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Validation model of fibrosis-8 index score to predict significant fibrosis among patients with nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2022年第15期28卷 1563-1573页

作者： Thaninee Prasoppokakorn Wah-Kheong Chan Vincent wai-Sun Wong Panyavee Pitisuttithum Sanjiv Mahadeva Nik Raihan Nik Mustapha Grace Lai-Hung Wong howard ho-wai leung Pimsiri Sripongpun Sombat Treeprasertsuk Department of Medicine Division of GastroenterologyFaculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalThai Red Cross SocietyBangkok 10330Thailand Department of Medicine Division of GastroenterologyDivision of Gastroenterology and Hepatology UnitFaculty of MedicineUniversity of MalayaKuala Lumpur 50603Malaysia Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Department of Medicine Division of General Internal MedicineFaculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalThai Red Cross SocietyBangkok 10330Thailand Department of Pathology Hospital Sultanah BahiyahAlor SetarKedah 05460Malaysia Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong KongChina Department of Internal Medicine Prince of Songkla UniversityHat Yai 90110Thailand Department of Medicine Division of Gastroenterology and HepatologyStanford University School of MedicinePalo AltoCA 94305United States

BACKGROUND Identifying hepatic fibrosis is crucial for nonalcoholic fatty liver disease(NAFLD)*** fibrosis-8(FIB-8)score,recently developed by incorporating four additional variables into the fibrosis-4(FIB-4)score,showed better performance in predicting significant fibrosis in *** To validate the FIB-8 score in a biopsy-proven NAFLD cohort and compare the diagnostic performance of the FIB-8 and FIB-4 scores and NAFLD fibrosis score(NFS)for predicting significant *** We collected the data of biopsy-proven NAFLD patients from three Asian centers in three *** the patients with available variables for the FIB-4 score(age,platelet count,and aspartate and alanine aminotransferase levels)and FIB-8 score(the FIB-4 variables plus 4 additional parameters:The body mass index(BMI),albumin to globulin ratio,gamma-glutamyl transferase level,and presence of diabetes mellitus)were *** fibrosis stage was scored using nonalcoholic steatohepatitis CRN criteria,and significant fibrosis was defined as at least fibrosis stage *** A total of 511 patients with biopsy-proven NAFLD and complete data were included for *** these 511 patients,271(53.0%)were female,with a median age of 51(interquartile range:41,58)*** median BMI was 29(26.3,32.6)kg/m2,and 268(52.4%)had *** the 511 NAFLD patients,157(30.7%)had significant fibrosis(≥F2).The areas under the receiver operating characteristic curves of the FIB-8 and FIB-4 scores and NFS for predicting significant fibrosis were 0.774,0.743,and 0.680,*** FIB-8 score demonstrated significantly better performance for predicting significant fibrosis than the NFS(P=0.001)and was also clinically superior to FIB-4,although statistical significance was not reached(P=0.073).The low cutoff point of the FIB-8 score for predicting significant fibrosis of 0.88 showed 92.36%sensitivity,and the high cutoff point of the FIB-8 score for predicting significant fibrosis of 1.

关键词： Nonalcoholic fatty liver disease Fibrosis-8 score Fibrosis-4 score Nonalcoholic fatty liver disease fibrosis score

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Enhancing the competitiveness and sustainability of social enterprises in hong Kong: A three-dimensional analysis

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China Journal of Accounting Research 2019年第2期12卷 157-176页

作者： Sidney leung Phyllis Mo howard Ling Yanto Chandra So Sum ho Department of Accountancy College of BusinessCity University of Hong KongHong KongChina Social Enterprise Business Centre Hong Kong Council of Social ServiceHong KongChina Department of Applied Social Science The Hong Kong Polytechnic UniversityHong KongChina

