Yuan Huang

Role of genetic mutations in folate-related enzyme genes on Male Infertility

Several studies showed that the genetic mutations in the folate-related enzyme genes might be associated with male infertility; however, the results were still inconsistent. We performed a meta-analysis with trial sequential analysis to investigate the associations between the MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G mutations and the MTHFR haplotype with the risk of male infertility. Overall, a total of 37 studies were selected. Our meta-analysis showed that the MTHFR C677T mutation was a risk factor for male infertility in both azoospermia and oligoasthenoteratozoospermia patients, especially in Asian population. Men carrying the MTHFR TC haplotype were most liable to suffer infertility while those with CC haplotype had lowest risk. On the other hand, the MTHFR A1298C mutation was not related to male infertility. MTR A2756G and MTRR A66G were potential candidates in the pathogenesis of male infertility, but more case-control studies were required to avoid false-positive outcomes. All of these results were confirmed by the trial sequential analysis. Finally, our meta-analysis with trial sequential analysis proved that the genetic mutations in the folate-related enzyme genes played a significant role in male infertility.

Genetic Variants in Caveolin-1 and RhoA/ROCK1 Are Associated with Clear Cell Renal Cell Carcinoma Risk in a Chinese Population

Background The RhoA/ROCK pathway and Caveolin-1 (Cav-1) participate in the process of tumorigenesis in numerous types of cancer. Up-regulation of RhoA/ROCK and Cav-1 expression is considered to be associated with the development and progression of clear cell renal cell carcinoma (ccRCC). We investigated the association between genetic variations of RhoA/ROCK and Cav-1 and the risk of ccRCC in the Chinese population. Methods Between May 2004 and March 2014, a total of 1,248 clear cell renal cell carcinoma cases and 1,440 cancer-free controls were enrolled in this hospital-based case-control study. Nine SNPs in RhoA/ROCK and Cav-1 were genotyped using the TaqMan assay. Result We found two SNPs (Cav-1 rs1049334 and ROCK1 rs35996865) were significantly associated with the increasing risk of ccRCC (P = 0.002 and P < 0.001 respectively). The analysis of combined risk alleles revealed that patients with 2–4 risk alleles showed a more remarkable growth of ccRCC risk than the patients with 0–1 risk alleles(OR = 1.66, 95%CI = 1.31–2.11, P < 0.001). Younger subjects (P = 0.001, OR = 1.83, 95%CI = 1.30–2.57), higher weight subjects (P = 0.001, OR = 1.76, 95%CI = 1.25–2.47), female subjects (P = 0.007, OR = 1.75, 95% CI = 1.17–2.62), nonsmokers (P < 0.001, OR = 1.67, 95%CI = 1.26–2.23), drinkers (P = 0.025, OR = 1.75, 95% CI = 1.07–2.85), subjects with hypertension (P = 0.025, OR = 1.75, 95% CI = 1.07–2.85) and diabetes (P = 0.026, OR = 4.31, 95% CI = 1.19–15.62) showed a stronger association between the combined risk alleles and the risk of ccRCC by using the stratification analysis. Furthermore, we observed higher Cav-1 mRNA levels in the presence of the rs1049334 A allele in normal renal tissues. Conclusion Our results indicate that the two SNPs (Cav-1 rs1049334 and ROCK1 rs35996865) and genotypes with a combination of 2–4 risk alleles were associated with the risk of ccRCC. The functional SNP rs1049334 may affect the risk of ccRCC by altering the expression of Cav-1 and the relevance between the risk effects and the functional impact of this polymorphism needs further validation.

Developing a Follow-Up Strategy for Patients with PSA Ranging from 4 to 10 ng/ml via a New Model to Reduce Unnecessary Prostate Biopsies

Objective The aim of this study was to develop a follow-up strategy based on the new model to reduce unnecessary prostate biopsies in patients with prostate specific antigen (PSA) ranging from 4 to 10 ng/ml. Methods A total of 436 patients with PSA ranging from 4 to 10 ng/ml who had undergone transrectal ultrasound (TRUS)-guided prostate biopsy were evaluated during the first stage. Age, PSA, free PSA (fPSA), digital rectal examination (DRE) findings, ultrasonic hypoechoic mass, ultrasonic microcalcifications, prostate volume (PV) and PSA density (PSAD) were considered as predictive factors. 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 risk of prostate cancer and an effective follow-up strategy. Results Age, PSA, PV, fPSA, rate of abnormal DRE findings and rate of hypoechoic masses detected by TRUS were included in our model. A significantly greater area under the receiver-operating characteristic curve was obtained in our model when compared with using PSA alone (0.782 vs. 0.566). Patients were grouped according to the value of prostate cancer risk (PCaR). In the second stage of our study, patients with PCaR>0.52 were recommended to undergo biopsies immediately while the rest of the patients continued close follow-up observation. Compared with the first stage, the detection rate of PCa in the second stage was significantly increased (33.0% vs 21.1%, p = 0.012). There was no significant difference between the two stages in distribution of the Gleason score (p = 0.808). Conclusions We developed a follow-up strategy based on the new model, which reduced unnecessary prostate biopsies without delaying patients’ diagnoses and treatments.

