Objective: Measures of ventilation-co_2 output relationship have been shown to be more prognostic than peak O_2 uptake in assessing life expectancy in patients with chronic heart failure(CHF). Because both the ratios(...Objective: Measures of ventilation-co_2 output relationship have been shown to be more prognostic than peak O_2 uptake in assessing life expectancy in patients with chronic heart failure(CHF). Because both the ratios(V4e/V4co_2) and slopes(V4e-vs-V4co_2) of ventilation-co_2 output of differing durations can be used, we aim to ascertain which measurements best predicted CHF life expectancy. Methods: Two hundred and seventy-one CHF patients with NYHA class II-IV underwent incremental cardiopulmonary exercise testing(CPET) and were followed-up for a median duration of 479 days. Four different linear regression V4e-vsV4co_2 slopes were calculated from warm-up exercise onset to: 180 s, anaerobic threshold(AT), ventilatory compensation point(VCP); and peak exercise. Five V4e/V4co_2 ratios were calculated for the following durations: rest(120 s), warm-up(30 s), AT(60 s), lowest value(90 s), and peak exercise(30 s). Death or heart transplant were considered end-points. Multiple statistical analyses were performed. Results: CHF patients had high lowest V4e/V4co_2(41.0±9.2, 141±30%pred), high V4e/V4co_2 at AT(42.5±10.4, 145±35%pred), and high V4e-vs-V4co_2 slope to VCP(37.6±12.1, 126±41%pred). The best predictor of death was a higher lowest V4e/V4co_2(≥42, ≥141%pred), whereas the V4e-vs-V4co_2 slope to VCP was less variable than other slopes. For death prognosis in 6 months, %pred values were superior: for longer times, absolute values were superior. Conclusion: The increased lowest V4e/V4co_2 ratio easily identifiable and simply measured during exercise, is the best measurement to assess the ventilation-co_2 output relationship in prognosticating death in CHF patients.展开更多
目的探讨程序性死亡受体-1(PD-1)、程序性死亡受体配体-1(PD-L1)抑制剂的三维定量构效关系和分子对接研究。方法针对现有的小分子化合物进行合理研究,取45个新型o-(联苯-3-基甲/氧基)硝基苯抑制剂进行三维定量构效关系研究,包括使用分...目的探讨程序性死亡受体-1(PD-1)、程序性死亡受体配体-1(PD-L1)抑制剂的三维定量构效关系和分子对接研究。方法针对现有的小分子化合物进行合理研究,取45个新型o-(联苯-3-基甲/氧基)硝基苯抑制剂进行三维定量构效关系研究,包括使用分子力场分析法(comparative molecular field analysis,CoMFA)和比较分子相似性指数法(comparative molecular similarity indices analysis,CoMSIA),并且对分子对接,观察小分子与5J89蛋白的结合效果。结果Co MFA模型(q^(2)=0.644,r^(2)=0.950)和CoMSIA模型(q^(2)=0.622,r^(2)=0.998)具有一定预测能力。TYR:56、GLN:66氨基酸是影响这些抑制剂活性的主要氨基酸。结论该研究是计算机辅助药物方法在抗肿瘤方面的应用,可为开发PD-1/PD-L1抑制剂作为抗癌药物提供参考。展开更多
基金partially supported by National Center of Cardiovascular Diseases,Fuwai Hospital,Chinese Academy of Medical Sciences,Beijing,ChinaThe clinical trials of the Resynchronization for Hemod Ynamic Treatment for Heart Failure Management(RHYTHM)[38]were funded by St Jude Medical
文摘Objective: Measures of ventilation-co_2 output relationship have been shown to be more prognostic than peak O_2 uptake in assessing life expectancy in patients with chronic heart failure(CHF). Because both the ratios(V4e/V4co_2) and slopes(V4e-vs-V4co_2) of ventilation-co_2 output of differing durations can be used, we aim to ascertain which measurements best predicted CHF life expectancy. Methods: Two hundred and seventy-one CHF patients with NYHA class II-IV underwent incremental cardiopulmonary exercise testing(CPET) and were followed-up for a median duration of 479 days. Four different linear regression V4e-vsV4co_2 slopes were calculated from warm-up exercise onset to: 180 s, anaerobic threshold(AT), ventilatory compensation point(VCP); and peak exercise. Five V4e/V4co_2 ratios were calculated for the following durations: rest(120 s), warm-up(30 s), AT(60 s), lowest value(90 s), and peak exercise(30 s). Death or heart transplant were considered end-points. Multiple statistical analyses were performed. Results: CHF patients had high lowest V4e/V4co_2(41.0±9.2, 141±30%pred), high V4e/V4co_2 at AT(42.5±10.4, 145±35%pred), and high V4e-vs-V4co_2 slope to VCP(37.6±12.1, 126±41%pred). The best predictor of death was a higher lowest V4e/V4co_2(≥42, ≥141%pred), whereas the V4e-vs-V4co_2 slope to VCP was less variable than other slopes. For death prognosis in 6 months, %pred values were superior: for longer times, absolute values were superior. Conclusion: The increased lowest V4e/V4co_2 ratio easily identifiable and simply measured during exercise, is the best measurement to assess the ventilation-co_2 output relationship in prognosticating death in CHF patients.
文摘目的探讨程序性死亡受体-1(PD-1)、程序性死亡受体配体-1(PD-L1)抑制剂的三维定量构效关系和分子对接研究。方法针对现有的小分子化合物进行合理研究,取45个新型o-(联苯-3-基甲/氧基)硝基苯抑制剂进行三维定量构效关系研究,包括使用分子力场分析法(comparative molecular field analysis,CoMFA)和比较分子相似性指数法(comparative molecular similarity indices analysis,CoMSIA),并且对分子对接,观察小分子与5J89蛋白的结合效果。结果Co MFA模型(q^(2)=0.644,r^(2)=0.950)和CoMSIA模型(q^(2)=0.622,r^(2)=0.998)具有一定预测能力。TYR:56、GLN:66氨基酸是影响这些抑制剂活性的主要氨基酸。结论该研究是计算机辅助药物方法在抗肿瘤方面的应用,可为开发PD-1/PD-L1抑制剂作为抗癌药物提供参考。
