Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objectiv...Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).展开更多
Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-c...Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.展开更多
Bismuth has garnered significant interest as an anode material for magnesium batteries(MBs) because of its high volumetric specific capacity and low working potential. Nonetheless, the limited cycling performance(≤10...Bismuth has garnered significant interest as an anode material for magnesium batteries(MBs) because of its high volumetric specific capacity and low working potential. Nonetheless, the limited cycling performance(≤100 cycles) limits the practical application of Bi as anode for MBs. Therefore, the improvement of Bi cycling performance is of great significance to the development of MBs and is also full of challenges. Here, Bi nanoparticles encapsulated in nitrogen-doped carbon with single-atom Bi embedded(Bi@NC) are prepared and reported as an anode material for MBs. Bi@NC demonstrates impressive performance, with a high discharge capacity of 347.5 mAh g^(-1) and good rate capability(206.4 mAh g^(-1)@500 mA g^(-1)) in a fluoride alkyl magnesium salt electrolyte. In addition, Bi@NC exhibits exceptional long-term stability, enduring 400 cycles at 500 mA g^(-1). To the best of our knowledge, among reported Bi and Bi-based compounds for MBs, Bi@NC exhibits the longest cycle life in this work. The magnesium storage mechanism of Bi@NC is deeply studied through X-ray diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy. This work provides some guidance for further improving the cycling performance of other alloy anodes in MBs.展开更多
Objective: Bethesda System for Reporting Thyroid Cytopathology(BSRTC) categories Ⅰ, Ⅲ, and Ⅴaccount for a significant proportion of fine needle aspiration cytology(FNAC) diagnoses. This study aimed to compare the d...Objective: Bethesda System for Reporting Thyroid Cytopathology(BSRTC) categories Ⅰ, Ⅲ, and Ⅴaccount for a significant proportion of fine needle aspiration cytology(FNAC) diagnoses. This study aimed to compare the diagnostic efficacy of BRAF^(V600E) mutation and the Thyroid Imaging Reporting and Data System(TIRADS) classification in differentiating papillary thyroid cancers(PTCs) from benign lesions among BSRTC I, III, and V nodules.Methods: A total of 472 patients with 479 nodules were enrolled in this prospective study. Ultrasound, BRAF^(V600E) mutation testing, and FNAC were performed in each nodule, followed by surgery or regular ultrasound examination.Results: In the BSRTC I category, BRAF^(V600E) showed similar sensitivity, higher specificity, and lower accuracy when compared with TIRADS. In the BSRTC III/V category, the sensitivity, specificity, and accuracy of BRAF^(V600E) were similar to those of TIRADS. In comparison to BRAF^(V600E) alone, the combination of the two methods significantly improved sensitivity(BSRTC Ⅰ:93.6% vs. 67.7%, P < 0.01; BSRTC Ⅲ: 93.8% vs. 75.0%, P < 0.01; BSRTC V: 96.0% vs. 85.3%, P < 0.001). When compared with TIRADS alone, the combination improved sensitivity in BSRTC Ⅰ nodules(93.6% vs. 74.2%, P < 0.05), increased sensitivity and decreased accuracy in BSRTC III nodules(93.8% vs. 75.0%, P < 0.01, 91.0% vs. 93.6%, P < 0.01), and improved both sensitivity and accuracy in BSRTC V nodules(96.0% vs. 82.0%, P < 0.001; 94.2% vs. 81.3%, P < 0.001).Conclusions: BRAF^(V600E) exhibited higher specificity and lower accuracy compared with TIRADS in BSRTC Ⅰ nodules, while the two methods showed similar diagnostic value in BSRTC Ⅲ/Ⅴ nodules. The combination of the two methods distinctly improved sensitivity in the diagnosis of PTCs in BSRTC Ⅰ, Ⅲ, and Ⅴ nodules.展开更多
Peridynamics is a nonlocal continuum mechanics theory.Peridynamics overcomes the computational challenges in classical continuum mechanics and enables the solution of complex mechanical and physical equations in the p...Peridynamics is a nonlocal continuum mechanics theory.Peridynamics overcomes the computational challenges in classical continuum mechanics and enables the solution of complex mechanical and physical equations in the presence of jump discontinuities or singularities with ease and simplicity,while preserving a length scale to capture nonlocal behavior.Peridynamics has been recently extended and further developed to solve mass and heat transfer and fluid dynamics.Therefore,peridynamics can now be used for analyzing multiphysics and multiscale problems involving damage and cracks.As a rapidly rising topic in computational mechanics,peridynamics has gained intensive and wide interests in the community.展开更多
Ivosidenib,an isocitrate dehydrogenase 1(IDH1)inhibitor,has demonstrated clinical benefits in a pivotal study(AG120-C-001)in patients with IDH1-mutated(mIDH1)acute myeloid leukemia(AML).A registry study(CS3010-101:NCT...Ivosidenib,an isocitrate dehydrogenase 1(IDH1)inhibitor,has demonstrated clinical benefits in a pivotal study(AG120-C-001)in patients with IDH1-mutated(mIDH1)acute myeloid leukemia(AML).A registry study(CS3010-101:NCT04176393)was conducted to assess the pharmacokinetic(PK)characteristics,safety,and efficacy of ivosidenib in Chinese patients with relapsed or refractory(R/R)mIDH1 AML.Patients received ivosidenib 500 mg once daily for 28-day cycles until disease progression.Ten subjects underwent intensive PK/progressive disease(PD)assessments.All subjects had the clinical response assessed at screening,every 28 days through month 12,and then every 56 days.Between November 12,2019,and April 2,2021,30 patients were enrolled;26(86.7%)had de novo AML and 18(60.0%)were transfusion-dependent at baseline.Following single and repeated doses of ivosidenib,median time to maximum plasma concentration(T_(max))was 4.0 and 2.0 hours,respectively.The inter-individual variability of pharmacokinetic exposure was moderate to high(coefficient of variation[CV],25%–53%).No obvious accumulation was observed after repeated doses at cycle 2 day 1.Regarding the clinical response,the CR+CRh rate was 36.7%(95%confidence interval[CI]:19.9%–56.1%),the median duration of CR+CRh was 19.7 months(95%CI:2.9 months–not reached[NR]),and median duration of response(DoR)was 14.3 months(95%CI:6.4 months–NR).Consistent clinical benefits and safety of ivosidenib were consistently observed at the final data cutoff with median follow-up time 26.0 months,as compared with primary data cutoff,and the data from Chinese R/R mIDH1 AML patients were also consistent with results from pivotal study.展开更多
