22家医院IT服务现状分析

目的了解深圳市某区各医院IT服务台的现状。方法资料来源于该区22家医院的IT服务台的状况调查资料,采用构成比等指标分析IT服务台的现状,对一家医院的IT服务台进行了典型调查与分析。结果只有一家医院开设了IT服务台且运转良好。结论需要普及IT服务台的知识。     

Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program

OBJECTIVE— Genome-wide association scans (GWASs) have identified novel diabetes-associated genes. We evaluated how these variants impact diabetes incidence, quantitative glycemic traits, and response to preventive interventions in 3,548 subjects at high risk of type 2 diabetes enrolled in the Diabetes Prevention Program (DPP), which examined the effects of lifestyle intervention, metformin, and troglitazone versus placebo.RESEARCH DESIGN AND METHODS— We genotyped selected single nucleotide polymorphisms (SNPs) in or near diabetes-associated loci, including EXT2, CDKAL1, CDKN2A/B, IGF2BP2, HHEX, LOC387761, and SLC30A8 in DPP participants and performed Cox regression analyses using genotype, intervention, and their interactions as predictors of diabetes incidence. We evaluated their effect on insulin resistance and secretion at 1 year.RESULTS— None of the selected SNPs were associated with increased diabetes incidence in this population. After adjustments for ethnicity, baseline insulin secretion was lower in subjects with the risk genotype at HHEX rs1111875 (P = 0.01); there were no significant differences in baseline insulin sensitivity. Both at baseline and at 1 year, subjects with the risk genotype at LOC387761 had paradoxically increased insulin secretion; adjustment for self-reported ethnicity abolished these differences. In ethnicity-adjusted analyses, we noted a nominal differential improvement in β-cell function for carriers of the protective genotype at CDKN2A/B after 1 year of troglitazone treatment (P = 0.01) and possibly lifestyle modification (P = 0.05).CONCLUSIONS— We were unable to replicate the GWAS findings regarding diabetes risk in the DPP. We did observe genotype associations with differences in baseline insulin secretion at the HHEX locus and a possible pharmacogenetic interaction at CDKNA2/B.The increasing incidence of diabetes continues to have a tremendous impact on diabetes-related morbidity and mortality around the world. Although much emphasis has been placed on the contribution of a Western lifestyle characterized by increasing caloric intake and physical inactivity to the diabetes epidemic, the role genetics plays in the development of diabetes is generally poorly understood. Additional insight into the contribution of genetic variants to diabetes incidence, gene-lifestyle interactions, and pharmacological response to antidiabetes medications is required to slow this tragic epidemic.The recent implementation of genome-wide association scans (GWASs) as an investigative tool has resulted in a qualitative leap in identifying diabetes-related genes (1,2). These surveys, which are agnostic to candidate genes, can cover ∼80% of common human genome variants with current technology, thus providing unprecedented insight into the genetic architecture of type 2 diabetes. In 2007, the first published type 2 diabetes GWAS confirmed the important impact of TCF7L2 on diabetes incidence (odds ratio [OR] 1.65, P < 1.0 × 10⁻⁷) and identified several new type 2 diabetes loci, SLC30A8 (1.26, P = 5.0 × 10⁻⁷), HHEX (1.21, P = 9.1 × 10⁻⁶), LOC38771 (1.14, P = 2.9 × 10⁻⁴), and EXT (1.26, P = 1.2 × 10⁻⁴) (3). SLC30A8 encodes a zinc transporter protein that carries zinc from the cytoplasm into insulin secretory vesicles within the pancreatic β-cell, an important step in insulin synthesis and secretion (4). HHEX is essential for the development of the pancreas and liver and is a target of the Wnt signaling pathway (5).After the initial GWAS publication, four other high-density scans were published simultaneously by different groups, confirming many of the initial findings. In addition to replicating the prior associations of TCF7L2, HHEX, and SCL30A8, investigators from Iceland identified CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1) as another potential diabetes-related gene (OR 1.2, P = 1.8 × 10⁻⁴) (6). This