthenozoospermia. In the current study, immunofluorescence staining localized ACO2 to the human sperm mid-piece. By immunoblotting, we demonstrated that the level of ACO2 protein in asthenozoospermic samples was significantly decreased compared with that in normal fertile men. Importantly, we first observed that co-incubation of isocitrate with low motile sperm suspensions significantly improved sperm motility, which might be due to elevated intracellular ATP. The improvement of the sperm motility by isocitrate may have important clinical implications in the treatment of asthenozoospermia and certainly warrants further investigation.

The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and tumor risk: evidence from 134 case-control studies.

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism, which is essential for DNA synthesis and methylation. Genetic variations in the MTHFR gene seem to contribute to a decreased activity of MTHFR, ultimately confer increased susceptibility to cancer. As the most extensively studied polymorphism, MTHFR C677T polymorphism was shown to contribute to cancer susceptibility but the results were inconsistent. The authors performed a meta-analysis including 134 studies (46,207 cases and 69,160 controls) to address the issue. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the association. Overall, a significant elevated risk of cancer was associated with the MTHFR C677T polymorphism in T-allele versus C-allele comparison (OR = 1.06, 95% CI 1.02-1.11, P(heterogeneity) < 0.001), homozygote model (OR = 1.08, 95% CI 1.01-1.17, P(heterogeneity) < 0.001) and dominant model (OR = 1.05, 95% CI 1.00-1.10, P(heterogeneity) < 0.001). In the stratified analyses, significantly increased cancer risks were indicated among Asians in all genetic models except for heterozygote model. Further analysis revealed that C677T was significantly associated with an increased risk of esophageal and stomach cancer. This meta-analysis supports an association between the MTHFR C677T polymorphism and increased risk of esophageal and stomach cancer, especially among Asians. Additionally, more high-quality studies and that the covariates responsible for heterogeneity should be controlled to obtain a more conclusive response about the function of MTHFR C677T in cancer.

[Water-soluble vitamin E protects post-thawing sperm against oxidative stress injury].

OBJECTIVE: To investigate the potential protective effect of water-soluble vitamin E (Trolox) against oxidative stress injury in post-thawing human sperm and its mechanism. METHODS: Semen samples from 16 fertile men were mixed with modified cryoprotectant and each sample was equally divided into groups 0 (G0), 1 (G1), 2 (G2) and 3 (G3) according to the concentration of Trolox measured by computer-assisted semen analysis (CASA). G0, with no Trolox in the mixed cryoprotectant, served as the control, while G1, G2 and G3 contained 50, 100 and 200 micromol/L of Trolox, respectively. Before and after thawing, the semen samples were subjected to CASA for sperm kinematics, flow cytometry for reactive oxygen species (ROS), and thiobarbituric acid assay for the concentration of malondialdehyde (MDA). RESULTS: After cryopreservation, sperm motility was markedly decreased in all the groups (P < (0.01), but less in G2 than in the control ([53.33 +/- 5.63]% vs [47.85 +/- 5.09]%, P < 0.05). Curvilinear velocity and average path velocity were remarkably higher in G2 (P < 0.05), and ROS and MDA significantly lower in G2 and G3 than in the control (P < 0.05). CONCLUSION: Addition of vitamin E (Trolox) to freezing extender at a moderate concentration may decrease surplus ROS in the freezing-thawing process, ease ROS-induced oxidative stress injury to the plasma membrane, and improve sperm motility and kinematic parameters after cryopreservation.

[Human sperm cryopreservation and protection: an update].

Human sperm cryopreservation has been widely applied in human assisted reproduction technologies, but ultra-low temperature may damage the structure and function of sperm, which in turn may affect the success rate of human reproductive technology. However, this view is not yet universally accepted. Researchers around the world are endeavoring for the mechanisms of cyrodamage and discoveries of cryo-protection. This article gives an overview on the types of human sperm cryodamage, mechanisms of sperm functional changes, and latest discoveries of cryo-protection.