CD19 chimeric antigen receptor(CAR)T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia(R/R ALL),but compromising result in chronic lymphoblastic leukemia(CLL)and non-Hodgkin’s l...CD19 chimeric antigen receptor(CAR)T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia(R/R ALL),but compromising result in chronic lymphoblastic leukemia(CLL)and non-Hodgkin’s lymphoma(NHL).CD19-relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome.CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure.Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape.Here,we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen.Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells,suggesting they exhibited dual antigen targeting of CD19 and CD20.By comparing the efficiency of four bispecific CAR modified T cells,it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients’primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model.These data highlighted the potential of loop2019 CAR-T in clinical treatment.展开更多
Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIP...Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIPI)risk group is still confusing.We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment.We identified 93 patients between 2013 and 2019 who received RM every 3 months for≥4 doses(RM group),and 60 patients who did not accept RM or received rituximab less than 4 doses(control group).After a median follow-up of 39 months,neither median overall survival(OS)nor PFS was reached for the entire population.The PFS was significantly prolonged in the RM group compared to the control group(median PFS NA vs 83.1 months,P=.00027).When the population was divided into the 3 FLIPI risk groups,the PFS differed significantly(4-year PFS rates,97.5%vs 88.8%vs 72.3%,P=.01)according to group.There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group(4-year PFS rates,100%vs 93.8%,P=.23).However,the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk(4-year PFS rates,100%vs 70.3%,P=.00077)and high-risk patients(4-year PFS rates,86.7%vs 57.1%,P=.023).These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate-and high-risk FLIPI groups but not to low-risk FLIPI group,and pending larger-scale studies to validate.展开更多
Patients with double-mutated CEBPA(CEBPAdm)AML were stratified into favorable risk group,however,few studies have investigated the heterogeneity of different CEBPAdm types in detail.In this study,we analyzed 2211 newl...Patients with double-mutated CEBPA(CEBPAdm)AML were stratified into favorable risk group,however,few studies have investigated the heterogeneity of different CEBPAdm types in detail.In this study,we analyzed 2211 newly diagnosed AML and identified CEBPAdm in 10.8%of the patients.Within the CEBPAdm cohort,225 of 239 patients(94.14%)presented with bZIP region mutations(CEBPAdmbZIP)while 14 of 239 patients(5.86%)without bZIP region mutation(CEBPAdmnonbZIP).Analysis of the accompanied molecular mutations showed statistically different incidences of GATA2 mutations between the CEBPAdmbZIP group and the CEBPAdmnonbZIP group(30.29%vs 0%).In the analysis of outcomes,patients with CEBPAdmnonbZIP were associated with shorter overall survival(OS)censored at hematopoietic stem cell transplantation(HSCT)during CR1 compared to those with CEBPAdmbZIP(hazard ratio(HR)=3.132,95%confidence interval(CI)=1.229–7.979,P=.017).Refractory or relapsed AML(R/RAML)patients with CEBPAdmnonbZIP were associated with shorter OS compared to those with CEBPAdmbZIP(HR=2.881,95%CI=1.021–8.131,P=.046).Taken together,AML with CEBPAdmbZIP and CEBPAdmnonbZIP showed different outcomes and might be regarded as distinctive AML entities.展开更多
Methotrexate(MTX)has an antitumor effect when used for the treatment of acute lymphoblastic leukemia(ALL).This study aims at evaluating the associations between 14 polymorphisms of six genes involved in MTX metabolism...Methotrexate(MTX)has an antitumor effect when used for the treatment of acute lymphoblastic leukemia(ALL).This study aims at evaluating the associations between 14 polymorphisms of six genes involved in MTX metabolism with serum MTX concentration and toxicity accompanying high-dose MTX.Polymorphisms in 183 Chinese patients with ALL were analyzed using TaqMan single nucleotide polymorphism genotyping assay.The serum MTX concentration was determined using homogeneous enzyme immunoassay.MTX-related toxicities were also evaluated.Renal toxicity was significantly associated with higher serum MTX concentrations at 24,48,and 72 hours,and MTX elimination delay(P=0.001,P<0.001,P<0.001,and P<0.001,respectively),whereas SLCO1B1 rs4149056 was associated with serum MTX concentrations at 48 and 72 hours,and MTX elimination delay in candidate polymorphisms(P=0.014,P=0.019,and P=0.007,respectively).SLC19A1 rs2838958 and rs3788200 were associated with serum MTX concentrations at 24 hours(P=0.016,P=0.043,respectively).MTRR rs1801394 was associated with serum MTX concentrations at 72 hours(P=0.045).Neutropenia was related to SLC19A1 rs4149056(odds ratio[OR]:3.172,95%confidence interval[CI]:1.310–7.681,P=0.011).Hepatotoxicity was associated with ABCC2 rs2273697(OR:3.494,95%CI:1.236–9.873,P=0.018)and MTRR rs1801394(OR:0.231,95%CI:0.084–0.632,P=0.004).Polymorphisms of SLCO1B1,SLC19A1,ABCC2,and MTRR genes help predict higher risk of increased MTX levels or MTX-related toxicities in adult ALL patients.展开更多
Dear Editor,Antigen escape is responsible for resistance[1]or disease relapse[2]from single-target chimeric antigen receptor(CAR)-T therapy.Dual-target CAR-T therapy has the potential to overcome the escape problem.Ho...Dear Editor,Antigen escape is responsible for resistance[1]or disease relapse[2]from single-target chimeric antigen receptor(CAR)-T therapy.Dual-target CAR-T therapy has the potential to overcome the escape problem.However,the efficacy and safety assessment of dual-target CAR-T therapy in treating acute myeloid leukemia(AML)need further investigation.Tandem CAR-T therapy has been widely used in research and clinic.However,clustering of two connected single-chain variable fragments(scFvs)[3]and the inappropriate conjugation distance[4]pose a risk of damaging tandem CAR-T cells’function.展开更多
