研究中药黄芪对小鼠心脏、大脑及血液代谢稳态的影响,从代谢调控角度阐明黄芪"修心健脑"的作用机制.13只ICR雄性小鼠随机分为两组,分别连续10 d灌胃给予超纯水和黄芪水提液,采用液相色谱-质谱(LC-MS)和气相色谱-质谱(GC-MS)联用分析全面表征小鼠血清、心脏和脑组织代谢指纹图谱,结合多元统计分析与非参数检验筛选、鉴定差异代谢物,聚焦相关代谢通路.多元统计分析表明,与对照组相比,黄芪干预后小鼠机体的代谢轮廓变化显著,在血清、心脏、脑中分别鉴定出15、19和17个差异代谢物,其中差异代谢物棕榈酸和LysoPC(20:3)为3种生物样本共有且变化趋势一致.代谢通路富集分析结果显示,氨基酸代谢、磷脂代谢、脂肪酸代谢和三羧酸循环等通路受到显著影响.研究结果显示,黄芪可能通过调节能量代谢、氨基酸代谢及脂代谢稳态发挥心脑血管保护作用.

Astragali radix (AR, the dried root of Astragalus) is a popular herbal remedy in both China and the United States. The commercially available AR is commonly classified into premium graded (PG) and ungraded (UG) ones only according to the appearance. To uncover novel sensitive and specific markers for AR grading, we took the integrated mass spectrometry-based untargeted and targeted metabolomics approaches to characterize chemical features of PG and UG samples in a discovery set (n=16 batches). A series of five differential compounds were screened out by univariate statistical analysis, including arginine, calycosin, ononin, formononetin, and astragaloside Ⅳ, most of which were observed to be accumulated in PG samples except for astragaloside Ⅳ. Then, we performed machine learning on the quantification data of five compounds and constructed a logistic regression prediction model. Finally, the external validation in an independent validation set of AR (n=20 batches) verified that the five compounds, as well as the model, had strong capability to distinguish the two grades of AR, with the prediction accuracy > 90%. Our findings present a panel of meaningful candidate markers that would significantly catalyze the innovation in AR grading.

为研究不同产地黄芪的化学成分差异,制备了甘肃和内蒙古2个产地共15批黄芪药材的水煎液,利用超快速液相色谱-离子阱飞行时间质谱仪(UFLC-IT-TOF/MS)采集15批黄芪药材水煎液化学成分的指纹图谱,进而运用偏最小二乘-判别分析(PLS-DA)和(非)参数检验对数据进行模式识别和统计分析,以变量投影重要性大于1、统计学差异小于0.05以及倍数变化大于1.5为阈值,筛选并鉴定其差异成分.结果发现,不同产地的黄芪水煎液中毛蕊异黄酮、芒柄花素、亚油酸等7个化学成分的含量有明显差异,涉及木脂素、黄酮、脂肪酸等4种类别.本研究为黄芪药材的全面质量控制、准确区分产地以及合理种植栽培提供了重要依据.

Glutaminolysis is the metabolic pathway that lyses glutamine to glutamate, alanine, citrate, aspartate, and so on. As partially recruiting reaction steps from the tricarboxylic acid (TCA) cycle and the malate-aspartate shuttle, glutaminolysis takes essential place in physiological and pathological situations. We herein developed a sensitive, rapid, and reproducible liquid chromatography-tandem mass spectrometry method to determine the perturbation of glutaminolysis in human plasma by quantifying 13 involved metabolites in a single 20-min run. A pHILIC column with a gradient elution system consisting of acetonitrile-5 mM ammonium acetate was used for separation, while an electrospray ionization source (ESI) operated in negative mode with multiple reaction monitoring was employed for detection. The method was fully validated according to FDA’s guidelines, and it generally provided good results in terms of linearity (the correlation coefficient no less than 0.9911 within the range of 0.05–800 μg/mL), intra- and inter-day precision (less than 18.38%) and accuracy (relative standard deviation between 89.24 and 113.4%), with lower limits of quantification between 0.05 and 10 μg/mL. The new analytical approach was successfully applied to analyze the plasma samples from 38 healthy volunteers and 34 patients with type 2 diabetes (T2D). Based on the great sensitivity and comprehensive capacity, the targeted analysis revealed the imperceptible abnormalities in the concentrations of key intermediates, such as iso-citrate and cis-aconitate, thus allowing us to obtain a thorough understanding of glutaminolysis disorder during T2D.