gene is hypothesized to lead to β-cell degeneration by modulating CDK5/CDK5R1 activity. The Diabetes Genetics Initiative, the Wellcome Trust Case Control Consortium, and the Finland–U.S. Investigation of Type 2 Diabetes Genetics concomitantly published GWASs that were combined in a preliminary meta-analysis of >30,000 samples (7–9). Again, the above findings were confirmed, and novel diabetes loci in or near IGF2BP2 (1.14, P = 8.9 × 10⁻¹⁶) and CDKN2A/B (1.2, P = 7.8 × 10⁻¹⁵) were identified. The EXT2 and LOC387761 gene regions have not been replicated in these or additional studies (10,11). Taken together, these studies support the potential power of GWASs in unraveling the genetic basis of type 2 diabetes.Several studies have attempted to characterize the physiological mechanisms affected by these genetic variants. Pascoe et al. (12) performed 75-g oral glucose tolerance tests (OGTTs) and hyperinsulinemic-euglycemic clamps on 1,276 healthy European subjects and demonstrated that common variants in CDKAL1 and HHEX are associated with decreased pancreatic β-cell function. Grarup et al. (13) reported that variants of HHEX, CDKN2A/B, and IFG2BP2 are associated with type 2 diabetes, and single nucleotide polymorphisms (SNPs) within the HHEX and CDKN2A/B loci impaired glucose-induced insulin release in healthy subjects, emphasizing the central role of pancreatic β-cell dysfunction in disease pathogenesis. Staiger et al. (14) found that the major alleles of the SLC30A8 and the HHEX SNPs associate with reduced insulin secretion stimulated by orally administered glucose but not with insulin resistance; the other reported type 2 diabetes SNPs within the EXT2 and LOC387761 loci did not associate with insulin resistance or β-cell dysfunction. Finally, a quantitative trait analysis of GWAS-identified type 2 diabetes susceptibility loci was recently completed by Palmer et al. (15) in their analysis of the Insulin Resistance Atherosclerosis Family Study (IRAS-FS). This study of 1,268 Hispanic and 581 African American subjects revealed that the increase in diabetes risk associated with variants in GWAS-identified gene regions, including CDKAL1, IGF2BP2, SLC30A8, and LOC387761, is mediated in part via defects primarily in insulin secretion. In Hispanic Americans, the acute insulinogenic response to glucose challenge decreased in high-risk genotype subjects at CDKAL1 (P = 0.005), and the disposition index was reduced in subjects with the high-risk genotype at IGF2BP2 (P = 0.01). Paradoxically, in Hispanic Americans, the previously identified risk allele of LOC387761 was significantly associated with an increased acute insulin response (P = 0.005) and disposition index (P = 0.036). IGF2BP2 rs4402960 was the only GWAS-identified SNP that associated with type 2 diabetes as a categorical trait (P = 0.02). Even fewer studies have attempted to analyze the influence of these genetic variants on response to pharmacological or behavioral interventions (16,17).The current study attempts to replicate and extend recent GWAS findings in the Diabetes Prevention Program (DPP) cohort. As a multiethnic, interventional study of >3,000 people at high risk for diabetes who have been carefully characterized, the DPP provides the opportunity to study insulin dynamics according to genotype and potential drug-genotype interactions. Studying pre-diabetic subjects as opposed to patients with overt diabetes provides insight into the role of genetic variation in the early stages of disease progression. As a longitudinal interventional study, the DPP provides the opportunity to carefully study the impact of genetic variation on insulin secretion and resistance over time. Finally, having multiple treatment arms allows for the identification of potential interactions of genotype with the results of the interventions. Studying gene-treatment interactions helps elucidate mechanisms of disease, identify specific treatments that may ameliorate the genetic predisposition to disease, and focus on subgroups that respond particularly well (or poorly) to specific therapies.     

