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TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization

Neuroscience Bulletin 2024年第1期40卷 17-34页

作者： Siying Qu Shengfeng Hu Huiting Xu Yongjian Wu Siqi Ming Xiaoxia Zhan Cheng Wang Xi Huang Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China The State Key Laboratory of Respiratory Disease Guangdong Provincial Key Laboratory of Allergy and Clinical ImmunologyThe Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China Department of Laboratory Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Division of Nephrology Department of Medicinethe Fifth Affliated Hospital of Sun Yat-sen UniversityZhuhai 519000China

Multiple sclerosis(MS)is a neuroinflammatory demyelinating disease,mediated by pathogenic T helper 17(Th17)***,the therapeutic effect is accompa-nied by the fluctuation of the proportion and function of Th17 cells,which prompted us to find the key regulator of Th17 differentiation in ***,we demonstrated that the triggering receptor expressed on myeloid cells 2(TREM-2),a modulator of pattern recognition receptors on innate immune cells,was highly expressed on pathogenic CD4-positive T lymphocyte(CD4^(+)T)cells in both patients with MS and experimental autoimmune encephalomyelitis(EAE)mouse *** knockout of Trem-2 in CD4^(+)T cells significantly alleviated the disease activity and reduced Th17 cell infiltration,activation,differentiation,and inflammatory cytokine production and secretion in EAE ***,with Trem-2 knockout in vivo experiments and in vitro inhibitor assays,the TREM-2/zeta-chain associated protein kinase 70(ZAP70)/signal transducer and activator of transcription 3(STAT3)signal axis was essential for Th17 activation and differentiation in EAE *** conclusion,TREM-2 is a key regulator of pathogenic Th17 in EAE mice,and this sheds new light on the potential of this therapeutic target for MS.

关键词： Multiple sclerosis experimental autoimmune encephalomyelitis T helper 17 Triggering receptor expressed on myeloid cells 2

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Evaluation of a complex couplet care intervention in a neonatal intensive care unit: A mixed methods study protocol

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儿科学研究(英文) 2024年第2期08卷 139-148页

作者： Bjerregaard Michella Axelin Anna Carlsen Emma Louise Malchau Birk Hans Okkels Poulsen Ingrid Palisz Patrick Kallemose Thomas Br?dsgaard Anne Department of Paediatric and Adolescent Medicine Copenhagen University Hospital Amager Hvidovre Hvidovre Denmark Department of Public Health Faculty of Health Research Unit for Nursing and Healthcare University of Aarhus Aarhus Denmark Department of Nursing Science University of Turku Turku Finland Department of clinical Medicine Faculty of Health and Medical Science University of Copenhagen Copenhagen Denmark Department of Public Health Section of Health Service Research University of Copenhagen Copenhagen Denmark Department of People and Technology Roskilde University Roskilde Denmark Department of clinical Research Copenhagen University Hospital Amager Hvidovre Hvidovre Denmark Department of Gynaecology and Obstetrics Copenhagen University Hospital Amager Hvidovre Hvidovre Denmark

Background: Families with an infant in need of intensive care most often experience a harmful separation after birth. This is due to a division of medical specialties into neonatal care and maternal care. Therefore, a couplet care intervention is implemented for mother-infant dyads in a neonatal intensive care unit. This study protocol provides a comprehensive evaluation of the intervention. The aim is to evaluate the effect and implementation of a complex couplet care intervention to promote zero separation between mother and ***: The couplet care intervention is a family-centered model of care, where treatment-requiring mother-infant dyads will be admitted together and receive couplet care by neonatal nurses. The study adheres to the framework of the Medical Research Council and will use a mixed methods embedded design comprising a quasi-experimental trial and a qualitative process evaluation. Finally, a health economic evaluation will be conducted to assess the cost-effectiveness of this complex couplet care ***: Separation of mother-infant dyads after birth has an adverse impact on family health and well-being. This study protocol evaluates a complex couplet care intervention. With this study, a first step is taken to help bridge the gap between current practices and a new care model to prevent the separation of mothers and their infants

关键词： Complex interventions Couplet care Family-centered care Neonatology Zero separation

