Dynamic Characteristics of Functionally Graded Timoshenko Beams by Improved Differential Quadrature Method

This study proposes an effective method to enhance the accuracy of the Differential Quadrature Method(DQM)for calculating the dynamic characteristics of functionally graded beams by improving the form of discrete node distribution.Firstly,based on the first-order shear deformation theory,the governing equation of free vibration of a functionally graded beam is transformed into the eigenvalue problem of ordinary differential equations with respect to beam axial displacement,transverse displacement,and cross-sectional rotation angle by considering the effects of shear deformation and rotational inertia of the beam cross-section.Then,ignoring the shear deformation of the beam section and only considering the effect of the rotational inertia of the section,the governing equation of the beam is transformed into the eigenvalue problem of ordinary differential equations with respect to beam transverse displacement.Based on the differential quadrature method theory,the eigenvalue problem of ordinary differential equations is transformed into the eigenvalue problem of standard generalized algebraic equations.Finally,the first several natural frequencies of the beam can be calculated.The feasibility and accuracy of the improved DQM are verified using the finite element method(FEM)and combined with the results of relevant literature.

Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs.identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia

Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.

Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation

Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.

Cellular immunotherapy for hematological malignancy: recent progress and future perspectives

Advancements in the field of cellular immunotherapy have accelerated in recent years and have changed the treatment landscape for a variety of hematologic malignancies.Cellular immunotherapy strategies exploit the patient’s immune system to kill cancer cells.The successful use of CD19 chimeric antigen receptor(CAR)T-cells in treating B-cell malignancies is the paradigm of this revolution,and numerous ongoing studies are investigating and extending this approach to other malignancies.However,resistance to CAR-Tcell therapy and non-durable efficacy have prevented CAR-T-cells from becoming the ultimate therapy.Because natural killer(NK)cells play an essential role in antitumor immunity,adoptively transferred allogeneic NK and CAR-modified NK cell therapy has been attempted in certain disease subgroups.Allogenic hematopoietic stem cell transplantation(allo-HSCT)is the oldest form of cellular immunotherapy and the only curative option for hematologic malignancies.Historically,the breadth of application of allo-HSCT has been limited by a lack of identical sibling donors(ISDs).However,great strides have recently been made in the success of haploidentical allografts worldwide,which enable everyone to have a donor.Haploidentical donors can achieve comparable outcomes to those of ISDs and even better outcomes in certain circumstances because of a stronger graft vs.tumor effect.Currently,novel strategies such as CAR-T or NK-based immunotherapy can be applied as a complement to allo-HSCT for curative effects,particularly in refractory cases.Here,we introduce the developments in cellular immunotherapy in hematology.

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

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.

Investigation of the Free Vibrations of Radial Functionally Graded Circular Cylindrical Beams Based on Differential Quadrature Method

In the current research,an effective differential quadrature method(DQM)has been developed to solve natural frequency and vibration modal functions of circular section beams along radial functional gradient.Based on the high-order theory of transverse vibration of circular cross-section beams,lateral displacement equation was reconstructed neglecting circumferential shear stress.Two equations coupled with deflection and rotation angles were derived based on elastic mechanics theory and further simplified into a constant coefficient differential equation with natural frequency as eigenvalue.Then,differential quadrature method was applied to transform the eigenvalue problem of the derived differential equation into a set of algebraic equation eigenvalue problems.Natural frequencies of the free vibrations of cylindrical beams with circular cross-sections were calculated at one time,and corresponding modal functions were solved together.The obtained numerical results indicated that the natural frequencies of functionally graded(FG)circular cylindrical beams obtained using differential quadrature method agreed with the results reported in related literatures.In addition,influences of varying gradient parameters on the modal shapes of circular cylindrical beams were found to be strongly consistent with previous studies.Numerical results further validated the feasibility and accuracy of the developed differential quadrature method in solving the transverse vibration of FG circular cross-section beams.

THE SYSTEMS WITH ALMOST BANACH-MEAN EQUICONTINUITY FOR ABELIAN GROUP ACTIONS

In this paper,we present the concept of Banach-mean equicontinuity and prove that the Banach-,Weyl-and Besicovitch-mean equicontinuities of a dynamic system of Abelian group action are equivalent.Furthermore,we obtain that the topological entropy of a transitive,almost Banach-mean equicontinuous dynamical system of Abelian group action is zero.As an application of our main result,we show that the topological entropy of the Banach-mean equicontinuous system under the action of an Abelian groups is zero.

