Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy(CAR–T)cell immunotherapy

Chimeric antigen receptor T-cesll therapy(CAR–T)has achieved groundbreaking advancements in clinical application,ushering in a new era for innovative cancer treatment.However,the challenges associated with implementing this novel targeted cell therapy are increasingly significant.Particularly in the clinical management of solid tumors,obstacles such as the immunosuppressive effects of the tumor microenvironment,limited local tumor infiltration capability of CAR–T cells,heterogeneity of tumor targeting antigens,uncertainties surrounding CAR–T quality,control,and clinical adverse reactions have contributed to increased drug resistance and decreased compliance in tumor therapy.These factors have significantly impeded the widespread adoption and utilization of this therapeutic approach.In this paper,we comprehensively analyze recent preclinical and clinical reports on CAR–T therapy while summarizing crucial factors influencing its efficacy.Furthermore,we aim to identify existing solution strategies and explore their current research status.Through this review article,our objective is to broaden perspectives for further exploration into CAR–T therapy strategies and their clinical applications.

The Problems and Solutions of Enterprise Financial Management in the Perspective of Digital Economy

From the perspective of the digital economy,enterprise financial management is facing unprecedented challenges and opportunities.Traditional financial management models are no longer suited to current development needs.Fine-tuning financial management is essential to support the modernization of enterprises,guard against operational risks,and promote coordination across the entire value chain for greater economic efficiency.With the help of digital technology,data-driven,highly interconnected,and intelligent decision-making processes are becoming more prominent,profoundly transforming the operational and financial management models of enterprises.This enables financial management to keep pace with modern developments.In light of this,the paper explores the connotations and mechanisms of the digital economy and enterprise financial management,clarifies relevant conceptual characteristics,and identifies problems in financial management under the digital economy.It also offers strategies for optimization and problem-solving,with the aim of providing valuable insights for educators and practitioners.

Fabrication of Cu_2O@Cu_2O core-shell nanoparticles and conversion to Cu_2O@Cu core-shell nanoparticles in solution

Cu2O@Cu2O core-shell nanoparticles (NPs) were prepared by using solution phase strategy. It was found that Cu2O@Cu2O NPs were easily converted to Cu2O@Cu NPs with the help of polyvinylpyrrolidine (PVP) and excessive ascorbic acid (AA) in air at room temperature, which was an interesting phenomenon. The features of the two kinds of NPs were characterized by XRD, TEM and extinction spectra. Cu2O@Cu NPs with different shell thicknesses showed wide tunable optical properties for the localized surface plasmon (LSP) in metallic Cu. But Cu2O@Cu2O NPs did not indicate this feature. FTIR results reveal that Cu+ ions on the surface of Cu2O shell coordinate with N and O atoms in PVP and are further reduced to metallic Cu by excessive AA and then form a nucleation site on the surface of Cu2O nanocrystalline. PVP binds onto different sites to proceed with the reduction utill all the Cu sources in Cu2O shell are completely assumed.

Comparative Study on the Policy of Multiplicity Issues in Clinical Trials at Home and Abroad

Objective To study the content of China’s guiding principles on multiplicity issues in clinical trials,and to provide reference for the revision of China’s relevant guiding principles.Methods Based on ICH E9,the similarities and differences of the guiding principles of US Food and Drug Administration(FDA),European Medicines Agency(EMA),and National Medical Products Administration(NMPA)on the multiplicity issues in clinical trials were compared one by one.Results and Conclusion In general,NMPA guidelines are based on ICH E9,but in detail,the guidelines of FDA and EMA focus differently on the multiplicity issues.Therefore,NMPA guidelines need to be detailed and comprehensive.NMPA guidelines can be refined by referring to foreign guidelines to improve the practical guiding significance for clinical research and promote the level of domestic clinical trials in line with international standards.

