Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(...Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(COMP),as a component of the vascular matrix,has been found to be an inhibitor of arterial calcification in basic studies.However,there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis(MHD)patients.The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients.Methods Serum COMP levels were compared between 54 MHD patients and 66 healthy people.MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events(MACEs),which were defined as a combined end point of new onset angina pectoris,nonfatal myocardial infarction,heart failure,coronary artery revascularization,hospitalization due to angina pectoris and all-cause deaths.The CAC score was calculated based on computed tomography scans.Results The serum COMP level in MHD patients was significantly higher than that in the general population[984.23(248.43-1902.61)ng/mL vs.219.01(97.26-821.92)ng/mL,P<0.01].Serum COMP levels were positively correlated with CAC(r=0.313,P=0.021)and serum parathyroid hormone in MHD patients(r=0.359,P<0.01).Linear regression suggested that after adjusting for age,fasting blood glucose(Glu)and glycosylated hemoglobin(HbAlc),CAC score was an independent predictor in the final model for COMP level(β=0.424,t=3.130,P<0.01).The receiver operating characteristic(ROC)curve showed that COMP≥994 mg/mL had 68.0%sensitivity and 72.4%specificity for the prediction of severe CAC[area under the curve(AUC):0.674,P=0.030,95%CI:0.526-0.882].After a median follow-up of 16 months(8-24 months),there was no difference in the incidence rate of MACEs between the upper,middle and lower serum COMP groups.Conclusions Our study found that MHD patients have higher levels of circulating COMP than controls.The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients.However,there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.展开更多
Background： Dorper is an important breed for meat purpose and widely used in the livestock industry of the world.However, the protein requirement of Dorper crossbred has not been investigated. The current paper repor...Background： Dorper is an important breed for meat purpose and widely used in the livestock industry of the world.However, the protein requirement of Dorper crossbred has not been investigated. The current paper reports the net protein（NP） and metabolizable protein（MP） requirements of Dorper crossbred ram lambs from 20 to 35 kg BW.Methods： Thirty-five Dorper × thin-tailed Han crossbred lambs weaned at approximately 50 d of age（20.3 ± 2.15 kg of BW） were used. Seven lambs of 25 kg BW were slaughtered as the baseline animals at the start of the trial. An intermediate group of seven randomly selected lambs fed ad libitum was slaughtered at 28.6 kg BW. The remaining 21 lambs were randomly divided into three levels of dry matter intake： ad libitum or 70% or 40% of ad libitum intake. Those lambs were slaughtered when the lambs fed ad libitum reached 35 kg BW. Total body N and N retention were measured.Results： The daily NP and MP requirements for maintenance were 1.89 and 4.52 g/kg metabolic shrunk BW（SBW0.75）.The partial efficiency of MP utilization for maintenance was 0.42. The NP requirement for growth ranged from 12.1 to 43.5 g/d, for the lambs gaining 100 to 350 g/d, and the partial efficiency of MP utilization for growth was 0.86.Conclusions： The NP and MP requirements for the maintenance and growth of Dorper crossbred male lambs were lower than the recommendations of American and British nutritional systems.展开更多
