背景嵌合抗原受体(CAR)-T细胞免疫疗法已在多发性骨髓瘤(MM)中取得较好的疗效,最常见的靶点为B细胞成熟抗原(BCMA)。单靶点CAR-T细胞免疫疗法的缺点是会导致疾病抵抗和复发,可能与抗原逃逸有关。为此,改进开发了双靶点CAR-T细胞治疗复...背景嵌合抗原受体(CAR)-T细胞免疫疗法已在多发性骨髓瘤(MM)中取得较好的疗效,最常见的靶点为B细胞成熟抗原(BCMA)。单靶点CAR-T细胞免疫疗法的缺点是会导致疾病抵抗和复发,可能与抗原逃逸有关。为此,改进开发了双靶点CAR-T细胞治疗复发难治多发性骨髓瘤(RRMM),此方面尚缺乏系统的临床分析。目的对RRMM患者应用双靶点CAR-T细胞免疫疗法治疗的有效性及安全性进行Meta分析。方法计算机检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方数据知识服务平台、维普网7个数据库中有关双靶点CAR-T细胞治疗RRMM的单组率研究,检索时限为建库至2023-02-06。由2名研究人员使用自制的数据表单来提取收集数据,并采用非随机对照试验方法学评价指标进行文献质量评价。采用R Studio软件进行数据分析。结果共纳入9篇文献,包括200例既往接受过多线治疗的RRMM患者。双靶点CAR-T细胞疗法根据不同靶点可分为4类:BCMA+CD19、BCMA+CD38,BCMA+跨膜剂与钙调节亲环素配体的相互作用者(TACI)、BCMA+人信号淋巴细胞激活分子家族成员7(CS1),其中BCMA+CD19靶点的研究较多。根据输注形式不同CAR-T细胞疗法可分为4类:双特异性CAR-T细胞、联合或序贯输注两种不同CAR-T细胞、双顺反子结构、共转导。Meta分析显示,双靶点CAR-T细胞治疗RRMM的总缓解率(ORR)为90.0%(95%CI=0.849~0.943),完全缓解率(CRR)为54.6%(95%CI=0.416~0.673),微小残留病(MRD)阴性率为75.6%(95%CI=0.489~0.952),髓外病变(EMD)总缓解率为55.1%(95%CI=0.234~0.851),最后一次随访时的复发率为29.7%(95%CI=0.141~0.454),最后一次随访时的生存率为75.6%(95%CI=0.554~0.915),3~4级细胞释放因子综合征(CRS)发生率为16.4%(95%CI=0.094~0.245),神经毒性(ICANS)发生率为4.0%(95%CI=0~0.120)。敏感性分析提示结果稳定。Egger's检验结果显示,ORR(P=0.03)及EMD总缓解率(P=0.02)提示存在一定的偏倚风险;CRR(P=0.53)、MRD阴性率(P=0.79)、最后一次随访时的复发率(P=0.71)、生存率(P=0.98)、3~4级CRS发生率(P=0.90)、ICANS发生率(P=0.30)提示不存在发表偏倚。结论双靶点CAR-T细胞免疫治疗RRMM显示出良好的疗效和安全性,未来需要多中心、大样本、更长随访期的研究来进一步评估其疗效和安全性。展开更多
This study aims at exploring the void space gas effect of earthquake-triggered slope instability and providing a new method for studying the formation mechanism of earthquake-triggered landslides. We analysed the basi...This study aims at exploring the void space gas effect of earthquake-triggered slope instability and providing a new method for studying the formation mechanism of earthquake-triggered landslides. We analysed the basic characteristics, kinematic characteristics, initiation mechanisms and physical mechanical parameters of the Daguangbao landslide, generalized a landslide prototype, and established a geological model and performed simulation tests. Based on the seismic wave propagation theory of rock-soil mass, rock fracture mechanics and the effective stress principle, we found that the void space gas effect is due to the occurrence of excess void space gas pressure when the dynamic response of seismic loads impacts the void space gas in weak intercalated layers of the slope. The excess void space gas pressure generated by the vibration(earthquake) damages the rock mass around the void space with a certain regularity. The model test results show that the effective shear strength of the rock mass can be reduced by 4.4% to 21.6% due to the void space gas effect.展开更多
The Diexi ancient dammed lake is in the upper reaches of the Minjiang River.Six terraces with lacustrine sediments occur at the base.These terraces are the products of the graded outburst of the Diexi ancient dammed l...The Diexi ancient dammed lake is in the upper reaches of the Minjiang River.Six terraces with lacustrine sediments occur at the base.These terraces are the products of the graded outburst of the Diexi ancient dammed lake.The outburst of the ancient dammed lake would certainly have had an impact on the Chengdu Plain in the lower reaches of the Minjiang River.In this paper,on-site sampling and laboratory analysis were used to analyze the sediments of the Diexi ancient dammed lake and the Jinsha site in Chengdu Plain,and the environmental indicators of each sediment layer were tested.Through a comparative analysis of the environmental indicators in the sediments at the two locations,the following results were obtained:the palaeoclimatic and palaeoenvironmental characteristics at the two locations generally show consistent changes.The most important finding is that the types and content of the major pollen taxa at the two locations are similar.The Pinus content strongly proves that the soil layers at the Jinsha site was sourced from the upper reaches of the Minjiang River.Considering that the demise of the ancient culture at the Jinsha site occurred close in time to the outburst of the ancient dammed lake,this similarity suggests that the cultural change at the Jinsha site may have been related to the outburst of the Diexi ancient dammed lake.展开更多
