Interaction between abnormal expression of fragile histidine triad and methyl-CpG-binding protein 2 on cervical cancerization / 中华流行病学杂志

Objective: To explore the relationship between abnormal expression of fragile histidine triad (FHIT) gene and methyl-CpG-binding protein 2 (MeCP2) as well as their interaction on cervical cancerization. Methods: A total of 73 patients with cervical squamous cell carcinoma (SCC), 113 patients with cervical intraepithelial neoplasia (CIN Ⅰ, n=45; CINⅡ/Ⅲ, n=68) and 60 women with normal cervix (NC) were included in the study. Real time PCR and Western blot were performed to detect the expression levels of mRNA and protein about FHIT and MeCP2, respectively. The methylation status of FHIT gene CpG island was tested by methylation-specifc PCR (MSP). Kruskal-Wallis H test, χ(2) test, trend χ(2) test and Spearman correlation analysis were conducted with software SPSS 20.0. The interaction was evaluated by generalized multifactor dimensionality reduction (GMDR) model. Results: With the deterioration of cervical lesion, the methylation rates of FHIT gene CpG island (χ(2)=18.64, P<0.001; trend χ(2)=18.08, P<0.001) increased gradually, while the expression levels of FHIT mRNA (H=27.32, P<0.001; trend χ(2)=12.65, P<0.001) and protein (H=47.10, P<0.001; trend χ(2)=29.79, P<0.001) decreased gradually. There was a negative correlation between the methylation rates of FHIT gene CpG island and the expression level of FHIT protein (r=-0.226, P<0.001). The levels of MeCP2 mRNA (H=26.19, P<0.001; trend χ(2)=11.81, P=0.001) and protein (H=69.02, P<0.001; trend χ(2)=47.44, P<0.001) increased gradually with the aggravation of cervical lesions. There was a positive correlation between the expression level of MeCP2 protein and the FHIT mRNA Ct ratio (r=0.254, P<0.001). Expression of proteins were negatively correlated between MeCP2 and FHIT (r=-0.213, P=0.001). The results analyzed by GMDR model showed that there were interactions among high MeCP2 protein expression, the CpG island methylation of FHIT and mRNA and protein expression in CINⅡ/Ⅲ group, and among high MeCP2 mRNA and protein expression, the CpG island methylation of FHIT and low mRNA and protein expression in SCC group. Conclusion: High expression of MeCP2 mRNA and protein, the CpG island methylation and low mRNA and protein expression of FHIT could increase the risk of cervical carcinogenesis, and there might be a synergistic effect on cervical carcinogenesis.

Relationship between daily exposure to bisphenol A and male sexual function-a study from the reproductive center / 中华流行病学杂志

Objective: To explore the relationship between male sexual function and daily exposure to bisphenol A (BPA) at a reproductive center in Taiyuan. Methods: Male patients who were seeking treatment of infertility due to problems caused by either of the spouse were selected from the Shanxi reproductive center between September 2014 and April 2015. Information on general characteristics, sexual function and fasting venous blood samples were collected. Total scores of sexual function were evaluated by Delphi expert scoring method. Levels of serum BPA were measured by high-performance liquid chromatography. Data was analyzed by Spearman rank correlation, rank sum test, multivariate logistic regression analysis and χ(2) trend test. Relationship between BPA and sexual function was presented as OR and corresponding 95%CI. Results: Among the 353 participants, 45.0% was defined as sexual dysfunction with low sexual desire (47.3%) as the major reason. BPA was detected in all the 353 patients, with a range of concentration as 0.38-21.93 ng/ml and an average as 5.79 ng/ml. Results from the Spearman rank correlation analysis revealed significant negative correlations between serum BPA and sexual function, sexual desire, erectile ability and ejaculation intensity, while serum BPA was positively correlated with premature ejaculation. According to the four percentile of BPA concentration (ng/ml), the subjects were divided into four groups. Compared with the low concentration group (0.38-3.79 ng/ml), the risk of sexual dysfunction significantly increased in the groups with higher BPA levels. Particularly, in the highest BPA group (8.68-21.93 ng/ml), more obvious effects were seen on sexual dysfunction (OR=1.55, 95%CI:1.00-3.23), reduced sexual desire (OR=4.75, 95%CI: 2.44-9.22), reduced erection ability (OR=2.40, 95%CI: 1.18-4.88), reduced ejaculation intensity (OR=2.53, 95%CI: 1.25-5.16) and premature ejaculation (OR=1.95, 95%CI: 1.02-3.72). Conclusion: Low sexual desire appeared as the main type of male sexual dysfunction, the exposure to higher levels of BPA in daily life might lead to male sexual dysfunction.

Effect of hnRNP K and its interaction with HPV16 on cervical intraepithelial neoplasia / 中华流行病学杂志

Objective: To investigate the effect of heterogeneous nuclear ribonucleoprotein K (hnRNP K) and its interaction with human papillomavirus 16 (HPV16) on cervical intraepithelial neoplasia (CIN). Methods: The participants included 67 women with normal cervix (NC), 69 women with CINⅠ and 68 women with CINⅡ/Ⅲ in a community cohort of pathologically diagnosed women established in Jiexiu of Shanxi province, from June 2014 to June 2015. A structured questionnaire was used to collect the demographic data of the subjects and the related factors of cervical lesions. Cervical exfoliated cells and cervical tissues from biopsy or surgery were selected. The infection status of HPV16 was detected by flow-through hybridization. The protein expression levels of hnRNP K were evaluated by Western blot. SPSS 23.0 software was used to collate and analyze the data. To study the differences in demographic characteristics, related factors, hnRNP K protein and HPV16 infection among NC, CINⅠand CINⅡ/Ⅲgroups, χ(2) test, trend χ(2) test, and Kruskal-Wallis H test were conducted. Multiple comparisons of hnRNP K protein in three groups were completed by using the Bonferroni method. The OR and its 95%CI of hnRNP K, HPV16 and CIN were calculated by using the unconditional logistic regression models. Two-way interactions between hnRNP K protein and HPV16 infection on CIN were analyzed by using additive model and related indicators. Results: HPV16 infection rates were 10.4% in women with normal cervix, 14.5% in women with CINⅠ and 41.2% in women with CINⅡ/Ⅲ, respectively. The differences among three groups were significant (P<0.001). Moreover, the infection rates of HPV16 gradually increased with the increasing severity of CIN (trend χ(2)=18.512, P<0.001). The differences in protein expression of hnRNP K among three groups were significant (H=48.138, P<0.001) and the expressionincreased with the development of cervical lesionss (trend χ(2)=21.765, P<0.001). Results from the interaction analysis indicated that there were additive effects between high expression of hnRNP K protein and HPV16 in CINⅡ/Ⅲ group compared with normal group (API=0.639, 95%CI: 0.083-1.196). In contrast, no such additive effect was found in CINⅠ group. Conclusions: HPV16 infection and over-expression of hnRNP K protein were associated with the increased risk of cervical intraepithelial neoplasia. There might be interaction between hnRNP K protein overexpression and HPV16 infection existed on the progress of CINⅡ/Ⅲ.