Suchergebnisse

BACKGROUND: Infectious causes of childhood deaths in the world have decreased substantially in the 21st century. This trend has exposed accidental deaths as an increasingly important future challenge. Presently, little is known about the cause structure of accidental childhood deaths in low- and middle-income country (LMIC) settings. In this paper, we aim to establish cause structure for accidental deaths in children aged 0-4 years in China in the year 2010. METHODS: In this paper, we explored the database of 208 multi-cause child mortality studies in Chinese that formed a basis for the first published estimate of the causes of child deaths in China (for the year 2008). Only five of those studies identified specific causes of accidental deaths. Because of this, we searched the Chinese medical literature databases CNKI and WanFang for single-cause mortality studies that were focused on accidental deaths. We identified 71 further studies that provided specific causes for accidental deaths. We used epidemiological modeling to estimate the number of accidental child deaths in China in 2010 and to assign those deaths to specific causes. RESULTS: In 2010, we estimated 314 581 deaths in children 0-4 years in China, of which 31 633 (10.1%) were accidental. Accidental deaths contributed 7240 (4.0%) of all deaths in neonatal period, 8838 (10.5%) among all post-neonatal infant deaths, and 15 554 (31.7%) among children with 1-4 years of age. Among four tested models, the most predictive was used to establish the likely cause structure of accidental deaths in China. We estimated that asphyxia caused 9490 (95% confidence interval (CI) 8224-11 072), drowning 5694 (95% CI 5061-6327), traffic accidents 3796 (95% CI 3163-4745), poisoning 3163 (95% CI 2531-3796) and falls 2531 (95% CI 2214-3163) deaths. Based on medians from a few rare studies, we also predict 633 (95% CI 316-1265) deaths to be due to burns and 316 (95% CI 0-633) due to falling objects. Together, these 7 causes explain more than 80% of all accidental deaths when modeling is primarily used, and more than 95% when the analysis is based purely on medians from the 76 available studies. CONCLUSIONS: Reduction in global child mortality is a leading political priority and accidental deaths will soon emerge as one of the main challenges. In this paper we provided a detailed breakdown of causes of these deaths in a large middle-income country. We noted that, wherever the share of accidental deaths among all child deaths is increased, drowning is more likely to be the leading cause; asphyxia seems to be equally important in all contexts, while traffic accidents, poisoning and falls are relatively more important in contexts where the overall share of accidents to all child deaths is low.

Abstract Some protein pharmaceuticals from Chinese medicine have been developed to treat cardiovascular diseases, genetic diseases, and cancer. Bioactive proteins with various pharmacological properties have been successfully isolated from animals such as Hirudo medicinalis (medicinal leech), Eisenia fetida (earthworm), and Mesobuthus martensii (Chinese scorpion), and from herbal medicines derived from species such as Cordyceps militaris , Ganoderma, Momordica cochinchinensis , Viscum album , Poria cocos , Senna obtusifolia , Panax notoginseng , Smilax glabra , Ginkgo biloba , Dioscorea batatas , and Trichosanthes kirilowii . This article reviews the isolation methods, molecular characteristics, bioactivities, pharmacological properties, and potential uses of bioactive proteins originating from these Chinese medicines.

AbstractTwins could play a crucial role in our understanding of genetic contributions to numerous etiologically complex disorders. In China, although adult twins are relatively rare, twins will become increasingly available due to increasing twin birth rates. Thus, child twin data will be a valuable resource to contribute to the field of child and adolescent psychopathology. The first twin database of children aged from 6 to 16 was established in Chongqing, R.P., China. In this article, we will discuss our experiences in establishing the twin database, completed in three steps — the first step being to search and identify twins, the second being to keep contact with the twins and the final being to seek cooperation with the twin families, and its future prospects. Our twin database has proven to be an efficient method for the investigation and data collection of twin children in China. The results of our present study suggest that the inclusion of twin information in the residence registration of the public security bureaus in the future may ensure a smooth run of research based on the demographic resources. We propose that school networks may be adopted as the preferred method of collection of twin records for future studies.

BACKGROUND: Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. METHODS AND FINDINGS: To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = -0.052, 0.254) and 0.497 × 106 IU/m2 (SE = 0.092, 95% CI = 0.316, 0.678), respectively. On analysis of secondary outcomes, using a highly sensitive IL-2 assay, the observed plasma concentrations of the drug at 90 min exceeded the hypothetical Treg-specific therapeutic window determined in vitro (0.015-0.24 IU/ml), even at the lowest doses (0.040 × 106 and 0.045 × 106 IU/m2) administered. A rapid decrease in Treg frequency in the circulation was observed at 90 min and at day 1, which was dose dependent (mean decrease 11.6%, SE = 2.3%, range 10.0%-48.2%, n = 37), rebounding at day 2 and increasing to frequencies above baseline over 7 d. Teffs, natural killer cells, and eosinophils also responded, with their frequencies rapidly and dose-dependently decreased in the blood, then returning to, or exceeding, pretreatment levels. Furthermore, there was a dose-dependent down modulation of one of the two signalling subunits of the IL-2 receptor, the β chain (CD122) (mean decrease = 58.0%, SE = 2.8%, range 9.8%-85.5%, n = 33), on Tregs and a reduction in their sensitivity to aldesleukin at 90 min and day 1 and 2 post-treatment. Due to blood volume requirements as well as ethical and practical considerations, the study was limited to adults and to analysis of peripheral blood only. CONCLUSIONS: The DILT1D trial results, most notably the early altered trafficking and desensitisation of Tregs induced by a single ultra-low dose of aldesleukin that resolves within 2-3 d, inform the design of the next trial to determine a repeat dosing regimen aimed at establishing a steady-state Treg frequency increase of 20%-50%, with the eventual goal of preventing T1D. TRIAL REGISTRATION: ISRCTN Registry ISRCTN27852285; ClinicalTrials.gov NCT01827735. ; JDRF (Grant ID: 9-2011-253), Wellcome Trust (Grant IDs: 091157, 089989, 097997/Z/11/Z), National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, European Union's 7th Framework Programme (FP7/2007-2013) (Grant ID: 241447 (NAIMIT)), Sir Jules Thorn Charitable Trust (Grant ID: 13/JTA), Medical Research Council (Grant ID: G0800860), The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (Grant ID: 100140) ; This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/10.1371/journal.pmed.1002139