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Background Vemurafenib (VEM) is a commonly used inhibitor of papillary thyroid cancer (PTC) and melanoma with the BRAFV600E mutation; however, acquired resistance is unavoidable. The present study aimed to identify a potential target to reverse resistance. Materials and methods A VEM-resistant PTC cell line (B-CPAP/VR) was established by gradually increasing the drug concentration, and a VEM-resistant BRAFV600E melanoma cell line (A375/VR) was also established. RNA sequencing and bioinformatics analyses were conducted to identify dysregulated genes and construct a transcription factor (TF) network. The role of a potential TF, forkhead box P2 (FOXP2), verified by qRT-PCR, was selected for further confirmation. Results The two resistant cell lines were tolerant of VEM and displayed higher migration and colony formation abilities (p p Conclusions The present study successfully established two VEM-resistant cell lines and identified a potential target for VEM-resistant PTC or melanoma.

This subanalysis of a cross-sectional, nationwide study was undertaken to assess the relationship between healthy lifestyle behaviors and multiple cardiovascular risk factors among people with type 2 diabetes mellitus (T2DM). Data collected from 25,454 participants, including demographics, lifestyle behaviors and cardiovascular risk profiles, were analyzed. Blood pressure control as well as blood glucose and blood lipid (3Bs) levels were measured as multi-risk factors for cardiovascular disease. Healthy lifestyle behaviors included regular exercise, nonsmoking status and no alcohol consumption. The relationship between the healthy lifestyle behavior(s) and control of 3B(s) was calculated. Of the 25,454 eligible participants, 4171 (16.4%) were current smokers, 2011 (7.9%) currently consumed alcohol, and 11,174 (43.9%) did not exercise. In total, 654 (2.6%) reported all three unhealthy lifestyle behaviors. Most participants (71.1%) had received at least a high school education and were more likely to smoke and drink as compared to those with lower education. Unhealthy lifestyle behaviors were commonly found in participants with low atherosclerosis risk, such as non-elderly people and those with an above-college education level. Unhealthy lifestyle is associated with poor 3B control and worse medication adherence. Unhealthy lifestyles are common in Chinese people with T2DM, especially in people who are non-elderly and above-college educated. Interventions aimed at changing risky lifestyle behaviors are required for improved outcomes for Chinese patients with T2DM.

Nonsyndromic orofacial cleft (NSOFC) is a severe birth defect that occurs early in embryonic development and includes the subtypes cleft palate only (CPO), cleft lip only (CLO) and cleft lip with cleft palate (CLP). Given a lack of specific genetic factor analysis for CPO and CLO, the present study aimed to dissect the landscape of genetic factors underlying the pathogenesis of these two subtypes using 6,986 cases and 10,165 controls. By combining a genome-wide association study (GWAS) for specific subtypes of CPO and CLO, as well as functional gene network and ontology pathway analysis, we identified 18 genes/loci that surpassed genome-wide significance (P < 5 × 10−8) responsible for NSOFC, including nine for CPO, seven for CLO, two for both conditions and four that contribute to the CLP subtype. Among these 18 genes/loci, 14 are novel and identified in this study and 12 contain developmental transcription factors (TFs), suggesting that TFs are the key factors for the pathogenesis of NSOFC subtypes. Interestingly, we observed an opposite effect of the genetic variants in the IRF6 gene for CPO and CLO. Moreover, the gene expression dosage effect of IRF6 with two different alleles at the same single-nucleotide polymorphism (SNP) plays important roles in driving CPO or CLO. In addition, PAX9 is a key TF for CPO. Our findings define subtypes of NSOFC using genetic factors and their functional ontologies and provide a clue to improve their diagnosis and treatment in the future., Author summary Although GWAS have discovered 43 genes/loci associated with NSOFC, most previous studies used mixed samples of CL/P subtypes rather than CPO or CLO separately. Our findings define the CPO and CLO subtypes using genetic factors and their functional ontologies based on CPO and CLO GWAS data. In this study, we identified 18 genes/loci that contribute to CPO, CLO or CLP. Fourteen of them are novel and identified, and 12 contain developmental transcription factors (TFs), suggesting that TFs are the key factors for the pathogenesis of NSOFC subtypes. We observed an opposite effect in the strongest associated locus IRF6 for CPO and CLO; this information was omitted by previous CL/P GWAS. Furthermore, we reveal that the gene expression dosage of IRF6 plays important roles in driving CPO or CLO. In addition, we found that PAX9 is a strong genetic factor for CPO. These results suggest that transcription factors are the key genetic reason for the pathogenesis of NSOFC subtypes.

Background Low socioeconomic status (SES) is associated with adverse cardiovascular risk factor patterns and poor outcomes in patients with diabetes. The aim of this study was to determine whether SES is associated with the control of blood glucose, blood pressure, blood cholesterol (3Bs), and diabetic complications in Chinese adults with type 2 diabetes. Methods Data regarding patients’ demographics, social economics, diabetes complications, and cardiovascular risk profiles were analyzed for 25,454 patients. The outcomes of interest were the proportions of patients with HbA1c

Additional file 1: Table S1. Association between Diabetic Complications and SES by logistic regression.