The Association between Abnormal Long Noncoding RNA MALAT-1 Expression and Cancer Lymph Node Metastasis: A Meta-Analysis

Previous studies have investigated that the expression levels of MALAT-1 were higher in cancerous tissues than matched histologically normal tissues. And, to some extent, overexpression of MALAT-1 was inclined to lymph node metastasis. This meta-analysis collected all relevant articles and explored the association between MALAT-1 expression levels and lymph node metastasis. We searched PubMed, EmBase, Web of Science, Cochrane Library, and OVID to address the level of MALAT-1 expression in cancer cases and noncancerous controls (accessed February 2015). And 8 studies comprising 696 multiple cancer patients were included to assess this association. The odds ratio (OR) and its corresponding 95% confidence interval (CI) were calculated to assess the strength of the association using Stata 12.0 version software. The results revealed there was a significant difference in the incidence of lymph node metastasis between high MALAT-1 expression group and low MALAT-1 expression group (OR = 1.94, 95% CI 1.15–3.28, P = 0.013 random-effects model). Subgroup analysis indicated that MALAT-1 high expression had an unfavorable impact on lymph node metastasis in Chinese patients (OR = 1.87, 95% CI 1.01–2.46). This study demonstrated that the incidence of lymph node metastasis in patients detected with high MALAT-1 expression was higher than that in patients with low MALAT-1 expression in China.

Characteristics of prostate cancer detection rate (PCDR) in Chinese Han population under different prostate biopsy methods

We analyzed the improvement of prostate cancer detection rate (PCDR) in Chinese Han population and summarized the characteristics of prostate cancer (PCa) with the advancement of prostate biopsy technologies. From March 1999 to March 2015, 3762 patients underwent the systematic 6-, 8- or 13-core biopsy, guided by finger or transrectal ultrasound (TRUS) at our center. The PCDR under different PSA intervals and different biopsy methods were analyzed. The trends of PSA level, age and Gleason score of PCa patients were summarized. The PCDR of finger-guided 6- and 8-core biopsies were 30.8% (340/1103) and 36.7% (147/401) respectively. In 2258 patients with TRUS-guided 13-core biopsies, 992 (43.9%) were diagnosed as PCa, higher than that with finger-guided biopsies (43.9% vs. 32.4%, p < 0.001). The PCDR of prostate peripheral zone was higher than that of medial zone (37.5% vs. 31.4%, p < 0.001). Interestingly, the PCDR of extra 13th core was higher than the mean positive rate of other 12 cores (70.7% vs. 56.0%, p < 0.001). The systematic 13-core prostate biopsy guided by TRUS is safe, effective, and economic for PCa diagnosis in developing countries like China. The extra 13th core biopsy is beneficial to increase the PCDR.

Developing a Correct System to Evaluate the Accuracy of Gleason Score in Prostate Cancer of Chinese Population.

Introduction: A study was conducted to develop a new correct system to improve the overall rate of Gleason sum concordance between biopsy and final pathology. Materials and Methods: A total of 592 consecutive patients who had undergone transrectal ultrasound-guided prostate biopsy and radical prostatectomy were evaluated during the first stage. Age, PSA, PSA density (PSAD), biopsy cores, positive cores, prostate volume, positive core rate (PCR), core volume rate (CVR) and digital rectal examination findings were considered predictive factors. A multiple logistic regression analysis involving a backward elimination selection procedure and linear regression analysis involving a stepwise procedure were applied to select independent predictors. Results: Positive cores, PCR, CVR and PSAD were included in our assessing credibility model in the first stage. A significantly higher area under the receiver-operating curve was obtained in our model compared with CVR alone (0.641 vs. 0.517). In the second stage, patients with credibility of pre-operative Gleason score <0.388 were subjected to further evaluation. Compared with the 2 statuses, the rate of overall concordance was significantly increased (60.3 vs. 50.2%, p = 0.002). Conclusions: We developed a follow-up strategy based on the new and correct system, which represents an important consideration procedure when clinicians make decisions with regard to treatment plans.

A modified surgical procedure for concealed penis

INTRODUCTION We described a modified surgical procedure for repairing a concealed penis and compared the efficacy and feasibility of modified repair with traditional repair. METHODS From March 2003 to December 2012, 96 patients with a concealed penis were recruited to undergo penile repair at our centre. Modified repair and traditional repair were performed respectively on 46 and 50 cases. We compared operative time, intraoperative blood loss, cosmetic result of operative scars, postoperative penile retraction, and complications. RESULTS All operations were completed successfully without serious complications. The mean operative time, intraoperative blood loss, and cosmetic result of the operative scar between the two surgical methods were similar. However, the postoperative penile retraction rate in patients undergoing modified repair decreased significantly than in the traditional repair. CONCLUSIONS Our modified surgical procedure is effective and feasible for a concealed penis. Although extra procedures were needed for the modified repair, the operative time, intraoperative blood loss and cosmetic result of operative scar between the two procedures were similar. Compared with traditional repair, modified repair has better clinical outcomes.