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Biomedical subjects

Jixian Wang

Publications and source records attributed to Jixian Wang.

8 recordsLinked to original sources

Use of gene expression profiling to identify a novel glucocorticoid sensitivity determining gene, BMPRII.

Wide variation in glucocorticoid (Gc) sensitivity exists between individuals which may influence susceptibility to, and treatment response of, inflammatory diseases. To determine a genetic fingerprint of Gc sensitivity 100 healthy human volunteers were polarized into the 10% most Gc-sensitive and 10% most Gc-resistant following a low dose dexamethasone (0.25 mg) suppression test. Gene expression profiling of primary lymphocytes identified the 98 most significantly Gc regulated genes. These genes were used to build a subnetwork of Gc signaling, with 54 genes mapping as nodes, and 6 non-Gc regulated genes inferred as signaling nodes. Twenty four of the 98 genes showed a difference in Gc response in vitro dependent on the Gc sensitivity of their donor individuals in vivo. A predictive model was built using both partial least squares discriminate analysis and support vector machines that predicted donor glucocorticoid sensitivity with 87% accuracy. Discriminating genes included bone morphogenetic protein receptor, type II (BMPRII). Transfection studies showed that BMPRII modulated Gc action. These studies reveal a broad base of gene expression that predicts Gc sensitivity and determine a Gc signaling network in human primary T lymphocytes. Furthermore, this combined gene profiling, and functional analysis approach has identified BMPRII as a modulator of Gc signaling.

Adult↗

An adaptive two-stage design with treatment selection using the conditional error function approach.

As an approach to combining the phase II dose finding trial and phase III pivotal trials, we propose a two-stage adaptive design that selects the best among several treatments in the first stage and tests significance of the selected treatment in the second stage. The approach controls the type I error defined as the probability of selecting a treatment and claiming its significance when the selected treatment is indifferent from placebo, as considered in Bischoff and Miller (2005). Our approach uses the conditional error function and allows determining the conditional type I error function for the second stage based on information observed at the first stage in a similar way to that for an ordinary adaptive design without treatment selection. We examine properties such as expected sample size and stage-2 power of this design with a given type I error and a maximum stage-2 sample size under different hypothesis configurations. We also propose a method to find the optimal conditional error function of a simple parametric form to improve the performance of the design and have derived optimal designs under some hypothesis configurations. Application of this approach is illustrated by a hypothetical example.

Biometry↗

Effects of zinc, copper, and selenium on placental cadmium transport.

The objective of the present study was to evaluate the potential effects of zinc, copper, and selenium on placental cadmium transport. From November 2002 through January 2003, a total of 47 healthy pregnant women from Da-Ye City, Hubei Province in Central China participated in the study. Their age, parity, gestational age, pregnancy history, and lifestyle data were obtained by questionnaire interview. The placental, whole-blood, and cord blood levels of cadmium were determined by inductively coupled plasma mass spectrometer (ICP-MS), whole-blood zinc was measured by flame atomic absorption spectrometry (F-AAS), whole-blood copper by ICP-MS, and selenium was by atomic fluorescence spectrophotometry (AFS). The cord blood cadmium concentration (0.020-1.48 microg/L) was significantly lower than in maternal blood (0.80-25.20 microg/L, p<0.01). The placental cadmium concentration was from 0.082 to 3.97 microg/g dry weight. Multiple linear regression analysis indicated that lower levels of maternal blood copper were significantly associated with higher cadmium concentrations in cord blood. Placental cadmium in women with lower levels of maternal blood zinc was significantly higher than in those with normal zinc levels. The placental cadmium level in women with lower whole-blood selenium was significantly lower than in subjects with normal selenium levels. It was concluded that the essential elements copper, selenium, and zinc might significantly affect placental cadmium transport.

Adult↗

Frequency of severe hypoglycemia requiring emergency treatment in type 1 and type 2 diabetes: a population-based study of health service resource use.

OBJECTIVE: To determine the incidence, predisposing factors, and costs of emergency treatment of severe hypoglycemia in people with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Over a 12-month period, routinely collected datasets were analyzed in a population of 367,051 people, including 8,655 people with diabetes, to measure the incidence of severe hypoglycemia that required emergency assistance from Ninewells Hospital and Medical School (NHS) personnel including those in primary care, ambulance services, hospital accident and emergency departments, and inpatient care. Associated costs with these episodes were calculated. RESULTS: A total of 244 episodes of severe hypoglycemia were recorded in 160 patients, comprising 69 (7.1%) people with type 1 diabetes, 66 (7.3%) with type 2 diabetes treated with insulin, and 23 (0.8%) with type 2 diabetes treated with sulfonylurea tablets. Incidence rates were 11.5 and 11.8 events per 100 patient-years for type 1 and type 2 patients treated with insulin, respectively. Age, duration, and socioeconomic status were identified as risk factors for severe hypoglycemia. One in three cases were treated solely by the ambulance service with no other contact from health care professionals. The total estimated cost of emergency treatment of severe hypoglycemia was </= pound 92,078 in one year. CONCLUSIONS: Hypoglycemia requiring emergency assistance from health service personnel is as common in people with type 2 diabetes treated with insulin as in people with type 1 diabetes. It is associated with considerable NHS resource use that has a significant economic and personal cost.

Adult↗

Comparison of cardiovascular risk between patients with type 2 diabetes and those who had had a myocardial infarction: cross sectional and cohort studies.

