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The pharmacokinetic (PK) characteristics of drugs were altered under high‐altitude hypoxia. We aim to describe the population PK of atorvastatin (ATV) to identify patient characteristics that are predictive of variability in the PK parameters of the ATV and investigate the effects of high‐altitude hypoxia on the blood concentration of ATV in patients with hyperlipidemia. A total of 160 plasma concentrations were collected from 40 patients with hyperlipidemia in plateau areas and 40 in plain areas. The population pharmacokinetic model of patients with hyperlipidemia in plateau and plain areas of China was established by a nonlinear mixed‐effects model. The PK of ATV were described by a 1‐compartment model with first‐order elimination. The main PK parameters of ATV were the first‐order absorption rate (0.76 hour−1 fixed); clearance (174.22 L/h) and apparent volume of distribution (1119.62 L). The values of area and age were identified as significant covariates for the clearance, area, age, and urea for the volume of distribution. The steady‐state peak concentration in the plateau area was higher than that in the plain area. This study may suggest dose reduction is necessary for patients with hyperlipidemia in high altitudes. [ABSTRACT FROM AUTHOR]

Rice black-streaked dwarf virus (RBSDV) is the main pathogen causing maize rough dwarf disease (MRDD) in China. Typical enation symptoms along the abaxial leaf veins prevail in RBSDV-infected maize inbred line B73 (susceptible to RBSDV), but not in X178 (resistant to RBSDV). Observation of the microstructures of epidermal cells and cross section of enations from RBSDV-infected maize leaves found that the increase of epidermal cell and phloem cell numbers is associated with enation formation. To identify proteins associated with enation formation and candidate proteins against RBSDV infection, comparative proteomics between B73 and X178 plants were conducted using isobaric tags for relative and absolute quantitation (iTRAQ) with leaf samples at the enation forming stage. The proteomics data showed that 260 and 316 differentially expressed proteins (DEPs) were identified in B73 and X178, respectively. We found that the majority of DEPs are located in the chloroplast and cytoplasm. Moreover, RBSDV infection resulted in dramatic changes of DEPs enriched by the metabolic process, response to stress and the biosynthetic process. Strikingly, a cell number regulator 10 was significantly down-regulated in RBSDV-infected B73 plants. Altogether, these data will provide value information for future studies to analyze molecular events during both enation formation and resistance mechanism to RBSDV infection. [ABSTRACT FROM AUTHOR]

Objective In this study, short-term prognosis of cerebral revascularization was evaluated by comparative analysis of patients with moyamoya disease (MMD) with different disease types and different bypass. Methods A total of 44 patients with MMD treated in Beijing Tiantan Hospital Affiliated to Capital Medical University from January 2010 to October 2011 were enrolled. All patients underwent cerebral revascularization. The improvement of neurological function was evaluated by National Institutes of Health Stroke Scale (NIHSS) 3 months after surgery, and the improvement of clinical symptoms was observed. DSA or CTA were reviewed to determine whether the bridge vessels were unobstructed and surgical complications were recorded. Results DSA or CTA reexamination showed that the anastomosis was unobstructed, and no surgical complications occurred. Patients with MMD were divided into 3 groups according to the onset type: ischemic, hemorrhagic and mixed. Compared with hemorrhagic type and mixed type, neurological function improved 3 months after surgery in patients with ischemic type (χ² = 3.853, P = 0.001; χ² = 4.110, P = 0.001) and improvement of clinical symptoms (χ² = 3.934, P = 0.000; χ² = 4.138, P = 0.000) were better. According to the operation type, the patients were divided into 4 groups: anterior-frontal, anterior-temporal, posterior-frontal and posterior-temporal bypass. The improvement of neurological function in anterior-frontal bypass group was higher than that in anterior-temporal bypass group (χ² = 2.079, P = 0.038). The improvement of neurological function and clinical symptoms in posterior-frontal bypass group were higher than those in anterior-temporal bypass group (χ² = 2.909; P = 0.004; x= 2.812, P = 0.005), and those in posterior-frontal bypass group were also higher than those in posterior-temporal bypass group (χ² = 2.295, P = 0.022; χ² = 2.580, P = 0.010). Conclusions Compared with the other 2 groups, symptoms of ischemic MMD may improved better than before, and the intraoperative selection of posterior-frontal and anterior-frontal bypass may be better than anterior-temporal and posterior-temporal bypass. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the population pharmacokinetics of cefoperazone in children and establish an evidence-based dosing regimen using a developmental pharmacokinetic-pharmacodynamic approach in order to optimize cefoperazone treatment.Methods: A model-based, open-label, opportunistic-sampling pharmacokinetic study was conducted in China. Blood samples from 99 cefoperazone-treated children were collected and quantified by HPLC/MS. NONMEM software was used for population pharmacokinetic-pharmacodynamic analysis. This study was registered at ClinicalTrials.gov (NCT03113344).Results: A two-compartment model with first-order elimination agreed well with the experimental data. Covariate analysis showed that current body weight had a significant effect on the pharmacokinetics of cefoperazone. Monte Carlo simulation showed that for bacteria for which cefoperazone has an MIC of 0.5 mg/L, 78.1% of hypothetical children treated with '40 mg/kg/day, q8h, IV drip 3 h' would reach the pharmacodynamic target. For bacteria for which cefoperazone has an MIC of 8 mg/L, 88.4% of hypothetical children treated with 80 mg/kg/day (continuous infusion) would reach the treatment goal. A 160 mg/kg/day (continuous infusion) regimen can cover bacteria for which cefoperazone has an MIC of 16 mg/L. Nevertheless, even if using the maximum reported dose of 160 mg/kg/day (continuous infusion), the ratio of hypothetical children reaching the treatment target was only 9.9% for bacteria for which cefoperazone has an MIC of 32 mg/L.Conclusions: For cefoperazone, population pharmacokinetics were evaluated in children and an appropriate dosing regimen was developed based on developmental pharmacokinetics-pharmacodynamics. The dose indicated in the instructions (20-160 mg/kg/day) can basically cover the clinically common bacteria for which cefoperazone has an MIC of ≤16 mg/L. However, for bacteria for which the MIC is >16 mg/L, cefoperazone is not a preferred choice. [ABSTRACT FROM AUTHOR]

