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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期68卷 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech cams Key Laboratory of translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteraction<0.001).Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNSCLCs（P=0.040） and sqNSCLCs（P=0.014）,*** the POPLAR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio（HR）=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del（HR=1.05,P=0.64）.Conversely,sqNSCLCs without LRP1B-del benefited more from atezolizumab（HR=0.60,P=0.002） than those with LRP1B-del（HR=1.30,P=0.31）.Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

关键词： non-squamous NSCLC squamous NSCLC LRP1B deleterious mutations predictive biomarker immune checkpoint inhibitor

CXCR4 and CXCR5 orchestrate dynamic germinal center reactions and may contribute to the pathogenesis of systemic lupus erythematosus

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Cellular & Molecular immunology 2019年第8期16卷 724-726页

作者： Bing-xuan Wu Li-dan Zhao Xuan Zhang Department of Rheumatology and Clinical immunology Clinical Immunology CenterMedical Epigenetics Research CenterChinese Academy of Medical Sciences(CAMS)&Peking Union Medical College Hospital100730 BeijingChina

In a previous publication in Cellular and Molecular immunology,Zhao et al.1 showed data from patients with treatment-naïve systemic lupus erythematosus(SLE),demonstrating the clinical significance and possible mechanisms of the aberrant expression of the chemokine receptor CXCR4 on lupus B *** this commentary,we will discuss the roles of CXCL12-CXCR4 and CXCL13-CXCR5 pairs and related signaling pathways in guiding dynamic germinal center(GC)reactions and B cell selection and describe how their dysregulation may contribute to the pathogenesis of SLE.

关键词： CXCL12 CXCR4 lupus erythematosus

Social support and long-term health outcomes after acute myocardial infarction:the China PEACE Prospective AMI Study

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中国循环杂志 2018年第S1期 117-118页

作者： Xiqian Huo Xueke Bai Lihua Zhang Qianying Wang Xiuling Wang Danwei Zhang Lixin Jiang China oxford center for International Health Research National Center for Cardiovascular Diseases Fuwai HospitalCAMS and PUMC

Background Social support is an important predictor of prognosis after acute myocardial infarction (AMI) in western populations,with previous studies suggested that social support may influence cardiovascular prognosi...

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VSL#3 can prevent ulcerative colitis-associated carcinogenesis in mice

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World Journal of Gastroenterology 2018年第37期24卷 4254-4262页

作者： Chun-Sai-Er Wang Wen-Bin Li Hong-Ying Wang Yi-Ming Ma Xin-Hua Zhao Hong Yang Jia-Ming Qian Jing-Nan Li Department of Gastroenterology PUMC Hospital CAMS and PUMC National Cancer center/Cancer Hospital CAMS and PUMC

AIM To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium(AOM/DSS) induced mice model. METHODS C57 BL/6 mice were administered AOM/DSS to develop the ulcerative colitis(UC) carcinogenesis model. Mice were treated with 5-ASA(75 mg/kg/d), VSL#3(1.5 × 109 CFU/d), or 5-ASA combined with VSL#3 by gavage from the day of AOM injection for three months(five days/week). The tumor load was compared in each group, and tumor necrosis factor(TNF-α) and interleukin(IL)-6 levels were evaluated in colon tissue. The stool and intestinal mucosa samples were collected to analyze the differences in the intestinal microbiota by 16 s rDNA sequencing *** VSL#3 significantly reduced the tumor load in AOM/DSS-induced mice model and decreased the level of TNF-α and IL-6 in colon tissue. The model group had a lower level of Lactobacillus and higher level of Oscillibacter and Lachnoclostridium in fecal microbiota than the control group. After the intervention with 5-ASA and VSL#3, Bacillus and Lactococcus were increased, while Lachnoclostridium and Oscillibacter were reduced. 5-ASA combined with VSL#3 increased the Lactobacillus and decreased the Oscillibacter. The intestinal mucosal microbiota analysis showed a lower level of Bifidobacterium and Ruminococcaceae_UCG-014 and higher level of Al oprevotel a in the model group as compared to the control group. After supplementation with VSL#3, Bifidobacterium was increased. 5-ASA combined with VSL#3 increased the level of both Lachnoclostridium and Bifidobacterium. CONCLUSION VSL#3 can prevent UC-associated carcinogenesis in mice, reduce the colonic mucosal inflammation levels, and rebalance the fecal and mucosal intestinal microbiota.

