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
Surface waves have a considerable effect on vertical mixing in the upper ocean.In the past two decades,the vertical mixing induced through nonbreaking surface waves has been used in ocean and climate models to improve...Surface waves have a considerable effect on vertical mixing in the upper ocean.In the past two decades,the vertical mixing induced through nonbreaking surface waves has been used in ocean and climate models to improve the simulation of the upper ocean.Thus far,several nonbreaking wave-induced mixing parameterization schemes have been proposed;however,no quantitative comparison has been performed among them.In this paper,a one-dimensional ocean model was used to compare the performances of five schemes,including those of Qiao et al.(Q),Hu and Wang(HW),Huang and Qiao(HQ),Pleskachevsky et al.(P),and Ghantous and Babanin(GB).Similar to previous studies,all of these schemes can decrease the simulated sea surface temperature(SST),increase the subsurface temperature,and deepen the mixed layer,thereby alleviating the common thermal deviation problem of the ocean model for upper ocean simulation.Among these schemes,the HQ scheme exhibited the weakest wave-induced mixing effect,and the HW scheme exhibited the strongest effect;the other three schemes exhibited roughly the same effect.In particular,the Q and P schemes exhibited nearly the same effect.In the simulation based on observations from the Ocean Weather Station Papa,the HQ scheme exhibited the best performance,followed by the Q scheme.In the experiment with the HQ scheme,the root-mean-square deviation of the simulated SST from the observations was 0.43℃,and the mixed layer depth(MLD)was 2.0 m.As a contrast,the deviations of the SST and MLD reached 1.25℃ and 8.4 m,respectively,in the experiment without wave-induced mixing.展开更多
Six novel hydrolytically degradable polyesters were synthesized from thiodipropionic acid(TDPA)and five diols by melt polycondensation,and characterized by FT-IR,1H NMR,gel permeation chromatography,differential scann...Six novel hydrolytically degradable polyesters were synthesized from thiodipropionic acid(TDPA)and five diols by melt polycondensation,and characterized by FT-IR,1H NMR,gel permeation chromatography,differential scanning calorimetry and thermogravimetry analysis.The polystyrene-equivalent number-average(Mn)and weight-average molecular weight(Mw)of these polyesters ranged from 4900-11100 Da and 7900-20879 Da,respectively,with PDI values of 1.48-1.98.The melting point varied from 62.3-127.9℃,and the 50%mass-loss temperature ranged between 387-417℃.The degradation of these polyesters was studied in terms of relative weight loss in distilled water at different pH.Weight losses of 14%-26%were obtained at pH 7.0,26%-38%at pH 6.0,and 32%-43%at pH 8.3 over a 20-week period.The ecotoxicity study suggested that safety of the synthesized polyesters for the eisenia foetida.These results indicate that these polyesters have a combination of good thermal and degradability behaviors,which can be tailored through selection of the diol monomers used in the synthesis.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supported by the Laoshan Laboratory(No.LSKJ202201600)the National Key Research and Development Program of China(No.2022YFC2808304).
文摘Surface waves have a considerable effect on vertical mixing in the upper ocean.In the past two decades,the vertical mixing induced through nonbreaking surface waves has been used in ocean and climate models to improve the simulation of the upper ocean.Thus far,several nonbreaking wave-induced mixing parameterization schemes have been proposed;however,no quantitative comparison has been performed among them.In this paper,a one-dimensional ocean model was used to compare the performances of five schemes,including those of Qiao et al.(Q),Hu and Wang(HW),Huang and Qiao(HQ),Pleskachevsky et al.(P),and Ghantous and Babanin(GB).Similar to previous studies,all of these schemes can decrease the simulated sea surface temperature(SST),increase the subsurface temperature,and deepen the mixed layer,thereby alleviating the common thermal deviation problem of the ocean model for upper ocean simulation.Among these schemes,the HQ scheme exhibited the weakest wave-induced mixing effect,and the HW scheme exhibited the strongest effect;the other three schemes exhibited roughly the same effect.In particular,the Q and P schemes exhibited nearly the same effect.In the simulation based on observations from the Ocean Weather Station Papa,the HQ scheme exhibited the best performance,followed by the Q scheme.In the experiment with the HQ scheme,the root-mean-square deviation of the simulated SST from the observations was 0.43℃,and the mixed layer depth(MLD)was 2.0 m.As a contrast,the deviations of the SST and MLD reached 1.25℃ and 8.4 m,respectively,in the experiment without wave-induced mixing.
基金Funded by the Program (BG20190227001)of High-end Foreign Experts of the State Administration of Foreign Experts Affairs (SAFEA)the Coal Conversion and New Carbon Materials Hubei Key Laboratory at Wuhan University of Science and Technology (WKDM202005)。
文摘Six novel hydrolytically degradable polyesters were synthesized from thiodipropionic acid(TDPA)and five diols by melt polycondensation,and characterized by FT-IR,1H NMR,gel permeation chromatography,differential scanning calorimetry and thermogravimetry analysis.The polystyrene-equivalent number-average(Mn)and weight-average molecular weight(Mw)of these polyesters ranged from 4900-11100 Da and 7900-20879 Da,respectively,with PDI values of 1.48-1.98.The melting point varied from 62.3-127.9℃,and the 50%mass-loss temperature ranged between 387-417℃.The degradation of these polyesters was studied in terms of relative weight loss in distilled water at different pH.Weight losses of 14%-26%were obtained at pH 7.0,26%-38%at pH 6.0,and 32%-43%at pH 8.3 over a 20-week period.The ecotoxicity study suggested that safety of the synthesized polyesters for the eisenia foetida.These results indicate that these polyesters have a combination of good thermal and degradability behaviors,which can be tailored through selection of the diol monomers used in the synthesis.