Introduction: High-dose intravenous esomeprazole is the only approved pharmacological treatment for the prevention of peptic ulcer rebleeding (currently approved in over 100 countries worldwide), but has not yet been approved in China. This study aimed to evaluate a high-dose esomeprazole intravenous regimen vs. an active control (cimetidine) for the prevention of rebleeding in Chinese patients with a high risk of peptic ulcer rebleeding who had undergone primary endoscopic hemostatic treatment.Methods: This was a parallel-group study conducted at 20 centers in China. The study comprised a randomized, double-blind, intravenous treatment phase of 72 h in which 215 patients received either high-dose esomeprazole (80 mg + 8 mg/h) or cimetidine (200 mg + 60 mg/h), followed by an open-label oral treatment phase in which all patients received esomeprazole 40 mg tablets once daily for 27 days. The primary outcome was the rate of clinically significant rebleeding within the first 72 h after initial endoscopic hemostatic therapy. Secondary outcomes included the rates of clinically significant rebleeding within 7 and 30 days; proportions of patients who had endoscopic retreatment and other surgery due to rebleeding; and number of blood units transfused.Results: The rate of clinically significant rebleeding within 72 h was low overall (3.3%) and numerically lower in patients treated with esomeprazole compared with cimetidine (0.9% vs. 5.6%). Overall, the results of the secondary outcomes also showed a numerical trend towards superiority of esomeprazole over cimetidine. All treatments were well tolerated.Conclusion: In this phase 3, multicenter, randomized trial conducted in China, esomeprazole showed a numerical trend towards superior clinical benefit over cimetidine in the prevention of rebleeding in patients who had successfully undergone initial hemostatic therapy of a bleeding peptic ulcer, with a similar safety and tolerability profile. These findings suggest that esomeprazole may be an alternative treatment option to cimetidine for this indication in China.Funding: AstraZeneca.Trial Registration: ClinicalTrials.gov identifier, NCT01757275. [ABSTRACT FROM AUTHOR]

Atmospheric PM10 were measured for 12 months at 18 sites along a 2500 km profile across northern China. Annual mean PM10 concentrations in urban, rural village, and rural field sites were 180 ± 171, 182 ± 154, and 128 ± 89 μg/m3, respectively. The similarities in PM10 concentrations between urban and rural village sites suggest that strong localized emissions and severe contamination in rural residential areas are derived from solid fuels combustion in households. High PM10 concentrations in Wuwei and Taiyuan were caused by either sandstorms or industrial activities. Relatively low PM10 concentrations were observed in coastal areas of Dalian and Yantai. Particulate air pollution was much higher in winter and spring than in summer and fall. Multiple regression analysis indicates that 35% of the total variance can be attributed to sandstorms, precipitation and residential energy consumption. Over 40% of the measurements in both urban and rural village areas exceeded the national ambient air quality standard. [Copyright &y& Elsevier]