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Association of apolipoprotein E epsilon 4 and cognitive impairment in adults living with human immunodeficiency virus: a meta-analysis

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Chinese Medical Journal 2022年第22期135卷 2677-2686页

作者： Tingting Mu Jiaqi Wei Jun Sun Junyan Jin Tong Zhang Hao Wu Bin Su beijing Key Laboratory for HIV/AIDS Research Clinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Department of Radiology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China

Background: It is controversial whether the apolipoprotein E epsilon 4 allele (APOE ε4) is a risk gene for human immunodeficiency virus (HIV)-related neurocognitive impairment. This meta-analysis aimed to summarize evidence of the associations betweenAPOE ε4 and cognitive impairment in people living with HIV (PLWH).Methods: Our study conducted a systematic literature search of PubMed, Web of Science, Embase, Google Scholar, and ProQuest for studies published before April 11, 2022 that evaluated associations betweenAPOE ε4 and cognitive impairment in adult PLWH (aged ≥18 years). We calculated pooled odds ratios (ORs) of global cognitive impairment and 95% confidence intervals (CIs) and standardized mean differences (SMDs) for specific cognitive domains betweenAPOE ε4 carriers and non-carriers. Subgroup meta-analyses were used to evaluate the result profiles across different categorical ***: Twenty studies met the inclusion criteria, including 19 that evaluated global cognitive *** ε4 was significantly associated with global cognitive impairment in PLWH (OR = 1.36, 95% CI = [1.05, 1.78], number of estimates [k] = 19,P = 0.02, random effects). Subgroup meta-analysis based percentage of females showed evident intergroup differences in global cognitive performance between ε4 carriers and non-carriers (P = 0.015).APOE ε4 carriers had lower cognitive test scores than non-carriers in all seven cognitive domains, including fluency (SMD = -0.51, 95% CI = [-0.76, -0.25],P < 0.001,k = 4,I^(2)= 0%), learning (SMD = -0.52, 95% CI = [-0.75, -0.28],P < 0.001,k = 5,I^(2) = 0%), executive function (SMD = -0.41, 95% CI= [-0.59, -0.23],P < 0.001,k= 8,I^(2)= 0%), memory (SMD=-0.41, 95% CI= [-0.61, -0.20],P < 0.001,k= 10,I^(2)= 36%), attention/working memory (SMD=-0.34, 95% CI= [-0.54, -0.14],P= 0.001,k= 6,I^(2)= 0%), speed of information processing (SMD = -0.34, 95% CI = [-0.53, -0.16],P < 0.001,k = 8,I^(2) = 0%), and motor function (SMD = -0.19, 95% CI = [-0.3

关键词： Apolipoprotein E epsilon 4 Cognition Gene Human immunodeficiency virus Meta-analysis

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Durable natural killer cell response after three doses of SARS-CoV-2 inactivated vaccine in HIV-infected individuals

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Chinese Medical Journal 2023年第24期136卷 2948-2959页

作者： Xiaodong Yang Xiuwen Wang Xin Zhang Haifeng Ding Hu Wang Tao Huang Guanghui Zhang Junyi Duan Wei Xia Bin Su Cong Jin Hao Wu Tong Zhang beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China Tian Yuan Studio Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Background:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 ***,it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer(NK)cell response in people living with human immunodeficiency virus(PLWH)and healthy ***:Forty-seven PLWH and thirty healthy controls(HCs)inoculated with SARS-CoV-2 inactivated vaccine were enrolled from beijing Youan Hospital in this *** effect of SARS-CoV-2 vaccine on NK cell frequency,phenotype,and function in PLWH and HCs was evaluated by flow cytometry,and the response of NK cells to SARS-CoV-2 Omicron Spike(SARS-2-OS)protein stimulation was also ***:SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH,which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of ***,in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned ***,the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0,4 and 12 weeks,but the percentage of CD16^(+)NK cells in PLWH was significantly higher than that in HCs at 2,4 and 12 weeks after the third dose of ***,the frequency of CD16^(+)NK cells was significantly negatively correlated with the proportion of CD107a^(+)NK cells in PLWH at each time point after the third ***,this phenomenon was also observed in HCs at 0,2,and 4 weeks after the third ***,regardless of whether NK cells were stimulated with SARS-2-OS or not,we did not observe any differences in the expression of NK cell degranulation markers between PLWH and ***:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells,indicating that the inoculation of

