目的 应用7 T MRI技术的磁敏感序列检测黑质小体1信号改变作为帕金森病(PD)影像标志物,并评价其诊断效力。方法 选择2021年6月至2022年1月首都医科大学附属北京天坛医院神经病学中心住院的PD患者29例(PD组),同期招募无神经系统疾病史的...目的 应用7 T MRI技术的磁敏感序列检测黑质小体1信号改变作为帕金森病(PD)影像标志物,并评价其诊断效力。方法 选择2021年6月至2022年1月首都医科大学附属北京天坛医院神经病学中心住院的PD患者29例(PD组),同期招募无神经系统疾病史的健康体检者22例(对照组)。PD组又根据黑质小体1影像学信号评分分为≤2.5分组26例和>2.5分组3例。PD组震颤为主型8例,姿势步态障碍型18例,其余3例为中间型。进行7 T MRI扫描,应用3D多回波T_(2)^(*)加权序列检测黑质小体1信号,对双侧黑质小体1信号的可见性分别进行评分,用ROC曲线计算2组黑质小体1评分临界值。结果 PD组黑质小体1评分显著低于对照组[0.0(0.0,0.0)分vs 4.0(3.8,4.0)分,P<0.01]。ROC曲线分析显示,黑质小体1评分最佳临界值为2.5分,其诊断的敏感性为89.7%,特异性为90.9%,阳性预测值为92.9%,阴性预测值为87.0%,曲线下面积为0.95。>2.5分组病程均短于5年,Hoehn-Yahr分期均低于3期。相关性分析显示,黑质小体1评分与病程及统一帕金森病评定量表Ⅲ评分呈负相关(r=-0.447,P=0.019;r=-0.435,P=0.018)。震颤为主型与姿势步态障碍型患者黑质小体1评分比较,差异无统计学意义(P>0.05)。结论 应用7 T MRI技术检测黑质小体1可作为PD诊断的影像学标志物,具有较高的诊断准确性和预测价值。黑质小体1信号改变与病程及疾病进展有关。展开更多
The Janus kinases(JAKs)are a family of intracellular tyrosine kinases that play an essential role in many basic biological processes,such as apoptosis and inflammation.Thus any dysfunction of the proteins in this path...The Janus kinases(JAKs)are a family of intracellular tyrosine kinases that play an essential role in many basic biological processes,such as apoptosis and inflammation.Thus any dysfunction of the proteins in this pathway may lead to a variety of diseases,including cancer and diseases that affect the immune system,such as severe combined immune deficient(SCID).Marine biological resources have become an important source in new drug research and development due to their diversity,complexity and speciality.In this study,Marine alkaloid Neobacillamide A was isolated from the greedy and stubborn sponge symbiotic Bacillus atrophicus C89 in the South China Sea.Totally 24 novel marine alkaloid Neobacillamide A derivatives were designed and synthesized,which were evaluated for their inhibitory activity against JAK/STAT signaling pathway and their cytotoxicity to A549 cells.Compounds 13c,13o,14d,14g and 14h showed potent JAK/STAT inhibition capability(concentration of 25μmol L^(-1),all inhibitory potencies were above 60%),especially compound 14g exhibited superior JAK/STAT inhibition effect(89.70%inhibition).In addition,all these compounds with a concentration of 25μmol L^(-1)displayed weak or no cytotoxicity to A549 cells,which means that these Neobacillamide A derivatives with JAK/STAT inhibition capability may have potential anti-inflammatory function.展开更多
文摘目的 应用7 T MRI技术的磁敏感序列检测黑质小体1信号改变作为帕金森病(PD)影像标志物,并评价其诊断效力。方法 选择2021年6月至2022年1月首都医科大学附属北京天坛医院神经病学中心住院的PD患者29例(PD组),同期招募无神经系统疾病史的健康体检者22例(对照组)。PD组又根据黑质小体1影像学信号评分分为≤2.5分组26例和>2.5分组3例。PD组震颤为主型8例,姿势步态障碍型18例,其余3例为中间型。进行7 T MRI扫描,应用3D多回波T_(2)^(*)加权序列检测黑质小体1信号,对双侧黑质小体1信号的可见性分别进行评分,用ROC曲线计算2组黑质小体1评分临界值。结果 PD组黑质小体1评分显著低于对照组[0.0(0.0,0.0)分vs 4.0(3.8,4.0)分,P<0.01]。ROC曲线分析显示,黑质小体1评分最佳临界值为2.5分,其诊断的敏感性为89.7%,特异性为90.9%,阳性预测值为92.9%,阴性预测值为87.0%,曲线下面积为0.95。>2.5分组病程均短于5年,Hoehn-Yahr分期均低于3期。相关性分析显示,黑质小体1评分与病程及统一帕金森病评定量表Ⅲ评分呈负相关(r=-0.447,P=0.019;r=-0.435,P=0.018)。震颤为主型与姿势步态障碍型患者黑质小体1评分比较,差异无统计学意义(P>0.05)。结论 应用7 T MRI技术检测黑质小体1可作为PD诊断的影像学标志物,具有较高的诊断准确性和预测价值。黑质小体1信号改变与病程及疾病进展有关。
基金financial supports granted by the National Natural Science Foundation of China(Nos.82073759 and 82003583)the Fund of Greater Bay Area Institute of Precision Medicine(Guangzhou)(No.IPM2021C009)the National Science and Technology Major Project for Significant New Drugs Development(No.2018ZX09735004)。
文摘The Janus kinases(JAKs)are a family of intracellular tyrosine kinases that play an essential role in many basic biological processes,such as apoptosis and inflammation.Thus any dysfunction of the proteins in this pathway may lead to a variety of diseases,including cancer and diseases that affect the immune system,such as severe combined immune deficient(SCID).Marine biological resources have become an important source in new drug research and development due to their diversity,complexity and speciality.In this study,Marine alkaloid Neobacillamide A was isolated from the greedy and stubborn sponge symbiotic Bacillus atrophicus C89 in the South China Sea.Totally 24 novel marine alkaloid Neobacillamide A derivatives were designed and synthesized,which were evaluated for their inhibitory activity against JAK/STAT signaling pathway and their cytotoxicity to A549 cells.Compounds 13c,13o,14d,14g and 14h showed potent JAK/STAT inhibition capability(concentration of 25μmol L^(-1),all inhibitory potencies were above 60%),especially compound 14g exhibited superior JAK/STAT inhibition effect(89.70%inhibition).In addition,all these compounds with a concentration of 25μmol L^(-1)displayed weak or no cytotoxicity to A549 cells,which means that these Neobacillamide A derivatives with JAK/STAT inhibition capability may have potential anti-inflammatory function.
