目的探讨慢性乙型肝炎病毒(HBV)感染者自然杀伤细胞(NK)G2D表达水平及临床意义。方法 2015年7月～2018年7月我院收治的慢性HBV携带者20例、慢性乙型肝炎(CHB)患者18例和HBV相关慢加急(亚急性)肝衰竭患者16例,另选健康体检者20例作为对照...目的探讨慢性乙型肝炎病毒(HBV)感染者自然杀伤细胞(NK)G2D表达水平及临床意义。方法 2015年7月～2018年7月我院收治的慢性HBV携带者20例、慢性乙型肝炎(CHB)患者18例和HBV相关慢加急(亚急性)肝衰竭患者16例,另选健康体检者20例作为对照,患者接受肝活检,正常肝组织取自肝血管瘤患者手术获得的肝组织。使用流式细胞术检测单个核细胞中NK细胞和NKG2D+NK细胞百分比,采用ELISA法检测血清穿孔素和颗粒酶B水平,采用荧光定量PCR法检测肝组织NKG2D m RNA,采用Western blot法检测NKG2D蛋白表达水平。组间比较采用单因素方差分析,两两比较采用SNK法。结果 HBV携带者NK细胞频率和NKG2D+NK细胞频率分别为(5.1±1.5)%和(3.4±1.1)%,CHB患者分别为(8.5±2.0)%和(12.3±2.1)%,肝衰竭患者分别为(8.8±1.6)%和(19.0±2.4)%,健康人分别为(14.2±2.1)%和(7.5±1.5)%,差异显著(P<0.05);HBV携带者血清穿孔素和颗粒酶B水平分别为(15.2±3.2)ng/L和(23.0±3.5)ng/L,CHB为(31.5±3.6)ng/L和(52.5±4.0)ng/L,肝衰竭为(60.2±11.0)ng/L和(126.8±30.1)ng/L,健康人为(13.9±4.0)ng/L和(21.1±3.9)ng/L,差异显著(P<0.05);HBV携带者肝组织NKG2D m RNA和NKG2D蛋白水平分别为(0.1±0.0)和(0.0±0.0),CHB为(3.5±0.9)和(1.1±0.2),肝衰竭为(7.0±1.2)和(1.8±0.2),健康肝组织为(0.6±0.2)和(0.3±0.0),差异显著(P<0.05)。结论 NKG2D可能通过NK细胞合成分泌穿孔素和颗粒酶B等杀伤介质因子发挥效应。不同免疫状态下慢性HBV感染者NKG2D水平存在差异,下调NKG2D表达可能通过抑制NK细胞而改善肝组织免疫损伤。展开更多
特征线方法(Method of Characteristics,MOC)因其具备强大的几何处理能力,且在计算过程中亦能兼顾计算成本和计算精度,被广泛应用于高保真数值模拟计算中。常见的中子输运计算方法除MOC外,还包括碰撞概率法(Collision Probability metho...特征线方法(Method of Characteristics,MOC)因其具备强大的几何处理能力,且在计算过程中亦能兼顾计算成本和计算精度,被广泛应用于高保真数值模拟计算中。常见的中子输运计算方法除MOC外,还包括碰撞概率法(Collision Probability method,CP)和界面流法(Interface Current method,IC)等。本文从方法理论以及数值计算两方面将MOC、CP和IC进行比较分析,评估其在pin-by-pin计算中的能力。同时在MOC计算中,不同的参数选择会对计算成本和计算精度产生影响,因此有必要进行敏感性分析以寻求最佳参数。本文首先将三种计算方法从原理上进行比较分析,再基于2D C5G7-MOX基准题完成了数值计算及MOC参数敏感性初步分析。计算结果表明:MOC在计算精度、计算效率和内存开销上均优于CP和IC。MOC的计算耗时和内存开销分别为23.9 min和37.5 MB,与参考解的相对误差仅为6.04×10^(-4)。而CP和IC的计算耗时分别为MOC的56.7倍和15.6倍,内存开销分别为MOC的407.7倍和32.8倍。进一步通过参数敏感性分析发现:网格划分对计算内存开销以及计算时间的影响最大,而极角的选择对计算精度的影响最大,并且给出一组综合优化建议参数:网格划分6×6,极角为GAUS且数目为2,方位角个数为30。该组参数的计算耗时为45.4 min,内存开销为264.7 MB,相对误差为5.9×10^(-5),归一化后的栅元均方根误差为0.002 55。展开更多
Molecular dipole moments computed at the levels of HF/STO-3G, HF/6-31G(d, p), HF/6-311+G(2d, 2p), MP2/6-31G(d, p) and MP2/6-311+G(2d, 2p) have been investigated. HF/6-311+G(2d, 2p) was found to be the relatively good ...Molecular dipole moments computed at the levels of HF/STO-3G, HF/6-31G(d, p), HF/6-311+G(2d, 2p), MP2/6-31G(d, p) and MP2/6-311+G(2d, 2p) have been investigated. HF/6-311+G(2d, 2p) was found to be the relatively good choice to compute MKS charges for reproducing the experimental values of molecular dipole moments. Root mean square deviation of computed dipole moments for 21 small polar molecules is about 0.1969 D.展开更多