During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite ...During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cell identity. This identity is maintained during cell replication in a heritable but DNAindependent manner. The preservation of cell identity is fundamental, especially when cells must undergo changes in response to intrinsic and extrinsic signals. The maintenance proteins, which are required for cell identity preservation, act epigenetically by regulating gene expression through DNA methylation, histone modification, and chromatin remodeling. Among the maintenance proteins, the Trithorax(TrxG) and Polycomb(PcG) group proteins are the best characterized. In this review, we summarize the structures and activities of the TrxG and PcG complexes and describe their pivotal roles in nuclear estrogen receptor activity. In addition, we provide evidence that perturbations in these epigenetic regulators are involved in disrupting epithelial cell identity, mammary gland remodeling, and breast cancer initiation.展开更多
目的:微小染色体维持蛋白4(minichromosome maintenance protein 4,MCM4)是DNA复制起始和延伸阶段的调控因子。本研究旨在探究肺腺癌(lung adenocarcinoma,LUAD)中MCM4的表达与肿瘤微环境(tumor microenvironment,TME)中免疫细胞和分子...目的:微小染色体维持蛋白4(minichromosome maintenance protein 4,MCM4)是DNA复制起始和延伸阶段的调控因子。本研究旨在探究肺腺癌(lung adenocarcinoma,LUAD)中MCM4的表达与肿瘤微环境(tumor microenvironment,TME)中免疫细胞和分子的相关性,以及MCM4预测患者免疫治疗敏感性和预后的能力。方法:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)、基因表达综合(Gene Expression Omnibus,GEO)数据库中下载并筛选LUAD患者的转录组数据和临床数据进行分析。其中TCGA数据集的503例患者为训练集,GEO数据集的857例患者为验证集。采用TIMER(Tumor Immune Estimation Resource)数据库对MCM4在正常组织和肿瘤组织中的表达情况进行分析。将LUAD患者肿瘤样本划分为MCM4低表达组和MCM4高表达组,采用R软件分析LUAD患者MCM4表达与总生存期(overall survival,OS)的关系;采用京都基因与基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)中的基因集进行基因富集分析,筛选与MCM4基因表达相关的生物学过程;采用肿瘤免疫功能障碍与排斥(tumor immune dysfunction and exclusion,TIDE)评分预测患者的免疫治疗的效果;评估LUAD患者TME的免疫评分、基质评分和ESTIMATE(estimation of stromal and immune cells in malignant tumor tissues using expression data)评分,分析MCM4表达与TME中免疫细胞、免疫检查点(immune checkpoint,ICs)之间的关系。收集武汉大学人民医院病理确诊为LUAD的穿刺或者手术切片60张(55张为LUAD的癌组织和癌旁组织,5张为正常肺组织)及临床病理资料,采用免疫组织化学染色法进行临床验证。结果:MCM4基因和蛋白质在肺正常组织和腺癌组织中差异表达。在训练集和验证集中,MCM4低表达组患者的OS均优于MCM4高表达组;MCM4均可以影响LUAD患者的预后;MCM4表达与卵母细胞减数分裂、细胞周期和DNA复制通路显著相关,且MCM4与Ki-67编码基因MKI67和增殖相关基因C1orf112均呈显著正相关;MCM4表达与TIDE评分均呈负相关,与ICs表达呈正相关,说明MCM4的表达可预测患者的免疫治疗效果;与MCM4低表达组比较,MCM4高表达组的肿瘤纯度均较高,基质细胞和免疫细胞比例均较低,且MCM4表达与CD8+T细胞均呈负相关,与Th2、骨髓来源抑制性细胞均呈显著正相关,说明肿瘤组织的MCM4高表达与患者预后不佳相关。泛癌分析结果表明:在33种肿瘤中,大部分肿瘤的MCM4表达与ICs、Th2细胞、调节性T细胞、程序性死亡受体1(programmed death-1,PD-1)、程序性死亡受体配体1(programmed death-ligand 1,PD-L1)的表达及PD-1-PD-L1评分均呈正相关,与CD8^(+)T细胞、NK细胞均呈负相关。临床数据验证结果表明:MCM4在肿瘤组织中的染色强度和阳性细胞占比高于肿瘤间质,肿瘤组织的MCM4表达水平高于正常组织;MCM4评分与Ki-67呈显著正相关。结论:MCM4作为增殖信号影响肺腺癌的免疫浸润和预后,且MCM4高表达与TME内抑制性免疫细胞浸润及免疫治疗获益概率升高相关。展开更多
目的探讨C反应蛋白/白蛋白比值(C-reactive protein to albumin ratio,CAR)与维持性血液透析(maintenance hemodialysis,MHD)患者出现心血管事件风险的相关性。方法选择2016年8月至2019年12月在广州医科大学附属第二医院血液净化中心进...目的探讨C反应蛋白/白蛋白比值(C-reactive protein to albumin ratio,CAR)与维持性血液透析(maintenance hemodialysis,MHD)患者出现心血管事件风险的相关性。方法选择2016年8月至2019年12月在广州医科大学附属第二医院血液净化中心进行治疗的MHD患者为研究对象,随访截止时间为2021年3月31日。收集符合研究纳入标准的患者的人口学资料、合并症、原发病因、规律透析治疗3个月后的生化指标及随访截止时间内心血管事件发生情况。采用Kaplan-Meier法估计MHD患者出现心血管事件的概率。基于广义倾向性得分加权(GPSW)的Cox比例风险回归模型评估CAR水平与MHD患者出现心血管事件风险的关联。结果共纳入符合标准的研究对象170例,其中64例患者出现心血管事件(占37.6%)。基于GPSW的Cox比例风险回归模型提示(HR_(CAR)=2.087,95%CI:1.085~4.015,P=0.028),说明MHD患者的CAR平均每增加一个单位,出现心血管事件的风险比为2.087。结论CAR与MHD患者的心血管事件风险存在显著的正相关关系,这将有助于临床工作者识别具有高心血管事件风险的MHD患者并及时干预。展开更多
基金supported by the National Natural Science Foundation of China(81400262)the Backbone Fund of Peking University Third Hospital(Y72497-04)