Running a social enterprise(SE) is more difficult than running a small or medium-sized enterprise because SEs have to achieve both economic sustainability as business enterprises and their social mission for the benefit of *** a few years of operation, many SEs fail or struggle for survival. In this study, we examine some of the factors that affect an SE’s profitability, financial management, and business planning and management. Based on in-depth interviews with 22 social enterprises in hong Kong, we find that SEs with the dual investment objectives of social mission and financial return are more sustainable and competitive than SEs with social impact as their sole objective. Furthermore, SEs managed by non-owner managers have better financial planning and performance than those managed by owner managers. In addition, SEs with an oversight/advisory committee are more competitive and have better management practices than those without such a committee. Our findings have policy implications for government, SEs, funding bodies, and non-profit organizations to enhance and promote the development of the social enterprise sector.

关键词： Social enterprises Corporate governance Sustainability Social mission Advisory committee Social enterprise performance

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Exploring the band structure of Wurtzite InAs nanowires using photocurrent spectroscopy

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Nano Research 2020年第6期13卷 1586-1591页

作者： Seyyedesadaf Pournia Samuel Linser Giriraj Jnawali howard E.Jackson Leigh M.Smith Amira Ameruddin Philippe Caroff Jennifer Wong-leung Hark hoe Tan Chennupati Jagadish Hannah J.Joyce Department of Physics University of CincinnatiCincinnatiOH45221-0011USA Department of Electronic Materials Engineering Research School of PhysicsThe Australian National UniversityCanberraACT2601Australia Department of Engineering University of Cambridge9 JJ Thomson AvenueCambridgeCB30FAUK

Nano Research volume We use polarized photocurrent spectroscopy in a nanowire device to investigate the band structure of hexagonal Wurtzite *** of optical transitions between four valence bands and two conduction bands are observed which are consistent with the symmetries expected from group *** ground state transition energy identified from photocurrent spectra is seen to be consistent with photoluminescence emitted from a cluster of nanowires from the same growth *** the energies of the observed bands we determine the spin orbit and crystal field energies in Wurtzite *** information is vital to the development of crystal phase engineering of this important III-V semiconductor.

关键词： nanowires Wurtzite InAs photocurrent measurement optical selection rules energy band structure

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Treatment with a JAK1/2 inhibitor ameliorates murine autoimmune cholangitis induced by IFN overexpression

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Cellular & Molecular Immunology 2022年第10期19卷 1130-1140页

作者： Tihong Shao Patrick S.C.leung Weici Zhang Koichi Tsuneyama William M.Ridgway howard A.Young Zongwen Shuai Aftab A.Ansari M.Eric Gershwi Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical UniversityHefeiChina Division of Rheumatology Allergyand Clinical ImmunologySchool of MedicineUniversity of CaliforniaDavisCAUSA Department of Pathology and Laboratory Medicine Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan Center for Cancer Research National Cancer Institute-FrederickFrederickMDUSA

The interferon(IFN)signaling pathways are major immunological checkpoints with clinical significance in the pathogenesis of *** have generated a unique murine model named ARE-Del,with chronic overexpression of IFNγ,by altering IFNγ***,these mice develop an immunologic and clinical profile similar to patients with primary biliary cholangitis,including high titers of autoantibodies and portal *** hypothesized that the downregulation of IFN signaling pathways with a JAK1/2 inhibitor would inhibit the development and progression of *** study this hypothesis,ARE-Del^(+/−)mice were treated with the JAK1/2 inhibitor ruxolitinib and serially *** inhibition resulted in a significant reduction in portal inflammation and bile duct damage,associated with a significant reduction in splenic and hepatic CD4^(+)T cells and CD8^(+)T ***,ruxolitinib inhibited the secretion of the proinflammatory cytokines IFNγand TNF from splenic CD4^(+)T ***,ruxolitinib treatment also decreased the frequencies of germinal center B(GC B)cells and T follicular helper(Tfh)cells and led to lower serological AMA *** note,liver and peritoneal macrophages were sharply decreased and polarized from M1 to M2 with a higher level of IRF4 expression after ruxolitinib ***,ruxolitinib inhibited the secretion of IL-6,TNF and MCP1 and the expression of STAT1 but promoted the expression of STAT6 in macrophages in vitro,indicating that M1 macrophage polarization to M2 occurred through activation of the STAT6-IRF4 *** data highlight the significance,both immunologically and clinically,of the JAK/STAT signaling pathway in autoimmune cholangitis.