OBJECTIVE: To compare risks of cardiovascular outcomes between patients with type 2 diabetes and patients with established coronary heart disease. DESIGN: Cross sectional study and cohort study using routinely collected datasets. SETTING: Tayside, Scotland (population 400 000) during 1988-95. SUBJECTS: In the cross sectional study, among patients aged 45-64, 1155 with type 2 diabetes were compared with 1347 who had had a myocardial infarction in the preceding 8 years. In the cohort study 3477 patients of all ages with newly diagnosed type 2 diabetes were compared with 7414 patients who had just had a myocardial infarction. MAIN OUTCOME MEASURES: Risk ratios for death from all causes, cardiovascular death, and hospital admission for myocardial infarction were calculated by Cox proportional hazards analysis and adjusted for age and sex. RESULTS: In the cross sectional study the adjusted risk ratio for death from all causes for patients who had myocardial infarction compared with those with diabetes was 1.33 (95% confidence interval 1.14 to 1.55) [corrected], and the risk ratio for hospital admission for myocardial infarction was 2.27 (1.82 to 2.83) [corrected]. In the cohort study, patients who had just had a myocardial infarction had a higher risk of death from all causes (adjusted risk ratio 1.35 (1.25 to 1.44)), cardiovascular death (2.93 (2.54 to 3.41)), and hospital admission for myocardial infarction (3.10 (2.57 to 3.73)). CONCLUSIONS: Patients with type 2 diabetes were at lower risk of cardiovascular outcomes than patients with established coronary heart disease.

Adult↗

An approximate Bayesian risk-analysis for the gastro-intestinal safety of ibuprofen.

PURPOSE: Although several studies on ibuprofen and its gastro-intestinal (GI) risk have been reported, the dose-response relationship was not clear due to the lack of information regarding high-dose exposure. Analysis using Bayesian methods is appropriate whenever data are sparse, although such methods are not easily implemented. METHODS: A retrospective cohort study to assess this dose-response relationship was carried out using a record linkage database. A Bayesian risk-analysis was conducted using the Bayesian bootstrap approximation. Risks of GI events at different dose levels were compared using the posterior distributions and the number of events predicted to occur in the future was estimated. Risk factors such as age, gender and co-morbidity were adjusted for in the analysis. This approximation was compared with the full Bayesian approach using the usual but more computer-intensive tool of Markov Chain Monte Carlo simulation. RESULTS: There were 1, 5 and 10 complicated GI events during exposure to high, medium and low dose ibuprofen with 0.2, 1.8 and 7.0 thousand person-years (PY) exposure, respectively. After adjusting for other risk factors the relative risks of high versus low and medium versus low doses were 6.3 (95% CI = 0.21, 24.17) and 2.5 (95% CI = 0.71, 5.85), respectively. Using the approximate Bayesian method prediction of the number of events in a population of females aged 50-59 with no previous medical problems with 1000 PY drug exposure showed that the estimated probability of having more than five events was 0.048 for the medium-dose group and 0.14 for the high-dose group. CONCLUSIONS: High dose ibuprofen appears to have a considerably greater risk of having a larger number of adverse GI events than a medium dose. The approximate Bayesian bootstrap method was demonstrated to be a robust and easily implemented alternative to the full Bayesian approach to risk analysis whenever data are sparse.

Anti-Inflammatory Agents, Non-Steroidal↗

Study in China on ingestion and organ content of trace elements of importance in radiological protection.

To improve knowledge of the ingestion and organ content of calcium, cesium, iodine, potassium, strontium, thorium, and uranium that have a high priority in radiological protection, a total diet and organ content studies was conducted. The total diet study used the market basket sample method with representative sampling. For the organ content specimens of muscle, skeleton, liver, kidney, lung, and thyroid were collected during autopsies of normal, healthy adult accidental death victims. The concentration of above stated elements in the diet and organs were analyzed by nuclear and nuclear-related techniques with strict quality assurance measures. The results are presented in the paper and compared with previous national and international data and the parameters of current International Commission on Radiological Protection (ICRP) Reference Man. The study provided a new and reliable database for setting the parameters for the Chinese reference man and the reference Asian man. It also facilitated the study on biokinetics behavior of their radiation counterparts in human body and helped in the realistic assessment of their internal radiation doses.

Body Composition↗

[Effects of cartilage-derived growth factor on cultured rabbit chondrocytes].

OBJECTIVE: To investigate the effect of cartilage-derived growth factor (CDGF) on cultured rabbit chondrocytes, and the relation between CDGF, insulin-like growth factor-I (IGF-I), and proliferation and metabolism of chondrocytes. METHODS: CDGF was extracted from chicken xiphoid in our laboratory. Chondrocytes were isolated from 3-week-old New Zealand male rabbits, and cultured in Ham's F-12 medium containing 10% fetal calf serum. The chondrocyts of second generation were treated with CDGF and/or IGF-I of different concentrations. With chloramine T method and MTT method, we compared the content of hydroxyproline in Ham's F-12 medium and observed proliferation and energy synthesis of chondrocytes. RESULTS: CDGF and IGF-I both stimulated the proliferation and synthesis of hydroxyproline of chondrocytes dose-dependently. The optimal concentration of CDGF was 16 ng/ml and 32 ng/ml respectively, and that of IGF-I was 30 ng/ml. There was obvious synergic effect between CDGF and IGF-I. CONCLUSION: CDGF can stimulate the proliferation and collagen synthesis of chondrocytes and has synergistic effect with IGF-I.

Animals↗