A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.

Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 × 10(-9)) and RASGRP1 (rs7403531: P = 3.9 × 10(-9)), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA(1c) and lower homeostasis model assessment of β-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility

Treatment–donation-stockpile dynamics in ebola convalescent blood transfusion therapy

The interim guidance issued by the World Health Organization during the West Africa 2014 Ebola outbreak provides guidelines on the use of convalescent blood from Ebola survivors for transfusion therapy. Here we develop a novel mathematical model, based on the interim guidance, to examine the nonlinear transmission–treatment–donation–stockpile dynamics during an Ebola outbreak and with a large scale use of the transfusion therapy in the population. We estimate the reduction of case fatality ratio by introducing convalescent blood transfusion as a therapy, and inform optimal treatment–donation–stockpile strategies to balance the treatment need for case fatality ratio reduction and the strategic need of maintaining a minimal blood bank stockpile for other control priorities. •A novel model for the large-scale use of the convalescent blood transfusion therapy.•Based on WHO׳s interim convalescent treatment guidance in 2014 Ebola outbreak.•Estimate the reduction of case fatality ratio by introducing convalescent therapy.•Inform optimal treatment-donation-stockpile strategies.•Guide convalescent blood transfusion services in future emerging disease outbreaks

Anti-allergic actions of a Chinese patent medicine, huoxiangzhengqi oral liquid, in RBL-2H3 cells and in mice

Context Huoxiangzhengqi oral liquid (HXZQ-OL), a traditional Chinese medicine formula, has antibacterial, anti-inflammation and gastrointestinal motility regulation effects. Objective The study investigates the anti-allergic activity and underlying mechanism of HXZQ-OL. Materials and methods IgE/Ag-mediated RBL-2H3 cells were used to evaluate the anti-allergic activity of HXZQ-OL (43.97, 439.7 and 4397 μg/mL) in vitro. The release of cytokines and eicosanoids were quantified using ELISA. RT-qPCR was used to measure the gene expression of cytokines. The level of intracellular Ca2+ was measured with Fluo 3/AM. Immunoblotting analysis was performed to investigate the mechanism of HXZQ-OL. In the passive cutaneous anaphylaxis (PCA), BALB/c mice (5 mice/group) were orally administrated with HXZQ-OL (263.8, 527.6 and 1055 mg/kg/d) or dexamethasone (5 mg/kg/d, positive control) for seven consecutive days. Results HXZQ-OL not only inhibited degranulation of mast cells (IC50, 123 μg/mL), but also inhibited the generation and secretion of IL-4 (IC50, 171.4 μg/mL), TNF-α (IC50, 88.4 μg/mL), LTC4 (IC50, 52.9 μg/mL) and PGD2 (IC50, 195.8 μg/mL). Moreover, HXZQ-OL suppressed the expression of IL-4 and TNF-α mRNA, as well as the phosphorylation of Fyn, Lyn and multiple downstream signalling proteins including MAPK and PI3K/NF-κB pathways. In addition, HXZQ-OL (527.5 mg/kg) attenuated the IgE-mediated PCA with 55% suppression of Evans blue exudation in mice. Conclusions HXZQ-OL attenuated the activation of mast cell and PCA. Therefore, HXZQ-OL might be used as an alternative treatment for allergic diseases