骨髓增生异常肿瘤(myelodysplastic neoplasms,MDS)患者的预后与其细胞遗传学和分子遗传学特征密切相关,TP53基因作为MDS最常见的突变基因之一,其异常是MDS独立的不良预后因素以及向急性髓系白血病(acute myeloid leuke⁃mia,AML)转化的...骨髓增生异常肿瘤(myelodysplastic neoplasms,MDS)患者的预后与其细胞遗传学和分子遗传学特征密切相关,TP53基因作为MDS最常见的突变基因之一,其异常是MDS独立的不良预后因素以及向急性髓系白血病(acute myeloid leuke⁃mia,AML)转化的危险因素之一。新近更新的第5版世界卫生组织血液淋巴肿瘤分类标准(the 5th edition of the who classifica⁃tion of haematolymphoid tumours,WHO 2022)以及髓系肿瘤和急性白血病的国际共识分类(international consensus classification of myeloid neoplasms and acute leukemia,ICC)将伴有TP53双等位基因失活(biallelic TP53 inactivation,biTP53)的MDS作为独立的亚型列出,该亚型患者预后极差,生存期极短。目前针对伴TP53基因异常的MDS患者的治疗尚未能有效改善该类患者预后,新型靶向药物、免疫治疗等均在探索中,本文就国内外对伴TP53基因异常的MDS的临床研究进展进行综述。展开更多
目的:探讨TP53突变和缺失对弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma, DLBCL)患者预后的影响。方法:收集我院2017至2020年94例初发DLBCL患者的石蜡病理组织,应用免疫组化及二代测序检测TP53突变,FISH技术检测TP53缺失,分析TP5...目的:探讨TP53突变和缺失对弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma, DLBCL)患者预后的影响。方法:收集我院2017至2020年94例初发DLBCL患者的石蜡病理组织,应用免疫组化及二代测序检测TP53突变,FISH技术检测TP53缺失,分析TP53突变、缺失与临床病理及分子分型的相关性,以及对生存的影响。应用COX回归分析DLBCL的生存影响因素。结果:27.7%(26/94)患者过表达p53,23.5%(19/81)患者存在TP53突变,16.0%(15/94)患者TP53缺失,结外受累(P=0.027)、MUM-1(P=0.04)及p53蛋白(P<0.01)表达在在TP53突变和/或缺失及TP53正常两组中存在明显差异。生存分析显示,“双阳性(TP53突变合并缺失)”组生存最差,“双阴性(无TP53突变及缺失)”组预后最好,TP53突变或缺失则次之,其中单突变与单缺失两组总生存无明显统计学差异(P=0.689),其余各组之间生存有显著差异(P<0.05)。GCB中,TP53突变组预后较差(P=0.046)。多因素分析显示合并B症状、TP53异常及双表达是影响DLBCL生存的独立危险因素。结论:TP53突变或缺失,特别是同时合并突变和缺失是DLBCL的不良预后因素,在新的分子分型中,其预后意义仍值得进一步的深入研究。展开更多
The Tibetan Plateau(TP)region,also known as the“Asian water tower”,provides a vital water resource for downstream regions.Previous studies of water cycle changes over the TP have been conducted with climate models o...The Tibetan Plateau(TP)region,also known as the“Asian water tower”,provides a vital water resource for downstream regions.Previous studies of water cycle changes over the TP have been conducted with climate models of coarse resolution in which deep convection must be parameterized.In this study,we present results from a first set of highresolution climate change simulations that permit convection at approximately 3.3-km grid spacing,with a focus on the TP,using the Icosahedral Nonhydrostatic Weather and Climate Model(ICON).Two 12-year simulations were performed,consisting of a retrospective simulation(2008–20)with initial and boundary conditions from ERA5 reanalysis and a pseudoglobal warming projection driven by modified reanalysis-derived initial and boundary conditions by adding the monthly CMIP6 ensemble-mean climate change under the SSP5-8.5 scenario.The retrospective simulation shows overall good performance in capturing the seasonal precipitation and surface air temperature.Over the central and eastern TP,the average biases in precipitation(temperature)are less than−0.34 mm d−1(−1.1℃)throughout the year.The simulated biases over the TP are height-dependent.Cold(wet)biases are found in summer(winter)above 5500 m.The future climate simulation suggests that the TP will be wetter and warmer under the SSP5-8.5 scenario.The general features of projected changes in ICON are comparable to the CMIP6 ensemble projection,but the added value from kilometer-scale modeling is evident in both precipitation and temperature projections over complex topographic regions.These ICON-downscaled climate change simulations provide a high-resolution dataset to the community for the study of regional climate changes and impacts over the TP.展开更多