关键词： Primary biliary cholangitis Autoimmunity Interferons Janus Kinase Inhibitors Ruxolitinib

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罗格列酮与全反式维甲酸对骨髓瘤细胞分化的影响及其可能机制

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中华肿瘤杂志 2009年第12期31卷 885-889页

作者：黄海雯陈广华常惠荣 howard C.H. Chow Anska Y.H. leung Raymond Liang 吴德沛苏州大学附属第一医院血液科江苏省血液研究所卫生部血栓与止血重点实验室 215006 香港大学玛丽医院内科

目的探讨过氧化物酶体增殖物活化受体γ（PPARγ）的配体罗格列酮（RGZ）与全反式维甲酸（ATRA）对骨髓瘤细胞分化的影响及其可能机制。方法以RGZ和ATRA处理人骨髓瘤细胞U266和RPMI-8226，用^3H-掺入法检测细胞增殖变化；碘化丙啶（PI... 详细信息

目的探讨过氧化物酶体增殖物活化受体γ（PPARγ）的配体罗格列酮（RGZ）与全反式维甲酸（ATRA）对骨髓瘤细胞分化的影响及其可能机制。方法以RGZ和ATRA处理人骨髓瘤细胞U266和RPMI-8226，用^3H-掺入法检测细胞增殖变化；碘化丙啶（PI）染色后，以流式细胞仪检测细胞周期变化；瑞氏-姬母萨染色观察细胞形态学变化；流式细胞仪分析细胞表面CD49e的表达变化；Western blot方法检测p27^Kip1和p21^Waf1的表达变化。结果RGZ能显著抑制U266和RPMI-8226细胞的增殖，并且这种抑制作用呈剂量依赖性。经5μmol／LRGZ处理后，U266和RPMI-8226细胞G0／G1期细胞的比例分别为（45．2±6．7）％和（40．3±7．3）％，较对照组明显增加（均P〈0．05）；G2／M期和S期细胞的比例分别为（52．2±7．4）％和（57．4±9．5）％，较对照组明显减少（均P〈0．05）；CIM9e的表达率分别为（8．7±1．5）％和（7．9±1．6）％，较对照组明显上调（均P〈0．05）。以10μmol／LRGZ处理后，U266和RPMI-8226细胞的G0／G1期、G2／M期和S期细胞比例、CD49e的表达率均较5μmol／LRGZ组的变化更加显著。同时，经RGZ处理后，U266和RPMI-8226细胞的形态学变化也符合骨髓瘤细胞分化成熟的规律，p27^Kip1和p21^Waf1蛋白的表达量也较对照组明显增加。RGZ和ATRA联合对U266和RPMI-8226细胞影响较RGZ单独作用更加明显。结论RGZ可能通过上调p27^Kip1和p21^Waf1蛋白的表达，介导骨髓瘤细胞的周期阻滞，并诱导骨髓瘤细胞分化，抑制骨髓瘤细胞增殖。ATRA能增强RGZ对骨髓瘤细胞的上述作用，两者联合具有协同效应。

关键词：骨髓瘤细胞罗格列酮维甲酸细胞分化细胞周期

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罗格列酮和全反式维甲酸对多发性骨髓瘤裸鼠移植瘤生长及血管形成的影响

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中华肿瘤杂志 2012年第9期34卷 652-657页

作者：黄海雯陈萍李炳宗傅晋翔李军张晓慧刘睿范银银张宏 howard C.H. Chow Anska Y. H. leung Raymond Liang 苏州大学附属第二医院血液科 215004 香港大学玛丽医院内科