关键词： Tumor necrosis factor-α VSL#3 Ulcerative colitis carcinogenesis Interleukin-6 Intestinal microbiota

A Novel DT40 Antibody Library for the Generation of Monoclonal Antibodies

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Virologica Sinica 2019年第6期34卷 641-647页

作者： Bei Wang Fei Wang He Huang Zhendong Zhao NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Clinical immunology center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China cams-oxford University International center for translational immunology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Early etiological diagnosis is very important for the control of sudden viral infections,and requires antibodies with both high sensitivity and high *** antibody preparation methods have limitations,such as a long and arduous cycle,complicated operation,and high expenses.A chicken lymphoma cell line,DT40,is known to produce IgM-type antibodies and undergo gene conversion and somatic mutation in the variable region of the immunoglobulin gene during ***,the DT40 cell line was developed to produce antibody libraries and prepare antibody rapidly in *** hypermutation in DT40 cells was regulated by the activation-induced cytidine deaminase(AID)gene,AID expression needs to be controlled to either fix the Ig sequence by stopping mutation or improve affinity by resuming mutation after the antibodies have been *** this study,we generated a novel AID-inducible DT40 cell line(DT40-H7),in which the endogenous AID gene was knocked out using the CRISPR/Cas9 genome editing system,and an inducible AID gene,based on the Tet-Off expression system,was stably *** expression was controlled in DT40-H7 cells in a simple and efficient manner;gene conversion and point mutations were observed only when AID was *** the antibody library generated from this cell line,we successfully obtained monoclonal antibodies against the NS1 protein of Zika *** DT40-H7 cell line represents a useful tool for the selection and evolution of antibodies and may also be a powerful tool for the rapid selection and generation of diagnostic antibodies for emerging infectious diseases.

关键词： Antibody library DT40 cell line Activation-induced cytidine deaminase(AID) Zika virus(ZIKV)

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HPV 6b L1VIRUS-LIKE PARTICLES ELICIT HUMORAL IMMUNITY IN MICE

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Chinese Medical Sciences Journal 2003年第3期18卷 185-188页

作者：刘跃华刘文军刘晓松 Ian H.Frazer Department of Dermatology PUMC Hospital CAMS & PUMC Beijing 100730 center for immunology and Cancer Research University of Queensland Qld 4102 Australia

*** test whether intramuscular,intranasal,intrarectal and intravagina l administration of HPV6b L 1 virus-like particlescould induce immune response in mice and to as sess whether intra-muscular and mucosal vaccination against HPV is *** ***6b L1proteins self-assembled into VLPs in Sf-9cell in *** e were immunized on day0and21with50ìg HPV6b L1VLPs intramuscularly,int ranasally,intrarectally and intravagi-nally *** were collected for testing IgG titer after a further7days and3months *** .After immunizations,all mice developed significant anti-HPV6b L1antibody titers in serum by7days after the second *** titer of the serum I gG antibody against HPV6b L1VLPs in the intramuscularly immunized group was h igher than that in the intranasally,intrarectally and intravaginally immunized groups respectively,indicating that both muscular and mucosal administration of HPV6b L1VLPs can stimulate a systemic HPV-specific antibody *** of the mice in the in-tramuscularly immunized group still maintained a high tit er of the serum IgG antibody against HPV6b L1VLPs 3months after the immunizat *** results demonstrated that the HPV6b L1VLPs maintain stro ng ***-nization with HPV6b L1VLPs via intramuscular and mucos al routes,without adjuvant ,can elicit spe-cific antibody in *** fin dings suggest that the VLPs are able to induce protective antibodies.