REVISITING A NON-DEGENERACY PROPERTY FOR EXTREMAL MAPPINGS

We extend an earlier result obtained by the author in [7].

THE PROXIMAL RELATION,REGIONALLY PROXIMAL RELATION AND BANACH PROXIMAL RELATION FOR AMENABLE GROUP ACTIONS

In this paper,we study the proximal relation,regionally proximal relation and Banach proximal relation of a topological dynamical system for amenable group actions.A useful tool is the support of a topological dynamical system which is used to study the structure of the Banach proximal relation,and we prove that above three relations all coincide on a Banach mean equicontinuous system generated by an amenable group action.

Commissioning experiment of the high-contrast SILEX-Ⅱ multi-petawatt laser facility

The results of a commissioning experiment on the SILEX-Ⅱlaser facility(formerly known as CAEP-PW)are reported.SILEX-Ⅱis a complete optical parametric chirped-pulse amplification laser facility.The peak power reached about 1 PWin a 30 fs pulse duration during the experiment.The laser contrast was better than 1010 at 20 ps ahead of the main pulse.In the basic laser foil target interaction,a set of experimental data were collected,including spatially resolved x-ray emission,the image of the coherent transition radiation,the harmonic spectra in the direction of reflection,the energy spectra and beam profile of accelerated protons,hot-electron spectra,and transmitted laser energy fraction and spatial distribution.The experimental results show that the laser intensity reached 531020 W/cm^(2) within a 5.8μm focus(FWHM).Significant laser transmission did not occur when the thickness of theCHfoil was equal to or greater than 50 nm.The maximum energy of the accelerated protons in the target normal direction was roughly unchanged when the target thickness varied between 50 nm and 15μm.The maximum proton energy via the target normal sheath field acceleration mechanism was about 21 MeV.We expect the on-target laser intensity to reach 10^(22) W/cm^(2) in the near future,after optimization of the laser focus and upgrade of the laser power to 3 PW.

Single-cell immune landscape of measurable residual disease in acute myeloid leukemia

Measurable residual disease(MRD)is a powerful prognostic factor of relapse in acute myeloid leukemia(AML).We applied the single-cell RNA sequencing to bone marrow(BM)samples from patients with(n=20)and without(n=12)MRD after allogeneic hematopoietic stem cell transplantation.A comprehensive immune landscape with 184,231 cells was created.Compared with CD8+T cells enriched in the MRDnegative group(MRD‒_CD8),those enriched in the MRD-positive group(MRD+_CD8)showed lower expression levels of cytotoxicity-related genes.Three monocyte clusters(i.e.,MRD+_M)and three B-cell clusters(i.e.,MRD+_B)were enriched in the MRD-positive group.Conversion from an MRD-positive state to an MRD-negative state was accompanied by an increase in MRD‒_CD8 clusters and vice versa.MRDenriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD‒_CD8 clusters.These findings revealed the characteristics of the immune cell landscape in MRD positivity,which will allow for a better understanding of the immune mechanisms for MRD conversion.

Bifurcation analysis of an SIS epidemic model with a generalized non-monotonic and saturated incidence rate

In this paper,a new generalized non-monotonic and saturated incidence rate was introduced into a susceptible-infected-susceptible(SIS)epidemic model to account for inhibitory effect and crowding effect.The dynamic properties of the model were studied by qualitative theory and bifurcation theory.It is shown that when the infuence of psychological factors is large,the model has only disease-free equilibrium point,and this disease-free equilibrium point is globally asymptotically stable;when the influence of psychological factors is small,for some parameter conditions,the model has a unique endemic equilibrium point,which is a cusp point of co-dimension two,and for other parameter conditions the model has two endemic equilibrium points,one of which could be weak focus or center.In addition,the results of the model undergoing saddle-node bifurcation,Hopf bifurcation and Bogdanov-Takens bifurcation as the parameters vary were also proved.These results shed light on the impact of psychological behavior of susceptible people on the disease transmission.

