Objective Mycobacterium tuberculosis(Mtb),the causative agent of tuberculosis(TB),causes an estimated 1.6 million human deaths annually,but the pathogenesis of TB remains unclear.Immunity plays a critical role in the ...Objective Mycobacterium tuberculosis(Mtb),the causative agent of tuberculosis(TB),causes an estimated 1.6 million human deaths annually,but the pathogenesis of TB remains unclear.Immunity plays a critical role in the onset and outcome of TB.This study aimed to uncover the roles of innate and adaptive immunity in TB.Methods The gene expression profiles generated by RNA sequencing from human peripheral blood mononuclear cells(PBMCs)stimulated with or without Mtb strain H37Rv antigens were analyzed.A total of 973 differentially expressed mRNAs were identified.Results The differentially expressed genes were enriched in innate immunity signaling functions.The mesenchymal-epithelial transition factor(MET)gene was significantly upregulated in CD14^(+)monocytes.A MET inhibitor improved the uptake of the BCG strain by monocytes and macrophages as well as inhibited the expression of indoleamine 2,3-dioxygenase(IDO).The expression of IDO was increased in PBMCs stimulated with Mtb antigens,and the IDO inhibitor promoted the expression of CD40,CD83,and CD86.Conclusion Our results might provide clues regarding the immunomodulatory mechanisms used by Mtb to evade the host defense system.展开更多
BACKGROUND Due to the rarity of mesenchymal-epithelial transition factor(MET)fusions,the clinical efficacy of crizotinib has only been described in a few patients with MET fusions involving various fusion partners.Her...BACKGROUND Due to the rarity of mesenchymal-epithelial transition factor(MET)fusions,the clinical efficacy of crizotinib has only been described in a few patients with MET fusions involving various fusion partners.Herein,we report the clinical response to crizotinib of a patient with advanced poorly differentiated non-small cell carcinoma(NSCLC)having concurrent MET fusions.CASE SUMMARY A 46-year-old woman was diagnosed with poorly differentiated NSCLC(T4 N3 M1).With no classic driver mutations,she was treated with two cycles of gemcitabine and cisplatin without clinical benefit.Targeted sequencing revealed the detection of two concurrent MET fusions,KIF5 B-MET and novel MET-CDR2.Crizotinib was initiated at a dose of 250 mg twice daily.Within 4 wk of crizotinib therapy,repeat computed chromatography revealed a dramatic reduction in primary and metastatic lesions,assessed as partial response.She continued to benefit from crizotinib for 3 mo until disease progression and died within 1 mo despite receiving nivolumab therapy.CONCLUSION Crizotinib sensitivity was observed in an advanced poorly differentiated NSCLC patient with concurrent MET fusions KIF5 B-MET and MET-CDR2.Crizotinib can serve as a therapeutic option for patients with MET fusions.In addition,our case also highlights the importance of comprehensive genomic profiling particularly in patients with no classic driver mutation for guiding alternative therapeutic decisions.展开更多
为了验证放大因子输运方程与Spalart-Allmaras(S-A)湍流模型耦合对转捩现象的模拟精度,选取Schubauer and Klebanoff(S-K)平板、S809低速翼型、30p30n多段翼型以及复杂的三维HiLiftPW-1构型进行自由转捩计算,并将计算结果与实验进行比...为了验证放大因子输运方程与Spalart-Allmaras(S-A)湍流模型耦合对转捩现象的模拟精度,选取Schubauer and Klebanoff(S-K)平板、S809低速翼型、30p30n多段翼型以及复杂的三维HiLiftPW-1构型进行自由转捩计算,并将计算结果与实验进行比较分析,其中针对S809算例,还与Langtry-Menter(L-M)转捩模型进行了比较.算例结果表明:放大因子输运方程与S-A湍流模型的耦合能够较好的捕捉转捩位置以及转捩发展过程,对分离泡诱导的转捩的模拟相比L-M转捩模型更精确,转捩位置的捕捉精度提升了10%;对比实验,多段翼转捩位置的捕捉误差最大为6.5%;针对三维高升力增升构型,以实验作为参考,全湍流计算与考虑边界层转捩的对比显示考虑边界层转捩能够更加精确的模拟气动力系数,升力和表面摩擦阻力系数的模拟精度精度提升1%.展开更多
基金This study was supported by the Thirteen-Fifth Mega-Scientific Project on“Prevention and Treatment of AIDS,Viral Hepatitis and Other Infectious Diseases”(No.2017ZX10201301-007-002)the National Natural Science Foundation of China(No.81571961 and No.82072233)the 309th Hospital(No.2017ZD-007).
