A rare homozygous variant of MC2R gene identified in a Chinese family with familial glucocorticoid deficiency type 1: A case report

BackgroundMelanocortin-2 receptor (MC2R), a member of the G protein-coupled receptor family, is selectively activated by adrenocorticotropic hormone (ACTH). variants in MC2R are associated with family glucocorticoid deficiency 1 (FGD1).Case presentationWe first reported a Chinese family with two affected siblings with a homozygotic variant of c.712C>T/p.H238Y in MC2R, presenting with skin hyperpigmentation, hyperbilirubinemia, and tall stature. These individuals showed novel clinical features, including congenital heart defects, not been found in other FGD1 patients.ConclusionsWe reported a Chinese family with affected siblings having a homozygotic variant of c.712C>T/p.H238Y in MC2R.Our report may expand the genetic and clinical spectrum of FGD1

The Oncogenic Roles of Nuclear Receptor Coactivator 1 in Human Esophageal Carcinoma

Nuclear receptor coactivator 1 (NCOA1) plays crucial roles in the regulation of gene expression mediated by a wide spectrum of steroid receptors such as androgen receptor (AR), estrogen receptor α (ER α), and estrogen receptor β (ER β). Therefore, dysregulations of NCOA1 have been found in a variety of cancer types. However, the clinical relevance and the functional roles of NCOA1 in human esophageal squamous cell carcinoma (ESCC) are less known. We found in this study that elevated levels of NCOA1 protein and/or mRNA as well as amplification of the NCOA1 gene occur in human ESCC. Elevated levels of NCOA1 due to these dysregulations were not only associated with more aggressive clinic-pathologic parameters but also poorer survival. Results from multiple cohorts of ESCC patients strongly suggest that the levels of NCOA1 could serve as an independent predictor of overall survival. In addition, silencing NCOA1 in ESCC cells remarkably decreased proliferation, migration, and invasion. These findings not only indicate that NCOA1 plays important roles in human ESCC but the levels of NCOA1 also could serve as a potential prognostic biomarker of ESCC and targeting NCOA1 could be an efficacious strategy in ESCC treatment

Effects of Body Fat on the Associations of High-Molecular-Weight Adiponectin, Leptin and Soluble Leptin Receptor with Metabolic Syndrome in Chinese

BACKGROUND: Little is known regarding the associations between high-molecular-weight (HMW-) adiponectin, leptin and soluble leptin receptor (sOB-R) and metabolic syndrome (MetS) in Chinese. Also few studies elucidate the effects of inflammation and body fat mass on the relations. METHODS: Plasma HMW-adiponectin, leptin and sOB-R were measured among 1055 Chinese men and women (35∼54 yrs). Whole body and trunk fat mass were determined by Dual-energy X-ray absorptiometry. MetS was defined by the updated NCEP/ATPIII criterion for Asian-Americans. RESULTS: HMW-adiponectin was inversely associated with MetS in multivariate model including fat mass index (FMI), inflammatory markers, leptin and sOB-R (OR in the highest quartile= 0.30, 95%CI 0.18∼0.50, P<.0001). Plasma sOB-R was also inversely associated with MetS independent of body fatness and inflammatory markers, whereas the association was somewhat attenuated after adjusting HMW-adiponectin (OR for the highest quartile = 0.78, 95%CI 0.47∼1.32, P = 0.15). In contrast, leptin was associated with increased odds of MetS independent of inflammatory markers, HMW-adiponectin, and sOB-R (OR for the highest quartile= 2.64, 95%CI 1.35∼5.18, P = 0.006), although further adjustment for FMI abolished this association. CONCLUSIONS: HMW-adiponectin exhibited strong inverse associations with MetS independent of body composition, inflammation, leptin and sOB-R; while the associations of leptin and sOB-R were largely explained by fat mass or HMW-adiponectin, respectively

Evaluation of the Development Level of Information and Communications Technology in Education Based on the Entire-Array-Polygon Indicator Method: Taking the Questionnaire Survey Data of 13 Cities in Province W as an Example

The objective assessment of the development level of information and communications technology (ICT) in education can support the government in formulating and implement ICT policies. The article first introduced the Entire-Array-Polygon (EAP) indicator method and then designed an evaluation indicator system which containing five first indicators and 31 secondary indicators. Finally, using the questionnaire survey data of 13 cities in Province W as an example, the EAP indicator method was used to carry out on the evaluation of ICT development level. The study drew the following conclusions: EAP indicator method can objectively assess the development level of ICT; the overall development level of ICT in the 13 cities in Province W is average and above, and most of them are level II. When using the EAP indicator method to assess the development level of ICT, experts do not need to determine the indicator's weight. Also, this method presents the evaluation results more concisely and intuitively, so it can be promoted as an essential method of evaluating on the development level of ICT in education

