目的免疫检查点基因是调控结肠癌患者免疫应答的关键机制,并对结肠癌患者的预后、治疗具有潜在的临床应用价值,然而目前尚无基于免疫检查点基因的预后模型来预测结肠癌患者的预后和免疫状态。方法从肿瘤基因组图谱(The Cancer Genome At...目的免疫检查点基因是调控结肠癌患者免疫应答的关键机制,并对结肠癌患者的预后、治疗具有潜在的临床应用价值,然而目前尚无基于免疫检查点基因的预后模型来预测结肠癌患者的预后和免疫状态。方法从肿瘤基因组图谱(The Cancer Genome Atlas,TCGA)和高通量基因表达(Gene Expression Omnibus,GEO)公共数据库获取并整理结肠癌患者的基因表达谱数据及其对应的临床信息,鉴定差异表达的免疫检查点基因。采用最小绝对收缩和选择算子(least absolute shrinkage and selection operator,LASSO)Cox回归分析构建免疫检查点基因相关的TCGA结肠癌患者预后模型。应用GEO结肠癌患者队列(GSE143985)进行验证。Kaplan⁃Meier曲线和受试者操作特征(receiver operating characteristic,ROC)曲线用于评估模型预测准确性。Spearman相关性分析观察预后模型与免疫细胞浸润情况。单因素和多因素回归分析免疫检查点风险基因及临床指标,并基于多因素回归结果构建临床列线图。结果在正常和结肠癌组织中共筛选出29个差异表达的免疫检查点相关基因,LASSO回归分析后构建了基于14个免疫检查点相关基因的预后模型。根据中位风险评分将TCGA结肠癌患者分为高、低危险组,Kaplan⁃Meier生存分析显示,相较于低危组,高危组患者的生存较差。ROC分析则显示TCGA训练队列的1年、3年预测曲线下面积(area under the curve,AUC)值均大于0.7,而GEO验证队列的1年、3年预测AUC值均大于0.8,显示了模型较高的准确性和稳定性。免疫细胞浸润分析显示风险评分与CD4+T细胞和CD8+T细胞有显著相关性。此外,基于免疫检查点风险基因及临床指标构建的列线图C⁃指数为0.767,显示了较高的临床应用价值。结论我们构建了一种新的免疫检查点基因相关的结肠癌预后模型,可用于结肠癌的预后及免疫状态预测,为结肠癌患者的临床预后提供一定的指导依据。展开更多
The effects of instilled silica have been studied on the serum-phospholipid (PL), lipid peroxide (LPO) and histopathology of rat lung up to 140 days from the first day of instillation. Silica induced relatively higher...The effects of instilled silica have been studied on the serum-phospholipid (PL), lipid peroxide (LPO) and histopathology of rat lung up to 140 days from the first day of instillation. Silica induced relatively higher serum-PL throughout the experiment. The level of LPO also increased appreciably. They presented positive linear correlation. The early lesion was acute alveolitis with silica particles. These lesions became silicotic nodules on the 30th day, which then were enlarged gradually and fused by fibrosis. Alveolar macrophages (AM) were activated and surface structure was damaged. These results indicate that instilled sillca can induce lipid peroxidation of cell membrane and selective accumulation of lung PL展开更多
Liver dysfunction was associated with poor outcomes in patients with ST-segment elevation myocardial infarction(STEMI).However,the optimal methods for assessing the liver function was unclear.This study was to compare...Liver dysfunction was associated with poor outcomes in patients with ST-segment elevation myocardial infarction(STEMI).However,the optimal methods for assessing the liver function was unclear.This study was to compare the predictive value of the different liver function assessment tools for in-hospital and oneyear adverse events in STEMI patients undergoing percutaneous coronary intervention(PCI).Methods A total of 1157 patients with STEMI undergoing PCI were enrolled from January 2012 to December 2015.The model for end-stage liver disease excluding international normalized ratio(MELD-XI)and albumin-bilirubin(ALBI)score were calculated at admission.The discrimination and calibration of these two scores for in-hospital and oneyear adverse events were compared.Results The in-hospital mortality was 4.0%.Both MELD-XI[area under the curve(AUC)=0.768,95%confidence interval(CI):0.691-0.845,P<0.001]and ALBI score(AUC=0.682,95%CI:0.602-0.761,P<0.001)had excellent discrimination for in-hospital death.The calibration for in-hospital death was good in MELD-XI(Hosmer-Lemeshow chi-square=7.2,P=0.520),but not good in ALBI score(Hosmer-Lemeshow chi-square=13.8,P=0.087).In addition,the predictive power of MELD-XI for in-hospital death was better than ALBI score(AUC:0.768 vs.0.682,P=0.037).1108(95.8%)patients completed one-year followup.Kaplan-Meier analysis showed that patients with a high MELD-XI score had high-risk of one-year mortality(Log-rank test:54.8,P<0.001).Conclusions As the method for assessing the liver function,MELD-XI was better than ALBI score in predicting the in-hospital and one-year adverse events in STEMI patients,which could be considered as a risk assessment tool.展开更多
