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AZD1775 and anti-PD-1 antibody synergistically sensitize hepatoma to radiotherapy

Chinese Medical Journal 2024年第2期137卷 222-231页

作者： Yichun Yin Jian Wang Junxuan Yi Kaiyue Zhang Zimeng Yin Shunzi Jin Baisong Zheng Public Health of College Jilin UniversityJilinChangchun 130021China Institute of Virology and AIDS Research The First Hospital of Jilin UniversityJilinChangchun 130021China NHC Key Laboratory of Radiobiology(jilin university) JilinChangchun 130021China

Background:Radiation(IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment(TME).Wee1,a cell cycle regulator,can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1(CDK1).Meanwhile,programed death-1/programed death ligand-1(PD-1/PDL-1)blockade is closely related to TME.This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody(anti-PD-1 Ab)on radiosensitization of hepatoma.Methods:The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide(MTT)assay on human and mouse hepatoma cells HepG2,Hepa1-6,and H22.The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro.A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice,which were divided into control group,IR group,AZD1775 group,IR+AZD1775 group,IR+anti-PD-1 Ab group,and the IR+AZD1775+anti-PD-1 Ab group.Cytotoxic CD8^(+)T cells in TME were analyzed by flow cytometry.Results:Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro.AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage.AZD1775 treatment also reduced the proportion of PD-1^(+)/CD8^(+)T cells in the spleen of hepatoma subcutaneous xenograft mice.Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferonγ(IFNγ)^(+)or Ki67^(+)CD8 T cells and decreasing the levels of CD8^(+)Tregs cells in the tumor and spleen of the hepatoma mice model,indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγexpression,enhancing CD8^(+)T cells proliferation,and weakening CD8^(+)T cells depletion.Conclusions:This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improv

关键词： Hepatoma Radiation AZD1775 Anti-PD-1 antibody DNA damage Tumor microenvironment

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Recent advances in age-related metabolic dysfunction-associated steatotic liver disease

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World Journal of Gastroenterology 2024年第7期30卷 652-662页

作者： Qian-Jun He Yi-Fei Li Ling-Tong Zhao Chun-Tong Lin Chun-Yan Yu Dan Wang College of Basic Medicine Beihua UniversityJilin 132013Jilin ProvinceChina Department of Traumatic Surgery Jilin Central HospitalJilin 132001Jilin ProvinceChina

Metabolic dysfunction-associated steatotic liver disease(MASLD)affects approximately 25%of the world's population and has become a leading cause of chronic liver disease.In recent years,an increasing amount of data suggests that MASLD is associated with aging.As the population ages,age-related MASLD will become a major global health problem.Targeting an aging will become a new approach to the treatment of MASLD.This paper reviews the current studies on the role of aging-related factors and therapeutic targets in MASLD,including:Oxidative stress,autophagy,mitochondrial homeostasis,bile acid metabolism homeostasis,and dysbiosis.The aim is to identify effective therapeutic targets for age-related MASLD and its progression.

关键词： Metabolic dysfunction-associated steatotic liver disease Aging Mitochondrial homeostasis Bile acid homeostasis Dysbiosis

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Biomarkers for neuromyelitis optica:a visual analysis of emerging research trends

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Neural Regeneration Research 2024年第12期19卷 2735-2749页

作者： Xiangjun Li Jiandong Zhang Siqi Zhang Shengling Shi Yi’an Lu Ying Leng Chunyan Li Department of Ophthalmology Affiliated Hospital of Beihua UniversityJilinJilin ProvinceChina Department of Ophthalmology Changchun Bright Eye HospitalChangchunJilin ProvinceChina Departemt of Endocrinology Affiliated Hospital of Beihua UniversityJilinJilin ProvinceChina

Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis.Over the past 20 years,the search for biomarke rs for neuromyelitis optica has been ongoing.Here,we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis optica.Research in this area is consistently increasing,with China and the United States leading the way on the number of studies conducted.The Mayo Clinic is a highly reputable institution in the United States,and was identified as the most authoritative institution in this field.Furthermore,Professor Wingerchuk from the Mayo Clinic was the most authoritative expe rt in this field.Keyword analysis revealed that the terms "neuro myelitis optica"(261 times), "multiple sclerosis"(220 times), "neuromyelitis optica spectrum disorder"(132 times), "aquaporin4"(99 times),and "optical neuritis"(87 times) were the most frequently used keywords in literature related to this field.Comprehensive analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple sclerosis.Furthermore,aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum disorder.Myelin oligodendrocyte glycoprotein-IgG is a diagnostic biomarke r for myelin oligodendrocyte glycoprotein antibody-associated disease.Recent biomarkers for neuromyelitis optica in clude cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein,serum astrocyte damage biomarkers like FAM19A5,serum albumin,and gammaaminobutyric acid.The latest prospective clinical trials are exploring the potential of these biomarkers.Preliminary results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelitis optica spectrum disorder.The ultimate goal of

关键词： aquaporin-4 autoantibody multiple sclerosis myelin oligodendrocyte glycoprotein antibody-associated disease neuromyelitis optica neuromyelitis optica spectrum disorder optical coherence tomography

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Emerging strategies for nerve repair and regeneration in ischemic stroke:neural stem cell therapy

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Neural Regeneration Research 2024年第11期19卷 2430-2443页

作者： Siji Wang Qianyan He Yang Qu Wenjing Yin Ruoyu Zhao Xuyutian Wang Yi Yang Zhen-Ni Guo Stroke Center Department of Neurologythe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Neuroscience Research Center Department of Neurologythe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Breast Surgery General Surgery Centerthe First Hospital of Jilin UniversityChangchunJilin ProvinceChina

Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.

关键词： bystander effect cell replacement extracellular vesicles ischemic stroke neural stem cells neural stem cell engineering

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Molecular classification of small cell lung cancer subtypes:Characteristics,prognostic factors,and clinical translation

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Chinese Medical Journal 2024年第2期137卷 130-139页

作者： Hanfei Guo Wenqian Li Ye Guo Naifei Chen Jiuwei Cui Cancer Center The First Hospital of Jilin UniversityChangchunJilin 130021China

Small cell lung cancer(SCLC)is a highly malignant tumor with a very poor prognosis;therefore,more effective treatments are urgently needed for patients afflicted with the disease.In recent years,emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology,metastasis,immune microenvironment,and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes.Additionally,advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease.Herein,we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.

关键词： Small cell lung carcinoma Molecular classification Tumor heterogeneity Drug resistance Transcription factors Genomics Phenotype Prognosis

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Mesenchymal stem cells and their derived exosomes for the treatment of COVID-19

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World Journal of Stem Cells 2024年第4期16卷 353-374页

作者： Xiang-Yi Hou La-Mu Danzeng Yi-Lin Wu Qian-Hui Ma Zheng Yu Mei-Ying Li Li-Sha Li The Key Laboratory of Pathobiology Ministry of EducationCollege of Basic Medical SciencesJilin UniversityChangchun 130021Jilin ProvinceChina Department of Pharmacy Jilin UniversityChangchun 130021Jilin ProvinceChina The First Hospital of jilin university Jilin UniversityChangchun 130021Jilin ProvinceChina

Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,which can progress to severe respiratory distress syndrome and multiple organ failure.In severe cases,these complications may even lead to death.One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response.Therefore,suppressing the overactive immune response may be an effective strategy for treating COVID-19.Mesenchymal stem cells(MSCs)and their derived exosomes(MSCs-Exo)have potent homing abilities,immunomodulatory functions,regenerative repair,and antifibrotic effects,promising an effective tool in treating COVID-19.In this paper,we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19.We also summarize relevant recent clinical trials,including the source of cells,the dosage and the efficacy,and the clinical value and problems in this field,providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.