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A strategy for mechanically integrating robust hydrogeltissue hybrid to promote the anti-calcification and endothelialization of bioprosthetic heart valve

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Regenerative Biomaterials 2024年第2期3卷 123-136页

作者： Haoshuang Wu Nuoya Chen Tiantian Zheng Li Li Mengyue Hu Yumei Qin Gaoyang Guo Li Yang Yunbing Wang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610065China Institute of clinical Pathology West China Hospital of Sichuan UniversityChengdu 610041China College of Polymer Science and Engineering Sichuan UniversityChengdu 610065China

Bioprosthetic heart valve(BHV)replacement has been the predo-minant treatment for severe heart valve diseases over *** clinically available BHVs are crosslinked by glutaraldehyde(GLUT),while the high toxicity of residual GLUT could initiate calcification,severe thrombosis,and delayed ***,we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of *** particular,recombinant humanized coilagen type Ⅲ(rhCOLⅢ),which was precisely customized with anti-coagulant and pro-endothelialization bioactivity,was first incorporated into the polyvinyl alcohol(PVA)-based hydrogel via hydrogen bond ***,tannic acid was introduced to enhance the mechanicalperfo of PVA-based hvdrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of *** vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLII and TA possessed long-term anti-coagulant,accelerated endothelialization,mild inflammatory response and anti-calcification ***,our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.

关键词： bioprosthetic heart valves recombinant humanized collagen typeⅢ endothelialization anti-calcification anti-coagulation

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Recurrent Spontaneous Abortion of Immune Origin and HLA Sensitization Immunotherapy

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Advances in Reproductive Sciences 2022年第1期10卷 12-18页

作者： Isabela Mansur Bandeira Juliana Vasconcelos Thiago Luiz Bandeira Jorge Oliveira Carla Goulart Aderbal Sabra Luiz Werber-Bandeira clinical and experimental immunology and allergy service Santa Casa da Misericordia do Rio de Janeiro Rio de Janeiro Brazil Food allergy and Autism Unit of the clinical immunology service Santa Casa da Misericordia do Rio de Janeiro Rio de Janeiro Brazil

Introduction: Spontaneous abortion is defined as pregnancy loss before the twentieth week and Recurrent Spontaneous Abortion (RSA) is defined as at least three spontaneous and successive pregnancy losses in the same period. Among the different types of immunological causes, this study refers specifically to the alloimmune cause. Women with RSA of alloimmune cause share a greater number of Human Leukocyte Antigen (HLA) with their husbands, leading to the inhibition of the production of anti-paternal asymmetric blocking antibodies, which would protect embryonic cells. Objectives: To evaluate the effect of immunotherapy with paternal HLA-sensitizing mononuclear cells in cases of RSA through the positivity of the cross-match test and its efficacy in pregnancy success. Patients and Methods: Written consent was obtained, 12 couples with a history of RSA presenting negative cross-match were included in the study. Blood samples were collected from the couple for cross-matching and the separation of paternal mononuclear cells. Immunotherapy was performed with paternal mononuclear cells intradermally in the wives’ arms on day (D) 0, D15 and D30. After the third dose, a second evaluation of the cross- match tests was performed. Results and Discussion: The age of the wives ranged from 28 to 41 years, with a mean of 34.5 years. The twelve couples had a negative cross-match test (100%). Eleven couples (96.6%) tested positive in the cross- match test after immunotherapy. Of these, 10 (90.9%) had successful pregnancies. Immunotherapy with paternal mononuclear cells showed an excellent ability to sensitize the maternal immune system, with positive cross-match, resulting in a successful pregnancy.

关键词： Spontaneous Abortion Immunotherapy Pregnancy Maternal-Fetal Relationships

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Genetic mutation of Tas2r104/Tas2r105/Tas2r114 cluster leads to a loss of taste perception to denatonium benzoate and cucurbitacin B

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Animal Models and experimental Medicine 2024年第3期7卷 324-336页

作者： Bowen Niu Lingling Liu Qian Gao Meng-Min Zhu Lixiang Chen Xiu-Hua Peng Boying Qin Xiaohui Zhou Feng Li Department of Laboratory Animal Science Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Biology College of Life SciencesShanghai Normal UniversityShanghaiPeople's Republic of China

Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic *** taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in ***:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the ***,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder *** real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste *** to taste substance was also studied using twobottle preference ***:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 *** results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant *** qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant *** two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of *** addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB ***:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.

