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.

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.

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.

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.

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。

Immune-related genetic prognostic index to predict prognosis and immune checkpoint inhibitor therapy efficiency in acute myeloid leukemia

To the Editor:Acute myeloid leukemia(AML)is a heterogeneous disease characterized by proliferation of abnormal myeloblasts in the bone marrow.Traditional treatment,such as chemotherapy with or without hematopoietic stem cell transplantation(HSCT),has been used as the first-line therapy in AML.However,the clinical outcome of patients with AML varies greatly due to several factors,such as the tumor immune microenvironment(TME).

An ultra-wideband coding polarizer for beam control and RCS reduction

Pancharatnam–Berry(PB)phase metasurface,as a special class of gradient metasurfaces,has been paid much attention owing to the robust performance for phase control of circularly polarized waves.Herein,we present an element-based polarizer for the first step,which enables the incident electromagnetic waves into the cross-polarized waves with the relative bandwidth of 71%,and the polarization conversion ratio exceeds 90%at 6.9–14.5 GHz.Then an eight-elements coding polarizer based on the PB phase is presented for the applications on beam control and radar cross section reduction.The simulated values indicate that the reduction of radar cross section is more than 10 dB at 6–16 GHz.Our work reveals the availability of manipulating the waves,beamforming in communication systems and electromagnetic stealth,and so on.

More than two courses of pre-transplant consolidation therapy benefits patients with acute myeloid leukemia in the first complete remission who underwent human leukocyte antigen-matched sibling allografts:a multicenter study

Background:Although the need for consolidation chemotherapy after successful induction therapy is well established in patients with acute myeloid leukemia(AML)in first complete remission(CR1),the value of consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation remains controversial.Methods:We retrospectively compared the effect of the number of pre-transplant consolidation chemotherapies on outcomes of human leukocyte antigen-matched sibling stem cell transplantation(MSDT)for patients with AML in CR1 in multicenters across China.In our study,we analyzed data of 373 AML patients in CR1 from three centers across China.Results:With a median follow-up of 969 days,patients with≥3 courses of consolidation chemotherapy had higher probabilities of leukemia-free survival(LFS)(85.6%vs.67.0%,P<0.001)and overall survival(89.2%vs.78.5%,P=0.007),and better cumulative incidences of relapse(10.5%vs.19.6%,P=0.020)and non-relapse mortality(4.2%vs.14.9%,P=0.001)than those with≤2 courses of consolidation chemotherapy.Pre-transplantation minimal residual disease-negative patients with AML in CR1 who received MSDT with≥3 courses of consolidation chemotherapy had a higher probability of LFS(85.9%vs.67.7%,P=0.003)and a lower cumulative incidence of relapse(9.6%vs.23.3%,P=0.013)than those with≤2 courses.Conclusion:Our results indicate that patients with AML in CR1 who received MSDT might benefit from pre-transplant consolidation chemotherapy.

Bridging chimeric antigen receptor T-cell before transplantation improves prognosis of relapsed/refractory B-cell acute lymphoblastic leukemia

To the Editor:For recipients with relapsed/refractory(R/R)B-cell acute lymphoblastic leukemia(B-ALL),allogeneic hematopoietic stem cell transplantation(allo-HSCT)often fails to provide them with a satisfactory prognosis.The chimeric antigen receptor T(CAR-T)cells are proven to be safe and effective for these patients.[1]But there are few published studies assessing the advantages of CAR-T compared to traditional chemotherapy as a bridging treatment followed by HSCT.Consequently,we conducted this study to confirm whether children and young adult R/R B-ALL patients with CAR-T therapy could expect a better post-HSCT prognosis,compared to R/R patients only receiving traditional chemotherapy before transplantation.

Is t(11;14)(q13;q32) good or bad for newly diagnosed multiple myeloma?

Cytogenetic aberrations(CAs)are vital markers for risk stratification of multiple myeloma(MM).The prognostic significance of the aberration,t(11;14)(q13;q32),in MM has remained controversial over recent years.In addition,studies on the heterogeneity of t(11;14)MM and the impact of additional CAs are rare.[1]We therefore conducted a retrospective study on relevant data collected at our center in order to further analyze the characteristics of Chinese patients with t(11;14)MM and elaborate on heterogeneity in their genetic profile.

Improved outcomes in E2A::HLF positive B-cell acute lymphoblastic leukemia by chimeric antigen receptor T cell therapy and BCL-2 inhibitor

To the Editor:The fusion gene E2A::HLF(TCF3::HLF)is formed by t(17;19)(q21-22;p13),which presents in<1%of B-cell acute lymphoblastic leukemia(B-ALL)and mainly occurs in older children and adolescents.[1]Such patients were often accompanied by drug resistance and early relapse,which confer an extremely poor prognosis,and even intensive chemotherapy and hematopoietic stem cell transplantation(HSCT)cannot improve their survival.[2]A few studies suggested that chimeric antigen receptor T(CAR-T)cell therapy or BCL-2 inhibitors might benefit such patients.

Current status and future perspective of natural killer cell therapy for cancer

Natural killer(NK)cells possess innate abilities to effectively eliminate cancer cells.However,because of difficulties of proliferation and easy to be induced dysfunction in the setting of cancer post NK cell therapy,the curative effect of NK cell infusion has been constrained and not been widely applicable in clinical practice.The rapid development of biotechnology has promoted the development of NK cell therapy for cancer treatment.In this review,we will provide a comprehensive analysis of the current status and future prospects of NK cell therapy for cancer,focusing on the biological characteristics of NK cells,as well as strategies to enhance their targeting capabilities and overcome tumor immune suppression within the microenvironment.

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.