Tumor-infiltrating lymphocytes（TILs）are the main anti-tumor immune cells in the tumor microenvironment and play a crucial role in the immunotherapy of solid tumors. However，the presence of an immunosuppressive microenvironment limits their clinical efficacy. As one of the most abundant immunosuppressive cells in the tumor microenvironment，tumor-associated macrophages（TAMs）have a close connection with TILs and play an important role in the immunosuppression on TILs. This review discusses the application of TILs in the field of tumor therapy and their immunosuppressive bottlenecks，elaborates on the role of TAMs in tumor immunosuppression，and summarizes the effects of TAMs on the immune function of TILs through mechanisms such as cytokine secretion，exosome release，metabolic reprogramming，and epigenetic remodeling. In addition，this article also explores the possibility of targeting TAMs as a strategy to improve the anti-tumor efficacy of TILs，aiming to provide new ideas for addressing the immunosuppressive challenges faced by TILs.

Myeloid-derived cells (MDCs) are crucial in immune response and tissue homeostasis. They have high functional plasticity and can be polarized according to microenvironment signals. These cells, including macrophages, neutrophils, and dendritic cells (DCs), exhibit different functional polarization states in different pathological environments and are involved in the occurrence and development of diseases such as inflammation and tumors. Studies have shown that metabolic reprogramming plays a key role in the functional polarization of MDCs, affecting the cellular energy supply and regulating immune function. This paper reviews classification, function and polarization mechanism of MDCs and discusses metabolic reprogramming. In addition, the therapeutic strategies targeting MDC are summarized, which is expected to provide new targets for tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Myeloid Cells/metabolism* ; Neoplasms/pathology* ; Animals ; Immunotherapy/methods* ; Dendritic Cells/immunology* ; Macrophages/immunology*

Tumor-infiltrating lymphocytes（TILs）are the main anti-tumor immune cells in the tumor microenvironment and play a crucial role in the immunotherapy of solid tumors. However，the presence of an immunosuppressive microenvironment limits their clinical efficacy. As one of the most abundant immunosuppressive cells in the tumor microenvironment，tumor-associated macrophages（TAMs）have a close connection with TILs and play an important role in the immunosuppression on TILs. This review discusses the application of TILs in the field of tumor therapy and their immunosuppressive bottlenecks，elaborates on the role of TAMs in tumor immunosuppression，and summarizes the effects of TAMs on the immune function of TILs through mechanisms such as cytokine secretion，exosome release，metabolic reprogramming，and epigenetic remodeling. In addition，this article also explores the possibility of targeting TAMs as a strategy to improve the anti-tumor efficacy of TILs，aiming to provide new ideas for addressing the immunosuppressive challenges faced by TILs.

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Tumor-associated macrophages (TAMs) are the predominant immune cells in the tumor microenvironment (TME). They have been shown to play an important immunosuppressive role in the development of TME and promote tumor immune escape, growth and metastasis. It is a current research hotspot to regulate the functional polarization of TAMs through trained immunity (metabolic reprogramming, epigenetic remodeling) to affect the occurrence and development of tumors. Therefore, in-depth research in this field not only presents a more comprehensive perspective on the pathogenesis of immune-mediated diseases, but also can provide new strategies for clinical anti-tumor immunotherapy. This paper outlines the origin of TAMs and the phenotypes and mechanisms of TAMs polarization, discusses the mechanisms by which metabolic reprogramming and epigenetic remodeling regulate TAMs, summarizes the regulation of TAMs activation and polarization by them, and provides an overview of the progress in TAMs at the current stage of clinical practice, hoping to provide reference for the development of new immunoprevention and treatment strategies.

目的：筛选果蝇Zeste基因增强子同源物2（EZH2）基因上游miRNA及lncRNA，分析其在胃癌细胞中的表达并验证其间的靶向关系，探讨它们对胃癌细胞增殖、迁移和凋亡的影响。方法：通过ENCORI、miRDB和Target Scan数据库查询并分析、筛选EZH2上游miRNA（has-miR-450b-5p），ENCORI数据库和DAINA数据库筛选has-miR-450b-5p上游lncRNA（lncRNA NEAT1），预测hsa-miR-450b-5p、lncRNA NEAT1与EZH2之间的结合位点，双荧光素酶报告基因实验验证hsa-miR-450b-5p与lncRNA NEAT1的结合关系。采用qPCR和WB法检测lncRNA NEAT1和EZH2在正常胃黏膜细胞（GES-1）与胃癌细胞（MGC-803、SGC-7901和MKN-28）中的表达量。按转染物的不同将MGC-803和SGC-7901细胞分为hsa-miR-450b-5p-mimic组、mimic-NC组、si-NEAT1组和si-NC组，转染36~48 h后qPCR法验证过表达及敲减效果；通过qPCR、WB法检测观察过表达hsa-miR-450b-5p对细胞中lncRNA NEAT1和EZH2 mRNA、蛋白表达的影响，以及敲减lncRNA NEAT1对hsa-miR-450b-5p和EZH2 mRNA表达的影响；CCK-8法、划痕愈合实验和流式细胞术分别检测敲减EZH2或敲减lncRNA NEAT1对细胞增殖、迁移和凋亡能力的影响。结果：生物信息学分析筛选获得EZH2上游miRNA和lncRNA为has-miR-450b-5p和lncRNA NEAT1，双荧光素酶报告基因实验验证了两者间存在靶向关系。lncRNA NEAT1和EZH2 mRNA、蛋白在胃癌细胞中均呈高表达（均P<0.05）。与mimic-NC组相比，hsa-miR-450b-5p-mimic组MGC-803、SGC-7901细胞中miR-450b-5p水平均显著升高，而EZH2 mRNA、蛋白和lncRNA NEAT1的表达量均显著降低（P<0.05或P<0.01）；与si-NC组相比，si-NEAT1组MGC-803、SGC-7901细胞中lncRNA NEAT1和EZH2 mRNA的表达量均显著降低（均P<0.01），SGC-7901细胞中hsa-miR-450b-5p表达量显著升高（P<0.05）。敲减EZH2或敲减lncRNA NEAT1后，MGC-803、SGC-7901细胞的增殖、迁移能力均显著降低（均P<0.01）。结论：lncRNA NEAT1 和EZH2在胃癌细胞中均呈高表达，lncRNA NEAT1可通过hsa-miR-450b-5p促进EZH2的表达并提高胃癌MGC-803和SGC-7901细胞的增殖和迁移能力。