[Modified prepuce-degloving repair for urethrocutaneous fistula following hypospadias surgery].

OBJECTIVE: To investigate the clinical effect and application value of the modified method of prepuce-degloving repair (PDR) in the treatment of urethrocutaneous fistula (UCF) following hypospadias surgery. METHODS: We retrospectively analyzed 87 cases of UCF caused by hypospadias repair from May 2001 to December 2011, of which 61 were treated by simple closure or Y-V plasty of the fistula (group A), and the other 26 by modified PDR (group B). We compared the success rate of surgery and long-term recurrence between the two groups. RESULTS: The total success rates of repair were 78.7 and 96.2% in groups A and B, respectively. Thirteen cases in group A did not respond to surgery, of which 6 failed to be cured by the second operation but later were treated successfully by modified PDR. In comparison, there was only 1 case of failure in group B, which was cured by a second PDR. CONCLUSION: Modified PDR can significantly improve the success rate and reduce the recurrence rate of UCF after hypospadias surgery, which deserves wide clinical application.

[Analysis of the pregnancy outcomes of 13 723 tubes of sperm specimens from the sperm bank].

OBJECTIVE: To investigate the safety of assisted reproductive technology (ART) with donated sperm from the sperm bank and the differences in the pregnancy outcomes of different means of promoting pregnancy. METHODS: We analyzed and compared the feedback data on promoting pregnancy with donated sperm from the sperm bank by artificial insemination by donor (AID), in vitro fertilization (IVF), and intracytoplasm sperm injection (ICSI). RESULTS: Totally, 13 723 tubes of sperm specimens were used for ART. The number of specimens used differed in different clinical reproductive centers, some using 1 tube and others using 2 tubes per cycle. The 13 723 tubes were used for a total of 7 743 cycles. Among the 7 123 cycles of AID, there were 1 415 clinical pregnancies (19.87%), 1 221 normal births (86.29%), 169 abortions (11.94%), 6 cases of birth defects (0.43%), 19 ectopic pregnancies (1.34%), and 0 sexually transmitted infection. Among the 571 cycles of IVF, there were 367 clinical pregnancies (64.27%), 330 normal births (89.92%), 35 abortions (9.54%), 0 birth defect, 2 ectopic pregnancies (0.54%), and 0 sexually transmitted infection. Among the 49 cycles of ICSI, there were 28 clinical pregnancies (57.14%), 25 normal births (89.29%), 3 abortions (10.71%), 0 birth defect, 0 ectopic pregnancy, and 0 sexually transmitted infection. There were statistically significant differences in the rate of clinical pregnancy among AID, IVF and ICSI (P < 0.05), but not between IVF and ICSI (P > 0.05), nor were there any significant differences in the rates of abortion, birth defects and ectopic pregnancy among AID, IVF and ICSI (P > 0.05). CONCLUSION: None of the recipients of the donated sperm from the sperm bank was infected with sexually transmitted diseases. AID, IVF and ICSI showed no significant differences from natural conception in the rates of abortion, birth defects and ectopic pregnancy. ART with donated sperm from the sperm bank is safe. IVF and ICSI are associated with a higher rate of pregnancy than AID, though the latter costs less than the former two.

A modified method for the treatment of urethral fistula after hypospadias repair.

Urethrocutaneous fistula (UCF) is a common complication of hypospadias surgery for severe hypospadias. We report our experience in the management of UCF following hypospadias surgery with a prepuce-degloving method (PDM). Our study included 87 patients who developed UCF after hypospadias repair from May 2001 to December 2011. Either simple closure or PDM was performed to repair the fistula. In total, 61 patients underwent a simple closure or Y-V plasty of the fistula, and 26 underwent a PDM repair. The success rate was 78.7% for simple closure or Y-V plasty and 96.2% for PDM repair (P<0.05). PDM repair represents a good choice for UCF repair after hypospadias, and our high 96.2% success rate demonstrates its applicability.