关键词： HIV SARS-CoV-2 inactivated vaccine COVID-19 Omicron variant NK cell response Immunologic memory

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Ex utero intrapartum therapy in infants with congenital diaphragmatic hernia:a propensity score matching analysis

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World Journal of Pediatric Surgery 2022年第4期5卷 267-274页

作者： Yunlong Zhao Ying Wang Chao Liu Yulin Jiang Yandong Wei Hua Meng Shan Jian Xiting Zhu Lijian Pei Xiaochen Bai Feng Feng Yan Lv Xiya Zhou Qingwei Qi Jingna Li Lishuang Ma Peking Union Medical College Graduate School BeijingChina Department of Neonatal Surgery Children’s Hospital of Capital Institute of PediatricsCapital Institute of PediatricsBeijingChina Department of Obstetrics Peking Union Medical College HospitalBeijingChina Department of Ultrasound Peking Union Medical College HospitalBeijingChina Department of Pediatrics Peking Union Medical College HospitalBeijingChina Department of Biostatistics and Statistical programming Everest Clinical Research CorporationBeijingChina Department of Anesthesiology Peking Union Medical College HospitalBeijingChina Department of Pediatrics Beijing Obstetrics and Gynecology HospitalCapital Medical UniversityBeijingChina Department of Radiology Peking Union Medical College HospitalBeijingChina

Objective Previous studies have shown that ex utero intrapartum therapy(EXIT)is safe and feasible for newborns with congenital diaphragmatic hernia(CDH).This study reports our experience with EXIT in fetuses with CDH in an attempt to explore the efficacy of EXIT on the survival rate of this *** A retrospective analysis of the clinical data of 116 children with CDH was *** children were assigned to EXIT and non-EXIT *** score matching(PSM)toward clinical data was performed,and the clinical characteristics and outcomes were *** survival at discharge as the main outcome,logistic regression analysis was carried out to explore the efficacy of EXIT on *** During the study period,30 of 116 children received *** PSM,the survival rates of the EXIT group and the non-EXIT group were 82.76%(24/29)and 48.28%(14/29),respectively(p=0.006).EXIT(OR=0.083,95%CI=0.013to 0.525,p=0.008),liver herniation(OR=16.955,95%CI=2.342 to 122.767,p=0.005),and gestational age at diagnosis(OR=0.662,95%CI=0.497 to 0.881,p=0.005)were independent mortality-related risk factors of all children with ***-nine of 116 children underwent *** PSM,the postoperative survival rates of the EXIT group and non-EXIT group were 84.6%(22/26)and 76.9%(20/26),respectively(p=0.754).Liver herniation(OR=10.451,95%CI=1.641 to 66.544,p=0.013)and gestational age at diagnosis(OR=0.736,95%CI=0.577 to 0.938,p=0.013)were independent mortality-related risk factors of children after *** EXIT can be performed safely for selected prenatally diagnosed CDH neonates with potentially better survival and does not cause more maternal complications compared with traditional cesarean section.

关键词： hernia diagnosis congenital

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Weak SARS-CoV-2-specific responses of TIGIT-expressing CD8^(+)T cells in people living with HIV after a third dose of a SARS-CoV-2 inactivated vaccine

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Chinese Medical Journal 2023年第24期136卷 2938-2947页

