第六届世界肺高血压会议对肺高血压(pulmonary hypertension,PH)的定义和诊断分类进行了修订和更新。PH的血流动力学定义维持不变,将毛细血管前性PH定义更新为:肺动脉平均压>20 mm Hg、肺动脉楔压<15 mm Hg且肺血管阻力>3 WU...第六届世界肺高血压会议对肺高血压(pulmonary hypertension,PH)的定义和诊断分类进行了修订和更新。PH的血流动力学定义维持不变,将毛细血管前性PH定义更新为:肺动脉平均压>20 mm Hg、肺动脉楔压<15 mm Hg且肺血管阻力>3 WU。诊断分类更新包括:增加急性肺血管扩张试验阳性肺动脉高压(pulmonary arterial hypertension,PAH)亚类,将甲基苯丙胺(冰毒)和达沙替尼致PAH作用由可能升级为肯定,将肺静脉闭塞病/肺毛细血管瘤病由特殊的1'更新为PAH的一个亚类,将脾切除术后和甲状腺疾病从PH诊断分类中移除等。本次PH定义和诊断分类更新将为临床实践提供重要指导意义。展开更多
目的探讨接受造血干细胞移植的Ph染色体阳性急性淋巴细胞白血病（Ph＋ALL）患者一线应用国产达沙替尼与一代酪氨酸激酶抑制剂（TKI）伊马替尼的疗效差异。
方法回顾性分析2014年1月至2017年6月期间就诊并行造血干细胞移植的63例Ph＋AL...目的探讨接受造血干细胞移植的Ph染色体阳性急性淋巴细胞白血病（Ph＋ALL）患者一线应用国产达沙替尼与一代酪氨酸激酶抑制剂（TKI）伊马替尼的疗效差异。
方法回顾性分析2014年1月至2017年6月期间就诊并行造血干细胞移植的63例Ph＋ALL患者的临床特征及转归，比较一线应用国产达沙替尼与伊马替尼的疗效。
结果应用国产达沙替尼者31例，应用伊马替尼者32例。两组患者诱导治疗4周完全缓解（CR）率分别为96.8%和93.8%（P=1.000），诱导治疗4周主要分子学反应（MMR，BCR-ABL拷贝数较基线下降3个对数级）率分别为41.9%和43.8%（χ2=0.021，P=0.884），移植前复发率分别为6.5%和12.5%（P=0.672），移植前MMR率分别为83.9%和68.8%（χ2=1.985，P=0.159），差异均无统计学意义。国产达沙替尼组和伊马替尼组20个月总生存（OS）率分别为95.5%、76.5%，20个月无事件生存（EFS）率分别为93.5%、61.4%，两组OS时间差异无统计学意义（χ2=0.990，P=0.320），EFS时间差异有统计学意义（χ2=5.926，P=0.015）。多因素分析显示应用国产达沙替尼（HR=0.201，95% CI 0.045~0.896，P=0.035）和移植前获得MMR（HR=0.344，95% CI 0.124~0.956，P=0.041）的患者具有更好的EFS。
结论TKI联合化疗并序贯造血干细胞移植治疗Ph＋ALL时，与一线应用伊马替尼相比，一线应用国产达沙替尼者EFS更优。展开更多
本文对药物达沙替尼的热稳定性和晶型进行分析与研究。通过差示扫描量热仪(DSC)和热重分析仪(TGA)分析达沙替尼的热稳定性;通过X射线粉末衍射仪(XRD)及其原位高温附件(in situ high temperature)测定达沙替尼试样的多晶型结构及相转变...本文对药物达沙替尼的热稳定性和晶型进行分析与研究。通过差示扫描量热仪(DSC)和热重分析仪(TGA)分析达沙替尼的热稳定性;通过X射线粉末衍射仪(XRD)及其原位高温附件(in situ high temperature)测定达沙替尼试样的多晶型结构及相转变。结果表明,达沙替尼存在两种晶型(分子中分别含1个结晶水和1.5个结晶水),在加热过程中两种晶型都会发生结构变化,失去结晶水后,最终变为相同的晶体结构,其熔点分别为285.68℃和285.50℃。展开更多
A sensitive, rapid, simple and economical ultra-performance liquid chromatography-tandem mass spectrometric method （UPLC-MS/MS） was developed and validated for simultaneous determination of imatinib, dasatinib and n...A sensitive, rapid, simple and economical ultra-performance liquid chromatography-tandem mass spectrometric method （UPLC-MS/MS） was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard （IS）. Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A （aqueous phase： 0.15% formic acid and 0.05% ammonium acetate） and B （organic phase： aeetonitrile） （A：B=40：60, v/v）. The flow rate was 0.25 mL/min and the total run time was 6 min. The multiple reaction monitoring （MRM） transitions, m/z 494.5-394.5 for imatinib, 488.7-401.5 for dasatinib, 530.7-289.5 for nilotinib and 528.5-403.4 for IS, were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity and good linearity over the concentration range of 2.6-5250.0 ng/mL for imatinib, 2.0-490.0 ng/mL for dasatinib, and 2.4-4700.0 ng/mL for nilotinib. The method showed acceptable results on sensitivity, specificity, recovery, precision, accuracy and stability tests. This UPLC-MS/MS assay was successfully used for human plasma samples analysis and no significant differences were found in imatinib steady-state trough concentrations among the SLC22A5 -1889T 〉 C or SLCOIB3 699G 〉 A genotypes （P 〉 0.05）. This validated method can provide support for clinical therapeutic drug monitoring and pharmacokinetic investigations of these three tyrosine kinase inhibitors （TKIs）.展开更多
