Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-de...Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.展开更多
目的探究呼气末正压(PEEP)和吸氧浓度(FiO_(2))调整顺序对急性呼吸窘迫综合征(ARDS)机械通气恢复期病人肺部损伤的影响。方法选取2016年7月至2020年8月在河北省人民医院急诊重症监护室(EICU)就诊的80例需机械通气的ARDS病人,采用随机数...目的探究呼气末正压(PEEP)和吸氧浓度(FiO_(2))调整顺序对急性呼吸窘迫综合征(ARDS)机械通气恢复期病人肺部损伤的影响。方法选取2016年7月至2020年8月在河北省人民医院急诊重症监护室(EICU)就诊的80例需机械通气的ARDS病人,采用随机数字表法分为PEEP固定组和FiO_(2)固定组,各40例。两组病人均采用肺保护性通气策略。病情稳定后,PEEP固定组维持呼吸机参数不变(PEEP=12~15 cmH_(2)O),FiO_(2)逐渐调整为80%、60%、40%;FiO_(2)固定组维持FiO_(2)=60%不变,PEEP水平逐渐调整为12、10、8 cm H_(2)O。对比不同时间肺泡灌洗液(BALF)中肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)和肺表面活性蛋白A(SP-A)水平。结果随着PEEP水平和FiO_(2)的降低,两组病人TNF-α、IL-6和SP-A水平呈下降趋势;但调整参数1 h后,TNF-α、IL-6和SP-A水平升高。两组病人在调整FiO_(2)=40%、PEEP=8 cm H_(2)O前0 h,TNF-α、IL-6和SP-A水平最低,且FiO_(2)固定组低于PEEP固定组(P<0.05)。结论降低PEEP水平和FiO_(2)有利于减轻ARDS病人炎症反应及降低SP-A水平,先降低PEEP水平后降低FiO_(2),对ARDS机械通气恢复期病人肺部炎性损伤的改善作用较好。展开更多
Lithium-sulfur(Li-S) batteries hold great promise in next-generation high-energy-density energy storage systems,but the intractable shuttle effect and the sluggish redox kinetics of polysulfides hinder the practical i...Lithium-sulfur(Li-S) batteries hold great promise in next-generation high-energy-density energy storage systems,but the intractable shuttle effect and the sluggish redox kinetics of polysulfides hinder the practical implementation of Li-S batteries.Here,heterostructured Fe_(3)C-FeN nanoparticles dotted in the threedimensional-ordered nitrogen-doped carbon framework(Fe_(3)C-FeN@NCF) were synthesized by molecular engineering combined with heterointerface engineering,and were applied to regulate the immobilization-diffusion-conversion behavior of polar polysulfides.It is experimentally and theoretically demonstrated that the heterointerface between Fe_(3)C and FeN exhibits high sulfiphilicity and high electronic/ionic conductivity,thus effectively capturing polysulfides and accelerating the bidirectional conversion of sulfur species.Meanwhile,the holey carbon framework functions as the scaffold to highly disperse binary nanoparticles,ensuring the sufficient exposure of active sites and the easy accessibility for lithium ions and electrons.By virtue of these synergistic merits,the Li-S batteries based on Fe_(3)CFeN@NCF-modified separators afford excellent electrochemical performances including a high rate capacity of 858 mA h g^(-1)at 2 C and a low capacity decay rate of 0.07% per cycle after 800 cycles at 1C This work provides inspiration for the design of heterostructured compounds and sheds light on the potential of heterostructure in high-efficiency Li-S batteries.展开更多
基金sponsored by BeiGene.Third-party medical writing assistance was provided by Ghina Yaacoub,MSc,of Ashfield MedComms,an Inizio Company,and funded by BeiGene.
文摘Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
文摘目的探究呼气末正压(PEEP)和吸氧浓度(FiO_(2))调整顺序对急性呼吸窘迫综合征(ARDS)机械通气恢复期病人肺部损伤的影响。方法选取2016年7月至2020年8月在河北省人民医院急诊重症监护室(EICU)就诊的80例需机械通气的ARDS病人,采用随机数字表法分为PEEP固定组和FiO_(2)固定组,各40例。两组病人均采用肺保护性通气策略。病情稳定后,PEEP固定组维持呼吸机参数不变(PEEP=12~15 cmH_(2)O),FiO_(2)逐渐调整为80%、60%、40%;FiO_(2)固定组维持FiO_(2)=60%不变,PEEP水平逐渐调整为12、10、8 cm H_(2)O。对比不同时间肺泡灌洗液(BALF)中肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)和肺表面活性蛋白A(SP-A)水平。结果随着PEEP水平和FiO_(2)的降低,两组病人TNF-α、IL-6和SP-A水平呈下降趋势;但调整参数1 h后,TNF-α、IL-6和SP-A水平升高。两组病人在调整FiO_(2)=40%、PEEP=8 cm H_(2)O前0 h,TNF-α、IL-6和SP-A水平最低,且FiO_(2)固定组低于PEEP固定组(P<0.05)。结论降低PEEP水平和FiO_(2)有利于减轻ARDS病人炎症反应及降低SP-A水平,先降低PEEP水平后降低FiO_(2),对ARDS机械通气恢复期病人肺部炎性损伤的改善作用较好。
基金supported by the National Natural Science Foundation of China(22005341 and 22138013)the Shandong Provincial Natural Science Foundation(ZR2020QB128 and ZR2020ZD08)+2 种基金the Taishan Scholar Project(ts201712020)the Major Scientific and Technological Innovation Project of Shandong Province(2020CXGC010402)the Independent Innovation Research Project of China University of Petroleum(22CX06026A)。
文摘Lithium-sulfur(Li-S) batteries hold great promise in next-generation high-energy-density energy storage systems,but the intractable shuttle effect and the sluggish redox kinetics of polysulfides hinder the practical implementation of Li-S batteries.Here,heterostructured Fe_(3)C-FeN nanoparticles dotted in the threedimensional-ordered nitrogen-doped carbon framework(Fe_(3)C-FeN@NCF) were synthesized by molecular engineering combined with heterointerface engineering,and were applied to regulate the immobilization-diffusion-conversion behavior of polar polysulfides.It is experimentally and theoretically demonstrated that the heterointerface between Fe_(3)C and FeN exhibits high sulfiphilicity and high electronic/ionic conductivity,thus effectively capturing polysulfides and accelerating the bidirectional conversion of sulfur species.Meanwhile,the holey carbon framework functions as the scaffold to highly disperse binary nanoparticles,ensuring the sufficient exposure of active sites and the easy accessibility for lithium ions and electrons.By virtue of these synergistic merits,the Li-S batteries based on Fe_(3)CFeN@NCF-modified separators afford excellent electrochemical performances including a high rate capacity of 858 mA h g^(-1)at 2 C and a low capacity decay rate of 0.07% per cycle after 800 cycles at 1C This work provides inspiration for the design of heterostructured compounds and sheds light on the potential of heterostructure in high-efficiency Li-S batteries.