In search of potential 2＇,3＇-dideoxyguanosine （ddG） and 2＇,3＇-didehydro-2＇,3＇-dideoxyguanosine （D4G） prodrugs, a series of 6-modified ddG, D4G analogs were synthesized and evaluated for their anti-HIV activi...In search of potential 2＇,3＇-dideoxyguanosine （ddG） and 2＇,3＇-didehydro-2＇,3＇-dideoxyguanosine （D4G） prodrugs, a series of 6-modified ddG, D4G analogs were synthesized and evaluated for their anti-HIV activities and cyto- toxities in cell-based assays. All analogs showed low cytotoxieities and some of them displayed benign anti-HIV activities. The active triphosphate forms in vivo, ddGTP and D4TTP, were also synthesized by a novel and facile ＂one-pot＂ method. The recognition of ddGTP and D4TTP by Taq, Therminater DNA polymerase and HIV reverse transcriptase （RT） incorporated in DNA/RNA strands were investigated by a non-radioactivity method and Km were determined.展开更多
文摘目的探讨慢性乙型肝炎病毒(HBV)感染者自然杀伤细胞(NK)G2D表达水平及临床意义。方法 2015年7月～2018年7月我院收治的慢性HBV携带者20例、慢性乙型肝炎(CHB)患者18例和HBV相关慢加急(亚急性)肝衰竭患者16例,另选健康体检者20例作为对照,患者接受肝活检,正常肝组织取自肝血管瘤患者手术获得的肝组织。使用流式细胞术检测单个核细胞中NK细胞和NKG2D+NK细胞百分比,采用ELISA法检测血清穿孔素和颗粒酶B水平,采用荧光定量PCR法检测肝组织NKG2D m RNA,采用Western blot法检测NKG2D蛋白表达水平。组间比较采用单因素方差分析,两两比较采用SNK法。结果 HBV携带者NK细胞频率和NKG2D+NK细胞频率分别为(5.1±1.5)%和(3.4±1.1)%,CHB患者分别为(8.5±2.0)%和(12.3±2.1)%,肝衰竭患者分别为(8.8±1.6)%和(19.0±2.4)%,健康人分别为(14.2±2.1)%和(7.5±1.5)%,差异显著(P<0.05);HBV携带者血清穿孔素和颗粒酶B水平分别为(15.2±3.2)ng/L和(23.0±3.5)ng/L,CHB为(31.5±3.6)ng/L和(52.5±4.0)ng/L,肝衰竭为(60.2±11.0)ng/L和(126.8±30.1)ng/L,健康人为(13.9±4.0)ng/L和(21.1±3.9)ng/L,差异显著(P<0.05);HBV携带者肝组织NKG2D m RNA和NKG2D蛋白水平分别为(0.1±0.0)和(0.0±0.0),CHB为(3.5±0.9)和(1.1±0.2),肝衰竭为(7.0±1.2)和(1.8±0.2),健康肝组织为(0.6±0.2)和(0.3±0.0),差异显著(P<0.05)。结论 NKG2D可能通过NK细胞合成分泌穿孔素和颗粒酶B等杀伤介质因子发挥效应。不同免疫状态下慢性HBV感染者NKG2D水平存在差异,下调NKG2D表达可能通过抑制NK细胞而改善肝组织免疫损伤。