1.INTRODUCTION With rapid developments in genetic engineering,tumor immunology,and cellular engineering,chimeric antigen receptor T cell(CAR-T)cell therapy has become a novel immunotherapy for oncology and other medic...1.INTRODUCTION With rapid developments in genetic engineering,tumor immunology,and cellular engineering,chimeric antigen receptor T cell(CAR-T)cell therapy has become a novel immunotherapy for oncology and other medical fields.1 The promising results of CD19 CAR-T treating B-cell malignancies were reported.2,3 Simultaneously,there existed many adverse events,the most reported of which including B-cell aplasia,hematological toxicity,cytokine release syndrome(CRS),and immune effector-cell–associated neurotoxicity syndrome(ICANS),3,4 but there is still lack of reports demonstrating the impact of CD19 CAR-T on the ABO blood group potency of patient’s serum.展开更多
This review article summarizes the advances in the surface stress effect in mechanics of nanostructured elements, including nanoparticles, nanowires, nanobeams, and nanofilms, and heterogeneous materials containing na...This review article summarizes the advances in the surface stress effect in mechanics of nanostructured elements, including nanoparticles, nanowires, nanobeams, and nanofilms, and heterogeneous materials containing nanoscale inhomogeneities. It begins with the fundamental formulations of surface mechanics of solids, including the definition of surface stress as a surface excess quantity, the surface constitutive relations, and the surface equilibrium equations. Then, it depicts some theoretical and experimental studies of the mechanical properties of nanostructured elements, as well as the static and dynamic behaviour of cantilever sensors caused by the surface stress which is influenced by adsorption. Afterwards, the article gives a summary of the analytical elasto-static and dynamic solutions of a single as well as multiple inhomogeneities embedded in a matrix with the interface stress prevailing. The effect of surface elasticity on the diffraction of elastic waves is elucidated. Due to the difficulties in the analytical solution of inhomogeneities of complex shapes and configurations, finite element approaches have been developed for heterogeneous materials with the surface stress. Surface stress and surface energy are inherently related to crack propagation and the stress field in the vicinity of crack tips. The solutions of crack prob- lems taking into account surface stress effects are also included. Predicting the effective elastic and plastic responses of heterogeneous materials while taking into account surface and interface stresses has received much attention. The advances in this topic are inevitably delineated. Mechanics of rough surfaces appears to deserve special attention due to its theoretical and practical implications. Some most recent work is reviewed. Finally, some challenges are pointed out. They include the characterization of surfaces and interfaces of real nanomaterials, experimental mea- surements and verification of mechanical parameters of complex surfaces, and the effects of the physical and chemical processes on the surface properties, etc.展开更多
Chimeric antigen receptor T-cell(CAR-T)therapy has greatly improved the disease remission rate and long-term survival rate of patients with relapsed/refractory hematological malignancies.[1-3]Currently,several commerc...Chimeric antigen receptor T-cell(CAR-T)therapy has greatly improved the disease remission rate and long-term survival rate of patients with relapsed/refractory hematological malignancies.[1-3]Currently,several commercial CAR-T products are available in the market and numerous CAR-T clinical trials have been conducted.Attention should be paid to the safety of CAR-T therapy.The main adverse effects of CAR-T therapy are cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS).[4]展开更多
Introduction:Acute promyelocytic leukemia(APL)is mostly due to the chromosome translocation t(15;17)(q22;q12),leading to the formation of PML-RARA fusion protein.Some patients carried rare translocation involving RARA...Introduction:Acute promyelocytic leukemia(APL)is mostly due to the chromosome translocation t(15;17)(q22;q12),leading to the formation of PML-RARA fusion protein.Some patients carried rare translocation involving RARA gene,who were called variant APL caused by RAR family(RARA,RARB,and RARG)and partner genes.STAT5b-RARA was a rare type of molecular genetic abnormality with unfavorable prognosis which have been reported in only 18 cases in variant APL.Knowledge of STAT5b-RARA(+)APL treatment is still limited.Case report:We presented a 38-year-old female variant APL case,who was STAT5b-RARA positive detected by reverse transcription polymerase chain reaction.The patient failed to respond after four-drug combined induction chemotherapy:idarubicin,cytarabine,all trans retinoic acid,and arsenic trioxide(As 2 O 3).Then,the patient was re-induced with azacytidine,but still failed to achieve complete remission(CR).Next,she was treated with Venetoclax combining with homoharringtonine and cytarabine as the salvage therapy and achieved CR.Later,the patient received hematopoietic stem cell transplantation after 4 cycles of consolidation therapy.Conclusion:Venetoclax combining with homoharringtonine and cytarabine has been used as the salvage therapy in the STAT5b-RARA positive APL successfully.展开更多
Dasatinib is a highly effective second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML).In 2007,a pivotal phase-2 study of dasatinib as second-line treatment was initiated in 140 Chine...Dasatinib is a highly effective second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML).In 2007,a pivotal phase-2 study of dasatinib as second-line treatment was initiated in 140 Chinese CML patients.This report from the 4-year follow-up revealed that 73% of 59 patients in chronic phase (CML-CP) and 32% of 25 patients in accelerated phase (CML-AP) remained under treatment.The initial dosage of dasatinib for CML-CP and CML-AP patients were 100 mg once daily and 70 mg twice daily (total=140 mg/ day),respectively.The cumulative major cytogenetic response (MCyR) rate among patients with CML-CP was 66.1%(versus 50.8% at 18 months),and the median time to MCyR was 12.7 weeks.All CML-CP patients who achieved MCyR after a 4-year follow-up also achieved a complete cytogenetic response.The cumulative complete hematological response (CHR) rate among patients with CML-AP was 64%(16/25),with three CML-AP patients achieving CHR between 18 months and 4 years of follow-up;the median time to CHR was 16.4 weeks.The adverse event (AE) profile of dasatinib at 4 years was similar to that at 6 and 18 months.The most frequently reported AEs (any grade) included pleural effusion,headache,and myelosuppression.These long-term follow-up data continue to support dasatinib as a second-line treatment for Chinese patients with CML.展开更多