关键词： human papillomavirus virus-like particle vaccine

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Exploring the role of N-acetyltransferases in diseases:a focus on N-acetyltransferase 9 in neurodegeneration

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Neural Regeneration Research 2025年第10期20卷 2862-2871页

作者： Prajakta Deshpande Anuradha Venkatakrishnan Chimata Amit Singh Department of Biology University of DaytonDaytonOHUSA Premedical Program University of DaytonDaytonOHUSA center for Tissue Regeneration and Engineering at Dayton(TREND) University of DaytonDaytonOHUSA Integrative Science and Engineering center University of DaytonDaytonOHUSA center for Genomic Advocacy(TCGA) Indiana State UniversityTerre HauteINUSA

Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and *** acetylation is a common post-translational modification pivotal to basic cellular *** to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and *** this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in ***,we have focused on N-acetyltransferase 9 and its role in microtubule *** have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative *** have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.

关键词： acetyl-coenzyme A Alzheimer’s disease animal models cell death drosophila eye human disease c-Jun N-terminal kinase signaling N-Acetyltransferases N-acetyltransferase 9 neurodegeneration

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ACE2 expression is regulated by AhR in SARS-CoV-2-infected macaques

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Cellular & Molecular immunology 2021年第5期18卷 1308-1310页

作者： Jiadi Lv Pin Yu Zhenfeng Wang Wei Deng Linlin Bao Jiangning Liu Fengli Li Qiangqiang Zhu Nannan Zhou Qi Lv Guanpeng Wang Shunyi Wang Yabo Zhou Jiangping Song Wei-Min Tong Yuying Liu Chuan Qin Bo Huang Department of immunology and National Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)and Peking Union Medical CollegeBeijingChina NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceCAMS and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesCAMS and Peking Union Medical CollegeBeijingChina Department of Pathology Institute of Basic Medical SciencesCAMS and Peking Union Medical CollegeBeijingChina Clinical immunology center CAMSBeijingChina Department of Biochemistry and Molecular Biology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

During the current outbreak of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),more than 115 million people have been infected,and 2.5 million have died.1,2 Despite such great harm to human health,the pathogenesis of COVID-19 remains *** the first step in the pathogenetic process,viral entry is mediated by the binding of the SARS-CoV-2 surface spike(S)protein to angiotensin-converting enzyme 2(ACE2)on host cells,such as lung epithelial *** an alternative to S protein-blocking strategies,manipulating host cell ACE2 expression may exert an inhibitory effect on SARS-CoV-2 ***,the molecular mechanism regulating ACE2 expression remains unclear.

关键词： ACE2 infected acute

Next generation sequencing reveals co-existence of hereditary spherocytosis and Dubin–Johnson syndrome in a Chinese gril: A case report

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World Journal of Clinical Cases 2019年第20期7卷 3303-3309页

作者： Yuan Li Yang Li Yang Yang Wen-Rui Yang Jian-Ping Li Guang-Xin Peng Lin Song Hui-Hui Fan Lei Ye You-Zhen Xiong Zhi-Jie Wu Kang Zhou Xin Zhao Li-Ping Jing Feng-Kui Zhang Li Zhang Anemia Therapeutic center Institute of Hematology and Blood Diseases HospitalCAMS and PUMC

BACKGROUND Hereditary spherocytosis(HS)is a hereditary disease of hemolytic anemia that occurs due to the erythrocyte membrane ***–Johnson syndrome(DJS),which commonly results in jaundice,is a benign hereditary disorder of bilirubin clearance that occurs only *** co-occurrence of HS and DJS is extremely *** recently diagnosed and treated a case of co-occurring HS and *** SUMMARY A 21-year-old female patient presented to our department because of severe jaundice,severe splenomegaly,and mild anemia since *** eventually confirmed the diagnosis of co-occurring DJS and HS by next generation sequencing(NGS).The treatment of ursodeoxycholic acid in combination with phenobarbital successfully increased hemoglobin and reduced total bilirubin and direct *** The routine application of NGS can efficiently render a definite diagnosis when inherited disorders are suspected.

关键词： Hereditary spherocytosis Dubin–Johnson syndrome Hemolytic anemia Jaundice Next generation sequencing ABCC2 SPTB Case report