文摘特征线方法(Method of Characteristics,MOC)因其具备强大的几何处理能力,且在计算过程中亦能兼顾计算成本和计算精度,被广泛应用于高保真数值模拟计算中。常见的中子输运计算方法除MOC外,还包括碰撞概率法(Collision Probability method,CP)和界面流法(Interface Current method,IC)等。本文从方法理论以及数值计算两方面将MOC、CP和IC进行比较分析,评估其在pin-by-pin计算中的能力。同时在MOC计算中,不同的参数选择会对计算成本和计算精度产生影响,因此有必要进行敏感性分析以寻求最佳参数。本文首先将三种计算方法从原理上进行比较分析,再基于2D C5G7-MOX基准题完成了数值计算及MOC参数敏感性初步分析。计算结果表明:MOC在计算精度、计算效率和内存开销上均优于CP和IC。MOC的计算耗时和内存开销分别为23.9 min和37.5 MB,与参考解的相对误差仅为6.04×10^(-4)。而CP和IC的计算耗时分别为MOC的56.7倍和15.6倍,内存开销分别为MOC的407.7倍和32.8倍。进一步通过参数敏感性分析发现:网格划分对计算内存开销以及计算时间的影响最大,而极角的选择对计算精度的影响最大,并且给出一组综合优化建议参数:网格划分6×6,极角为GAUS且数目为2,方位角个数为30。该组参数的计算耗时为45.4 min,内存开销为264.7 MB,相对误差为5.9×10^(-5),归一化后的栅元均方根误差为0.002 55。
基金The project was supported by the National Science Foundation (29773021) Provincial Educational Foundation of Jiangsu (98KJB150001).
文摘Molecular dipole moments computed at the levels of HF/STO-3G, HF/6-31G(d, p), HF/6-311+G(2d, 2p), MP2/6-31G(d, p) and MP2/6-311+G(2d, 2p) have been investigated. HF/6-311+G(2d, 2p) was found to be the relatively good choice to compute MKS charges for reproducing the experimental values of molecular dipole moments. Root mean square deviation of computed dipole moments for 21 small polar molecules is about 0.1969 D.
基金The research was supported by the fund of the National Natural Science Foundation of China，the Ministry of Science and Technology of China (No.2008ZX10303).Anti-HIV activity evaluation in pseudotyped HIV system was performed by Institute of Materia Medica,Chinese Academy of Medical Science and Peking Union Medical College.Anti-HIV activity evaluation in HIV-1/MT2 cells was performed by HD
文摘In search of potential 2＇,3＇-dideoxyguanosine （ddG） and 2＇,3＇-didehydro-2＇,3＇-dideoxyguanosine （D4G） prodrugs, a series of 6-modified ddG, D4G analogs were synthesized and evaluated for their anti-HIV activities and cyto- toxities in cell-based assays. All analogs showed low cytotoxieities and some of them displayed benign anti-HIV activities. The active triphosphate forms in vivo, ddGTP and D4TTP, were also synthesized by a novel and facile ＂one-pot＂ method. The recognition of ddGTP and D4TTP by Taq, Therminater DNA polymerase and HIV reverse transcriptase （RT） incorporated in DNA/RNA strands were investigated by a non-radioactivity method and Km were determined.