目的研究罗格列酮（RGZ）和全反式维甲酸（ATRA）对多发性骨髓瘤裸鼠移植瘤生长和血管形成的影响。方法分别以不同浓度的RGZ和ATRA或RGZ＋ATRA处理U266细胞24h，采用半定量RT—PCR法检测各组U266细胞中血管内皮细胞生长因子（VEGF）的... 详细信息

目的研究罗格列酮（RGZ）和全反式维甲酸（ATRA）对多发性骨髓瘤裸鼠移植瘤生长和血管形成的影响。方法分别以不同浓度的RGZ和ATRA或RGZ＋ATRA处理U266细胞24h，采用半定量RT—PCR法检测各组U266细胞中血管内皮细胞生长因子（VEGF）的表达。将U266细胞接种于4周龄Balb／c裸鼠一侧肩胛部皮下，接种1周后分别以RGZ和RGZ＋ATRA腹腔注射干预，连续给药21d。第21天处死裸鼠，剥离皮下肿瘤并称重，将肿瘤组织分别进行HE和CD34、VEGF免疫组化染色。结果未经处理的对照组U266细胞中VEGFmRNA高表达；经RGZ处理后，VEGFmRNA的表达水平下调；经RGZ＋ATRA处理后，VEGFmRNA的表达水平较RGZ组更低。U266细胞接种后，在裸鼠皮下均可形成肿瘤。腹腔用药后，RGZ组裸鼠移植瘤的体积和重量分别为（785±262）mm3和（1748±365）mg，均明显低于对照组（均P〈0．01）；RGZ＋ATRA组移植瘤的体积和再量分别为（154±89）mm3和（626±102）mg3均明显低于RGZ组（均P〈0．05）。各组裸鼠移植瘤中均有VEGF蛋白的表达，其中对照组VEGF蛋白的平均染色强度（IS）为2．20±0．40，明显高于RGZ组（1.48±0．37，P〈0．01）；RGZ＋ATRA组的Is为0．58±0．26，明显低于RGZ组（P〈0．01）。各组裸鼠移植瘤中均有CD34的表达，其中对照组CD34表达最强，微血管密度（MVD）为（56．4±15．2）个／高倍视野，明显高于RGZ组[（44．6±11．2）个／高倍视野，P〈0．05]；RGZ＋ATRA组CD34表达最弱，MVD为（21．5±8．6）个／高倍视野，明显低于RGZ组（P〈0．01）。结论RGZ和ATRA存体内环境中也能发挥抑制骨髓瘤细胞增殖和生长的作用。通过抑制骨髓瘤细胞中VEGF的表达从而阻断血管形成，可能也足RGZ和ATRA抗肿瘤作用的重要机制之一。

关键词：多发性骨髓瘤罗格列酮全反式维甲酸裸鼠血管内皮生长因子

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Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel leung Xiwei Wang Xiaofeng Mu Yuet Chung Tsun Ming Lau Manni Wang Wenyue Zhang Yanmei Zhang howard H.W.Wong Leo C.H.Tsang Sara Chaothai Tsz Chun Kwan John K.C.Li Karl C.K.Chan Leo L.H.Luk Jenson C.H.ho Wing Yan Li Amos M.T.Lee Jennifer H.Y.Lam Sau Man Chan Wilfred H.S.Wong Issan Y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei Tu Yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina HKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is *** study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

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Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver

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Cellular & Molecular Immunology 2022年第7期19卷 834-847页