关键词： COVID-19 Cytokine storm Immunomodulation Mesenchymal stem cell Mesenchymal stem cell-derived exosomes

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Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

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World Journal of Gastroenterology 2024年第10期30卷 1295-1312页

作者： Hui Ma Qing-Zhu Yan Jing-Ru Ma Dong-Fu Li Jun-Ling Yang Department of Clinical Laboratory The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina Department of Ultrasound Medicine The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina Digestive Diseases Center Department of Hepatopancreatobiliary MedicineThe Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina Department of Respiratory and Critical Care Medicine The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

关键词： Hepatitis B virus reactivation Immunological mechanisms Disease progression Management strategies Immune response

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Gut flora in multiple sclerosis:implications for pathogenesis and treatment

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Neural Regeneration Research 2024年第7期19卷 1480-1488页

作者： Weiwei Zhang Ying Wang Mingqin Zhu Kangding Liu Hong-Liang Zhang Department of Neurology the First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina Department of Life Sciences National Natural Science Foundation of ChinaBeijingChina

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

关键词： gut flora gut-brain axis multiple sclerosis pathogenesis treatment

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Optimization of extreme ultraviolet vortex beam based on high harmonic generation

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Chinese Physics B 2024年第5期33卷 459-464页

作者：肖礴赵逸文程方晶王革文姜威王一琛胡杰梁红静马日 Institute of Atomic and Molecular Physics Jilin UniversityChangchun 130012China College of Science Jilin Institute of Chemical TechnologyJilin 132022China

In high harmonic generation(HHG),Laguerre–Gaussian(LG) beams are used to generate extreme ultraviolet(XUV)vortices with well-defined orbital angular momentum(OAM),which have potential applications in fields such as microscopy and spectroscopy.An experimental study on the HHG driven by vortex and Gaussian beams is conducted in this work.It is found that the intensity of vortex harmonics is positively correlated with the laser energy and gas pressure.The structure and intensity distribution of the vortex harmonics exhibit significant dependence on the relative position between the gas jet and the laser focus.The ring-like structures observed in the vortex harmonics,and the interference of quantum paths provide an explanation for the distinct structural characteristics.Moreover,by adjusting the relative position between the jet and laser focus,it is possible to discern the contributions from different quantum paths.The optimization of the HH vortex field is applicable to the XUV,which opens up a new way for exploiting the potential in optical spin or manipulating electrons by using the photon with tunable orbital angular momentum.

关键词： high harmonic generation phase matching extreme ultraviolet vortex beam quantum path interference

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A novel graph oversampling framework for node classification in class-imbalanced graphs

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Science China(Information Sciences) 2024年第6期67卷 214-229页

作者： Riting XIA Chunxu ZHANG Yan ZHANG Xueyan LIU Bo YANG Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education Jilin University College of Artificial Intelligence Jilin University College of Computer Science and Technology Jilin University College of Communication Engineering Jilin University

Graph neural network(GNN) is a promising method to analyze graphs. Most existing GNNs adopt the class-balanced assumption, which cannot deal with class-imbalanced graphs well. The oversampling technique is effective in alleviating class-imbalanced problems. However, most graph oversampling methods generate synthetic minority nodes and their edges after applying GNNs. They ignore the problem that the representations of the original and synthetic minority nodes are dominated by majority nodes caused by aggregating neighbor information through GNN before oversampling. In this paper, we propose a novel graph oversampling framework, termed distribution alignment-based oversampling for node classification in classimbalanced graphs(named Graph-DAO). Our framework generates synthetic minority nodes before GNN to avoid the dominance of majority nodes caused by message passing in GNNs. Additionally, we introduce a distribution alignment method based on the sum-product network to learn more information about minority nodes. To our best knowledge, it is the first to use the sum-product network to solve the class-imbalanced problem in node classification. A large number of experiments on four real datasets show that our method achieves the optimal results on the node classification task for class-imbalanced graphs.

关键词： graph neural network class-imbalanced graphs sum-product network oversampling node classification

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