文摘Objective Mycobacterium tuberculosis(Mtb),the causative agent of tuberculosis(TB),causes an estimated 1.6 million human deaths annually,but the pathogenesis of TB remains unclear.Immunity plays a critical role in the onset and outcome of TB.This study aimed to uncover the roles of innate and adaptive immunity in TB.Methods The gene expression profiles generated by RNA sequencing from human peripheral blood mononuclear cells(PBMCs)stimulated with or without Mtb strain H37Rv antigens were analyzed.A total of 973 differentially expressed mRNAs were identified.Results The differentially expressed genes were enriched in innate immunity signaling functions.The mesenchymal-epithelial transition factor(MET)gene was significantly upregulated in CD14^(+)monocytes.A MET inhibitor improved the uptake of the BCG strain by monocytes and macrophages as well as inhibited the expression of indoleamine 2,3-dioxygenase(IDO).The expression of IDO was increased in PBMCs stimulated with Mtb antigens,and the IDO inhibitor promoted the expression of CD40,CD83,and CD86.Conclusion Our results might provide clues regarding the immunomodulatory mechanisms used by Mtb to evade the host defense system.
基金Supported by the National Key R&D Program of ChinaNo. 2017YFC0907900 and 2017YFC0907904
文摘BACKGROUND Due to the rarity of mesenchymal-epithelial transition factor(MET)fusions,the clinical efficacy of crizotinib has only been described in a few patients with MET fusions involving various fusion partners.Herein,we report the clinical response to crizotinib of a patient with advanced poorly differentiated non-small cell carcinoma(NSCLC)having concurrent MET fusions.CASE SUMMARY A 46-year-old woman was diagnosed with poorly differentiated NSCLC(T4 N3 M1).With no classic driver mutations,she was treated with two cycles of gemcitabine and cisplatin without clinical benefit.Targeted sequencing revealed the detection of two concurrent MET fusions,KIF5 B-MET and novel MET-CDR2.Crizotinib was initiated at a dose of 250 mg twice daily.Within 4 wk of crizotinib therapy,repeat computed chromatography revealed a dramatic reduction in primary and metastatic lesions,assessed as partial response.She continued to benefit from crizotinib for 3 mo until disease progression and died within 1 mo despite receiving nivolumab therapy.CONCLUSION Crizotinib sensitivity was observed in an advanced poorly differentiated NSCLC patient with concurrent MET fusions KIF5 B-MET and MET-CDR2.Crizotinib can serve as a therapeutic option for patients with MET fusions.In addition,our case also highlights the importance of comprehensive genomic profiling particularly in patients with no classic driver mutation for guiding alternative therapeutic decisions.
文摘为了验证放大因子输运方程与Spalart-Allmaras(S-A)湍流模型耦合对转捩现象的模拟精度,选取Schubauer and Klebanoff(S-K)平板、S809低速翼型、30p30n多段翼型以及复杂的三维HiLiftPW-1构型进行自由转捩计算,并将计算结果与实验进行比较分析,其中针对S809算例,还与Langtry-Menter(L-M)转捩模型进行了比较.算例结果表明:放大因子输运方程与S-A湍流模型的耦合能够较好的捕捉转捩位置以及转捩发展过程,对分离泡诱导的转捩的模拟相比L-M转捩模型更精确,转捩位置的捕捉精度提升了10%;对比实验,多段翼转捩位置的捕捉误差最大为6.5%;针对三维高升力增升构型,以实验作为参考,全湍流计算与考虑边界层转捩的对比显示考虑边界层转捩能够更加精确的模拟气动力系数,升力和表面摩擦阻力系数的模拟精度精度提升1%.