作者： Junyan Jin Xiuwen Wang Yongzheng Li Xiaodong Yang Hu Wang Xiaoxu Han Jin Sun Zhenglai Ma Junyi Duan Guanghui Zhang Tao Huang Tong Zhang Hao Wu Xin Zhang Bin Su beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Biomedical Pioneering Innovation Center(BIOPIC) Peking UniversityBeijing 100871China Tian Yuan Studio Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Background:T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains(TIGIT),an inhibitory receptor expressed on T cells,plays a dysfunctional role in antiviral infection and antitumor ***,it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)inactivated ***:Forty-five people living with HIV(PLWH)on antiretroviral therapy(ART)for more than two years and 31 healthy controls(HCs),all received a third dose of a SARS-CoV-2 inactivated vaccine,were enrolled in this *** amounts,activation,proportion of cell subsets,and magnitude of the SARS-CoV-2-specific immune response of TIGIT^(+)CD4^(+)and TIGIT^(+)CD8^(+)T cells were investigated before the third dose but 6 months after the second vaccine dose(0W),4 weeks(4W)and 12 weeks(12W)after the third ***:Compared to that in HCs,the frequency of TIGIT^(+)CD8^(+)T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine,and the immune activation of TIGIT^(+)CD8^(+)T cells also increased.A decrease in the ratio of both T naïve(T_(N))and central memory(T_(CM))cells among TIGIT^(+)CD8^(+)T cells and an increase in the ratio of the effector memory(T_(EM))subpopulation were observed at 12W in ***,particularly at 12W,a higher proportion of TIGIT^(+)CD8^(+)T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker *** with 0W,SARS-CoV-2-specific TIGIT^(+)CD8^(+)T-cell responses in PLWH were not enhanced at 12W but were enhanced in ***,at all time points,the SARS-CoV-2-specific responses of TIGIT^(+)CD8^(+)T cells in PLWH were significantly weaker than those of TIGIT-CD8^(+)T ***,in HCs,the difference in the SARS-CoV-2-specific responses induced between TIGIT^(+)CD8^(+)T cells and TIGIT-CD8^(+)T cells was in

关键词： HIV TIGIT T-lymphocytes SARS-CoV-2 Booster vaccination Immunity

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Targeting the HIV reservoir:chimeric antigen receptor therapy for HIV cure

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Chinese Medical Journal 2023年第22期136卷 2658-2667页

作者： Shuang Li Hu Wang Na Guo Bin Su Olivier Lambotte Tong Zhang beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Department of Internal Medicine AP-HPBicêtre HospitalUMR1184 INSERM CEALe Kremlin BicêtreUniversity Paris SaclayParis 94270France

Although antiretroviral therapy(ART)can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus(HIV)-infected individuals,ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral *** achieve a functional cure for HIV infection,numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of *** studies have tested adoptive T-cell therapies in HIV-infected individuals,but their effectiveness was *** recent years,with the technological progress and great success of chimeric antigen receptor(CAR)therapy in the treatment of hematological malignancies,CAR therapy has gradually shown its advantages in the field of HIV *** studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector ***,CAR therapy may be beneficial for enhancing HIV immunity,achieving HIV control,and eliminating HIV reservoirs,gradually becoming a promising strategy for achieving a functional HIV *** this review,we provide an overview of the design of anti-HIV CAR proteins,the cell types of anti-HIV CAR(including CAR T cells,CAR natural killer cells,and CAR-encoding hematopoietic stem/progenitor cells),the clinical application of CAR therapy in HIV infection,and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.

关键词： Functional HIV cure HIV reservoir Chimeric antigen receptor therapy CAR T cells CAR natural killer cells

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Glut1 expression on CD8^(dim)T cells is associated with immune recovery in HIV-1-infected individuals

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Chinese Medical Journal 2023年第24期136卷 2999-3001页

作者： Xiuwen Wang Xin Zhang Xiaofan Lu Zhen Li Lifeng Liu Hao Wu Tong Zhang Bin Su beijing Key Laboratory for HIV/AIDS Research Clinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China

To the Editor:Immune non-responders(INRs),who account for approximately 10-40%of human immunodeficiency virus(HIV)-infected individuals,have received effective treatment and exhibit persistent suppression of viral replication,but their CD4^(+)T-cell counts are not *** are likely to have an increased risk of non-acquired immunodeficiency syndrome(AIDS)-related morbidity and mortality compared with immune responders(IRs).[1]CD8^(+)T cells play an important role in viral infection,and the functional properties of circulating CD8^(+)T cells have been associated with immune control of *** CD8^(+)T-cell counts are beneficial for persistent viral decay and CD4 T-cell recovery in immune-restored patients during long-term antiretroviral therapy(ART).[2]Two subsets of CD8^(+)T cells have been identified according to their intensity of CD8 expression:CD8^(bri)and CD8^(dim)T *** was demonstrated that CD3^(+)CD8^(dim)T cells,with weaker function than CD3^(+)CD8^(bri)T cells,were associated with disease progression during HIV infection.[3]However,dynamic changes in the numbers of CD8^(bri)and CD8^(dim)T cells in INRs and IRs before and after ART have not yet been reported.

