Dabigatran is a novel direct oral anticoagulant agent, whose plasma concentration is closely related to bleeding risk. Genetic polymorphisms can affect the level of plasma dabigatran. The purpose of this study was to understand the relationship between dabigatranrelated genes and the plasma level of dabigatran in healthy Chinese subjects after taking a single oral dose. This study was performed with a single-center, single-dose, randomized, open-label, and four-period crossover trial design under both fasting and fed conditions. A total of 106 eligible healthy subjects were enrolled in the study and 104 were genotyped. One-way analysis of variance (ANOVA) was used to compare pharmacokinetic parameters among different genotypes and linear regression was applied to explore the multiplicative interaction between variables. In this study, we found that the genotype frequencies of CES1 rs2244613 and CES1 rs8192935 were significantly different between Chinese and Caucasians, but the genotype frequencies of ABCB1 rs1045642 and ABCB1 rs4148738 were similar in both populations. CES1 rs8192935 were associated with the peak concentration of dabigatran. There was no significant gender difference in the exposure level of dabigatran. Furthermore, food significantly delayed the absorption of dabigatran but had little effect on C max and AUC 0-∞ .

High risk (oncogenic) human papillomavirus (HPV) infection causes cervical cancer. Infections are common but most clear naturally. Persistent infection can progress to cancer. Pre-neoplastic disease (cervical intraepithelial neoplasia/CIN) is classified by histology (CIN1-3) according to severity. Cervical abnormalities are screened for by cytology and/or detection of high risk HPV but both methods are imperfect for prediction of which women need treatment. There is a need to understand the host virus interactions that lead to different disease outcomes and to develop biomarker tests for accurate triage of infected women. As cancer is increasingly presumed to develop from proliferative, tumour initiating, cancer stem cells (CSCs), and as other oncogenic viruses induce stem cell associated gene expression, we evaluated whether presence of mRNA (detected by qRT-PCR) or proteins (detected by flow cytometry and antibody based proteomic microarray) from stem cell associated genes and/or increased cell proliferation (detected by flow cytometry) could be detected in well-characterised, routinely collected cervical samples from high risk HPV+ve women. Both cytology and histology results were available for most samples with moderate to high grade abnormality. We found that stem cell associated proteins including human chorionic gonadotropin, the oncogene TP63 and the transcription factor SOX2 were upregulated in samples from women with CIN3 and that the stem cell related, cell surface, protein podocalyxin was detectable on cells in samples from a subset of women with CIN3. SOX2, TP63 and human gonadotrophin mRNAs were upregulated in high grade disease. Immunohistochemistry showed that SOX2 and TP63 proteins clearly delineated tumour cells in invasive squamous cervical cancer. Samples from women with CIN3 showed increased proliferating cells. We believe that these markers may be of use to develop triage tests for women with high grade cervical abnormality to distinguish those who may progress to cancer from those who may be treated more conservatively.

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