In terfaces that exist in composites greatly influence their mechanical and conductive properties.There are usually three interface models to characterize the elastic and conductive properties of the interface in comp...In terfaces that exist in composites greatly influence their mechanical and conductive properties.There are usually three interface models to characterize the elastic and conductive properties of the interface in composites.For elastic problems,they are the interface stress model(ISM),linear spring model(LSM),and interphase model.For conductive problems,they are the high conducting(HC)interface model,low conducting(LC)interface model,and interphase model.For elastic problems with the interface effects,they can be divided into two types.The first kind of elastic problem concerns the solution of boundary value problems and aims to predict the effective properties of composites with interface effects.The second kind of elastic problem concerns the surface/interface stress effects on the elastic properties of nanostructured materials,which is usually characterized by the ISM.In this paper,three aspects in the elastic problems with interface effects are first reviewed,i.e.,equivalent relations among the three interface models,Eshelby formalism,and micromechanical frameworks.Special emphasis is placed on the ISM to show how classical models can be extended to the nano-scale by supplementing the interface elasticity to the basic equations of the classical elastic problems.Then,the conductive problems of the composites with the interface effects are also reviewed,and the general frameworks for predicting the effective conductivity of the composites are given.Finally,scaling laws depicting the size-dependent elastic and conductive properties of the composites are discussed.展开更多
The effective properties of composite materials have been predicted by various micromechanical schemes.For composite materials of constituents which are described by the classical governing equations of the local form...The effective properties of composite materials have been predicted by various micromechanical schemes.For composite materials of constituents which are described by the classical governing equations of the local form,the conventional micromechanical schemes usually give effective properties of the local form.However,it is recognized that under general loading conditions,spatiotemporal nonlocal constitutive equations may better depict the macroscopic behavior of these materials.In this paper,we derive the thermo-elastic dynamic effective governing equations of a fibre-reinforced composite in a coupled spatiotemporal integral form.These coupled equations reduce to the spatial nonlocal peridynamic formulation when the microstructural inertial effects are neglected.For static deformation and steady-state heat conduction,we show that the integral formulation is superior at capturing the variations of the average displacement and temperature in regions of high gradients than the conventional micromechanical schemes.The approach can be applied to analogous multi-field coupled problems of composites.展开更多
The peridynamic model of a solid is suitable for studying the dynamics of defects in materials.We use the bond-based peridynamic theory to propose a one-dimensional nonlocal continuum model to study a defect in equili...The peridynamic model of a solid is suitable for studying the dynamics of defects in materials.We use the bond-based peridynamic theory to propose a one-dimensional nonlocal continuum model to study a defect in equilibrium and in steady propagation.As the defect propagates,the material particles undergo a transition between two states.By using the Wiener–Hopf method,an explicit analytical solution of the problem is obtained.The relation between the applied force and the propagation speed of the defect is determined;our results show that the defect does not propagate if the applied force is less than a critical value,whereas propagation occurs when the force exceeds that value.The energy properties of the system are investigated.展开更多
Introduction:Mature plasmacytoid dendritic cells(pDCs)proliferation associated with myeloid neoplasms(MPDMN)are recognized as a neoplasm related to fully differentiated pDCs.Although it has been reported for many year...Introduction:Mature plasmacytoid dendritic cells(pDCs)proliferation associated with myeloid neoplasms(MPDMN)are recognized as a neoplasm related to fully differentiated pDCs.Although it has been reported for many years,the genomic landscape of MPDMN is poorly understood.Methods:We reported two patients who developed acute myeloid leukemia(French-American-British M5 subtype)coexisted with immunophenotypically mature pDCs proliferation,which fit the diagnosis of MPDMN.We sorted pDCs from myeloid blasts by flow cytometry and performed whole-exome sequencing and RNA sequencing of the two cell populations,respectively.Results:The immunophenotypes of pDCs in both patients were positive for CD123bri,HLA-DR,CD4,CD303,CD304,and negative for CD56,CD34,CD117,and TdT.The variant allele frequency of gene mutations in myeloid blasts and pDCs were similar.The expression data showed myeloid blasts clustered tightly with hematopoietic stem cells,and pDCs from patients clustered tightly with granulocyte-monocyte progenitors/common myeloid progenitor,rather than with pDCs from the GEO platform.Conclusion:Our study suggested that pDCs derived from the leukemic clone,evidenced by a shared mutation profile and similar transcriptional signatures between pDCs and concurrent myeloid blasts.展开更多
基金supported by grants from CAMS Innovation Fund for Medical Sciences(CIFMSGrant No.2022-I2M-1-022)。
文摘Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).
