目的:明确两个中国北方汉族马凡综合征(Marfan syndrome,MFS)家系的临床特点,并对其进行基因诊断。方法:对两个家系进行家系调查和系谱分析,应用聚合酶链式反应-DNA测序方法对原纤维蛋白1基因(Fibrillin-1,FBN1)的所有外显子进行测序。...目的:明确两个中国北方汉族马凡综合征(Marfan syndrome,MFS)家系的临床特点,并对其进行基因诊断。方法:对两个家系进行家系调查和系谱分析,应用聚合酶链式反应-DNA测序方法对原纤维蛋白1基因(Fibrillin-1,FBN1)的所有外显子进行测序。应用Swiss-model、Polyphen-2和SIFT软件对发现的变异位点进行功能预测。结果:两个家系均呈常染色显性遗传特点,在家系1患者中发现一个新的插入突变,即第13外显子1691位碱基处插入碱基A(1691 ins A),导致蛋白在第571位氨基酸处翻译提前终止。此外,在家系2患者中发现一个已知的点突变,即第27外显子第3463位碱基由G变为A(3463 G>A),导致第1155位氨基酸由天冬氨酸变为天冬酰胺。这两个变异位点在家系的健康人及50例健康对照中均未出现。功能预测发现这两个变异位点均可能会影响FBN1蛋白的结构或功能。结论:在两个MFS家系中发现一个新插入突变位点(1691 ins A)和一个已知点突变位点(3463 G>A),为扩大FBN1基因的突变谱及进一步阐明FBN1基因突变在MFS中的作用提供理论依据。展开更多
本文通过建立肿瘤免疫微环境多尺度数学模型,结合小鼠实验数据,探讨了前列腺素E2受体4亚型(Prostaglandin E2 Receptor 4,EP4)拮抗剂MF-766和抗程序性细胞死亡蛋白1(Anti-programmed Cell Death Protein 1,Anti-PD-1)联合治疗对肿瘤免...本文通过建立肿瘤免疫微环境多尺度数学模型,结合小鼠实验数据,探讨了前列腺素E2受体4亚型(Prostaglandin E2 Receptor 4,EP4)拮抗剂MF-766和抗程序性细胞死亡蛋白1(Anti-programmed Cell Death Protein 1,Anti-PD-1)联合治疗对肿瘤免疫微环境及肿瘤生长的调控机制。模型定量分析了免疫抑制细胞、效应性免疫细胞以及细胞因子的动态变化,揭示了联合治疗在降低髓源性抑制细胞(Myeloid-derived Suppressor Cells,MDSCs)浓度和增强效应性免疫细胞功能中的协同作用。实验验证表明,模型能够准确描述肿瘤体积的动态变化及药物的免疫调节效应,并揭示了药物剂量与用药间隔对治疗效果的非线性影响。基于此模型的模拟结果,本文不仅加深了对肿瘤转移机制的理解,还为优化免疫治疗的剂量和用药策略提供了理论依据,为精准治疗的设计与推进奠定了坚实基础。展开更多
Boundary layer transition(BLT)can cause a sharp rise in heat flux and skin friction,which can seriously affect the flight performance and safety of hypersonic flight vehicles.Therefore,the mechanism,prediction and con...Boundary layer transition(BLT)can cause a sharp rise in heat flux and skin friction,which can seriously affect the flight performance and safety of hypersonic flight vehicles.Therefore,the mechanism,prediction and control of transition have become important issues that must be dealt with for the development of advanced flight vehicles,and it is also a research hotspot of particular interest to major aerospace countries.Compared to other transition research approaches,model flight tests can better present the transition problems under real flight conditions,thus have been carried out extensively over the past 30 years.The United States,Germany,France,Australia,and other countries have carried out transition research based on flight tests,such as the Pegasus wing-glove crossflow transition and the Hypersonic Boundary Layer Transition(HyBOLT)transition control flight test of the United States,the joint research project of the Hypersonic International Flight Research and Experimentation-1(HIFiRE-1)circular cone and the HIFiRE-5 elliptic cone transition flight tests between the United States and Australia,the flight test of compression surface transition of the scramjet forebody(LEA)in France and so on.Although these flight tests suffered various setbacks,they still obtained valuable transition data.Recently,the United States is carrying out the concave-surface transition flight tests of Hypersonic Boundary Layer Transition(BOLT)and BOLT-II.Since its first model flight test mission for verification purpose launched successfully in 2015,several hypersonic BLT flight tests have been conducted by China Aerodynamics Research and Development Center(CARDC).The flight tests have measured valid transition data under flight conditions,obtained the transition front and its dynamical variation on blunt cones at various angles of attack and a lifting body Hypersonic Transition Research Vehicle(HyTRV).The crossflow traveling waves in high-altitude flight were measured for the first time,and our understanding of hypersonic BLT has been greatly improved.展开更多