文摘骨髓增生异常肿瘤(myelodysplastic neoplasms,MDS)患者的预后与其细胞遗传学和分子遗传学特征密切相关,TP53基因作为MDS最常见的突变基因之一,其异常是MDS独立的不良预后因素以及向急性髓系白血病(acute myeloid leuke⁃mia,AML)转化的危险因素之一。新近更新的第5版世界卫生组织血液淋巴肿瘤分类标准(the 5th edition of the who classifica⁃tion of haematolymphoid tumours,WHO 2022)以及髓系肿瘤和急性白血病的国际共识分类(international consensus classification of myeloid neoplasms and acute leukemia,ICC)将伴有TP53双等位基因失活(biallelic TP53 inactivation,biTP53)的MDS作为独立的亚型列出,该亚型患者预后极差,生存期极短。目前针对伴TP53基因异常的MDS患者的治疗尚未能有效改善该类患者预后,新型靶向药物、免疫治疗等均在探索中,本文就国内外对伴TP53基因异常的MDS的临床研究进展进行综述。
文摘目的:探讨TP53突变和缺失对弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma, DLBCL)患者预后的影响。方法:收集我院2017至2020年94例初发DLBCL患者的石蜡病理组织,应用免疫组化及二代测序检测TP53突变,FISH技术检测TP53缺失,分析TP53突变、缺失与临床病理及分子分型的相关性,以及对生存的影响。应用COX回归分析DLBCL的生存影响因素。结果:27.7%(26/94)患者过表达p53,23.5%(19/81)患者存在TP53突变,16.0%(15/94)患者TP53缺失,结外受累(P=0.027)、MUM-1(P=0.04)及p53蛋白(P<0.01)表达在在TP53突变和/或缺失及TP53正常两组中存在明显差异。生存分析显示,“双阳性(TP53突变合并缺失)”组生存最差,“双阴性(无TP53突变及缺失)”组预后最好,TP53突变或缺失则次之,其中单突变与单缺失两组总生存无明显统计学差异(P=0.689),其余各组之间生存有显著差异(P<0.05)。GCB中,TP53突变组预后较差(P=0.046)。多因素分析显示合并B症状、TP53异常及双表达是影响DLBCL生存的独立危险因素。结论:TP53突变或缺失,特别是同时合并突变和缺失是DLBCL的不良预后因素,在新的分子分型中,其预后意义仍值得进一步的深入研究。
基金jointly supported by the National Key Research and Development Program of China (Grant No. 2022YFF0802004)the National Natural Science Foundation of China (Grant Nos. 41988101 and 42275182)+2 种基金the K.C. Wang Education Foundation (Grant No. GJTD-2019-05)the Jiangsu Collaborative Innovation Center for Climate Changethe National Key Scientific and Technological Infrastructure project “Earth System Science Numerical Simulator Facility” (Earth Lab)
文摘The Tibetan Plateau(TP)region,also known as the“Asian water tower”,provides a vital water resource for downstream regions.Previous studies of water cycle changes over the TP have been conducted with climate models of coarse resolution in which deep convection must be parameterized.In this study,we present results from a first set of highresolution climate change simulations that permit convection at approximately 3.3-km grid spacing,with a focus on the TP,using the Icosahedral Nonhydrostatic Weather and Climate Model(ICON).Two 12-year simulations were performed,consisting of a retrospective simulation(2008–20)with initial and boundary conditions from ERA5 reanalysis and a pseudoglobal warming projection driven by modified reanalysis-derived initial and boundary conditions by adding the monthly CMIP6 ensemble-mean climate change under the SSP5-8.5 scenario.The retrospective simulation shows overall good performance in capturing the seasonal precipitation and surface air temperature.Over the central and eastern TP,the average biases in precipitation(temperature)are less than−0.34 mm d−1(−1.1℃)throughout the year.The simulated biases over the TP are height-dependent.Cold(wet)biases are found in summer(winter)above 5500 m.The future climate simulation suggests that the TP will be wetter and warmer under the SSP5-8.5 scenario.The general features of projected changes in ICON are comparable to the CMIP6 ensemble projection,but the added value from kilometer-scale modeling is evident in both precipitation and temperature projections over complex topographic regions.These ICON-downscaled climate change simulations provide a high-resolution dataset to the community for the study of regional climate changes and impacts over the TP.