Histological characterization and development of mesial surface sulci in the human brain at 13–15 gestational weeks through high-resolution histology

Cellular-level anatomical data from early fetal brain are sparse yet critical to the understanding of neurodevelopmental disorders. We characterize the organization of the human cerebral cortex between 13 and 15 gestational weeks using high-resolution whole-brain histological data sets complimented with multimodal imaging. We observed the heretofore underrecognized, reproducible presence of infolds on the mesial surface of the cerebral hemispheres. Of note at this stage, when most of the cerebrum is occupied by lateral ventricles and the corpus callosum is incompletely developed, we postulate that these mesial infolds represent the primordial stage of cingulate, callosal, and calcarine sulci, features of mesial cortical development. Our observations are based on the multimodal approach and further include histological three-dimensional reconstruction that highlights the importance of the plane of sectioning. We describe the laminar organization of the developing cortical mantle, including these infolds from the marginal to ventricular zone, with Nissl, hematoxylin and eosin, and glial fibrillary acidic protein (GFAP) immunohistochemistry. Despite the absence of major sulci on the dorsal surface, the boundaries among the orbital, frontal, parietal, and occipital cortex were very well demarcated, primarily by the cytoarchitecture differences in the organization of the subplate (SP) and intermediate zone (IZ) in these locations. The parietal region has the thickest cortical plate (CP), SP, and IZ, whereas the orbital region shows the thinnest CP and reveals an extra cell-sparse layer above the bilaminar SP. The subcortical structures show intensely GFAP-immunolabeled soma, absent in the cerebral mantle. Our findings establish a normative neurodevelopment baseline at the early stage.     

Thymoglobulin dose optimization for induction therapy in high risk kidney transplant recipients

BACKGROUND: Thymoglobulin (rATG) has become the agent of choice for induction therapy in high immunological risk kidney transplant recipients. However, its optimal dosing in this subgroup has not been studied. METHODS: To evaluate the effect of total rATG dosing on graft outcomes in such patients, we conducted a retrospective cohort study of 96 adult patients who received repeat transplants (85%) or had panel reactive antibody more than 40% (19%) and were maintained on tacrolimus, mycophenolate mofetil, and steroid. Group 1 (n=33) received less than or equal to 7.5 and group 2 (n=63) received more than 7.5 mg/kg rATG. Graft and patient survival, incidence of acute rejection (AR), and 12-month serum creatinine (SCr) were examined. RESULTS: The groups were comparable regarding demographics, donor source, retransplantation, panel reactive antibody, and human leukocyte antigen mismatch. Group 2 had more African Americans (44.4% vs. 21.2%, P=0.03). During the 25.4+/-18.0 months follow-up graft survival was 82.5% and 79.4%, respectively (P=0.54). Three in group 1 and four in group 2 died (P=0.65). The incidence of biopsy proven AR during the first 12-months did not differ between the groups (9.5% vs. 8.8%, respectively, P=0.9). SCr at 12 months was 1.6+/-0.7 in group 1 and 1.8+/-1.0 in group 2 (P=0.3). There was no independent association between rATG dose and graft survival (hazard ratio: 0.85, P=0.79, 95% CI: 0.26-2.7 for group 2 vs. 1) or 1-year SCr (regression coefficient=0.02 for ln(SCr), P=0.3; 95%CI: -0.01 to 0.6). CONCLUSION: Our results suggest that in high risk kidney transplant recipients total rATG doses less than or equal to 7.5 mg/kg are safe and effective in achieving a low rate of AR and graft outcomes comparable to higher doses.     

Beneficial effects of Centella asiatica aqueous extract against arsenic-induced oxidative stress and essential metal status in rats

The efficacy of an aqueous extract of Centella asiatica (100, 200 and 500 mg/kg for 5 consecutive days) was studied in the depletion of arsenic and in the recovery of a few altered biochemical variables in arsenic pre-exposed rats (20 ppm in drinking water for 5 weeks). Exposure to arsenic significantly depleted delta-aminolevulinic acid dehydratase (ALAD) activity, reduced glutathione (GSH) level, superoxide dismutase (SOD) and increased thiobarbituric acid reactive substance (TBARS) activity in red blood cells. Significant depletion of ALAD activity, GSH level, glutathione peroxidase (GPx), SOD and catalase (CAT) activities and an increase in TBARS levels in liver tissues was also noted. There was a significant depletion of SOD, CAT and GPx activities in kidneys and an increased TBARS levels in kidney and brain accompanied by increased arsenic concentration in blood and soft tissues. Treatment with aqueous extract of Centella asiatica provided significant protection against ALAD, GSH and TBARS levels, particularly at doses of 200 and 500 mg. Centella asiatica also provided significant recovery in the inhibited liver ALAD and G6PD activities. Arsenic concentration in blood and soft tissues remained uninfluenced after Centella asiatica administration. The present study thus suggests a beneficial effect of Centella asiatica against arsenic-induced oxidative stress but possesses no chelating property.