Comparison of clinical features of nephrotic syndrome after haploidentical and matched donor hematopoietic stem cell transplantation

To the Editor:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is one of the most effective options for hematological diseases.However,allo-HSCT treatment can cause serious complications.Post-transplant kidney damage is an important complication.In this study,we retrospectively analyzed the frequency of nephrotic syndrome(NS)after allo-HSCT and compared the frequency and clinical characteristics of NS between haploidentical donor(HID)and matched donor(MD)HSCT(including matched sibling donors[MSD]and unrelated donors[URD]).

Current situation and development of hematopoietic cell transplantation centers:A nationwide survey in China

To the Editor:Hematopoietic cell transplantation(HCT)is a vital modality to cure severe hematological disorders.[1]Global or regional summarized data of HCT are annually reported by the Chinese Blood and Marrow Transplantation Registry Group(CBMTRG),European Society for Blood and Marrow Transplantation(EBMT)and Center for International Blood and Marrow Transplant Research(CIBMTR).It is shown that the number of transplants is continuously increasing,particularly in China in recent years.[2]Since the donor accessibility is significantly addressed by the well-established protocol of haplo-identical HCT(haplo-HCT).

异基因造血干细胞移植后腺病毒感染的临床特征分析

目的分析异基因造血干细胞移植(allo-HSCT)后人腺病毒(HAdV)感染患者的临床特征及预后。方法回顾性病例系列研究。收集2015年8月至2019年10月在北京大学人民医院血液科接受allo-HSCT后出现疑似感染症状但感染病原不明的2728例患者标本,采用荧光定量PCR法检测HAdV DNA,HAdV DNA检测阳性视为HAdV感染。分析HAdV感染患者临床表现,并根据患者年龄、移植类型、移植年份、随访时间采用巢式病例配对按1∶3匹配了未发生HAdV感染的患者作为对照组,采用Kaplan-Meier法分析并进行Log-rank检验,比较HAdV感染组和对照组的临床预后。结果共检测7119份标本,其中36例患者99例次HAdV DNA阳性。36例HAdV感染患者中22例发生HAdV血症;24例除HAdV感染外合并1种或多种其他病毒感染;19例(53%)有发热,25例(69%)有消化道症状,11例(31%)有呼吸道症状,9例(25%)有肝功能异常,6例(17%)有神经系统症状;23例同时发生2度及以上急性移植物抗宿主病;9例患者接受西多福韦抗病毒治疗,其中7例HAdV转阴,2例治疗无效。所有患者随访时间[M(Q_(1),Q_(3))]为496(216,940)d,Kaplan-Meier分析显示HAdV感染组5年总体生存率低于对照组(48.4%±9.2%比91.3%±3.5%;χ^(2)=65.03,P<0.001),移植后5年的非复发死亡率高于对照组(40.8%±8.8%比4.0%±2.0%;χ^(2)=34.17,P<0.001)。结论allo-HSCT后HAdV感染者以消化道、呼吸道症状为主,合并2度以上急性移植物抗宿主病的风险增加,HAdV感染患者总体生存差,非复发死亡率高。

可数无限群作用子集的单纯Bowen拓扑熵 献给杨乐教授80华诞

本文研究紧度量空间上可数无限群作用给出的动力系统G■X.特别地,对于X的任何一个子集Z,定义这个群作用相对于子集Z的单纯(naive) Bowen拓扑熵htopnv(G, Z).进一步,本文研究这种熵的基本性质,并且对于非顺从的可数无限群,计算这种熵的取值范围.事实证明,这种单纯熵的取值真的很单纯,反映了动力系统复杂度的一种二分现象.

Comparison analysis between haplo identical stem cell transplantation and matched sibling donor stem cell transplantation for high-risk acute myeloid leukemia in first complete remission

In order to compare the effect between haploidentical(HID) stem cell transplantation(HSCT) and matched sibling donor(MSD)stem cell transplantation for high-risk acute myeloid leukemia(AML) in first complete remission status(CR1), we retrospectively studied 170 cases who received stem cell transplantation from Jan 2008 to Jul 2015 in Peking University People's Hospital. We divided all cases into MSD group(43 cases) and HID(127 cases) group. Patients in HID and MSD group displayed similar baseline characteristics except for age distribution. There were no statistic differences for overall survival(OS), cumulative incidence of relapse, leukemia free survival(LFS), transplantation related mortality(TRM) between HID and MSD group. The 3-year OS, LFS for all patients was 63.9% and 59.7% respectively. Multivariate analysis showed that grade III-IV acute graft versus host disease(aGVHD) was an independent risk factor for treatment related mortality(HR=8.134, 95% CI:3.210–20.611, P<0.001), monosomy/complex chromosomal karyotype and white blood cell count more than 50×109 L-1 were two independent factors for relapse(HR=1.533, 95% CI: 1.040–2.260, P=0.031)(HR=1.004, 95% CI: 1.001–1.008, P=0.015).Grade III-IV aGVHD was an independent factor for mortality(HR=3.184, 95% CI: 1.718–5.902, P<0.001). These results demonstrated some risk factors for high-risk AML leukemia transplantation and indicated for AML patients in CR1 status, haplo stem cell transplantation could have the same therapeutic effect as MSD transplantation.

