Common variants of transcription factor 7-like 2 (TCF7L2) are associated with reduced insulin secretion in women with polycystic ovary syndrome.

Common variants of the transcription factor 7-like 2 (TCF7L2) gene were identified as one of the few genetic polymorphisms with powerful effects on the risk of type 2 diabetes (T2D). Given the genetic overlap between polycystic ovary syndrome (PCOS) and T2D, the present study was undertaken to investigate whether the TCF7L2 variants are also associated with PCOS. We analyzed single nucleotide polymorphisms (SNPs) rs11196218 and rs290487 of the TCF7L2 gene, which showed robust associations with T2D in Chinese population, in 430 PCOS patients and 360 control subjects by pyrosequencing, and also assessed the effect of genotype on clinical and biochemical traits in the PCOS group. We found no evidence for association between SNP rs11196218 and PCOS. The SNP rs290487 showed marginal differences in genotype frequencies between the PCOS and control group, with the minor C allele being the at-risk allele for PCOS. In PCOS women, the C allele carriers of rs290487 had higher levels of 2h blood glucose but lower insulinogenic index than noncarriers, suggesting impaired insulin secretion. Our data suggested that the TCF7L2 variants may confer an increased risk for early impairment of glucose homeostasis in PCOS.

Triage human papillomavirus testing for cytology-based cervical screening in women of different ages in primary hospitals: A retrospective clinical study.

Cervical cancer is a serious global health problem. The objective of this study was to provide a suitable cytology-based cervical screening method in women of different ages in primary hospitals.This study was a retrospective cohort study that included 9765 women who underwent primary cytology-based cervical screening and were grouped by age (35-44, 45-54, and 55-64 years old). Patients with abnormal cytology on the primary cervical thin-prep cytologic test (TCT) were advised to undergo triage human papillomavirus (HPV) test. Furthermore, patients with positive outcomes of the 2 indices underwent cervical tissue biopsy. The positive rate of TCT and HPV was compared among the 3 defined age groups. The sensitivity, specificity, and positive predictive value of TCT and HPV were assessed.In total, 2.5% (241/9765) of women had atypical squamous cells of undetermined significance or worse by TCT. High-risk (HR)-HPV infection was found in 70 triage participants. Neoplastic changes were confirmed in 95 patients (95/437, 21.7%) by biopsies. Among the different age groups, the positive rate of abnormal cytology was significantly different (P = .003), and the positive rate of HR-HPV was similar (P = .299). The sensitivity of initial TCT testing to detect intraepithelial neoplasia was higher than that of triage HPV testing, whereas the specificity, the positive predictive value of triage HPV testing was higher than that of TCT. The Youden index of HPV testing was higher than that of TCT detection in the 3 age groups, namely 0.582 versus 0.432, 0.553 versus 0.228, and 0.416 versus 0.332, respectively.The results of this study indicate that TCT testing is suitable as a cervical cancer screening method for women ≥35 years old in primary hospitals. Triage testing for women with HR-HPV has a high negative predictive value, reduces the rate of misdiagnosis, seems to be an excellent triage method for repeat atypical squamous cells of undetermined significance, and reduces the number of referral colposcopies preventing unnecessary overtreatment. The results of this study provide a crucial foundation for a unified guideline cervical cancer screening for primary health care institutions.

Raised serum levels of matrix metalloproteinase-9 in women with polycystic ovary syndrome and its association with insulin-like growth factor binding protein-1.

BACKGROUND: It has been suggested in recent studies that matrix metalloproteinases (MMPs) may be implicated in the pathogenesis of polycystic ovary syndrome (PCOS) through regulating ovarian tissue remodeling. In addition to degrading the extracellular matrix, MMPs exhibit the ability to cleave insulin-like growth factor binding protein-1 (IGFBP-1), the major regulator of insulin-like growth factor-I (IGF-I) in serum. The present study aimed to investigate the possible role of MMPs in the pathophysiology of PCOS. METHODS: Serum levels of MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), IGF-I and IGFBP-1 were measured in 42 patients with PCOS and 30 healthy women with regular menstruation, matched for age and body mass index. Correlation between IGFBP-1 and other parameters in the PCOS group was analyzed by Pearson's linear correlations. RESULTS: Serum MMP-9 concentrations and MMP-9/TIMP-1 ratios were significantly higher in PCOS women than in controls. Serum levels of IGFBP-1 were markedly lower in the PCOS group. There was a negative correlation between serum IGFBP-1 and MMP-9 in women with PCOS. CONCLUSION: Our results raise the possibility that MMPs may be implicated in the pathophysiology of PCOS either by regulating ovarian tissue remodeling or indirectly by facilitating IGF-I bioavailability through proteolysis of IGFBP-1.

The expression of PLK-1 in cervical carcinoma: a possible target for enhancing chemosensitivity.

BACKGROUND: Polo-like kinase-1 (PLK-1) is reported to be upregulated in a variety of human tumors and is implicated in cell proliferation and survival. However, its importance in cervical carcinoma has not yet been fully elucidated. METHODS: We examined PLK-1 expression in cervical carcinoma tissues using immunohistochemical staining. Furthermore, we blocked PLK-1 expression in HeLa cells using specific siRNA and detected the cell cycle, cell proliferation and chemosensitivity using western blotting, MTT and flow cytometry. RESULTS: We provide evidence that expression of PLK-1 exists in human cervical carcinoma tissues and establish an association with tumor size. Furthermore, we show that PLK-1 knockdown by transfection of siRNA induces accumulation of HeLa cells in the G2/M cell cycle phase and enhances cisplatin-induced apoptosis. CONCLUSION: Our results indicate that PLK-1 production in HeLa cells might be critical in determining whether cells survive or undergo apoptosis. Therefore, targeting PLK-1 might be a promising strategy for enhancing sensitivity to chemotherapeutic reagents in cervical carcinoma.