Undruggable targets typically refer to a class of therapeutic targets that are difficult to target through conventional methods or have not yet been targeted,but are of great clinical significance.According to statist...Undruggable targets typically refer to a class of therapeutic targets that are difficult to target through conventional methods or have not yet been targeted,but are of great clinical significance.According to statistics,over 80%of disease-related pathogenic proteins cannot be targeted by current conventional treatment methods.In recent years,with the advancement of basic research and new technologies,the development of various new technologies and mechanisms has brought new perspectives to overcome challenging drug targets.Among them,targeted protein degradation technology is a breakthrough drug development strategy for challenging drug targets.This technology can specifically identify target proteins and directly degrade pathogenic target proteins by utilizing the inherent protein degradation pathways within cells.This new form of drug development includes various types such as proteolysis targeting chimera(PROTAC),molecular glue,lysosome-targeting Chimaera(LYTAC),autophagosometethering compound(ATTEC),autophagy-targeting chimera(AUTAC),autophagy-targeting chimera(AUTOTAC),degrader-antibody conjugate(DAC).This article systematically summarizes the application of targeted protein degradation technology in the development of degraders for challenging drug targets.Finally,the article looks forward to the future development direction and application prospects of targeted protein degradation technology.展开更多
目的磁共振成像(magnetic resonance imaging,MRI)临床应用广泛,但国内没有相应的临床效果评价标准,本研究通过Logistic回归模型建立一套标准化的临床效果评价标准,从而促进MR产业健康发展。材料与方法临床收集165张MR图像,评价每张图...目的磁共振成像(magnetic resonance imaging,MRI)临床应用广泛,但国内没有相应的临床效果评价标准,本研究通过Logistic回归模型建立一套标准化的临床效果评价标准,从而促进MR产业健康发展。材料与方法临床收集165张MR图像,评价每张图像中影响腰椎患者T2抑脂序列MRI质量的10个指标及MRI质量,通过Logistic回归科学建模,并采用H-L卡方检验和受试者工作特征曲线下面积(the area under the receiver-operating characteristic curve,AUC)检验模型的标定能力和区分能力。结果模型显示当总分低于3分时,MRI质量好的最高概率为0.02,认为MRI质量较差,不能应用于临床诊断,建议患者需重新拍摄MR图像;当总分在5~6分时,对应概率为0.22~0.52,认为MRI质量一般,勉强应用于临床诊断;当总分在8~9时,对应概率为0.94~0.98,认为MRI质量非常好,可很好地应用于临床诊断。H-L χ~2值为1.457(P=0.962),AUC为0.878(95%CI:0.814~0.941)。结论基于Logistic回归建立的MRI临床效果评价模型,具有很好的标定能力和区分能力,可很好地应用于临床。展开更多
基金supported by the National Natural Science Foundation of China(U22A20328 and 22074043)Science and Technology Commission of Shanghai Municipality(20430711800 and23ZR1475000)Lingang Laboratory(LG-QS-202206-04)。
基金supported by the National Key R&D Program of China(2021YFA1300200,2021YFA1302100 and 2020YFE0202200)the National Natural Science Foundation of China(82125034,82330115)。
文摘Undruggable targets typically refer to a class of therapeutic targets that are difficult to target through conventional methods or have not yet been targeted,but are of great clinical significance.According to statistics,over 80%of disease-related pathogenic proteins cannot be targeted by current conventional treatment methods.In recent years,with the advancement of basic research and new technologies,the development of various new technologies and mechanisms has brought new perspectives to overcome challenging drug targets.Among them,targeted protein degradation technology is a breakthrough drug development strategy for challenging drug targets.This technology can specifically identify target proteins and directly degrade pathogenic target proteins by utilizing the inherent protein degradation pathways within cells.This new form of drug development includes various types such as proteolysis targeting chimera(PROTAC),molecular glue,lysosome-targeting Chimaera(LYTAC),autophagosometethering compound(ATTEC),autophagy-targeting chimera(AUTAC),autophagy-targeting chimera(AUTOTAC),degrader-antibody conjugate(DAC).This article systematically summarizes the application of targeted protein degradation technology in the development of degraders for challenging drug targets.Finally,the article looks forward to the future development direction and application prospects of targeted protein degradation technology.
文摘目的磁共振成像(magnetic resonance imaging,MRI)临床应用广泛,但国内没有相应的临床效果评价标准,本研究通过Logistic回归模型建立一套标准化的临床效果评价标准,从而促进MR产业健康发展。材料与方法临床收集165张MR图像,评价每张图像中影响腰椎患者T2抑脂序列MRI质量的10个指标及MRI质量,通过Logistic回归科学建模,并采用H-L卡方检验和受试者工作特征曲线下面积(the area under the receiver-operating characteristic curve,AUC)检验模型的标定能力和区分能力。结果模型显示当总分低于3分时,MRI质量好的最高概率为0.02,认为MRI质量较差,不能应用于临床诊断,建议患者需重新拍摄MR图像;当总分在5~6分时,对应概率为0.22~0.52,认为MRI质量一般,勉强应用于临床诊断;当总分在8~9时,对应概率为0.94~0.98,认为MRI质量非常好,可很好地应用于临床诊断。H-L χ~2值为1.457(P=0.962),AUC为0.878(95%CI:0.814~0.941)。结论基于Logistic回归建立的MRI临床效果评价模型,具有很好的标定能力和区分能力,可很好地应用于临床。
