目的评价阿帕替尼联合程序性死亡受体1/程序性死亡受体配体1(PD-1/PD-L1)抑制剂治疗恶性实体瘤的有效性与安全性。方法检索PubMed、Web of Science、Embase、Cochrane Library、中国知网、维普网、万方数据、中国生物医学文献数据库,收...目的评价阿帕替尼联合程序性死亡受体1/程序性死亡受体配体1(PD-1/PD-L1)抑制剂治疗恶性实体瘤的有效性与安全性。方法检索PubMed、Web of Science、Embase、Cochrane Library、中国知网、维普网、万方数据、中国生物医学文献数据库,收集阿帕替尼联合PD-1/PD-L1抑制剂和(或)化疗/其他疗法(联合组)对比阿帕替尼或PD-1/PD-L1抑制剂单药和(或)化疗/其他疗法(对照组)治疗恶性实体瘤的随机对照研究(RCT),检索时限为建库至2025年5月。筛选文献、提取资料、评价文献质量后,采用RevMan 5.3和Stata 14.0软件进行Meta分析。结果共纳入28篇RCTs,包括2974例患者。联合组患者的客观缓解率[RR=1.639,95%CI(1.452,1.851),P<0.00001],疾病控制率[RR=1.284,95%CI(1.178,1.399),P<0.00001],CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)以及高血压、疲劳乏力、蛋白尿、血小板减少等不良反应的发生率均显著高于对照组(P<0.05或P<0.00001);疾病进展率[RR=0.497,95%CI(0.437,0.566),P<0.00001]、血清肿瘤标志物水平、CD8^(+)均显著低于对照组(P<0.05或P<0.00001)。不同类型肿瘤的亚组分析结果显示,联合组患者的客观缓解率和疾病控制率均显著高于对照组(P<0.05)。敏感性分析结果显示,本研究结果的稳定性良好。发表偏倚分析结果显示,本研究存在发表偏倚的可能性较大。结论阿帕替尼联合PD-1/PD-L1抑制剂治疗不同类型肿瘤的疗效显著,但需注意高血压、疲劳乏力、蛋白尿、血小板减少的发生。展开更多
【目的】通过研究猪圆环病毒Ⅱ型(porcine circovirus type Ⅱ,PCV2)感染过程中程序性死亡受体1(programmed cell death protein 1,PD-1)及其配体(programmed cell death 1 ligands,PD-Ls)信号通路作用,寻找调节PCV2免疫抑制新途径,减少...【目的】通过研究猪圆环病毒Ⅱ型(porcine circovirus type Ⅱ,PCV2)感染过程中程序性死亡受体1(programmed cell death protein 1,PD-1)及其配体(programmed cell death 1 ligands,PD-Ls)信号通路作用,寻找调节PCV2免疫抑制新途径,减少PCV2感染造成的经济损失。【方法】利用实验室构建的重组表达宿主菌pET32a-PD1/Rosetta(DE)进行诱导表达、纯化,获得猪可溶性PD-1蛋白(soluble PD-1,sPD-1)的诱导表达条件;制备大量具有活性的猪sPD-1蛋白,体外作用于PCV2感染的猪外周血单个核细胞(peripheral blood mononuclear cell,PBMCs),分别通过CCK-8和流式细胞术检测PBMCs的增殖情况,间接免疫荧光法和RT-qPCR检测猪sPD-1蛋白对PCV2病毒载量的影响,RT-qPCR和ELISA检测猪sPD-1蛋白对免疫相关细胞因子IL-2、IL-12、IL-21、IL-17A和IFN-γ等的转录水平和分泌水平的影响。【结果】通过诱导表达、纯化获得了高纯度、高活性的重组猪sPD-1蛋白。与未使用猪sPD-1蛋白处理的PCV2感染PBMCs组相比,10μg·mL−1猪sPD-1蛋白处理的猪PCV2病毒载量下降至1000 copies·μL−1以下;CCK-8检测结果显示猪sPD-1蛋白处理组细胞增殖指数显著提高(P<0.05);流式细胞术检测发现猪sPD-1蛋白组的平均荧光强度为(68.60±10.14)%,相对于PCV2病毒组(28.70±3.18)%显著增强(P<0.05);反转录荧光定量PCR和ELISA检测,发现猪sPD-1蛋白处理组的细胞因子IL-2、IL-12和IFN-γ的转录水平和分泌水平显著升高(P<0.05)。【结论】猪sPD-1蛋白可以通过阻断PD-1/PD-Ls通路降低PCV2的病毒载量,促进PBMCs的增殖,增强PBMCs细胞因子的转录水平和分泌水平免疫反应。因此,猪sPD-1蛋白在体外可以增强PCV2感染PBMCs的免疫反应,进一步为病毒性疾病的防控提供理论依据。展开更多
The successful control of hydrocarbon and CO emissions from low-temperature diesel exhausts requires the use of highly active co-oxidation catalysts.In this study,Sn was used to enhance the catalytic performance of Pd...The successful control of hydrocarbon and CO emissions from low-temperature diesel exhausts requires the use of highly active co-oxidation catalysts.In this study,Sn was used to enhance the catalytic performance of Pd/CeO_(2)in CO and C_(3)H_(6)co-oxidation conditions.CeO_(2)with added stannum(Sn)was prepared as a support using the co-precipitation method,and Pd was loaded onto the support using the impregnation method.After Sn addition(the optimal Ce/Sn ratio is 0.75:0.25),the T_(50)values of CO and C_(3)H_(6)are reduced by 20 and 32℃,respectively.A series of characterization methods indicates that the addition of Sn to the support greatly enhances its lattice oxygen mobility and increases the proportion of PdO.During the co-oxidation process,stronger lattice oxygen mobility allows CO to react faster through the Mars-van Krevelen mechanism,weakening the competition with C_(3)H_(6)for O_(2).A higher PdO content