Purpose: No consensus exists about the causal relationship between vitamin D (VD) and male factor infertility due to heterogeneity and confounding factors even in randomized controlled trials (RCTs). This study aimed to investigate the causal association between 25 hydroxyvitamin D (25OHD) levels and male factor infertility through Mendelian randomization (MR) and provide complementary information for optimization of future RCTs. Materials and Methods: Two-sample MR analyses with four steps were performed. Single-nucleotide polymorphisms (SNPs) for VD were extracted from 417,580 Europeans in the UK Biobank, and the summary-level data of male factor infertility (825 cases and 85,722 controls) were extracted from the FinnGen. Results: Totally 99 SNPs robustly associated with the 25OHD were included, and a 1-unit increase in genetically predicted natural-log transformed 25OHD levels was associated with decreased risk of male factor infertility (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44–0.89; p=0.010), which was consistent in all three sensitivity analyses (MR-Egger, weighted median, and weighted mode methods). The conclusion still stands after removing SNPs which explained more variation in the male factor infertility than the 25OHD (OR, 0.61; 95% CI, 0.42–0.88; p=0.009; n=62), and which were associated with confounders (body mass index, type 2 diabetes, smoking, and coronary artery diseases) of male factor infertility (OR, 0.58; 95% CI, 0.39–0.85; p=0.005; n=55). Conclusions VD supplement to increase serum 25OHD levels may be clinically beneficial for male factor infertility in the general population. The well-designed RCTs should be performed in priority to address this question.

Objective To explore the expressions of trefoil factors (TFFs) in bladder cancers and their clinical significance.Methods Using real-time fluorescence quantitative PCR and immunohistochemical staining from January 2013 to December 2013 in our hospital underwent surgical resection in 50 cases of superficial bladder cancer (including 20 cases of primary and 30 cases of recurrent bladder cancer) expression of TFF1,TFF2 and TFF3 and 10 cases of adjacent normal tissues.There were 32 males and 18 females,aged 45-73 years,with an average of 57 years.Pathological T staging:25 cases (50％) in pTa,25 cases in pT1 phase (50％),pathological grade:low grade 24 cases (48％),26 high grade (52％).Results TFF1,TFF2,TFF3 and mRNA in primary bladder cancer tissue expression levels were 2.04 (1.86-2.22) 、0.88 (0.11-1.6) 、0.92 (0.11-1.73) the recurrence of bladder cancer tissue expression levels were 2.22 (1.94-2.22) 、2.32 (0.22-4.42) 、2.45 (0.35-4.55) while in the adjacent normal tissues were 0.60(0.52-0.68) 、0.58(0.18-0.98) 、0.56(0.16-0.96).The adjacent normal tissues of TFF1,TFF2,TFF3 mRNA was lower than that of bladder cancer (P ＜ 0.05) and the recurrent bladder cancer,the relative expression of TFF2,TFF3 of mRNA was higher than that of primary bladder cancer (P ＜ 0.05),while the recurrent bladder cancer and primary bladder carcinoma TFF1 mRNA expression showed no significant difference (P ＞ 0.05).There was no significant difference in the positive expression rate of TFF1 between high-grade and low-grade bladder cancer [71％ (17/24) vs.77％ (20/26),P =0.88].And the positive rates of TFF2 and TFF3 in high-grade bladder cancer were 83％ (20/24) and 83 ％ (20/24) respectively,which were higher than those in low-grade bladder cancer [65 ％ (17/26),77％ (20/26),all P ＜0.05].The results of follow-up showed that the median recurrence-free survival (RFS) for 50 patients was 31 (18-38) months.The median RFS of patients with strong positive TFF1 and with weak positive (25 months and 27 months) were shorter than TFF1 negative (31 months,all P ＜0.05).The median RFS of patients with strong positive TFF2 (24 months) and TFF2 negative (30 months) were shorter than those of the weakly positive patients (median 33 months,all P ＜ 0.05).The median RFS of patients with TFF3 strongly positive (24 months) and weakly positive (28 months) were shorter than that of TFF3 negative patients (31 months,all P ＜ 0.05),and TFF3 strong positive RFS was shorter than TFF3 weak positive (P ＜ 0.05).Conclusions The expression rates of TFF1,TFF2 and TFF3 in bladder cancer tissues are higher than that of normal tissue,and they are higher than that of the primary bladder cancer tissue in the recurrent bladder cancer.TFF1 and TFF2 may be involved in the recurrence and progression of bladder cancer,and the role of TFF3 needs to be further verified.

Objective:To explore the risk factors for urethral stricture after transperineal anastomotic urethroplasty (TAU) by retrospectively analyzing patient data and to develop a nomogram to predict the risk of recurrence before the surgery.Methods:Clinical data of patients who underwent TAU because of post-traumatic urethral stricture from January 2016 to December 2017 in West China Hospital, Sichuan University were reviewd. A total of 78 patients were included in the retrospective analysis, with 13 of them having recurrence. The patients in the recurrence group had a median age of 49.8 and 76.9% (10/13) of them had membranous urethral stricture. The proximal urethra end was located above the superior margin of the pubic ramus (higher stricture site) in 53.8%(7/13)of patients in the recurrence group and the length of the stricture measured in the operation was (2.19±0.22) cm. In the non-recurrence group, the median age was (44.8±13.6) years old, 58.5% (38/65) of them had membranous urethral stricture, 21.5% (14/65) had higher stricture site, and the length of the stricture was (2.03±0.11) cm. Both univariate and multivariate logistics analyses were performed to evaluate the risk factors of recurrence of urethral stricture 5 years after surgery. The nomogram was built based on the multivariate logistics analysis. The Concordance Index (C-index), Receiver Operating Characteristic(ROC) curve and Calibration curve were used to evaluate the nomogram.Results:Univariate logistics analysis showed that higher stricture site, history of urethral dilation, smoking, diabetes and total serum protein may be associated with recurrence after surgery. Multivariate logistics analysis further confirmed that higher stricture site ( OR=34.64, 95% CI 3.71-754.53), history of urethral dilation( OR=13.15, 95% CI 1.27-210.00), smoking ( OR=13.75, 95% CI 2.15-166.05) and diabetes ( OR=64.98, 95% CI 3.80-1957.60) were independent risk factors for recurrent urethral stricture while higher total serum protein before surgery was related to lower recurrence risk ( OR=0.78, 95% CI 0.62-0.93). A nomogram was built based on the results. The C-index of the nomogram was 0.923(95% CI 0.908-0.938), the area under curve (AUC) was 0.923 (95% CI 0.855-0.991), and the Brier Score was 0.079. Conclusion:Higher stricture site, history of urethral dilation before surgery, smoking, diabetes and lower total serum protein before surgery are associated with higher recurrence TAU of post-traumatic urethral stricture patients. With the nomogram developed, prediction of the risk of recurrence could be achieved prior surgery.