文摘目的免疫检查点基因是调控结肠癌患者免疫应答的关键机制,并对结肠癌患者的预后、治疗具有潜在的临床应用价值,然而目前尚无基于免疫检查点基因的预后模型来预测结肠癌患者的预后和免疫状态。方法从肿瘤基因组图谱(The Cancer Genome Atlas,TCGA)和高通量基因表达(Gene Expression Omnibus,GEO)公共数据库获取并整理结肠癌患者的基因表达谱数据及其对应的临床信息,鉴定差异表达的免疫检查点基因。采用最小绝对收缩和选择算子(least absolute shrinkage and selection operator,LASSO)Cox回归分析构建免疫检查点基因相关的TCGA结肠癌患者预后模型。应用GEO结肠癌患者队列(GSE143985)进行验证。Kaplan⁃Meier曲线和受试者操作特征(receiver operating characteristic,ROC)曲线用于评估模型预测准确性。Spearman相关性分析观察预后模型与免疫细胞浸润情况。单因素和多因素回归分析免疫检查点风险基因及临床指标,并基于多因素回归结果构建临床列线图。结果在正常和结肠癌组织中共筛选出29个差异表达的免疫检查点相关基因,LASSO回归分析后构建了基于14个免疫检查点相关基因的预后模型。根据中位风险评分将TCGA结肠癌患者分为高、低危险组,Kaplan⁃Meier生存分析显示,相较于低危组,高危组患者的生存较差。ROC分析则显示TCGA训练队列的1年、3年预测曲线下面积(area under the curve,AUC)值均大于0.7,而GEO验证队列的1年、3年预测AUC值均大于0.8,显示了模型较高的准确性和稳定性。免疫细胞浸润分析显示风险评分与CD4+T细胞和CD8+T细胞有显著相关性。此外,基于免疫检查点风险基因及临床指标构建的列线图C⁃指数为0.767,显示了较高的临床应用价值。结论我们构建了一种新的免疫检查点基因相关的结肠癌预后模型,可用于结肠癌的预后及免疫状态预测,为结肠癌患者的临床预后提供一定的指导依据。
文摘The effects of instilled silica have been studied on the serum-phospholipid (PL), lipid peroxide (LPO) and histopathology of rat lung up to 140 days from the first day of instillation. Silica induced relatively higher serum-PL throughout the experiment. The level of LPO also increased appreciably. They presented positive linear correlation. The early lesion was acute alveolitis with silica particles. These lesions became silicotic nodules on the 30th day, which then were enlarged gradually and fused by fibrosis. Alveolar macrophages (AM) were activated and surface structure was damaged. These results indicate that instilled sillca can induce lipid peroxidation of cell membrane and selective accumulation of lung PL
基金supported by grants from Science and Technology Projects of Guangzhou(No.201903010097)。
文摘Liver dysfunction was associated with poor outcomes in patients with ST-segment elevation myocardial infarction(STEMI).However,the optimal methods for assessing the liver function was unclear.This study was to compare the predictive value of the different liver function assessment tools for in-hospital and oneyear adverse events in STEMI patients undergoing percutaneous coronary intervention(PCI).Methods A total of 1157 patients with STEMI undergoing PCI were enrolled from January 2012 to December 2015.The model for end-stage liver disease excluding international normalized ratio(MELD-XI)and albumin-bilirubin(ALBI)score were calculated at admission.The discrimination and calibration of these two scores for in-hospital and oneyear adverse events were compared.Results The in-hospital mortality was 4.0%.Both MELD-XI[area under the curve(AUC)=0.768,95%confidence interval(CI):0.691-0.845,P<0.001]and ALBI score(AUC=0.682,95%CI:0.602-0.761,P<0.001)had excellent discrimination for in-hospital death.The calibration for in-hospital death was good in MELD-XI(Hosmer-Lemeshow chi-square=7.2,P=0.520),but not good in ALBI score(Hosmer-Lemeshow chi-square=13.8,P=0.087).In addition,the predictive power of MELD-XI for in-hospital death was better than ALBI score(AUC:0.768 vs.0.682,P=0.037).1108(95.8%)patients completed one-year followup.Kaplan-Meier analysis showed that patients with a high MELD-XI score had high-risk of one-year mortality(Log-rank test:54.8,P<0.001).Conclusions As the method for assessing the liver function,MELD-XI was better than ALBI score in predicting the in-hospital and one-year adverse events in STEMI patients,which could be considered as a risk assessment tool.