关键词： bitter taste receptor CRISPR/Cas9 genetic mutation two-bottle preference test type 2 taste receptors(Tas2rs)

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clinical Study on Respiratory Medicine Treatment of Chronic Obstructive Pulmonary Disease Combined with Respiratory Failure

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Journal of clinical and Nursing Research 2024年第5期8卷 293-298页

作者： Jianhua Yu Sanshandao Street Community Health service Center Laizhou CityYantai 261418Shandong ProvinceChina

Objective:To explore the respiratory medicine treatment methods for treating chronic obstructive pulmonary disease(COPD)combined with respiratory ***:70 cases of COPD patients with combined respiratory failure admitted to our hospital from January 2021 to January 2023 were selected as the study subjects,and randomly divided into the control group and the experimental group,each with 35 *** control group received only conventional treatment,and the experimental group received non-invasive positive pressure ventilation,and the treatment effects and changes in the levels of IL-18,hs-CRP,and CES2 inflammatory factors were observed and evaluated in the two ***:There was no significant difference between the general data of the two groups(P>0.05);after treatment,the total effective rate of clinical efficacy of the observation group(91.43%)was significantly higher than that of the control group(71.43%),and the difference showed a significant correlation(Pclinical application prospect.

关键词： Chronic obstructive pulmonary disease Respiratory failure Non-invasive positive pressure ventilation Therapeutic effect Inflammatory factor

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Beyond monogenetic rare variants:tackling the low rate of genetic diagnoses in predominantly antibody deficiency

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Cellular & Molecular immunology 2021年第3期18卷 588-603页

作者： Emily S.J.Edwards Julian J.Bosco Samar Ojaimi Robyn E.O’Hehir Menno C.van Zelm Department of immunology and Pathology Central Clinical SchoolMonash UniversityMelbourneVICAustralia The Jeffrey Modell Diagnostic and Research Centre for Primary Immunodeficiencies MelbourneVICAustralia Department of allergy Immunology and Respiratory MedicineCentral Clinical SchoolMonash University and AllergyAsthma and Clinical Immunology ServiceAlfred HospitalMelbourneVICAustralia Department of Infectious Diseases Monash HealthClaytonVICAustralia Centre for Inflammatory Diseases Monash HealthClaytonVICAustralia Department of allergy and immunology Monash HealthClaytonVICAustralia

Predominantly antibody deficiency(PAD)is the most prevalent form of primary immunodeficiency,and is characterized by broad clinical,immunological and genetic *** the current gold standard of whole exome sequencing for diagnosis,pathogenic gene variants are only identified in less than 20% of *** elucidation of the causal genes underlying PAD has provided many insights into the cellular and molecular mechanisms underpinning disease pathogenesis,many other genes may remain as yet undefined to enable definitive diagnosis,prognostic monitoring and targeted therapy of *** that many patients display a relatively late onset of disease presentation in their 2^(nd) or 3^(rd) decade of life,it is questionable whether a single genetic lesion underlies disease in all ***,combined effects of other gene variants and/or non-genetic factors,including specific infections can drive disease *** this review,we define(1)the clinical and immunological variability of PAD,(2)consider how genetic defects identified in PAD have given insight into B-cell immunobiology,(3)address recent technological advances in genomics and the challenges associated with identifying causal variants,and(4)discuss how functional validation of variants of unknown significance could potentially be translated into increased diagnostic rates,improved prognostic monitoring and personalized medicine for PAD patients.A multidisciplinary approach will be the key to curtailing the early mortality and high morbidity rates in this immune disorder.