文摘目的:明确两个中国北方汉族马凡综合征(Marfan syndrome,MFS)家系的临床特点,并对其进行基因诊断。方法:对两个家系进行家系调查和系谱分析,应用聚合酶链式反应-DNA测序方法对原纤维蛋白1基因(Fibrillin-1,FBN1)的所有外显子进行测序。应用Swiss-model、Polyphen-2和SIFT软件对发现的变异位点进行功能预测。结果:两个家系均呈常染色显性遗传特点,在家系1患者中发现一个新的插入突变,即第13外显子1691位碱基处插入碱基A(1691 ins A),导致蛋白在第571位氨基酸处翻译提前终止。此外,在家系2患者中发现一个已知的点突变,即第27外显子第3463位碱基由G变为A(3463 G>A),导致第1155位氨基酸由天冬氨酸变为天冬酰胺。这两个变异位点在家系的健康人及50例健康对照中均未出现。功能预测发现这两个变异位点均可能会影响FBN1蛋白的结构或功能。结论:在两个MFS家系中发现一个新插入突变位点(1691 ins A)和一个已知点突变位点(3463 G>A),为扩大FBN1基因的突变谱及进一步阐明FBN1基因突变在MFS中的作用提供理论依据。
文摘本文通过建立肿瘤免疫微环境多尺度数学模型,结合小鼠实验数据,探讨了前列腺素E2受体4亚型(Prostaglandin E2 Receptor 4,EP4)拮抗剂MF-766和抗程序性细胞死亡蛋白1(Anti-programmed Cell Death Protein 1,Anti-PD-1)联合治疗对肿瘤免疫微环境及肿瘤生长的调控机制。模型定量分析了免疫抑制细胞、效应性免疫细胞以及细胞因子的动态变化,揭示了联合治疗在降低髓源性抑制细胞(Myeloid-derived Suppressor Cells,MDSCs)浓度和增强效应性免疫细胞功能中的协同作用。实验验证表明,模型能够准确描述肿瘤体积的动态变化及药物的免疫调节效应,并揭示了药物剂量与用药间隔对治疗效果的非线性影响。基于此模型的模拟结果,本文不仅加深了对肿瘤转移机制的理解,还为优化免疫治疗的剂量和用药策略提供了理论依据,为精准治疗的设计与推进奠定了坚实基础。
基金This work was supported by the National Natural Science Foundation of China(Grants 11772350,92052301).
文摘Boundary layer transition(BLT)can cause a sharp rise in heat flux and skin friction,which can seriously affect the flight performance and safety of hypersonic flight vehicles.Therefore,the mechanism,prediction and control of transition have become important issues that must be dealt with for the development of advanced flight vehicles,and it is also a research hotspot of particular interest to major aerospace countries.Compared to other transition research approaches,model flight tests can better present the transition problems under real flight conditions,thus have been carried out extensively over the past 30 years.The United States,Germany,France,Australia,and other countries have carried out transition research based on flight tests,such as the Pegasus wing-glove crossflow transition and the Hypersonic Boundary Layer Transition(HyBOLT)transition control flight test of the United States,the joint research project of the Hypersonic International Flight Research and Experimentation-1(HIFiRE-1)circular cone and the HIFiRE-5 elliptic cone transition flight tests between the United States and Australia,the flight test of compression surface transition of the scramjet forebody(LEA)in France and so on.Although these flight tests suffered various setbacks,they still obtained valuable transition data.Recently,the United States is carrying out the concave-surface transition flight tests of Hypersonic Boundary Layer Transition(BOLT)and BOLT-II.Since its first model flight test mission for verification purpose launched successfully in 2015,several hypersonic BLT flight tests have been conducted by China Aerodynamics Research and Development Center(CARDC).The flight tests have measured valid transition data under flight conditions,obtained the transition front and its dynamical variation on blunt cones at various angles of attack and a lifting body Hypersonic Transition Research Vehicle(HyTRV).The crossflow traveling waves in high-altitude flight were measured for the first time,and our understanding of hypersonic BLT has been greatly improved.