文摘第六届世界肺高血压会议对肺高血压(pulmonary hypertension,PH)的定义和诊断分类进行了修订和更新。PH的血流动力学定义维持不变,将毛细血管前性PH定义更新为:肺动脉平均压>20 mm Hg、肺动脉楔压<15 mm Hg且肺血管阻力>3 WU。诊断分类更新包括:增加急性肺血管扩张试验阳性肺动脉高压(pulmonary arterial hypertension,PAH)亚类,将甲基苯丙胺(冰毒)和达沙替尼致PAH作用由可能升级为肯定,将肺静脉闭塞病/肺毛细血管瘤病由特殊的1'更新为PAH的一个亚类,将脾切除术后和甲状腺疾病从PH诊断分类中移除等。本次PH定义和诊断分类更新将为临床实践提供重要指导意义。
文摘目的探讨接受造血干细胞移植的Ph染色体阳性急性淋巴细胞白血病（Ph＋ALL）患者一线应用国产达沙替尼与一代酪氨酸激酶抑制剂（TKI）伊马替尼的疗效差异。
方法回顾性分析2014年1月至2017年6月期间就诊并行造血干细胞移植的63例Ph＋ALL患者的临床特征及转归，比较一线应用国产达沙替尼与伊马替尼的疗效。
结果应用国产达沙替尼者31例，应用伊马替尼者32例。两组患者诱导治疗4周完全缓解（CR）率分别为96.8%和93.8%（P=1.000），诱导治疗4周主要分子学反应（MMR，BCR-ABL拷贝数较基线下降3个对数级）率分别为41.9%和43.8%（χ2=0.021，P=0.884），移植前复发率分别为6.5%和12.5%（P=0.672），移植前MMR率分别为83.9%和68.8%（χ2=1.985，P=0.159），差异均无统计学意义。国产达沙替尼组和伊马替尼组20个月总生存（OS）率分别为95.5%、76.5%，20个月无事件生存（EFS）率分别为93.5%、61.4%，两组OS时间差异无统计学意义（χ2=0.990，P=0.320），EFS时间差异有统计学意义（χ2=5.926，P=0.015）。多因素分析显示应用国产达沙替尼（HR=0.201，95% CI 0.045~0.896，P=0.035）和移植前获得MMR（HR=0.344，95% CI 0.124~0.956，P=0.041）的患者具有更好的EFS。
结论TKI联合化疗并序贯造血干细胞移植治疗Ph＋ALL时，与一线应用伊马替尼相比，一线应用国产达沙替尼者EFS更优。
文摘本文对药物达沙替尼的热稳定性和晶型进行分析与研究。通过差示扫描量热仪(DSC)和热重分析仪(TGA)分析达沙替尼的热稳定性;通过X射线粉末衍射仪(XRD)及其原位高温附件(in situ high temperature)测定达沙替尼试样的多晶型结构及相转变。结果表明,达沙替尼存在两种晶型(分子中分别含1个结晶水和1.5个结晶水),在加热过程中两种晶型都会发生结构变化,失去结晶水后,最终变为相同的晶体结构,其熔点分别为285.68℃和285.50℃。
文摘A sensitive, rapid, simple and economical ultra-performance liquid chromatography-tandem mass spectrometric method （UPLC-MS/MS） was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard （IS）. Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A （aqueous phase： 0.15% formic acid and 0.05% ammonium acetate） and B （organic phase： aeetonitrile） （A：B=40：60, v/v）. The flow rate was 0.25 mL/min and the total run time was 6 min. The multiple reaction monitoring （MRM） transitions, m/z 494.5-394.5 for imatinib, 488.7-401.5 for dasatinib, 530.7-289.5 for nilotinib and 528.5-403.4 for IS, were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity and good linearity over the concentration range of 2.6-5250.0 ng/mL for imatinib, 2.0-490.0 ng/mL for dasatinib, and 2.4-4700.0 ng/mL for nilotinib. The method showed acceptable results on sensitivity, specificity, recovery, precision, accuracy and stability tests. This UPLC-MS/MS assay was successfully used for human plasma samples analysis and no significant differences were found in imatinib steady-state trough concentrations among the SLC22A5 -1889T 〉 C or SLCOIB3 699G 〉 A genotypes （P 〉 0.05）. This validated method can provide support for clinical therapeutic drug monitoring and pharmacokinetic investigations of these three tyrosine kinase inhibitors （TKIs）.