This study discussed how cavity gas pressure affects the stability of rock mass with fractures under well controlled laboratory experiments.Suddenly-created void space created and the induced gas pressures have been t...This study discussed how cavity gas pressure affects the stability of rock mass with fractures under well controlled laboratory experiments.Suddenly-created void space created and the induced gas pressures have been the focus of active researches because they are associated with fast movement of large-scale landslides.A shaking table experiment was set up to mimic weak-intercalated rock slope under seismic loads.Excessive cavity gas pressure would be produced in weak spots upon a sudden vibration load.The drastically elevated gas pressure is believed to be responsible for the creation of cavities surrounding the tension fracture.With dissipation of the excessive cavity gas pressure,the fractures are in unbounded closed-state.This observation explains that the slope body would be split and loosened under several aftershocks,and with the expanding of the cracks,the slope failure eventually occurred.The research of the mechanism of cavity gas pressure could provide a novel insight into the formation mechanism of landslides under seismic load and has implications for the disaster prevention and control theory for the slope stability evaluation.展开更多
文摘背景嵌合抗原受体(CAR)-T细胞免疫疗法已在多发性骨髓瘤(MM)中取得较好的疗效,最常见的靶点为B细胞成熟抗原(BCMA)。单靶点CAR-T细胞免疫疗法的缺点是会导致疾病抵抗和复发,可能与抗原逃逸有关。为此,改进开发了双靶点CAR-T细胞治疗复发难治多发性骨髓瘤(RRMM),此方面尚缺乏系统的临床分析。目的对RRMM患者应用双靶点CAR-T细胞免疫疗法治疗的有效性及安全性进行Meta分析。方法计算机检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方数据知识服务平台、维普网7个数据库中有关双靶点CAR-T细胞治疗RRMM的单组率研究,检索时限为建库至2023-02-06。由2名研究人员使用自制的数据表单来提取收集数据,并采用非随机对照试验方法学评价指标进行文献质量评价。采用R Studio软件进行数据分析。结果共纳入9篇文献,包括200例既往接受过多线治疗的RRMM患者。双靶点CAR-T细胞疗法根据不同靶点可分为4类:BCMA+CD19、BCMA+CD38,BCMA+跨膜剂与钙调节亲环素配体的相互作用者(TACI)、BCMA+人信号淋巴细胞激活分子家族成员7(CS1),其中BCMA+CD19靶点的研究较多。根据输注形式不同CAR-T细胞疗法可分为4类:双特异性CAR-T细胞、联合或序贯输注两种不同CAR-T细胞、双顺反子结构、共转导。Meta分析显示,双靶点CAR-T细胞治疗RRMM的总缓解率(ORR)为90.0%(95%CI=0.849~0.943),完全缓解率(CRR)为54.6%(95%CI=0.416~0.673),微小残留病(MRD)阴性率为75.6%(95%CI=0.489~0.952),髓外病变(EMD)总缓解率为55.1%(95%CI=0.234~0.851),最后一次随访时的复发率为29.7%(95%CI=0.141~0.454),最后一次随访时的生存率为75.6%(95%CI=0.554~0.915),3~4级细胞释放因子综合征(CRS)发生率为16.4%(95%CI=0.094~0.245),神经毒性(ICANS)发生率为4.0%(95%CI=0~0.120)。敏感性分析提示结果稳定。Egger's检验结果显示,ORR(P=0.03)及EMD总缓解率(P=0.02)提示存在一定的偏倚风险;CRR(P=0.53)、MRD阴性率(P=0.79)、最后一次随访时的复发率(P=0.71)、生存率(P=0.98)、3~4级CRS发生率(P=0.90)、ICANS发生率(P=0.30)提示不存在发表偏倚。结论双靶点CAR-T细胞免疫治疗RRMM显示出良好的疗效和安全性,未来需要多中心、大样本、更长随访期的研究来进一步评估其疗效和安全性。
基金funded by the State Key Laboratory of Geohazard Prevention and Geoenvironment Protection (No.SKLGP2016Z015)the Natural Science Foundation of China (No. 41572308)
