Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with ...Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.展开更多
In order to understand the dominant factors of the physical properties of ice in ice thermodynamics and mechanics,in-situ observations of ice growth and decay processes were carried out.Two samplings were conducted in...In order to understand the dominant factors of the physical properties of ice in ice thermodynamics and mechanics,in-situ observations of ice growth and decay processes were carried out.Two samplings were conducted in the fast and steady ice growth stages.Ice pieces were used to observe ice crystals and gas bubbles in ice,and to measure the ice density.Vertical profiles of the type and size of ice crystals,shape and size of gas bubbles,and gas bubble content,as well as the ice density,were obtained.The results show that the upper layer of the ice pieces is granular ice and the lower layer is columnar ice;the average crystal size increases with the ice depth and remains steady in the fast and steady ice growth stages;the shape of gas bubbles in the upper layer of ice pieces is spherical with higher total content,and the shape in the middle and lower layers is cylinder with lower total content;the gas bubble size and content vary with the ice growth stage;and the ice density decreases with the increase of the gas bubble content.展开更多
This paper presents a simple approach for improving the performance of the weighted essentially nonoscillatory(WENO) finite volume scheme on non-uniform grids. This technique relies on the reformulation of the fifthor...This paper presents a simple approach for improving the performance of the weighted essentially nonoscillatory(WENO) finite volume scheme on non-uniform grids. This technique relies on the reformulation of the fifthorder WENO-JS(WENO scheme presented by Jiang and Shu in J. Comput. Phys. 126:202–228, 1995) scheme designed on uniform grids in terms of one cell-averaged value and its left and/or right interfacial values of the dependent variable.The effect of grid non-uniformity is taken into consideration by a proper interpolation of the interfacial values. On nonuniform grids, the proposed scheme is much more accurate than the original WENO-JS scheme, which was designed for uniform grids. When the grid is uniform, the resulting scheme reduces to the original WENO-JS scheme. In the meantime,the proposed scheme is computationally much more efficient than the fifth-order WENO scheme designed specifically for the non-uniform grids. A number of numerical test cases are simulated to verify the performance of the present scheme.展开更多
基金the National Natural Science Foundation of China(No.81960043 and No.81600180)Natural Science Foundation of Jiangxi Province(No.20192ACB20030 and No.20203BBGL73197)Science and Technology Innovation Base Construction Project of Jiangxi Province(No.20212BCG74001 and No.20211ZDG02006).
文摘Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.
基金supported by the National Natural Science Foundation of China (Grant No.50879008)the Open Fund of State Key Laboratory of Frozen Soil Engineering (Grant No. SKLFSE200904)+1 种基金the Vilho,Yrj and Kalle Visl Fund of the Finnish Academy of Sciences and Lettersthe Norwegian Research Council Project AMORA (Grant No.193592/S30)
文摘In order to understand the dominant factors of the physical properties of ice in ice thermodynamics and mechanics,in-situ observations of ice growth and decay processes were carried out.Two samplings were conducted in the fast and steady ice growth stages.Ice pieces were used to observe ice crystals and gas bubbles in ice,and to measure the ice density.Vertical profiles of the type and size of ice crystals,shape and size of gas bubbles,and gas bubble content,as well as the ice density,were obtained.The results show that the upper layer of the ice pieces is granular ice and the lower layer is columnar ice;the average crystal size increases with the ice depth and remains steady in the fast and steady ice growth stages;the shape of gas bubbles in the upper layer of ice pieces is spherical with higher total content,and the shape in the middle and lower layers is cylinder with lower total content;the gas bubble size and content vary with the ice growth stage;and the ice density decreases with the increase of the gas bubble content.
基金supported by the National Natural Science Foundation of China (Grant 11672160)the National Key Research and Development Program of China (Grant 2016YF A0401200)
文摘This paper presents a simple approach for improving the performance of the weighted essentially nonoscillatory(WENO) finite volume scheme on non-uniform grids. This technique relies on the reformulation of the fifthorder WENO-JS(WENO scheme presented by Jiang and Shu in J. Comput. Phys. 126:202–228, 1995) scheme designed on uniform grids in terms of one cell-averaged value and its left and/or right interfacial values of the dependent variable.The effect of grid non-uniformity is taken into consideration by a proper interpolation of the interfacial values. On nonuniform grids, the proposed scheme is much more accurate than the original WENO-JS scheme, which was designed for uniform grids. When the grid is uniform, the resulting scheme reduces to the original WENO-JS scheme. In the meantime,the proposed scheme is computationally much more efficient than the fifth-order WENO scheme designed specifically for the non-uniform grids. A number of numerical test cases are simulated to verify the performance of the present scheme.
