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Metabonomic analysis of hepatitis B virus-induced liver failure:identification of potential diagnostic biomarkers by fuzzy support vector machine 被引量:11
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作者 Yong MAO Xin HUANG +3 位作者 Ke YU Hai-bin QU Chang-xiao LIU Yi-yu CHENG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2008年第6期474-481,共8页
Hepatitis B virus (HBV)-induced liver failure is an emergent liver disease leading to high mortality. The severity of liver failure may be reflected by the profile of some metabolites. This study assessed the potent... Hepatitis B virus (HBV)-induced liver failure is an emergent liver disease leading to high mortality. The severity of liver failure may be reflected by the profile of some metabolites. This study assessed the potential of using metabolites as biomarkers for liver failure by identifying metabolites with good discriminative performance for its phenotype. The serum samples from 24 HBV-indueed liver failure patients and 23 healthy volunteers were collected and analyzed by gas chromatography-mass spectrometry (GC-MS) to generate metabolite profiles. The 24 patients were further grouped into two classes according to the severity of liver failure. Twenty-five eommensal peaks in all metabolite profiles were extracted, and the relative area values of these peaks were used as features for each sample. Three algorithms, F-test, k-nearest neighbor (KNN) and fuzzy support vector machine (FSVM) combined with exhaustive search (ES), were employed to identify a subset of metabolites (biomarkers) that best predict liver failure. Based on the achieved experimental dataset, 93.62% predictive accuracy by 6 features was selected with FSVM-ES and three key metabolites, glyeerie acid, cis-aeonitie acid and citric acid, are identified as potential diagnostic biomarkers. 展开更多
关键词 metabolite profile analysis Potential diagnostic biomarker identification k-nearest neighbor (KNN) Fuzzy supportvector machine (FsVM) Exhaustive search (Es Gas chromatography-mass spectrometry (GC-Ms Hepatitis B virus (HBV)-induced liver failure
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反义寡核苷酸药物AD00510-AS在小鼠、大鼠、猴、人肝S9和血浆中的代谢产物研究
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作者 柳庆龙 纪海霞 +6 位作者 李伦 张云 祁佳琦 刘添浩 梁柳艺 陶桂勇 周绍联 《中国新药杂志》 CAS CSCD 北大核心 2024年第2期151-158,共8页
目的:建立反义寡核酸药物AD00510-AS的LC-UV-Q-TOF方法,并探索小核酸药物AD00510-AS在体外肝S9和血浆中的代谢产物和代谢途径.方法:基于固相萃取的方法对孵育24h后的肝S9和血浆样品进行处理,采用SCIEX OS进行数据采集,采用Molecule Prof... 目的:建立反义寡核酸药物AD00510-AS的LC-UV-Q-TOF方法,并探索小核酸药物AD00510-AS在体外肝S9和血浆中的代谢产物和代谢途径.方法:基于固相萃取的方法对孵育24h后的肝S9和血浆样品进行处理,采用SCIEX OS进行数据采集,采用Molecule ProfilerTM软件分析空白样品和给药后孵育24h样品的提取离子流图(XIC)的差异,得到可能的代谢产物,并推测代谢途径.结果:AD00510-AS分别与小鼠、大鼠、猴、人肝S9孵育24h后,共检测到3个代谢产物(M1,M4和M5),母药的相对丰度分别为73.9%,87.1%,78.4%和81.3%;AD00510-AS分别与小鼠、大鼠、猴、人血浆孵育24h后,共检测到4个代谢产物(M2,M3,M4和M5),母药的相对丰度分别为69.1%,94.5%,67.8%和68.1%;通过MS及MS/MS的测定,鉴定的代谢产物如下:M1:3'末端丢失9个核苷酸代谢产物(MW=4544);M2:3'末端丢失2个核苷酸代谢产物(MW=6857);M3:3'末端丢失1个核苷酸代谢产物(MW=7232);M4:双脱硫代谢产物(MW=7559);M5:脱硫代谢产物(MW=7575).结论:采用确认的LC-UV-Q-TOF方法可以检测到AD00510-AS及其5个代谢产物,AD00510-AS在体外肝S9和血浆中主要通过降解(丢失核苷酸)和脱硫进行代谢. 展开更多
关键词 反义寡核苷酸 s9 血浆 代谢产物鉴定 固相萃取
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