Background Pathogenic variation in BRCA1 and BRCA2 (BRCA) is one of the most frequent genetic predispositions for hereditary breast cancer. The identification of the variant carriers plays an important role in prevention and treatment of cancer. Despite a population size of 1.4 billion and a quarter million annual new breast cancer cases, knowledge regarding the prevalence of BRCA variation in the Chinese population remains elusive. Methods In this study, we used BRCA-targeted sequencing and bioinformatics approaches to screen for BRCA variants in 11 386 Chinese Han individuals, including 9331 females and 2055 males. Results We identified 1209 BRCA variants, 34 of which were pathogenic, including 11 in BRCA1 and 23 in BRCA2. These variants were distributed among 43 individuals (37 females and 6 males), with 13 carrying BRCA1 and 30 carrying BRCA2 variants. Based on these data, we determined a prevalence of 0.38%, or 1 carrier of a BRCA pathogenic variant out of every 265 Chinese Han individuals, and 5.1 million carriers among the Chinese Han population of 1.3 billion. Conclusion Our study provides basic knowledge about the prevalence of BRCA pathogenic variation in the Chinese Han population. This information should be valuable for BRCA-related cancer prevention and treatment in the population.As the crucial non-cellular component of tissues, the extracellular matrix (ECM) provides both physical support and signaling regulation to cells. Some ECM molecules provide a fibrillar environment around cells, while others provide a sheet-like basement membrane scaffold beneath epithelial cells. In this Review, we focus on recent studies investigating the mechanical, biophysical and signaling cues provided to developing tissues by different types of ECM in a variety of developing organisms. In addition, we discuss how the ECM helps to regulate tissue morphology during embryonic development by governing key elements of cell shape, adhesion, migration and differentiation.Objective Disease severity in SLE is an important concept related to disease activity, treatment burden and prognosis. We set out to evaluate if high disease activity status (HDAS), based on ever attainment of a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) disease activity score of ≥10, is an indicator for disease severity in SLE. Methods Using prospectively collected data, we assessed the association of HDAS with sociodemographic and disease characteristics and adverse clinical outcomes using logistic regression or generalised estimating equations. Results Of 286 patients with SLE, who were observed for a median (range) of 5.1 years (1-10.8 years), 43.7% experienced HDAS at least once during the observational period. Autoantibody positivity, particularly anti-dsDNA and anti-Sm positivity, were associated with increased likelihood of HDAS. Age ≥45 years at diagnosis was associated with reduced likelihood of HDAS (p=0.002). Patients with HDAS had higher Physician Global Assessment score (>1 OR 8.1, p0.001), higher corticosteroid exposure (corticosteroid dose in highest quartile OR 7.7, 95% CI 3.9 to 15.3; p less then 0.001) and damage accrual (OR 2.3, 95% CI 1.3 to 3.9; p=0.003) when compared with non-HDAS patients. Conclusions HDAS is associated with more severe disease, as measured by higher disease activity across time, corticosteroid exposure and damage accrual. The occurrence of HDAS may be a useful prognostic marker in the management of SLE.Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common and deteriorating event leading to in-hospital morbidity and mortality. Identification of predictors for in-hospital mortality of AECOPD patients could aid clinicians in identifying patients with a higher risk of death during their hospitalisation. Objective To explore potential prognostic indicators associated with in-hospital mortality of AECOPD patients. Setting General medical ward and medical intensive care unit of a university-affiliated tertiary care centre. Methods A prognostic factor research was conducted with a retrospective cohort design. All admission records of AECOPD patients between October 2015 and September 2016 were retrieved. Stratified Cox's regression was used for the primary analysis. Results A total of 516 admission records of 358 AECOPD patients were included in this study. The in-hospital mortality rate of the cohort was 1.9 per 100 person-day. From stratified Cox's proportional hazard regression, the predictors of in-hospital mortality were aged 80 years or more (HR=2.16, 95% CI 1.26 to 3.72, p=0.005), respiratory failure on admission (HR=2.50, 95% CI 1.12 to 5.57, p=0.025), body temperature more than 38°C (HR=2.97, 95% CI 1.61 to 5.51, p=0.001), mean arterial pressure lower than 65 mm Hg (HR=4.01, 95% CI 1.88 to 8.60, p less then 0.001), white blood cell count more than 15 x 109/L (HR=3.51, 95% CI 1.90 to 6.48, p less then 0.001) and serum creatinine more than 1.5 mg/dL (HR=2.08, 95% CI 1.17 to 3.70, p=0.013). Conclusion Six independent prognostic indicators for in-hospital mortality of AECOPD patients were identified. All of the parameters were readily available in routine practice and can be used as an aid for risk stratification of AECOPD patients.Ductal carcinoma in situ (DCIS), which accounts for one out of every five new breast cancer diagnoses, will progress to potentially lethal invasive ductal carcinoma (IDC) in about 50% of cases. Vitamin D compounds have been shown to inhibit progression to IDC in the MCF10DCIS model. This inhibition appears to involve a reduction in the cancer stem cell-like population in MCF10DCIS tumors. To identify genes that are involved in the vitamin D effects, a global transcriptomic analysis was undertaken of MCF10DCIS cells grown in mammosphere cultures, in which cancer stem-like cells grow preferentially and produce colonies by self-renewal and maturation, in the presence and absence of 1α25(OH)2D3 and a vitamin D analog, BXL0124. Using next-generation RNA sequencing, we found that vitamin D compounds down-regulated genes involved in maintenance of breast cancer stem-like cells (e.g. GDF15), epithelial-mesenchymal transition, invasion and metastasis (e.g.  https://www.selleckchem.com/products/ziritaxestat.html  LCN2, S100A4), chemo-resistance (e.g. NGFR, PPP1R1B, AGR2), while up-regulating genes associated with a basal-like phenotype (e.