作者： Wenshu Tang Jingying Zhou Weiqin Yang Yu Feng Haoran Wu Myth T.S.Mok Lingyun Zhang Zhixian Liang Xiaoyu Liu Zhewen Xiong Xuezhen Zeng Jing Wang Jiahuan Lu Jingqing Li Hanyong Sun Xiaoyu Tian Philip Chun Yeung Yong hou Heung Man Lee Candice C.H.Lam howard H.W.leung Anthony W.H.Chan Ka Fai To John Wong Paul B.S.Lai Kelvin K.C.Ng Simon K.H.Wong Vincent W.S.Wong Alice P.S.Kong Joseph J.Y.Sung Alfred S.L.Cheng school of Biomedical Sciences The Chinese University of Hong KongHong Kong SAR 999077China Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong Kong SAR 999077China Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Department of Surgery The Chinese University of Hong KongHong Kong SAR 999077China Department of Medicine and Therapeutics The Chinese University of Hong Kong.Hong Kong SAR 999077China State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong Kong SAR 999077China Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore 639798Singapore Institute of Precision Medicine The First Affliated HospitalSun Yat-sen UniversityGuangzhou 510080China

Obesity is a major risk factor for cancers including hepatocellular carcinoma(HCC)that develops from a background of non-alcoholic fatty liver disease(NAFLD).Hypercholesterolemia is a common comorbidity of *** cholesterol biosynthesis mainly occurs in the liver,its role in HCC development of obese people remains *** high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models,we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T(NKT)cell-mediated antitumor *** analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD ***,cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC ***,suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin(mTOR)inhibitor vistusertib preceded tumor regression,which was abolished by NKT inactivation but not CD8^(+)T cell ***,sterol regulatory element-binding protein 2(SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells,which were supported by findings in people with obesity,NAFLD and *** study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment,providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic.

关键词： Cancer microenvironment Cancer models Tumour immunology

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Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents

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Signal Transduction and Targeted Therapy 2023年第1期8卷 266-275页

作者： Xiaofeng Mu Carolyn A.Cohen Daniel leung Jaime S.Rosa Duque Samuel M.S.Cheng Yuet Chung howard H.W.Wong Amos M.T.Lee Wing Yan Li Issan Y.S.Tam Jennifer H.Y.Lam Derek H.L.Lee Sau Man Chan Leo C.H.Tsang Karl C.K.Chan John K.C.Li Leo L.H.Luk Sara Chaothai Kelvin K.H.Kwan Nym Coco Chu Masashi Mori Trushar Jeevan Ahmed Kandeil Richard JWebby Wenwei Tu Sophie A.Valkenburg Malik Peiris Yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina HKU-Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Infectious Diseases St Jude Children’s Research HospitalMemphisTNUSA Department of Microbiology and Immunology Peter Doherty Institute for Infection and ImmunityUniversity of MelbourneMelbourneVICAustralia Centre for Immunology&Infection C2i Hong KongChina

The high effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported in some studies,but immune responses conferring this protection are not yet *** this analysis,our study(NCT04800133)aims to evaluate the humoral and cellular responses against wild-type and Omicron(BA.1,BA.2 and/or BA.5)SARS-CoV-2 before and after a third dose of BNT162b2 in healthy *** 5 months after 2 doses,S IgG,S IgG Fc receptor-binding,and neutralising antibody responses waned significantly,yet neutralising antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 *** antibody responses and S-specific IFN-γ^(+)and IL-2^(+)CD8^(+)T cell responses were significantly boosted in healthy adolescents after a homologous third dose of *** to adults,humoral responses for the third dose were non-inferior or superior in *** S-specific IFN-γ^(+)and IL-2^(+)CD4^(+)and CD8^(+)T cell responses in adolescents and adults were comparable or ***,after 3 doses,adolescents had preserved S IgG,S IgG avidity,S IgG FcγRIIIa-binding,against Omicron BA.2,as well as preserved cellular responses against BA.1 S and moderate neutralisation levels against BA.1,BA.2 and *** from 100 and 96%of adolescents tested at 1 and 5 months after two doses could also neutralise *** study found high antibody and T cell responses,including potent cross-variant reactivity,after three doses of BNT162b2 vaccine in adolescents in its current formulation,suggesting that current vaccines can be protective against symptomatic Omicron disease.

关键词： doses neutral protective

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