文摘Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(COMP),as a component of the vascular matrix,has been found to be an inhibitor of arterial calcification in basic studies.However,there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis(MHD)patients.The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients.Methods Serum COMP levels were compared between 54 MHD patients and 66 healthy people.MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events(MACEs),which were defined as a combined end point of new onset angina pectoris,nonfatal myocardial infarction,heart failure,coronary artery revascularization,hospitalization due to angina pectoris and all-cause deaths.The CAC score was calculated based on computed tomography scans.Results The serum COMP level in MHD patients was significantly higher than that in the general population[984.23(248.43-1902.61)ng/mL vs.219.01(97.26-821.92)ng/mL,P<0.01].Serum COMP levels were positively correlated with CAC(r=0.313,P=0.021)and serum parathyroid hormone in MHD patients(r=0.359,P<0.01).Linear regression suggested that after adjusting for age,fasting blood glucose(Glu)and glycosylated hemoglobin(HbAlc),CAC score was an independent predictor in the final model for COMP level(β=0.424,t=3.130,P<0.01).The receiver operating characteristic(ROC)curve showed that COMP≥994 mg/mL had 68.0%sensitivity and 72.4%specificity for the prediction of severe CAC[area under the curve(AUC):0.674,P=0.030,95%CI:0.526-0.882].After a median follow-up of 16 months(8-24 months),there was no difference in the incidence rate of MACEs between the upper,middle and lower serum COMP groups.Conclusions Our study found that MHD patients have higher levels of circulating COMP than controls.The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients.However,there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.
基金supported by the earmarked fund for the China Agriculture Research System(CARS-39)
文摘Background： Dorper is an important breed for meat purpose and widely used in the livestock industry of the world.However, the protein requirement of Dorper crossbred has not been investigated. The current paper reports the net protein（NP） and metabolizable protein（MP） requirements of Dorper crossbred ram lambs from 20 to 35 kg BW.Methods： Thirty-five Dorper × thin-tailed Han crossbred lambs weaned at approximately 50 d of age（20.3 ± 2.15 kg of BW） were used. Seven lambs of 25 kg BW were slaughtered as the baseline animals at the start of the trial. An intermediate group of seven randomly selected lambs fed ad libitum was slaughtered at 28.6 kg BW. The remaining 21 lambs were randomly divided into three levels of dry matter intake： ad libitum or 70% or 40% of ad libitum intake. Those lambs were slaughtered when the lambs fed ad libitum reached 35 kg BW. Total body N and N retention were measured.Results： The daily NP and MP requirements for maintenance were 1.89 and 4.52 g/kg metabolic shrunk BW（SBW0.75）.The partial efficiency of MP utilization for maintenance was 0.42. The NP requirement for growth ranged from 12.1 to 43.5 g/d, for the lambs gaining 100 to 350 g/d, and the partial efficiency of MP utilization for growth was 0.86.Conclusions： The NP and MP requirements for the maintenance and growth of Dorper crossbred male lambs were lower than the recommendations of American and British nutritional systems.
文摘During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cell identity. This identity is maintained during cell replication in a heritable but DNAindependent manner. The preservation of cell identity is fundamental, especially when cells must undergo changes in response to intrinsic and extrinsic signals. The maintenance proteins, which are required for cell identity preservation, act epigenetically by regulating gene expression through DNA methylation, histone modification, and chromatin remodeling. Among the maintenance proteins, the Trithorax(TrxG) and Polycomb(PcG) group proteins are the best characterized. In this review, we summarize the structures and activities of the TrxG and PcG complexes and describe their pivotal roles in nuclear estrogen receptor activity. In addition, we provide evidence that perturbations in these epigenetic regulators are involved in disrupting epithelial cell identity, mammary gland remodeling, and breast cancer initiation.