Clinical risk score for invasive fungal diseases in patients with hematological malignancies undergoing chemotherapy:China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study

Invasive fungal disease (IFD) is a major infectious complication in patients with hematological malignancies.In this study,we examined 4889 courses of chemotherapy in patients with hematological diseases to establish a training dataset (n=3500) by simple random sampling to develop a weighted risk score for proven or probable IFD through multivariate regression,which included the following variables: male patients,induction chemotherapy for newly diagnosed or relapsed disease,neutropenia,neutropenia longer than 10 days,hypoalbuminemia,central-venous catheter,and history of IFD.The patients were classified into three groups,which had low (0-10,~1.2%),intermediate (11-15,6.4%),and high risk (> 15,17.5%) of IFD.In the validation set (n=1389),the IFD incidences of the groups were ~1.4%,5.0%,and 21.4%.In addition,we demonstrated that antifungal prophylaxis offered no benefits in low-risk patients,whereas benefits were documented in intermediate (2.1% vs.6.6%,P=0.007) and high-risk patients (8.4% vs.23.3%,P=0.007).To make the risk score applicable for clinical settings,a pre-chemo risk score that deleted all unpredictable factors before chemotherapy was established,and it confirmed that anti-fungal prophylaxis was beneficial in patients with intermediate and high risk of IFD.In conclusion,an objective,weighted risk score for IFD was developed,and it may be useful in guiding antifungal prophylaxis.

Everyone has a donor:contribution of the Chinese experience to global practice of haploidentical hematopoietic stem cell transplantation

Human leukocyte antigen (HLA)-matched donors for hematopoietic stem cell transplantation (HSCT) have long been scarce in China. Haploidentical (haplo) donors are available for the vast majority of patients, but toxicity has limited this approach. Three new approaches for haplo-HSCT originated from Italy, China, and USA in 1990 and have been developed to world-renowned system up to now. The Chinese approach have been greatly improved by implementing new individualized conditioning regimens, donor selection based on non-HLA systems, risk-directed strategies for graft-versus-host disease and relapse, and infection management. Haplo-HSCT has exhibited similar efficacy to HLA-matched HSCT and has gradually become the predominant donor source and the first alternative donor choice for allo-HSCT in China. Registry-based analyses and multicenter studies adhering to international standards facilitated the transformation of the unique Chinese experience into an inspiration for the refinement of global practice.This review will focus on how the new era in which "everyone has a donor" will become a reality in China.

Rapid reconstitution of NK1 cells after allogeneic transplantation is associated with a reduced incidence of graft-versus-host disease

The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Thl, Th2, Th3 and Trl cells. Here, we investigate levels of type 1 （IFN-gamma; NK1）, type 2 （IL-13; NK2）, type 3 （TGF-beta; NK3） and regulatory （IL-10; NKr） cytokines in peripheral blood to assess the cytokine profiles of natural killer （NK） cells following human allogeneic hematopoietic stem cell transplantation （allo-HSCT）. NK2 and NK3 cell expansion was observed after aUo-HSCT; levels of NKr ceils reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT. Multivariate analysis showed that a higher level of NK1 cells by day 15 was associated with a lower overall risk of acute graft-versus-host disease （GVHD） （HR 0.157, P=-0.010） as well as II-IV acute GVHD （HR 0.260, P=-0.059）. Furthermore, higher levels of NK1 cells by day 15 were correlated with lower rates of cytomegalovirus （CMV） reactivation （HR 0.040, 0.005-0.348,/9=-0.003）. These results indicate that rapid reconstitution of NK cells, especially NK1 cells, can help prevent the development of GVHD as well as CMV reactivation after allogeneic transplantation.