基金supported by funds from the National Natural Science Foundation of China(Grant Nos.81830002,81830004,82070168,and 32070951)the Translational Research grant of NCRCH(Grant No.2020ZKZC04)National Key R&D Program of China(Grant No.2021YFA1100800)。
文摘Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.
基金supported by the National Natural Science Foundation of China (51972259,52127816,and 52202290)the National Key Research and Development Program of China (2020YFA0715000)+1 种基金the Natural Science Foundation of Hubei Province (2022CFA087)the funding support from China Scholarship Council/University College London for the joint Ph.D.scholarship (CXXM2110070005)。
文摘Bismuth has garnered significant interest as an anode material for magnesium batteries(MBs) because of its high volumetric specific capacity and low working potential. Nonetheless, the limited cycling performance(≤100 cycles) limits the practical application of Bi as anode for MBs. Therefore, the improvement of Bi cycling performance is of great significance to the development of MBs and is also full of challenges. Here, Bi nanoparticles encapsulated in nitrogen-doped carbon with single-atom Bi embedded(Bi@NC) are prepared and reported as an anode material for MBs. Bi@NC demonstrates impressive performance, with a high discharge capacity of 347.5 mAh g^(-1) and good rate capability(206.4 mAh g^(-1)@500 mA g^(-1)) in a fluoride alkyl magnesium salt electrolyte. In addition, Bi@NC exhibits exceptional long-term stability, enduring 400 cycles at 500 mA g^(-1). To the best of our knowledge, among reported Bi and Bi-based compounds for MBs, Bi@NC exhibits the longest cycle life in this work. The magnesium storage mechanism of Bi@NC is deeply studied through X-ray diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy. This work provides some guidance for further improving the cycling performance of other alloy anodes in MBs.
基金supported by grants from the National Natural Science Foundation of China (Grant No. 81261120566)Jiangsu Province Key Medical Personnel Project (Grant No. RC2011068)+2 种基金333 Projects in the Fourth Phase of Jiangsu Province (Grant No. BRA2015389)Jiangsu Province "Six First Project" Research Program (Grant No. LGY2016004)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Objective: Bethesda System for Reporting Thyroid Cytopathology(BSRTC) categories Ⅰ, Ⅲ, and Ⅴaccount for a significant proportion of fine needle aspiration cytology(FNAC) diagnoses. This study aimed to compare the diagnostic efficacy of BRAF^(V600E) mutation and the Thyroid Imaging Reporting and Data System(TIRADS) classification in differentiating papillary thyroid cancers(PTCs) from benign lesions among BSRTC I, III, and V nodules.Methods: A total of 472 patients with 479 nodules were enrolled in this prospective study. Ultrasound, BRAF^(V600E) mutation testing, and FNAC were performed in each nodule, followed by surgery or regular ultrasound examination.Results: In the BSRTC I category, BRAF^(V600E) showed similar sensitivity, higher specificity, and lower accuracy when compared with TIRADS. In the BSRTC III/V category, the sensitivity, specificity, and accuracy of BRAF^(V600E) were similar to those of TIRADS. In comparison to BRAF^(V600E) alone, the combination of the two methods significantly improved sensitivity(BSRTC Ⅰ:93.6% vs. 67.7%, P < 0.01; BSRTC Ⅲ: 93.8% vs. 75.0%, P < 0.01; BSRTC V: 96.0% vs. 85.3%, P < 0.001). When compared with TIRADS alone, the combination improved sensitivity in BSRTC Ⅰ nodules(93.6% vs. 74.2%, P < 0.05), increased sensitivity and decreased accuracy in BSRTC III nodules(93.8% vs. 75.0%, P < 0.01, 91.0% vs. 93.6%, P < 0.01), and improved both sensitivity and accuracy in BSRTC V nodules(96.0% vs. 82.0%, P < 0.001; 94.2% vs. 81.3%, P < 0.001).Conclusions: BRAF^(V600E) exhibited higher specificity and lower accuracy compared with TIRADS in BSRTC Ⅰ nodules, while the two methods showed similar diagnostic value in BSRTC Ⅲ/Ⅴ nodules. The combination of the two methods distinctly improved sensitivity in the diagnosis of PTCs in BSRTC Ⅰ, Ⅲ, and Ⅴ nodules.
文摘Peridynamics is a nonlocal continuum mechanics theory.Peridynamics overcomes the computational challenges in classical continuum mechanics and enables the solution of complex mechanical and physical equations in the presence of jump discontinuities or singularities with ease and simplicity,while preserving a length scale to capture nonlocal behavior.Peridynamics has been recently extended and further developed to solve mass and heat transfer and fluid dynamics.Therefore,peridynamics can now be used for analyzing multiphysics and multiscale problems involving damage and cracks.As a rapidly rising topic in computational mechanics,peridynamics has gained intensive and wide interests in the community.
文摘Ivosidenib,an isocitrate dehydrogenase 1(IDH1)inhibitor,has demonstrated clinical benefits in a pivotal study(AG120-C-001)in patients with IDH1-mutated(mIDH1)acute myeloid leukemia(AML).A registry study(CS3010-101:NCT04176393)was conducted to assess the pharmacokinetic(PK)characteristics,safety,and efficacy of ivosidenib in Chinese patients with relapsed or refractory(R/R)mIDH1 AML.Patients received ivosidenib 500 mg once daily for 28-day cycles until disease progression.Ten subjects underwent intensive PK/progressive disease(PD)assessments.All subjects had the clinical response assessed at screening,every 28 days through month 12,and then every 56 days.Between November 12,2019,and April 2,2021,30 patients were enrolled;26(86.7%)had de novo AML and 18(60.0%)were transfusion-dependent at baseline.Following single and repeated doses of ivosidenib,median time to maximum plasma concentration(T_(max))was 4.0 and 2.0 hours,respectively.The inter-individual variability of pharmacokinetic exposure was moderate to high(coefficient of variation[CV],25%–53%).No obvious accumulation was observed after repeated doses at cycle 2 day 1.Regarding the clinical response,the CR+CRh rate was 36.7%(95%confidence interval[CI]:19.9%–56.1%),the median duration of CR+CRh was 19.7 months(95%CI:2.9 months–not reached[NR]),and median duration of response(DoR)was 14.3 months(95%CI:6.4 months–NR).Consistent clinical benefits and safety of ivosidenib were consistently observed at the final data cutoff with median follow-up time 26.0 months,as compared with primary data cutoff,and the data from Chinese R/R mIDH1 AML patients were also consistent with results from pivotal study.