enhances the C_(3)H_(6)oxidation capability.Moreover,CO can more readily reduce PdO than Pd^(2+)in solid solution with the support,which consequently further enhances co-oxidation activity.Therefore,the addition of Sn is a simple and effective strategy for enhancing the performance of Pd/CeO_(2)catalysts in CO and C_(3)H_(6)co-oxidation reactions.Furthermore,the promotional effect of CO achieved in this study contributes to a deeper understanding of the interactions that occur during the co-oxidation of C_(3)H_(6)and CO.展开更多
文摘【目的】通过研究猪圆环病毒Ⅱ型(porcine circovirus type Ⅱ,PCV2)感染过程中程序性死亡受体1(programmed cell death protein 1,PD-1)及其配体(programmed cell death 1 ligands,PD-Ls)信号通路作用,寻找调节PCV2免疫抑制新途径,减少PCV2感染造成的经济损失。【方法】利用实验室构建的重组表达宿主菌pET32a-PD1/Rosetta(DE)进行诱导表达、纯化,获得猪可溶性PD-1蛋白(soluble PD-1,sPD-1)的诱导表达条件;制备大量具有活性的猪sPD-1蛋白,体外作用于PCV2感染的猪外周血单个核细胞(peripheral blood mononuclear cell,PBMCs),分别通过CCK-8和流式细胞术检测PBMCs的增殖情况,间接免疫荧光法和RT-qPCR检测猪sPD-1蛋白对PCV2病毒载量的影响,RT-qPCR和ELISA检测猪sPD-1蛋白对免疫相关细胞因子IL-2、IL-12、IL-21、IL-17A和IFN-γ等的转录水平和分泌水平的影响。【结果】通过诱导表达、纯化获得了高纯度、高活性的重组猪sPD-1蛋白。与未使用猪sPD-1蛋白处理的PCV2感染PBMCs组相比,10μg·mL−1猪sPD-1蛋白处理的猪PCV2病毒载量下降至1000 copies·μL−1以下;CCK-8检测结果显示猪sPD-1蛋白处理组细胞增殖指数显著提高(P<0.05);流式细胞术检测发现猪sPD-1蛋白组的平均荧光强度为(68.60±10.14)%,相对于PCV2病毒组(28.70±3.18)%显著增强(P<0.05);反转录荧光定量PCR和ELISA检测,发现猪sPD-1蛋白处理组的细胞因子IL-2、IL-12和IFN-γ的转录水平和分泌水平显著升高(P<0.05)。【结论】猪sPD-1蛋白可以通过阻断PD-1/PD-Ls通路降低PCV2的病毒载量,促进PBMCs的增殖,增强PBMCs细胞因子的转录水平和分泌水平免疫反应。因此,猪sPD-1蛋白在体外可以增强PCV2感染PBMCs的免疫反应,进一步为病毒性疾病的防控提供理论依据。
基金Project supported by the National Key R&D Program of China(2022YFC3701804)the National Natural Science Foundation of China(52225004)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA23010201)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2022309)。
文摘The successful control of hydrocarbon and CO emissions from low-temperature diesel exhausts requires the use of highly active co-oxidation catalysts.In this study,Sn was used to enhance the catalytic performance of Pd/CeO_(2)in CO and C_(3)H_(6)co-oxidation conditions.CeO_(2)with added stannum(Sn)was prepared as a support using the co-precipitation method,and Pd was loaded onto the support using the impregnation method.After Sn addition(the optimal Ce/Sn ratio is 0.75:0.25),the T_(50)values of CO and C_(3)H_(6)are reduced by 20 and 32℃,respectively.A series of characterization methods indicates that the addition of Sn to the support greatly enhances its lattice oxygen mobility and increases the proportion of PdO.During the co-oxidation process,stronger lattice oxygen mobility allows CO to react faster through the Mars-van Krevelen mechanism,weakening the competition with C_(3)H_(6)for O_(2).A higher PdO content enhances the C_(3)H_(6)oxidation capability.Moreover,CO can more readily reduce PdO than Pd^(2+)in solid solution with the support,which consequently further enhances co-oxidation activity.Therefore,the addition of Sn is a simple and effective strategy for enhancing the performance of Pd/CeO_(2)catalysts in CO and C_(3)H_(6)co-oxidation reactions.Furthermore,the promotional effect of CO achieved in this study contributes to a deeper understanding of the interactions that occur during the co-oxidation of C_(3)H_(6)and CO.