Characteristic equation solution strategy for deriving fundamental analytical solutions of 3D isotropic elasticity

A simple characteristic equation solution strategy for deriving the fun- damental analytical solutions of 3D isotropic elasticity is proposed. By calculating the determinant of the differential operator matrix obtained from the governing equations of 3D elasticity, the characteristic equation which the characteristic general solution vectors must satisfy is established. Then, by substitution of the characteristic general solution vectors, which satisfy various reduced characteristic equations, into various reduced ad- joint matrices of the differential operator matrix, the corresponding fundamental analyt- ical solutions for isotropic 3D elasticity, including Boussinesq-Galerkin （B-G） solutions, modified Papkovich-Neuber solutions proposed by Min-zhong WANG （P-N-W）, and quasi HU Hai-chang solutions, can be obtained. Furthermore, the independence characters of various fundamental solutions in polynomial form are also discussed in detail. These works provide a basis for constructing complete and independent analytical trial func- tions used in numerical methods.

Misuse of Teaching Gesture from the Perspective of Multi-modal Discourse Analysis and Its Solutions

Based on the teaching video of middle school English teachers, through observation and analysis, it puts forward the problem of less use, wrong use and abuse in the use of teachers' teaching gestures in middle school English teaching. And then it puts forward corresponding solutions from three aspects: concept, theory and practice. Hoping to provide further reference to the complementary role of teaching gesture and teaching discourse.

Analysis of Several Problems in the Construction of Sponge City

Sponge city refers to a new urban construction concept used to solve urban flood disasters and water ecological problems.It is important for the construction of ecological civilization.It plays an important role in the green development and livability of the city.In the construction of a sponge city,it is necessary to make special urban planning and improve the top-level design.In recent years,China has developed a number of sponge city pilot projects.The numerous experiments act as important references for the urban construction in China.This paper mainly analyzes the requirements for the construction of sponge city and discusses several problems as well as solutions in the construction.

Look from the empty nester problem of urban and rural dual structure of society

More and more empty nest has become a social problem that couldn＇t ignore. The problem of empty nester is the essence of urban and rural dual structure social changing. The emergence of empty-nesters is a serious problem in China＇s social development process, with the aging of the population increasing, urban-rural divide more and more obvious. The condition of the human society has gradually formed the rural and the division of labor and the dual structure of the city. This paper expounds the connotation, significance and characteristics of empty nest elderly, analyzes on the problems existing in current urban and rural society and the problem of empty nest elderly in the new situation puts forward the suggestions and countermeasures.

A Robust and Efficient Adaptive Multigrid Solver for the Optimal Control of Phase Field Formulations of Geometric Evolution Laws

We propose and investigate a novel solution strategy to efficiently and accurately compute approximate solutions to semilinear optimal control problems,focusing on the optimal control of phase field formulations of geometric evolution laws.The optimal control of geometric evolution laws arises in a number of applications in fields including material science,image processing,tumour growth and cell motility.Despite this,many open problems remain in the analysis and approximation of such problems.In the current work we focus on a phase field formulation of the optimal control problem,hence exploiting the well developed mathematical theory for the optimal control of semilinear parabolic partial differential equations.Approximation of the resulting optimal control problemis computationally challenging,requiring massive amounts of computational time and memory storage.The main focus of this work is to propose,derive,implement and test an efficient solution method for such problems.The solver for the discretised partial differential equations is based upon a geometric multigrid method incorporating advanced techniques to deal with the nonlinearities in the problem and utilising adaptive mesh refinement.An in-house twogrid solution strategy for the forward and adjoint problems,that significantly reduces memory requirements and CPU time,is proposed and investigated computationally.Furthermore,parallelisation as well as an adaptive-step gradient update for the control are employed to further improve efficiency.Along with a detailed description of our proposed solution method together with its implementation we present a number of computational results that demonstrate and evaluate our algorithms with respect to accuracy and efficiency.A highlight of the present work is simulation results on the optimal control of phase field formulations of geometric evolution laws in 3-D which would be computationally infeasible without the solution strategies proposed in the present work.