基金supported by the National Key Research&Development Program of China(2019YFA0110200)the National Natural Science Foundation of China(81830005)+1 种基金the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-041)the Tianjin Applied Fundamental Research Planning Key Project(20JCZDJC00120)。
文摘CD19 chimeric antigen receptor(CAR)T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia(R/R ALL),but compromising result in chronic lymphoblastic leukemia(CLL)and non-Hodgkin’s lymphoma(NHL).CD19-relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome.CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure.Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape.Here,we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen.Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells,suggesting they exhibited dual antigen targeting of CD19 and CD20.By comparing the efficiency of four bispecific CAR modified T cells,it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients’primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model.These data highlighted the potential of loop2019 CAR-T in clinical treatment.
基金the National Natural Science Foundation of China(81970187,82170193,81920108006,and 81900203)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-C&T-B-081).
文摘Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIPI)risk group is still confusing.We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment.We identified 93 patients between 2013 and 2019 who received RM every 3 months for≥4 doses(RM group),and 60 patients who did not accept RM or received rituximab less than 4 doses(control group).After a median follow-up of 39 months,neither median overall survival(OS)nor PFS was reached for the entire population.The PFS was significantly prolonged in the RM group compared to the control group(median PFS NA vs 83.1 months,P=.00027).When the population was divided into the 3 FLIPI risk groups,the PFS differed significantly(4-year PFS rates,97.5%vs 88.8%vs 72.3%,P=.01)according to group.There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group(4-year PFS rates,100%vs 93.8%,P=.23).However,the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk(4-year PFS rates,100%vs 70.3%,P=.00077)and high-risk patients(4-year PFS rates,86.7%vs 57.1%,P=.023).These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate-and high-risk FLIPI groups but not to low-risk FLIPI group,and pending larger-scale studies to validate.
基金the National Key Research and Development Program of China(2021YFC2500300)the National Natural Science Foundation of China(82141122)+2 种基金CAMS Innovation Fund for Medical Sciences(2020-I2M-C&T-B084)Tianjin Municipal Science and Technology Commission Grant(21ZXGWSY00030)Haihe Laboratory of Cell Ecosystem Innovation Fund(HH22KYZX0039).
文摘Patients with double-mutated CEBPA(CEBPAdm)AML were stratified into favorable risk group,however,few studies have investigated the heterogeneity of different CEBPAdm types in detail.In this study,we analyzed 2211 newly diagnosed AML and identified CEBPAdm in 10.8%of the patients.Within the CEBPAdm cohort,225 of 239 patients(94.14%)presented with bZIP region mutations(CEBPAdmbZIP)while 14 of 239 patients(5.86%)without bZIP region mutation(CEBPAdmnonbZIP).Analysis of the accompanied molecular mutations showed statistically different incidences of GATA2 mutations between the CEBPAdmbZIP group and the CEBPAdmnonbZIP group(30.29%vs 0%).In the analysis of outcomes,patients with CEBPAdmnonbZIP were associated with shorter overall survival(OS)censored at hematopoietic stem cell transplantation(HSCT)during CR1 compared to those with CEBPAdmbZIP(hazard ratio(HR)=3.132,95%confidence interval(CI)=1.229–7.979,P=.017).Refractory or relapsed AML(R/RAML)patients with CEBPAdmnonbZIP were associated with shorter OS compared to those with CEBPAdmbZIP(HR=2.881,95%CI=1.021–8.131,P=.046).Taken together,AML with CEBPAdmbZIP and CEBPAdmnonbZIP showed different outcomes and might be regarded as distinctive AML entities.
基金National Key Research and Development Program of China(No.2019YFC0840605)National Science and Technology Major Project(No.2017ZX09304024).
文摘Methotrexate(MTX)has an antitumor effect when used for the treatment of acute lymphoblastic leukemia(ALL).This study aims at evaluating the associations between 14 polymorphisms of six genes involved in MTX metabolism with serum MTX concentration and toxicity accompanying high-dose MTX.Polymorphisms in 183 Chinese patients with ALL were analyzed using TaqMan single nucleotide polymorphism genotyping assay.The serum MTX concentration was determined using homogeneous enzyme immunoassay.MTX-related toxicities were also evaluated.Renal toxicity was significantly associated with higher serum MTX concentrations at 24,48,and 72 hours,and MTX elimination delay(P=0.001,P<0.001,P<0.001,and P<0.001,respectively),whereas SLCO1B1 rs4149056 was associated with serum MTX concentrations at 48 and 72 hours,and MTX elimination delay in candidate polymorphisms(P=0.014,P=0.019,and P=0.007,respectively).SLC19A1 rs2838958 and rs3788200 were associated with serum MTX concentrations at 24 hours(P=0.016,P=0.043,respectively).MTRR rs1801394 was associated with serum MTX concentrations at 72 hours(P=0.045).Neutropenia was related to SLC19A1 rs4149056(odds ratio[OR]:3.172,95%confidence interval[CI]:1.310–7.681,P=0.011).Hepatotoxicity was associated with ABCC2 rs2273697(OR:3.494,95%CI:1.236–9.873,P=0.018)and MTRR rs1801394(OR:0.231,95%CI:0.084–0.632,P=0.004).Polymorphisms of SLCO1B1,SLC19A1,ABCC2,and MTRR genes help predict higher risk of increased MTX levels or MTX-related toxicities in adult ALL patients.