关键词： infected mortality likely

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Changing roles of CD3^(+)CD8^(low) T cells in combating HIV-1 infection

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Chinese Medical Journal 2023年第4期136卷 433-445页

作者： Xin Zhang Xiuwen Wang Ling Qin Xiaofan Lu Zhiying Liu Zhen Li Lin Yuan Rui Wang Junyan Jin Zhenglai Ma Hao Wu Yonghong Zhang Tong Zhang Bin Su beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Research Center for Biomedical Resources Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(low))or high levels(CD8^(high))on HIV-1 replication inhibition after HIV-1 invasion into ***:Nineteen patients who had been acutely infected with HIV-1(AHI)and 20 patients with chronic infection(CHI)for≥2 years were enrolled in this study to investigate the dynamics of the quantity,activation,and immune responses of CD3^(+)CD8^(low) T cells and their counterpart CD3^(+)CD8^(high) T cells at different stages of HIV-1 ***:Compared with healthy donors,CD3^(+)CD8^(low) T cells expanded in HIV-1-infected individuals at different stages of *** HIV-1 infection progressed,CD3^(+)CD8^(low) T cells gradually ***,CD3^(+)CD8^(high) T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection *** classical activation of CD3^(+)CD8^(low) T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic ***,activated CD38^(-)HLA-DR^(+)CD8^(low) T cells did not increase in the first month of AHI,and the number of these cells was inversely associated with viral load(r=-0.664,P=0.004)but positively associated with the CD4 T-cell count(r=0.586,P=0.014).Increased programmed cell death protein 1(PD-1)abundance on CD3^(+)CD8^(low) T cells was observed from the 1st month of AHI but did not continue to be enhanced,while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domains(TIGIT)abundance increase was observed in the 12th month of ***,increased PD-1 and TIGIT abundance on CD3^(+)CD8^(low) T cells was associated with a low CD4 T-cell count(PD-1:r=-0.456,P=0.043;TIGIT:r=-0.488,P=0.029)in ***,the nonincrease i

关键词： Acute human immunodeficiency virus-1 infection HIV CD3^(+)CD8^(low)T cells Immune activation programmed cell death protein 1 T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains

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Advances in Research on COVID-19 Vaccination for People Living with HIV

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Infectious Diseases & Immunity 2022年第4期2卷 213-218页

作者： Junyan Jin Xiuwen Wang Raphael Carapito Christiane Moog Bin Su beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Laboratoire d’ImmunoRhumatologie Moléculaire Institut National de la Santéet de la Recherche Médicale(INSERM)UMR_S 1109Institut Thématique Interdisciplinaire(ITI)de Médecine de Précision de StrasbourgTransplantex NGFacultéde MédecineFédération Hospitalo-Universitaire OMICAREFédération de Médecine Translationnelle de Strasbourg(FMTS)Universitéde StrasbourgStrasbourg 67000France

Introduction In December 2019,multiple cases of aggravated pneumonia of unidentified origin were reported inWuhan,*** were confirmed to be caused by a novel *** World health Organization(WHO)named the disease coronavirus disease 2019(COVID-19).The International Committee on Taxonomy of Viruses officially identified the novel virus severe acute respiratory syndrome coronavirus 2(SARSCoV-2).[1]Although China is now a low endemic areawith a downward trend in the number of confirmed and suspected cases,[2]the threat of the COVID-19 pandemic remains *** mid-March 2022,the cumulative number of reported confirmed cases of COVID-19 worldwide exceeded 450 million,with more than 6 million deaths.[3]Since there is no specific therapeutic drug for the treatment of COVID-19,it is important to control the epidemic by actively promoting SARS-CoV-2 vaccination globally,reducing the risk of viral transmission and the incidence of severe COVID-19,thus improving prognoses.[4]

