目的:股骨头坏死(osteonecrosis of the femoral head,ONFH)又被称为股骨头缺血性坏死,多数患者并发脂肪代谢紊乱。本研究探讨不同亚型的ONFH的脂代谢表达谱模式。方法:将受试者分为酒精性股骨头坏死(alcohol-induced osteonecrosis of ...目的:股骨头坏死(osteonecrosis of the femoral head,ONFH)又被称为股骨头缺血性坏死,多数患者并发脂肪代谢紊乱。本研究探讨不同亚型的ONFH的脂代谢表达谱模式。方法:将受试者分为酒精性股骨头坏死(alcohol-induced osteonecrosis of the femoral head,AONFH)组(n=16)、激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SONFH)组(n=29)、正常对照(normal control,NC)组(n=32)。运用超高效液相色谱-质谱/质谱串联(ultra high performance liquid chromatography-mass spectrometry/mass spectrometry tandem apparatus,UPLC-MS/MS)技术对受试者的外周血标本进行脂质代谢物的检测,鉴定疾病潜在的生物标志物。对代谢物表达谱进行预处理,再通过偏最小二乘法判别分析(partial least squares discriminant analysis,PLS-DA)计算变量投影重要度(variable importance for the projection,VIP)来衡量各脂质代谢物的表达模式对各组样本分类判别的影响强度和解释能力。筛选出不同组间倍数改变(fold change,FC)>2、P<0.05且VIP>1的脂质代谢物作为差异脂质物。其中,AONFH组和SONFH组中共同存在的差异脂质物被视为ONFH的共有差异脂质物,单独存在的差异脂质物被视为AONFH组或SONFH组的特异性差异脂质物。在差异脂质物的受试者操作特征(receiver operator characteristic,ROC)曲线分析的基础上,采用二元logistic回归评价差异脂质物对疾病的诊断价值。依据AONFH组和SONFH组患者的疾病分期信息,分析差异脂质物与疾病分期之间的相关性。结果:在血浆样本中共检测到1358种脂质代谢物。与NC组相比,AONFH组和SONFH组脂质代谢谱表达模式均有显著差异。分别在AONFH组和SONFH组患者外周血中筛选出62和64种差异脂质物(FC>2,P<0.05,VIP>1),且均以上调为主。进一步鉴定出AONFH组和SONFH组共有的差异脂质物有9种,AONFH组有6种脂质物的ROC曲线下面积大于0.7,它们分别为1-myristoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine、次黄嘌呤(hypoxanthin)、血清素(serotonin)、PE(19:0/22:5)、PE(19:0/22:5)、cholest-5-en-3-yl beta-Dglucopyranosiduronic acid;AONFH组鉴定出特异性差异脂质物53种。SONFH组鉴定出特异性差异脂质物55种,SONFH组有6种脂质物的曲线下面积大于0.9,分别为1D-myo-Inositol 1,2-cyclic phosphate、L-pyroglutamic acid、DL-carnitine、8-amino-7-oxononanoic acid、Clobetasol和presqualene diphosphate。AONFH组中有9种差异脂质代谢物与疾病分期有关,分别为LPG 18:1、serotonin、PC(22:4e/23:0)、PC(19:2/18:5)、hypoxanthin、PE(18:1/20:3)、LPE18:1、1-stearoyl-2-arachidonoyl-sn-glycerol、PE(16:0/18:1);随着AONFH疾病分期由Ⅰ/Ⅱ期向Ⅲ/Ⅳ期进展,该9种差异脂质物含量呈升高趋势。SONFH组中有8种差异脂质代谢物与疾病分期有关,分别为TM6076000、4-(1,1-dimethylpropyl)phenol、D-617、asarone、phenylac-gln-OH、肌酸(creatine)、leu-pro、8-amino-7-oxononanoic acid;随着SONFH疾病分期由Ⅰ/Ⅱ期向Ⅲ/Ⅳ期进展,该8种差异脂质物含量逐渐升高。结论:本研究分析了临床工作中常见AONFH和SONFH患者的血浆脂质表达谱特征,鉴定出了与疾病诊断及病情评估有关的差异脂质物,为探索ONFH的脂质代谢变化和挖掘新型敏感性、特异性生物标志物提供了依据。展开更多
疫苗的接种、人类卫生意识的提高、抗病毒药物的逐渐开发降低了乙型肝炎病毒(hepatitis B virus,HBV)的感染,但HBV的消除仍是一大难题,因此HBV的精准检出率极为重要。传统的血清标志物HBV DNA和乙肝表面抗原(hepatitis B surface antige...疫苗的接种、人类卫生意识的提高、抗病毒药物的逐渐开发降低了乙型肝炎病毒(hepatitis B virus,HBV)的感染,但HBV的消除仍是一大难题,因此HBV的精准检出率极为重要。传统的血清标志物HBV DNA和乙肝表面抗原(hepatitis B surface antigen,HBsAg)在准确反映共价闭合环状DNA(covalently closed circular DNA,cccDNA)转录活性与用药检测方面存在一定的局限性。为此,研究者陆续开发出新型HBV血清标志物,如HBV表面抗原、HBV RNA、HBV核心相关抗原、HBV大表面蛋白。基于不同标志物在疾病诊断中的不同参考价值,本文简要对这些标志物的临床应用及面临挑战进行小结,旨在为HBV的高效、准确检出及临床预后提供参考。展开更多
Objective We examined alterations in the expression of tumorigenesis‐related genes in the pituitary gland of rats exposed to electromagnetic pulses （EMP）.Methods The global gene expression profiles of the pituitary...Objective We examined alterations in the expression of tumorigenesis‐related genes in the pituitary gland of rats exposed to electromagnetic pulses （EMP）.Methods The global gene expression profiles of the pituitary gland in EMP‐exposed and control groups were detected by cDNA microarray analysis.We then validated and further investigated the reduced expression of two tumorigenesis‐related genes,Pten,and Jund,by assessing their mRNA and protein expression by quantitative real‐time‐PCR,western blotting,and immunohistochemistry in the pituitary gland of rats 6 months after exposure to EMP.Results EMP exposure induced genome‐wide gene expression changes in the rat pituitary gland.There was decreased expression of the Pten and Jund mRNAs and proteins in EMP‐exposed rats compared with in unexposed control animals.Conclusion EMP exposure alters the expression of tumorigenesis‐related genes in the pituitary gland.These tumorigenesis‐related genes are potentially involved in the development of pituitary gland tumors in rats.展开更多