文摘This study aims at exploring the void space gas effect of earthquake-triggered slope instability and providing a new method for studying the formation mechanism of earthquake-triggered landslides. We analysed the basic characteristics, kinematic characteristics, initiation mechanisms and physical mechanical parameters of the Daguangbao landslide, generalized a landslide prototype, and established a geological model and performed simulation tests. Based on the seismic wave propagation theory of rock-soil mass, rock fracture mechanics and the effective stress principle, we found that the void space gas effect is due to the occurrence of excess void space gas pressure when the dynamic response of seismic loads impacts the void space gas in weak intercalated layers of the slope. The excess void space gas pressure generated by the vibration(earthquake) damages the rock mass around the void space with a certain regularity. The model test results show that the effective shear strength of the rock mass can be reduced by 4.4% to 21.6% due to the void space gas effect.
基金funded by the National Natural Science Foundation of China(No.41977226)the State Key Laboratory of Geohazard Prevention and Geoenvironment Protection(No.SKLGP2016Z015)。
文摘The Diexi ancient dammed lake is in the upper reaches of the Minjiang River.Six terraces with lacustrine sediments occur at the base.These terraces are the products of the graded outburst of the Diexi ancient dammed lake.The outburst of the ancient dammed lake would certainly have had an impact on the Chengdu Plain in the lower reaches of the Minjiang River.In this paper,on-site sampling and laboratory analysis were used to analyze the sediments of the Diexi ancient dammed lake and the Jinsha site in Chengdu Plain,and the environmental indicators of each sediment layer were tested.Through a comparative analysis of the environmental indicators in the sediments at the two locations,the following results were obtained:the palaeoclimatic and palaeoenvironmental characteristics at the two locations generally show consistent changes.The most important finding is that the types and content of the major pollen taxa at the two locations are similar.The Pinus content strongly proves that the soil layers at the Jinsha site was sourced from the upper reaches of the Minjiang River.Considering that the demise of the ancient culture at the Jinsha site occurred close in time to the outburst of the ancient dammed lake,this similarity suggests that the cultural change at the Jinsha site may have been related to the outburst of the Diexi ancient dammed lake.
基金financially supported by Project of the National Natural Science Foundation of China (Grant No.41072230)Project of State Key Laboratory of Geohazard Prevention and Geoenvironment Protection (No.SKLGP2012Z008)Project of Chengdu University of Technology Research and Innovation Team
文摘This study discussed how cavity gas pressure affects the stability of rock mass with fractures under well controlled laboratory experiments.Suddenly-created void space created and the induced gas pressures have been the focus of active researches because they are associated with fast movement of large-scale landslides.A shaking table experiment was set up to mimic weak-intercalated rock slope under seismic loads.Excessive cavity gas pressure would be produced in weak spots upon a sudden vibration load.The drastically elevated gas pressure is believed to be responsible for the creation of cavities surrounding the tension fracture.With dissipation of the excessive cavity gas pressure,the fractures are in unbounded closed-state.This observation explains that the slope body would be split and loosened under several aftershocks,and with the expanding of the cracks,the slope failure eventually occurred.The research of the mechanism of cavity gas pressure could provide a novel insight into the formation mechanism of landslides under seismic load and has implications for the disaster prevention and control theory for the slope stability evaluation.