脑卒中是一种严重威胁中老年人健康的常见病、难治病,存在着明显的四高一多现象(发病率高、死亡率高、致残率高、复发率高、并发症多).应激性溃疡是脑卒中众多并发症中较为常见且严重的一种.本文从发病机制、防治方法 等方面,对近年来脑卒中并发应激性溃疡的研究进展进行总结,为其临床准确诊断和有效防治提供参考.

Saikosaponins are the representative bioactive ingredient in the Radix Bupleuri. Previous studies have reported that saikosaponins are prone to losing their glycones and being converted to corresponding prosaikogenins and saikogenins by intestinal bacteria. However, the microsomal cytochrome P450-mediated metabolism of these deglycosylated metabolites is still unknown. This research performed in vitro studies of five saikogenins in rat and human liver microsomes. High-performance liquid chromatography coupled with a hybrid ion trap and time-of-flight mass spectrometry (HPLC-IT/TOF-MS) was employed to identify the metabolites. To confirm the metabolites detected in vitro, plasma and feces obtained from rats administrating several saikogenins were also analyzed by high-performance liquid chromatography with triple-quadrupole mass spectrometry (HPLC-QqQ-MS). The in vitro metabolic stability of saikogenins was ranked as follows: SGF＞SGG＞SGE＞SGA＞SGD. A total of 71 metabolites generated by hydroxylation, carboxylation, and dehydrogenation, as well as combinations of these steps, were identified by accurate mass measurement and MSn fragmentation behavior. Among eight metabolic pathways, monohydroxylation or carboxylation was the major metabolic pathway both in vitro and in vivo. Analysis of in vivo biological samples suggested that analytical targets for saikogenins should be the compounds themselves and their oxidized metabolites. This research provides a basis for further studies of the in vivo metabolism of saikosaponins in humans.

Chronic heart failure (CHF) is an ongoing clinical syndrome with cardiac dysfunction that can be traced to alterations in cardiac metabolism. The identification of metabolic biomarkers in easily accessible fluids to improve the early diagnosis of CHF has been elusive to date. In this study, we took multidimensional analytical techniques to discover potentially new diagnostic biomarkers by focusing on the dynamic changes of metabolites in serum during the progression of CHF. Using mass-spectrometry-based untargeted metabolomics, we identified 23 cardiac metabolites that were altered in a rat model of myocardial infarction induced CHF. Among these differential metabolites, branched-chain amino acids (BCAAs) in serum, especially leucine and valine, showed a high capability to differentiate between CHF and sham-operated rats, of which area under the receiver operating characteristic curve was greater than 0.75. Combining with targeted analysis of the amino acids and related proteins and genes, we confirmed that BCAA metabolic pathway was significantly inhibited in rat failing hearts. On the basis of the time series data of serum samples, we characterized the fluctuation pattern of circulating BCAAs by the disease progression model. Finally, the time-resolved diagnostic potential of serum BCAAs was evaluated by the machine-learning-based classifier, and high diagnostic accuracy of 93.75% was achieved within 3 weeks after surgery. These findings provide a promising metabolic signature that can be further exploited for CHF early diagnostic development.

Realgar nanoparticles are a nano-drug prepared from the traditional Chinese medicine realgar, with high bioavailability, strong targeting and other biological characteristics. This paper reviewed the research progress of pharmacological and toxic effects of realgar nanoparticles in recent years and provided references for further research and development.

范围管理是项目管理的重要知识领域之一。实行范围管理对于油气勘探项目降低风险、提高收益具有重要意义。油气勘探项目的范围管理主要涉及定义及控制油气勘探项目应该包括的内容,可分为范围规划、范围定义、制作工作分解结构、范围核实和范围控制五个过程来进行。本文结合项目管理知识体系指南(第3版)的最新内容,具体探讨油气勘探项目范围管理的流程及相关问题。