Impulsive functional observers for linear systems

The impulsive functional observer design problem for linear systems is addressed. Piecewise differentiable Lyapunov functions are introduced to analyze the stability of the error dynamics. Sufficient conditions for the existence of the impulsive functional observers that are capable of exponentially estimating any given function of the state vector are derived. Numerical examples are presented to demonstrate the effectiveness of the proposed results

Impulsive observers with variable update intervals for Lipschitz nonlinear time-delay systems

This article is concerned with the design of impulsive observers with variable update intervals for Lipschitz nonlinear systems with delays in state. Discontinuous Lyapunov function/funtional approaches are developed to analyse the stability of error dynamics. Delay-independent sufficient conditions for uniform exponential stability of the error dynamics over variable update intervals are derived in terms of linear matrix inequalities (LMIs). When these LMIs are feasible, the observer gain matrix can be solved numerically with an LMI-based optimisation algorithm. Numerical examples are provided to show the efficiency of the proposed approach

Distribution characteristics of circulating B cell subpopulations in patients with chronic kidney disease

Abstract This study compared the levels of circulating B cell subpopulations in patients with different stages of chronic kidney disease (CKD), investigated the effects of haemodialysis (HD) on the B cell-related immune spectrum in patients with end-stage renal disease, and evaluated the link between renal function and immune homeostasis. Overall, 197 patients with CKD (158 non-dialysis patients with CKD stages I–V and 39 end-stage patients undergoing maintenance HD) and 77 healthy controls were included. Compared to healthy controls, patients with CKD stages I–II showed no significant differences except for the proportion of transitional B cells; patients with CKD stage V showed a significant decrease in the proportions of transitional B cells and CD5+ B cells and a significant increase in double-negative (DN) B cells. Compared with early-stage patients with CKD, the absolute count of various B cell subpopulations in advanced-stage patients with CKD showed a significant decrease. The distribution of circulating B cell subpopulations in patients with CKD was significantly altered and was associated with CKD progression. Furthermore, the proportion of DN B cells and CD5+ B cells was inconsistent pre- and post-HD. This in-depth study of the immune status of patients with CKD may have important clinical value

Detection of UGT1A1*28 Polymorphism Using Fragment Analysis

Background and objective Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1), UGT1A1*28 polymorphism can reduce UGT1A1 enzymatic activity, which may lead to severe toxicities in patients who receive irinotecan. This study tries to build a fragment analysis method to detect UGT1A1*28 polymorphism. Methods A total of 286 blood specimens from the lung cancer patients who were hospitalized in Guangdong General Hospital between April 2014 to May 2015 were detected UGT1A1*28 polymorphism by fragment analysis method. Results Comparing with Sanger sequencing, precision and accuracy of the fragment analysis method were 100%. Of the 286 patients, 236 (82.5% harbored TA6/6 genotype, 48 (16.8%) TA 6/7 genotype and 2 (0.7%) TA7/7 genotype. Conclusion Our data suggest hat the fragment analysis method is robust for detecting UGT1A1*28 polymorphism in clinical practice. It’s simple, time-saving, and easy-to-carry

Associations between Ionomic Profile and Metabolic Abnormalities in Human Population

<div><h3>Background</h3><p>Few studies assessed effects of individual and multiple ions simultaneously on metabolic outcomes, due to methodological limitation.</p> <h3>Methodology/Principal Findings</h3><p>By combining advanced ionomics and mutual information, a quantifying measurement for mutual dependence between two random variables, we investigated associations of ion modules/networks with overweight/obesity, metabolic syndrome (MetS) and type 2 diabetes (T2DM) in 976 middle-aged Chinese men and women. Fasting plasma ions were measured by inductively coupled plasma mass spectroscopy. Significant ion modules were selected by mutual information to construct disease related ion networks. Plasma copper and phosphorus always ranked the first two among three specific ion networks associated with overweight/obesity, MetS and T2DM. Comparing the ranking of ion individually and in networks, three patterns were observed (1) “Individual ion,” such as potassium and chrome, which tends to work alone; (2) “Module ion,” such as iron in T2DM, which tends to act in modules/network; and (3) “Module-individual ion,” such as copper in overweight/obesity, which seems to work equivalently in either way.</p> <h3>Conclusions</h3><p>In conclusion, by using the novel approach of the ionomics strategy and the information theory, we observed potential associations of ions individually or as modules/networks with metabolic disorders. Certainly, these findings need to be confirmed in future biological studies.</p> </div

Characteristics of ion concentrations in study participants.

<p>Data are arithmetic mean (SD).</p>*<p>Data not adjusted for itself.</p>†<p>Data are geometric mean (95% CI).</p>‡<p><i>P</i> value<0.05 between 2 groups after adjustment for age and sex. Percentages may not sum to 100 because of rounding.</p