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Retinopathy of prematurity(ROP)is a retinal vascular proliferative disease that occurs in preterm low-birth-weight infants and is the leading cause of blindness in children worldwide.Currently,with the intensive study of ROP,it has been found that retinal neovascularization can spontaneously regress at any time in the early stages of the disease.Therefore,early screening,diagnosis and intervention are particularly important in children with ROP.However,the exist-ing screening methods have problems such as long screening times and poor cooperation of infants and children,which may lead to missed diagnoses,thus more reliable prediction methods are needed.This article briefly describes the screening and prediction methods for ROP at home and abroad in recent years,and systematically analyzes the predictive value of different types of biomarkers for ROP,with a view to providing a basis for establishing a reasonable prediction model for ROP.

Objective : To investigate the effect of lncRNA SNHG16 (SNHG16) on the proliferation and migration of gastric cancer cells and its molecular regulatory mechanism. Methods : The expression of SNHG16 in gastric cancer tissue was retrieved based on online database and the downstream target gene of SNHG16 was screened. The interaction between SNHG16 and miR⁃195 ⁃5p was verified by bioinformatics analysis and double luciferase reporter gene experiment. The expression of SNHG16 , miR⁃195 ⁃5p and MYB in gastric cancer cells (HGC⁃27 , MKN⁃28) was detected by real⁃time fluorescent quantitative PCR (qRT⁃PCR) ; SNHG16 was knocked down to detect the expression of miR⁃195 ⁃5p or MYB ; The expression of MYB was detected by overexpression of miR⁃195 ⁃5p;Western blot analysis was used to detect the protein expression level of MYB in each group. Knock down SNHG16 or overexpress miR⁃195 ⁃5p , and the proliferation and migration ability of gastric cancer cells (HGC⁃27 , MKN⁃28) were detected through cell proliferation and scratch test. Results : The expression of LncRNA SNHG16 increased in gastricancer tissues and gastric cancer cells (HGC⁃27 , MKN⁃28 , MKN⁃45 , NCI⁃N87) . The results of double luciferase reporter gene experiment showed that psiCHECK2⁃SNHG16⁃WT and miR⁃195⁃5p mimic were transfected into HGC⁃27 at the same time , significantly inhibiting the luciferase activity of HGC⁃27 cells. The results of qRT PCR and WB experiments showed that knocking down SNHG16 in HGC⁃27 and MKN⁃28 cells upregulated miR⁃195⁃5p and inhibited the expression of MYB at the transcription and translation levels ; Overexpression of miR⁃195 ⁃5p in HGC⁃27 and MKN⁃28 cells inhibited MYB expression. The results of CCK8 proliferation test and cell scratch test showed that knocking down SNHG16 or overexpressing miR⁃195 ⁃5p could inhibit the proliferation and migration of HGC⁃27 and MKN⁃28 cells. Conclusion LncRNA SNHG16 can regulate the expression of MYB in gastric cancer cells through miR⁃195 ⁃5p , and the high expression of SNHG16 can promote the proliferation and migration of gastric cancer cells.

Illness anxiety disorder (IAD) is a psychiatric disorder defined by excessive worry about having or developing a serious undiagnosed medical condition. IAD can affect the social functions of patients and increase burdens imposed on the family and society. The concept of IAD was first proposed in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013. However, the rates of screening and identification of IAD are at a relatively low level in clinical practice, and the effectiveness of pharmacological and psychological intervention on IAD are still in the process of exploration and validation. The recognition of IAD should be enhanced and the efficacy of intervention need to be further improved. This article reviews the progress of clinical studies on IAD to improve clinicians′ understanding of the disease, and help them adopt appropriate treatments as early as possible to alleviate patient suffering and improve disease prognosis.