基金supported by the National Key Research and Development Program of China(2021YFC2500300)the National Natural Science Foundation of China(81830005)+1 种基金Haihe Laboratory of Cell Ecosystem Innova-tion Fund(HH22KYZX0032)the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2020-I2M-C&T-A-019).
文摘Dear Editor,Antigen escape is responsible for resistance[1]or disease relapse[2]from single-target chimeric antigen receptor(CAR)-T therapy.Dual-target CAR-T therapy has the potential to overcome the escape problem.However,the efficacy and safety assessment of dual-target CAR-T therapy in treating acute myeloid leukemia(AML)need further investigation.Tandem CAR-T therapy has been widely used in research and clinic.However,clustering of two connected single-chain variable fragments(scFvs)[3]and the inappropriate conjugation distance[4]pose a risk of damaging tandem CAR-T cells’function.
基金the CAMS Innovation Fund for Medical Sciences(Grant no.2021-1-I2M-041)Tianjin Municipal Science and Technology Commission Grant(Grant no.20JCZDJC00120).
文摘1.INTRODUCTION With rapid developments in genetic engineering,tumor immunology,and cellular engineering,chimeric antigen receptor T cell(CAR-T)cell therapy has become a novel immunotherapy for oncology and other medical fields.1 The promising results of CD19 CAR-T treating B-cell malignancies were reported.2,3 Simultaneously,there existed many adverse events,the most reported of which including B-cell aplasia,hematological toxicity,cytokine release syndrome(CRS),and immune effector-cell–associated neurotoxicity syndrome(ICANS),3,4 but there is still lack of reports demonstrating the impact of CD19 CAR-T on the ABO blood group potency of patient’s serum.
基金the support of the National Natural Science Foundation of China (NSFC) through grants Nos.10032010,10072002,10372004,10525209,10872003 and 10932001the Foundation for the Author of National Excellent Doctoral Dissertation of China (FANEDD,Grant No.2007B2)+5 种基金Research Fund for the New Teacher Program of the State Education Ministry of China (Grant No.200800011011)Scientific Research Foundation for the Returned Overseas Chinese Scholars of the State Education Ministry of Chinathe support of NSFC (Grants Nos.10772093 and 10732050)the support of NSFC (Nos.11072186,10902081 and 11021202)973-Program (Nos.2007CB936803 and 2010CB631005)973-Program (No.2007CB707702)
文摘This review article summarizes the advances in the surface stress effect in mechanics of nanostructured elements, including nanoparticles, nanowires, nanobeams, and nanofilms, and heterogeneous materials containing nanoscale inhomogeneities. It begins with the fundamental formulations of surface mechanics of solids, including the definition of surface stress as a surface excess quantity, the surface constitutive relations, and the surface equilibrium equations. Then, it depicts some theoretical and experimental studies of the mechanical properties of nanostructured elements, as well as the static and dynamic behaviour of cantilever sensors caused by the surface stress which is influenced by adsorption. Afterwards, the article gives a summary of the analytical elasto-static and dynamic solutions of a single as well as multiple inhomogeneities embedded in a matrix with the interface stress prevailing. The effect of surface elasticity on the diffraction of elastic waves is elucidated. Due to the difficulties in the analytical solution of inhomogeneities of complex shapes and configurations, finite element approaches have been developed for heterogeneous materials with the surface stress. Surface stress and surface energy are inherently related to crack propagation and the stress field in the vicinity of crack tips. The solutions of crack prob- lems taking into account surface stress effects are also included. Predicting the effective elastic and plastic responses of heterogeneous materials while taking into account surface and interface stresses has received much attention. The advances in this topic are inevitably delineated. Mechanics of rough surfaces appears to deserve special attention due to its theoretical and practical implications. Some most recent work is reviewed. Finally, some challenges are pointed out. They include the characterization of surfaces and interfaces of real nanomaterials, experimental mea- surements and verification of mechanical parameters of complex surfaces, and the effects of the physical and chemical processes on the surface properties, etc.
文摘Chimeric antigen receptor T-cell(CAR-T)therapy has greatly improved the disease remission rate and long-term survival rate of patients with relapsed/refractory hematological malignancies.[1-3]Currently,several commercial CAR-T products are available in the market and numerous CAR-T clinical trials have been conducted.Attention should be paid to the safety of CAR-T therapy.The main adverse effects of CAR-T therapy are cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS).[4]
基金The authors would like to appreciate the funding of National Key Research and Development Program of China(2019YFC0840605).
文摘Introduction:Acute promyelocytic leukemia(APL)is mostly due to the chromosome translocation t(15;17)(q22;q12),leading to the formation of PML-RARA fusion protein.Some patients carried rare translocation involving RARA gene,who were called variant APL caused by RAR family(RARA,RARB,and RARG)and partner genes.STAT5b-RARA was a rare type of molecular genetic abnormality with unfavorable prognosis which have been reported in only 18 cases in variant APL.Knowledge of STAT5b-RARA(+)APL treatment is still limited.Case report:We presented a 38-year-old female variant APL case,who was STAT5b-RARA positive detected by reverse transcription polymerase chain reaction.The patient failed to respond after four-drug combined induction chemotherapy:idarubicin,cytarabine,all trans retinoic acid,and arsenic trioxide(As 2 O 3).Then,the patient was re-induced with azacytidine,but still failed to achieve complete remission(CR).Next,she was treated with Venetoclax combining with homoharringtonine and cytarabine as the salvage therapy and achieved CR.Later,the patient received hematopoietic stem cell transplantation after 4 cycles of consolidation therapy.Conclusion:Venetoclax combining with homoharringtonine and cytarabine has been used as the salvage therapy in the STAT5b-RARA positive APL successfully.
