长效甾体避孕药RP-HPLC流动相选择性优化与定量分析

采用极角混合设计技术,模拟溶质色谱保留行为的数学模型,用预测优化流动相实验,对溶质色谱保留行为的数学模型进行修正。通过数次预测、迭代、修正数学模型,提高模型的拟合精度,采用多目标优化指标,计算机辅助,寻求三元流动相的最佳组成。首次利用可编程序紫外检测器的时间程序检测功能,提高微量组分的检测灵敏度,成功地解决了两种长效避孕药制剂的定量分析。     

Revealing the human mutome

Chen JM, Férec C, Cooper DN. Revealing the human mutome. The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database). However, for a variety of reasons, this figure is likely to represent only a small proportion of the clinically relevant genetic variants that remain to be identified in the human genome (the ‘mutome’). With the advent of next‐generation sequencing, we are currently witnessing a revolution in medical genetics. In particular, whole‐genome sequencing (WGS) has the potential to identify all disease‐causing or disease‐associated DNA variants in a given individual. Here, we use examples of recent advances in our understanding of mutational/pathogenic mechanisms to guide our thinking about possible locations outwith gene‐coding sequences for those disease‐causing or disease‐associated variants that are likely so often to have been overlooked because of the inadequacy of current mutation screening protocols. Such considerations are important not only for improving mutation‐screening strategies but also for enhancing the interpretation of findings derived from genome‐wide association studies, whole‐exome sequencing and WGS. An improved understanding of the human mutome will not only lead to the development of improved diagnostic testing procedures but should also improve our understanding of human genome biology.     

Administration of hydrogen sulfide via extracorporeal membrane lung ventilation in sheep with partial cardiopulmonary bypass perfusion: a proof of concept study on metabolic and vasomotor effects

Introduction  

Although inhalation of 80 parts per million (ppm) of hydrogen sulfide (H₂S) reduces metabolism in mice, doses higher than 200 ppm of H₂S were required to depress metabolism in rats. We therefore hypothesized that higher concentrations of H₂S are required to reduce metabolism in larger mammals and humans. To avoid the potential pulmonary toxicity of H₂S inhalation at high concentrations, we investigated whether administering H₂S via ventilation of an extracorporeal membrane lung (ECML) would provide means to manipulate the metabolic rate in sheep.     

Elevated serum uric acid is a predictor of contrast associated acute kidney injury in patient with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

BackgroundContrast associated-acute kidney injury (CA-AKI) has been associated with adverse outcomes after ST-segment elevation myocardial infarction (STEMI). However, early markers of CA-AKI are still needed to improve risk stratification. We investigated the association between elevated serum uric acid (eSUA) and CA-AKI in patients with STEMI treated with primary percutaneous coronary intervention (pPCI).Methods and resultsSerum creatinine (Scr) was measured at admission and 24, 48 and 72 h after pPCI. CA-AKI was defined as an increase of 25% (CA-AKI 25%) or 0.5 mg/dl (CA-AKI 0.5) of Scr level above the baseline after 48 h following contrast administration. Multivariable analyses to investigate CA-AKI predictors were performed by binary logistic regression and multivariable backward logistic regression model.In the 3023 patients considered, CA-AKI was more frequent among patients with eSUA as compared with patients with normal SUA levels, considering both CA-AKI definitions (CA-AKI25%: 20.8% vs 16.2%, p < 0.012; CA-AKI 0.5: 10.1% vs 5.8%, p < 0.001). The association between eSUA and CA-AKI was confirmed at multivariable analyses (CA-AKI 25%: odd ratio 1.32, 95% CI 1.03–1.69, p = 0.027; CA-AKI 0.5: odd ratio 1.76, 95% CI 1.11–2.79, p = 0.016).ConclusionElevated serum uric acid is associated with CA-AKI after reperfusion in patients with STEMI treated with pPCI.