关键词： HIV SARS-CoV-2 COVID-19 Vaccination PLWH

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HIV reservoir: antiviral immune responses and immune interventions for curing HIV infection

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Chinese Medical Journal 2022年第22期135卷 2667-2676页

作者： Shuang Li Christiane Moog Tong Zhang Bin Su beijing Key Laboratory for HIV/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Laboratoire d’ImmunoRhumatologie Moléculaire Institut national de la santéet de la recherche médicale(INSERM)UMR_S 1109Institut thématique interdisciplinaire(ITI)de Médecine de Précision de StrasbourgTransplantex NGFacultéde MédecineFédération Hospitalo-Universitaire OMICAREFédération de Médecine Translationnelle de Strasbourg(FMTS)Universitéde StrasbourgStrasbourg 67000France

Antiretroviral therapy against human immunodeficiency virus (HIV) is effective in controlling viral replication but cannot completely eliminate HIV due to the persistence of the HIV reservoir. Innate and adaptive immune responses have been proposed to contribute to preventing HIV acquisition, controlling HIV replication and eliminating HIV-infected cells. However, the immune responses naturally induced in HIV-infected individuals rarely eradicate HIV infection, which may be caused by immune escape, an inadequate magnitude and breadth of immune responses, and immune exhaustion. Optimizing these immune responses may solve the problems of epitope escape and insufficient sustained memory responses. Moreover, immune interventions aimed at improving host immune response can reduce HIV reservoirs, which have become one focus in the development of innovative strategies to eliminate HIV reservoirs. In this review, we focus on the immune response against HIV and how antiviral immune responses affect HIV reservoirs. We also discuss the development of innovative strategies aiming to eliminate HIV reservoirs and promoting functional cure of HIV infection.

关键词： Antiviral immune response Functional HIV cure HIV reservoir Human immunodeficiency virus Immune interventions

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Comprehensive analysis reveals hub genes associated with immune cell infiltration in allergic rhinitis

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2023年第4期9卷 340-351页

作者： Hui Li Shi-En Huang Cong-Li Geng Yu-Xiao Wu Mu-Han Shi Min Wang Department of Otorhinolaryngology Peking University People's HospitalBeijingChina Department of Rhinology The First Affliated Hospital of Zhengzhou UniversityZhengzhouChina

Objectives:Allergic rhinitis(AR)refers to a form of respiratory inflammation that mainly affects the sinonasal *** purpose of this study was to explore the level of immune cell infiltration and the pathogenesis of ***:We performed a comprehensive analysis of two gene expression profiles(GSE50223 and GSE50101,a total of 30 patients with AR and 31 healthy controls).CIBERSORT was used to evaluate the immune cell infiltration *** gene coexpression network analysis was applied to explore potential genes or gene modules related to immune status,and enrichment analyses including gene ontology,Kyoto Encyclopedia of Genes and Genomes,gene set enrichment analysis,and gene set variation analysis,were performed to analyze the potential mechanisms in AR.A protein–protein interaction network was constructed to investigate the hub genes,and consensus clustering was conducted to identify the molecular subtypes of ***:Compared to the healthy controls,patients with AR had high abundance levels and proportions of CD4+memory‐activated T *** hundred and eight immune‐related differentially expressed genes were *** analysis suggested that AR was mainly related to leukocyte cell‐cell adhesion,cytokine‐cytokine receptor interaction,T‐cell activation,and T‐cell receptor signaling *** hub genes,includingTYROBP,CSF1R,TLR8,FCER1G,SPI1,ITGAM,CYBB,FCGR2A,CCR1,andHCK,which were related to immune response,might be crucial to the pathogenesis of *** molecular subtypes with significantly different immune statuses were ***:This study improves our understanding of the molecular mechanisms in AR via comprehensive strategies and provides potential diagnostic biomarkers and therapeutic targets of AR.

关键词： allergic rhinitis CIBERSORT consensus cluster GSEA GSVA immune cell infiltration WGCNA

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