文摘目的:股骨头坏死(osteonecrosis of the femoral head,ONFH)又被称为股骨头缺血性坏死,多数患者并发脂肪代谢紊乱。本研究探讨不同亚型的ONFH的脂代谢表达谱模式。方法:将受试者分为酒精性股骨头坏死(alcohol-induced osteonecrosis of the femoral head,AONFH)组(n=16)、激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SONFH)组(n=29)、正常对照(normal control,NC)组(n=32)。运用超高效液相色谱-质谱/质谱串联(ultra high performance liquid chromatography-mass spectrometry/mass spectrometry tandem apparatus,UPLC-MS/MS)技术对受试者的外周血标本进行脂质代谢物的检测,鉴定疾病潜在的生物标志物。对代谢物表达谱进行预处理,再通过偏最小二乘法判别分析(partial least squares discriminant analysis,PLS-DA)计算变量投影重要度(variable importance for the projection,VIP)来衡量各脂质代谢物的表达模式对各组样本分类判别的影响强度和解释能力。筛选出不同组间倍数改变(fold change,FC)>2、P<0.05且VIP>1的脂质代谢物作为差异脂质物。其中,AONFH组和SONFH组中共同存在的差异脂质物被视为ONFH的共有差异脂质物,单独存在的差异脂质物被视为AONFH组或SONFH组的特异性差异脂质物。在差异脂质物的受试者操作特征(receiver operator characteristic,ROC)曲线分析的基础上,采用二元logistic回归评价差异脂质物对疾病的诊断价值。依据AONFH组和SONFH组患者的疾病分期信息,分析差异脂质物与疾病分期之间的相关性。结果:在血浆样本中共检测到1358种脂质代谢物。与NC组相比,AONFH组和SONFH组脂质代谢谱表达模式均有显著差异。分别在AONFH组和SONFH组患者外周血中筛选出62和64种差异脂质物(FC>2,P<0.05,VIP>1),且均以上调为主。进一步鉴定出AONFH组和SONFH组共有的差异脂质物有9种,AONFH组有6种脂质物的ROC曲线下面积大于0.7,它们分别为1-myristoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine、次黄嘌呤(hypoxanthin)、血清素(serotonin)、PE(19:0/22:5)、PE(19:0/22:5)、cholest-5-en-3-yl beta-Dglucopyranosiduronic acid;AONFH组鉴定出特异性差异脂质物53种。SONFH组鉴定出特异性差异脂质物55种,SONFH组有6种脂质物的曲线下面积大于0.9,分别为1D-myo-Inositol 1,2-cyclic phosphate、L-pyroglutamic acid、DL-carnitine、8-amino-7-oxononanoic acid、Clobetasol和presqualene diphosphate。AONFH组中有9种差异脂质代谢物与疾病分期有关,分别为LPG 18:1、serotonin、PC(22:4e/23:0)、PC(19:2/18:5)、hypoxanthin、PE(18:1/20:3)、LPE18:1、1-stearoyl-2-arachidonoyl-sn-glycerol、PE(16:0/18:1);随着AONFH疾病分期由Ⅰ/Ⅱ期向Ⅲ/Ⅳ期进展,该9种差异脂质物含量呈升高趋势。SONFH组中有8种差异脂质代谢物与疾病分期有关,分别为TM6076000、4-(1,1-dimethylpropyl)phenol、D-617、asarone、phenylac-gln-OH、肌酸(creatine)、leu-pro、8-amino-7-oxononanoic acid;随着SONFH疾病分期由Ⅰ/Ⅱ期向Ⅲ/Ⅳ期进展,该8种差异脂质物含量逐渐升高。结论:本研究分析了临床工作中常见AONFH和SONFH患者的血浆脂质表达谱特征,鉴定出了与疾病诊断及病情评估有关的差异脂质物,为探索ONFH的脂质代谢变化和挖掘新型敏感性、特异性生物标志物提供了依据。
基金supported by the Research Fund of the National Natural Science Foundation of China (No: 60871068 30970670)
文摘Objective We examined alterations in the expression of tumorigenesis‐related genes in the pituitary gland of rats exposed to electromagnetic pulses （EMP）.Methods The global gene expression profiles of the pituitary gland in EMP‐exposed and control groups were detected by cDNA microarray analysis.We then validated and further investigated the reduced expression of two tumorigenesis‐related genes,Pten,and Jund,by assessing their mRNA and protein expression by quantitative real‐time‐PCR,western blotting,and immunohistochemistry in the pituitary gland of rats 6 months after exposure to EMP.Results EMP exposure induced genome‐wide gene expression changes in the rat pituitary gland.There was decreased expression of the Pten and Jund mRNAs and proteins in EMP‐exposed rats compared with in unexposed control animals.Conclusion EMP exposure alters the expression of tumorigenesis‐related genes in the pituitary gland.These tumorigenesis‐related genes are potentially involved in the development of pituitary gland tumors in rats.