关键词： Predominantly antibody deficiency Genetic diagnosis Genomics Functional validation

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Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota

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World Journal of Gastroenterology 2023年第27期29卷 4236-4251页

作者： Roman Maslennikov Aliya Alieva Elena Poluektova Yury Zharikov Andrey Suslov Yana Letyagina Ekaterina Vasileva Anna Levshina Evgenii Kozlov Vladimir Ivashkin Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia The Scientific Community for Human Microbiome Research Moscow 119435Russia Department of Human Anatomy and Histology Sechenov UniversityMoscow 119435Russia Laboratory of Immunopathology Department of Clinical Immunology and AllergySechenov UniversityMoscow 119991Russia

Decreased muscle mass and function,also known as sarcopenia,is common in patients with cirrhosis and is associated with a poor *** the pathogenesis of this disorder has not been fully elucidated,a disordered gutmuscle axis probably plays an important *** barrier function of the gut and liver,gut dysbiosis,and small intestinal bacterial overgrowth(SIBO)can lead to increased blood levels of ammonia,lipopolysaccharides,pro-inflammatory mediators,and *** factors have complex negative effects on muscle mass and *** interventions that target the gut microbiota(long-term use of rifaximin,lactulose,lactitol,or probiotics)positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia,bacterial translocation,and systemic inflammation and correcting gut dysbiosis and ***,although these drugs are promising,they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with *** data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis;however,the results of animal experimental studies are promising.

关键词： Cirrhosis Muscle Fragility Liver Microbiota Microbiome

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Anaphylaxis and generalized urticaria from eating Chinese bayberry fruit

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2012年第10期13卷 851-854页

作者： Hui-ying WANG Zhong-shan GAO Zhao-wei YANG Jing-xin SHAO Xiu-zhen ZHAO Yu DAI Ronald VAN REE Department of allergy and clinical immunology the Second Affili-ated HospitalSchool of MedicineZhejiang UniversityHangzhou310013China allergy Research Center Department of HorticultureCollege ofAgriculture and BiotechnologyZhejiang UniversityHangzhou310058China Department of Clinic Laboratory the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310013China Department of experimental immunology and Department ofOtorhinolaryngology Academic Medical CenterUniversity of Am-sterdamMeibergdreef 91105 AZAmsterdamthe Netherlands

Chinese bayberry Myrica rubra is a very popular fruit in southeastern *** spite of its wide consumption,no allergies to this fruit have been reported *** we report on a 40-year-old woman suffering from anaphylaxis to Chinese bayberry ***-prick skin tests revealed strong reactions to fresh Chinese bayberry fruits as well as to peach,and weaker reactions to some other fruits including apple,melon,and *** analysis revealed identical titers of specific IgE(4.3 kU A /L) to peach extract and its lipid transfer protein(LTP,rPru p 3),which was confirmed by detection of a 9 kD band following *** analysis with Chinese bayberry extract gave bands of 22,45,and 90 kD,but no 9 kD band was *** was also no evidence of LTP recognition for loquat(36 kD) or melon(24 kD).This first report of a severe allergic reaction to Chinese bayberry fruit in a patient with LTP-mediated peach allergy indicates that other as yet unidentified non-pollen related fruit allergens are involved in this new severe fruit allergy.

关键词： Chinese bayberry Fruit allergy Anaphylaxis

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experimental evidence on the immunopathogenesis of primary biliary cirrhosis

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Cellular & Molecular immunology 2010年第1期7卷 1-10页

作者： Carlo Selmi Francesca Meda Anaid Kasangian Pietro Invernizzi Zhigang Tian Zhexiong Lian Mauro Podda M Eric Gershwin Department of Translational Medicine Universitàdegli Studi di MilanoMilanItaly Department of Medicine IRCCS Istituto Clinico Humanitas RozzanoMilanItaly Divisionof Rheumatology Allergyand Clinical ImmunologyUniversity of California at DavisDavisCAUSA Institute of immunology University of Science and Technology of ChinaHefeiChina

Primary biliary cirrhosis(PBC)is a chronic cholestatic liver disease for which an autoimmune pathogenesis is supported by clinical and experimental data,including the presence of autoantibodies and autoreactive T *** etiology remains to be determined,yet data suggest that both a susceptible genetic background and unknown environmental factors determine disease *** infectious and chemical candidates have been proposed to trigger the disease in a genetically susceptible host,mostly by molecular *** recently,several murine models have been reported,including genetically determined models as well as models induced by immunization with xenobiotics and bacteria.

关键词： pathogenesis cirrhosis biliary

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