文摘Dasatinib is a highly effective second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML).In 2007,a pivotal phase-2 study of dasatinib as second-line treatment was initiated in 140 Chinese CML patients.This report from the 4-year follow-up revealed that 73% of 59 patients in chronic phase (CML-CP) and 32% of 25 patients in accelerated phase (CML-AP) remained under treatment.The initial dosage of dasatinib for CML-CP and CML-AP patients were 100 mg once daily and 70 mg twice daily (total=140 mg/ day),respectively.The cumulative major cytogenetic response (MCyR) rate among patients with CML-CP was 66.1%(versus 50.8% at 18 months),and the median time to MCyR was 12.7 weeks.All CML-CP patients who achieved MCyR after a 4-year follow-up also achieved a complete cytogenetic response.The cumulative complete hematological response (CHR) rate among patients with CML-AP was 64%(16/25),with three CML-AP patients achieving CHR between 18 months and 4 years of follow-up;the median time to CHR was 16.4 weeks.The adverse event (AE) profile of dasatinib at 4 years was similar to that at 6 and 18 months.The most frequently reported AEs (any grade) included pleural effusion,headache,and myelosuppression.These long-term follow-up data continue to support dasatinib as a second-line treatment for Chinese patients with CML.
基金the National Natural Science Foundation of China(Grant Nos.11988102,11872004,and 91848201).
文摘In terfaces that exist in composites greatly influence their mechanical and conductive properties.There are usually three interface models to characterize the elastic and conductive properties of the interface in composites.For elastic problems,they are the interface stress model(ISM),linear spring model(LSM),and interphase model.For conductive problems,they are the high conducting(HC)interface model,low conducting(LC)interface model,and interphase model.For elastic problems with the interface effects,they can be divided into two types.The first kind of elastic problem concerns the solution of boundary value problems and aims to predict the effective properties of composites with interface effects.The second kind of elastic problem concerns the surface/interface stress effects on the elastic properties of nanostructured materials,which is usually characterized by the ISM.In this paper,three aspects in the elastic problems with interface effects are first reviewed,i.e.,equivalent relations among the three interface models,Eshelby formalism,and micromechanical frameworks.Special emphasis is placed on the ISM to show how classical models can be extended to the nano-scale by supplementing the interface elasticity to the basic equations of the classical elastic problems.Then,the conductive problems of the composites with the interface effects are also reviewed,and the general frameworks for predicting the effective conductivity of the composites are given.Finally,scaling laws depicting the size-dependent elastic and conductive properties of the composites are discussed.
文摘The effective properties of composite materials have been predicted by various micromechanical schemes.For composite materials of constituents which are described by the classical governing equations of the local form,the conventional micromechanical schemes usually give effective properties of the local form.However,it is recognized that under general loading conditions,spatiotemporal nonlocal constitutive equations may better depict the macroscopic behavior of these materials.In this paper,we derive the thermo-elastic dynamic effective governing equations of a fibre-reinforced composite in a coupled spatiotemporal integral form.These coupled equations reduce to the spatial nonlocal peridynamic formulation when the microstructural inertial effects are neglected.For static deformation and steady-state heat conduction,we show that the integral formulation is superior at capturing the variations of the average displacement and temperature in regions of high gradients than the conventional micromechanical schemes.The approach can be applied to analogous multi-field coupled problems of composites.
基金the support of the National Natural Science Foundation of China under Grant Nos.12002010 and 11872075.
文摘The peridynamic model of a solid is suitable for studying the dynamics of defects in materials.We use the bond-based peridynamic theory to propose a one-dimensional nonlocal continuum model to study a defect in equilibrium and in steady propagation.As the defect propagates,the material particles undergo a transition between two states.By using the Wiener–Hopf method,an explicit analytical solution of the problem is obtained.The relation between the applied force and the propagation speed of the defect is determined;our results show that the defect does not propagate if the applied force is less than a critical value,whereas propagation occurs when the force exceeds that value.The energy properties of the system are investigated.
基金was supported in part by State Key Program of National Natural Science of China(81830005)J.W.,National Natural Science Foundation of China(81770181)+3 种基金J.W.,National Key Research and Development Program of China(2019YFC0840605)Y.M.,Tianjin Natural Science Foundation(18JCZDJC45000)H.W.,CAMS Innovation Fund for Medical Sciences(2020-I2M-C&T-B-084)H.W.Funders had no role in the study design,analyses,or decision to publish.
文摘Introduction:Mature plasmacytoid dendritic cells(pDCs)proliferation associated with myeloid neoplasms(MPDMN)are recognized as a neoplasm related to fully differentiated pDCs.Although it has been reported for many years,the genomic landscape of MPDMN is poorly understood.Methods:We reported two patients who developed acute myeloid leukemia(French-American-British M5 subtype)coexisted with immunophenotypically mature pDCs proliferation,which fit the diagnosis of MPDMN.We sorted pDCs from myeloid blasts by flow cytometry and performed whole-exome sequencing and RNA sequencing of the two cell populations,respectively.Results:The immunophenotypes of pDCs in both patients were positive for CD123bri,HLA-DR,CD4,CD303,CD304,and negative for CD56,CD34,CD117,and TdT.The variant allele frequency of gene mutations in myeloid blasts and pDCs were similar.The expression data showed myeloid blasts clustered tightly with hematopoietic stem cells,and pDCs from patients clustered tightly with granulocyte-monocyte progenitors/common myeloid progenitor,rather than with pDCs from the GEO platform.Conclusion:Our study suggested that pDCs derived from the leukemic clone,evidenced by a shared mutation profile and similar transcriptional signatures between pDCs and concurrent myeloid blasts.