文摘目的:微小染色体维持蛋白4(minichromosome maintenance protein 4,MCM4)是DNA复制起始和延伸阶段的调控因子。本研究旨在探究肺腺癌(lung adenocarcinoma,LUAD)中MCM4的表达与肿瘤微环境(tumor microenvironment,TME)中免疫细胞和分子的相关性,以及MCM4预测患者免疫治疗敏感性和预后的能力。方法:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)、基因表达综合(Gene Expression Omnibus,GEO)数据库中下载并筛选LUAD患者的转录组数据和临床数据进行分析。其中TCGA数据集的503例患者为训练集,GEO数据集的857例患者为验证集。采用TIMER(Tumor Immune Estimation Resource)数据库对MCM4在正常组织和肿瘤组织中的表达情况进行分析。将LUAD患者肿瘤样本划分为MCM4低表达组和MCM4高表达组,采用R软件分析LUAD患者MCM4表达与总生存期(overall survival,OS)的关系;采用京都基因与基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)中的基因集进行基因富集分析,筛选与MCM4基因表达相关的生物学过程;采用肿瘤免疫功能障碍与排斥(tumor immune dysfunction and exclusion,TIDE)评分预测患者的免疫治疗的效果;评估LUAD患者TME的免疫评分、基质评分和ESTIMATE(estimation of stromal and immune cells in malignant tumor tissues using expression data)评分,分析MCM4表达与TME中免疫细胞、免疫检查点(immune checkpoint,ICs)之间的关系。收集武汉大学人民医院病理确诊为LUAD的穿刺或者手术切片60张(55张为LUAD的癌组织和癌旁组织,5张为正常肺组织)及临床病理资料,采用免疫组织化学染色法进行临床验证。结果:MCM4基因和蛋白质在肺正常组织和腺癌组织中差异表达。在训练集和验证集中,MCM4低表达组患者的OS均优于MCM4高表达组;MCM4均可以影响LUAD患者的预后;MCM4表达与卵母细胞减数分裂、细胞周期和DNA复制通路显著相关,且MCM4与Ki-67编码基因MKI67和增殖相关基因C1orf112均呈显著正相关;MCM4表达与TIDE评分均呈负相关,与ICs表达呈正相关,说明MCM4的表达可预测患者的免疫治疗效果;与MCM4低表达组比较,MCM4高表达组的肿瘤纯度均较高,基质细胞和免疫细胞比例均较低,且MCM4表达与CD8+T细胞均呈负相关,与Th2、骨髓来源抑制性细胞均呈显著正相关,说明肿瘤组织的MCM4高表达与患者预后不佳相关。泛癌分析结果表明:在33种肿瘤中,大部分肿瘤的MCM4表达与ICs、Th2细胞、调节性T细胞、程序性死亡受体1(programmed death-1,PD-1)、程序性死亡受体配体1(programmed death-ligand 1,PD-L1)的表达及PD-1-PD-L1评分均呈正相关,与CD8^(+)T细胞、NK细胞均呈负相关。临床数据验证结果表明:MCM4在肿瘤组织中的染色强度和阳性细胞占比高于肿瘤间质,肿瘤组织的MCM4表达水平高于正常组织;MCM4评分与Ki-67呈显著正相关。结论:MCM4作为增殖信号影响肺腺癌的免疫浸润和预后,且MCM4高表达与TME内抑制性免疫细胞浸润及免疫治疗获益概率升高相关。
文摘目的探讨C反应蛋白/白蛋白比值(C-reactive protein to albumin ratio,CAR)与维持性血液透析(maintenance hemodialysis,MHD)患者出现心血管事件风险的相关性。方法选择2016年8月至2019年12月在广州医科大学附属第二医院血液净化中心进行治疗的MHD患者为研究对象,随访截止时间为2021年3月31日。收集符合研究纳入标准的患者的人口学资料、合并症、原发病因、规律透析治疗3个月后的生化指标及随访截止时间内心血管事件发生情况。采用Kaplan-Meier法估计MHD患者出现心血管事件的概率。基于广义倾向性得分加权(GPSW)的Cox比例风险回归模型评估CAR水平与MHD患者出现心血管事件风险的关联。结果共纳入符合标准的研究对象170例,其中64例患者出现心血管事件(占37.6%)。基于GPSW的Cox比例风险回归模型提示(HR_(CAR)=2.087,95%CI:1.085~4.015,P=0.028),说明MHD患者的CAR平均每增加一个单位,出现心血管事件的风险比为2.087。结论CAR与MHD患者的心血管事件风险存在显著的正相关关系,这将有助于临床工作者识别具有高心血管事件风险的MHD患者并及时干预。
