Inhibition of guanosine triphosphate（GTP） and cytidine triphosphate（CTP） biosynthetic pathways induces cells to assemble rod/ring（RR） structures,also named cytoophidia,which consist of the enzymes cytidine triph...Inhibition of guanosine triphosphate（GTP） and cytidine triphosphate（CTP） biosynthetic pathways induces cells to assemble rod/ring（RR） structures,also named cytoophidia,which consist of the enzymes cytidine triphosphate synthase（CTPS） and inosine-50-monophosphate dehydrogenase 2（IMPDH2）.We aim to explore the interaction of CTPS and IMPDH2 in the generation of RR structures.He La and COS-7 cells were cultured in normal conditions or in the presence of 6-diazo-5-oxo-L-norleucine（DON）,ribavirin,or mycophenolic acid（MPA）.Over 90% of DON-treated cells presented RR structures.In He La cells,35% of the RR structures were positive for IMPDH2 alone,26% were CTPS alone,and 31% were IMPDH2/CTPS mixed,while in COS-7 cells,42% of RR were IMPDH2 alone,41% were CTPS alone,and 10% were IMPDH2/CTPS mixed.Ribavirin and MPA treatments induced only IMPDH2-based RR.Cells were also transfected with an N-terminal hemagglutinin（NHA）-tagged CTPS1 construct.Over 95% of NHA-CTPS1 transfected cells with DON treatment presented IMPDH2-based RR and almost 100% presented CTPS1-based RR;when treated with ribavirin,over 94% of transfected cells presented IMPDH2-based RR and 37% presented CTPS1-based RR,whereas 2% of untreated transfected cells presented IMPDH2-based RR and 28% presented CTPS1-based RR.These results may help in understanding the relationship between CTP and GTP biosynthetic pathways,especially concerning the formation of filamentous RR structures.展开更多
目的构建并验证基于CT及灌注特征的分级预测模型,评估其对急性缺血性卒中血管内治疗后神经功能改善的预测价值。方法回顾性分析2019年1月至2024年3月重庆医科大学附属永川医院收治的183例接受机械取栓治疗的缺血性卒中患者的临床资料。...目的构建并验证基于CT及灌注特征的分级预测模型,评估其对急性缺血性卒中血管内治疗后神经功能改善的预测价值。方法回顾性分析2019年1月至2024年3月重庆医科大学附属永川医院收治的183例接受机械取栓治疗的缺血性卒中患者的临床资料。根据6个月mRS评分将患者分为未改善组(n=44)和改善组(n=139)。收集临床资料、CT平扫及CTP参数,构建6个创新性综合指标,包括早期神经功能严重程度指数(ENSI)、灌注-核心不匹配指数(PCMI)等。采用分级建模策略构建基础模型(临床变量)、增强模型(+CT形态学)和综合模型(+CTP及创新性变量),通过受试者工作特征(ROC)曲线、净重分类改善指数(NRI)和综合判别改善指数(IDI)评估模型性能。结果未改善组患者的基线NIHSS评分[(18.45±5.68)分vs(12.41±5.70)分]、血糖水平[(8.76±4.68)mmol/L vs(6.70±2.25)mmol/L]和核心梗死体积[20.28(1.92~67.59)mL vs 3.68(0.86~11.80)mL]均明显高于改善组,差异均有统计学意义(P<0.01)。多因素分析结果显示,基线NIHSS(OR=1.231,P<0.001)、血糖(OR=1.285,P=0.001)、核心梗死体积(OR=1.016,P=0.037)和ENSI(OR=0.831,P=0.006)是独立预测因子。综合模型AUC值(0.855)优于增强模型(0.830)和基础模型(0.825)。相对于增强模型,综合模型NRI达0.677,IDI为0.091。结论整合CTP参数和创新性综合指标的分级预测模型可有效预测缺血性卒中血管内治疗后神经功能改善。ENSI作为独立预测因子,计算简便,具有良好的临床应用前景。展开更多
基金supported by the Brazilian Government Research Foundation CAPES (Coordination for the Improvement of Higher Education Personnel,No.9028-11-0)the Sao Paulo State Research Foundation (Sao Paulo Government agency FAPESP,No.2011/12448-0)both granted to LECA and GDK,and by the research grant from Brazilian Government Agency CNPq (No.305064/2011-8) to LECA
文摘Inhibition of guanosine triphosphate（GTP） and cytidine triphosphate（CTP） biosynthetic pathways induces cells to assemble rod/ring（RR） structures,also named cytoophidia,which consist of the enzymes cytidine triphosphate synthase（CTPS） and inosine-50-monophosphate dehydrogenase 2（IMPDH2）.We aim to explore the interaction of CTPS and IMPDH2 in the generation of RR structures.He La and COS-7 cells were cultured in normal conditions or in the presence of 6-diazo-5-oxo-L-norleucine（DON）,ribavirin,or mycophenolic acid（MPA）.Over 90% of DON-treated cells presented RR structures.In He La cells,35% of the RR structures were positive for IMPDH2 alone,26% were CTPS alone,and 31% were IMPDH2/CTPS mixed,while in COS-7 cells,42% of RR were IMPDH2 alone,41% were CTPS alone,and 10% were IMPDH2/CTPS mixed.Ribavirin and MPA treatments induced only IMPDH2-based RR.Cells were also transfected with an N-terminal hemagglutinin（NHA）-tagged CTPS1 construct.Over 95% of NHA-CTPS1 transfected cells with DON treatment presented IMPDH2-based RR and almost 100% presented CTPS1-based RR;when treated with ribavirin,over 94% of transfected cells presented IMPDH2-based RR and 37% presented CTPS1-based RR,whereas 2% of untreated transfected cells presented IMPDH2-based RR and 28% presented CTPS1-based RR.These results may help in understanding the relationship between CTP and GTP biosynthetic pathways,especially concerning the formation of filamentous RR structures.
文摘目的构建并验证基于CT及灌注特征的分级预测模型,评估其对急性缺血性卒中血管内治疗后神经功能改善的预测价值。方法回顾性分析2019年1月至2024年3月重庆医科大学附属永川医院收治的183例接受机械取栓治疗的缺血性卒中患者的临床资料。根据6个月mRS评分将患者分为未改善组(n=44)和改善组(n=139)。收集临床资料、CT平扫及CTP参数,构建6个创新性综合指标,包括早期神经功能严重程度指数(ENSI)、灌注-核心不匹配指数(PCMI)等。采用分级建模策略构建基础模型(临床变量)、增强模型(+CT形态学)和综合模型(+CTP及创新性变量),通过受试者工作特征(ROC)曲线、净重分类改善指数(NRI)和综合判别改善指数(IDI)评估模型性能。结果未改善组患者的基线NIHSS评分[(18.45±5.68)分vs(12.41±5.70)分]、血糖水平[(8.76±4.68)mmol/L vs(6.70±2.25)mmol/L]和核心梗死体积[20.28(1.92~67.59)mL vs 3.68(0.86~11.80)mL]均明显高于改善组,差异均有统计学意义(P<0.01)。多因素分析结果显示,基线NIHSS(OR=1.231,P<0.001)、血糖(OR=1.285,P=0.001)、核心梗死体积(OR=1.016,P=0.037)和ENSI(OR=0.831,P=0.006)是独立预测因子。综合模型AUC值(0.855)优于增强模型(0.830)和基础模型(0.825)。相对于增强模型,综合模型NRI达0.677,IDI为0.091。结论整合CTP参数和创新性综合指标的分级预测模型可有效预测缺血性卒中血管内治疗后神经功能改善。ENSI作为独立预测因子,计算简便,具有良好的临床应用前景。
