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World Journal of gastroenterology 2008年第21期14卷 3360-3367页

作者： giorgina mieli-vergani Diego vergani Institute of Liver Studies King's College London School of Medicine at King's College HospitalLondon SE5 9RSUnited Kingdom

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis(AIH),autoimmune sclerosing cholangitis(ASC),and de novo AIH after liver *** is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody(SMA/ANA,type 1) or liver kidney microsomal antibody(LKM1,type 2).There is a female predominance in ***1 positive patients tend to present more acutely,at a younger age,and commonly have partial IgA deficiency,while duration of symptoms before diagnosis,clinical signs,family history of autoimmunity,presence of associated autoimmune disorders,response to treatment,and long-term prognosis are similar in both *** most common type of paediatric sclerosing cholangitis is *** clinical,biochemical,immunological,and histological presentation of ASC is often indistinguishable from that of AIH type *** both,there are high Igg,non-organ specific autoantibodies,and interface *** is made by *** with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates,times to normalization of biochemical parameters,and decreased inflammatory activity on follow up liver ***,the cholangiopathy can *** may be evolution from AIH to ASC over the years,despite *** novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies,hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and *** classical AIH,it responds to treatment with prednisolone and *** novo AIH postliver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and *** this condition is a distinct entity or a form of atypical rejection

关键词： Autoimmune hepatitis Autoimmunesclerosing cholangitis Liver transplant Children

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Aetiopathogenesis of autoimmune hepatitis

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World Journal of gastroenterology 2008年第21期14卷 3306-3312页

作者： Diego vergani giorgina mieli-vergani Institute of Liver Studies King's College London School of Medicine at King's College HospitalLondon SE5 9RSUnited Kingdom Institute of Liver Studies King’s College London School of Medicine at King’s College HospitalLondon SE5 9RSUnited Kingdom

The histological hallmark of autoimmune hepatitis（AIH） is a dense portal mononuclear cell infiltrate that invades the surrounding parenchyma and comprises T and B lymphocytes,macrophages,and plasma *** unknown but powerful stimulus must be promoting the formation of this massive inflammatory cellular reaction that is likely to initiate and perpetuate liver *** autoimmune attack can follow different pathways to inflict damage on *** damage is likely to be orchestrated by CD4^＋ T lymphocytes recognizing an autoantigenic liver *** trigger an autoimmune response,the peptide must be embraced by an HLA class Ⅱ molecule and presented to naive CD4^＋ T helper（Th0） cells by professional antigen presenting cells,with the co-stimulation of ligand-ligand fostering interaction between the two ***0 cells become activated,differentiate into functional phenotypes according to the cytokines prevailing in the microenvironment and the nature of the antigen,and initiate a cascade of immune reactions determined by the cytokines produced by the activated T ***1 cells,arising in the presence of the macrophage-derived interleukin（IL） -12,secrete mainly IL-2 and interferon-gamma（IFN-γ）,which activate macrophages,enhance expression of HLA classⅠ（increasing liver cell vulnerability to a CD8^＋ T cell cytotoxic attack）,and induce expression of HLA class Ⅱ molecules on ***2 cells,which differentiate from Th0 if the microenvironment is rich in IL-4,produce mainly IL-4,IL-10,and IL-13 which favour autoantibody production by B ***,Th1 and Th2 antagonize each ***17 cells,a recently described population,arise in the presence of transforming growth factor beta（TgF-β） and IL-6 and appear to have an important effector role in inflammation and *** of autoantigen recognition is strictly controlled by regulatory mechanisms,such as those exerted by CD4^＋CD25^＋ regulatory T cells,which derive from Th0 in the

关键词： Autoimmune hepatitis Aetiopathogenesis Lymphocyte, Cellular immune attack Histocompatibility lymphocyte antigen

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拉米夫定/干扰素-α联合治疗围生期感染乙肝的免疫耐受患儿:一项初步研究

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世界核心医学期刊文摘（儿科学分册） 2006年第8期2卷 42-42页

作者： D'Antiga L. Aw M. Atkins M. g.mieli-vergani 王一飞 Department of Paediatric Hepatology Institute of Liver StudiesKing's College HospitalDenmark HillLondon SE5 9RSUnited Kingdom Dr.

Objective:To investigate whether combining the antiviral effect of lamivudine with the immune-boosting action of interferon-alpha(IFN-α)is effective in treating hepatitis B virus(HBV)“immunotolerant”*** design:Twen tythree children(8 boys;mean age,10 years)infected during the first year of life(17 Asian,21 with normal aminotransferase levels,15 with HBV-DNA > 1000 pg/mL by hybridization and all with mild histologic changes)were treated with l amivudine(3 mg/kg)for 8 weeks alone and then lamivudine(3 mg/kg)-and IFN-α(5 MU/m2,3 times weekly)in combination for 10 ***:Seventy-eight percent became HBV-DNA negative at the end of treatment,5(22%)seroconverted to anti-HBe,4(17%)of whom achieved complete viral control,becoming persis tently HBsAg negative and anti-HBs *** had YMDD *** viral status of the patients has not changed after a median follow-up of 40 months(range,36 to 48).Conclusions:This pilot study suggests that lamivudine pretrea tment followed by a combination of lamivudine and IFN-αcan induce complete vir al control in HBV immunotolerant children,hitherto considered poor responders.

关键词：乙肝病毒(HBV) 围生期感染干扰素-α 联合治疗拉米夫定免疫耐受患儿步研究免疫增强作用抗病毒效应

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Autoimmmune hepatitis

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Cellular & Molecular Immunology 2022年第2期19卷 158-176页

作者： Benedetta Terziroli Beretta-Piccoli giorgina mieli-vergani Diego vergani Epatocentro Ticino&Facoltàdi Scienze Biomediche Universitàdella Svizzera ItalianaLuganoSwitzerland Institute for Research in Biomedicine BellinzonaSwitzerland. King’s College London Faculty of Life Sciences&Medicine at King’s College Hospital LondonUK. Paediatric Liver GI and Nutrition CentreMowatLabsKing’s College HospitalLondonUK. Institute of Liver Studies MowatLabsKing’s College HospitalLondonUK.

Autoimmune hepatitis(AIH)is a T-cell mediated,inflammatory liver disease affecting all ages and characterized by female preponderance,elevated serum transaminase and immunoglobulin g levels,positive circulating autoantibodies,and presence of interface hepatitis at liver *** type 1,affecting both adults and children,is defined by positive anti-nuclear and/or antismooth muscle antibodies,while type 2 AIH,affecting mostly children,is defined by positive anti-liver-kidney microsomal type 1 and/or anti-liver cytosol type 1 *** the autoantigens of type 2 AIH are well defined,being the cytochrome P4502D6(CYP2D6)and the formiminotransferase cyclodeaminase(FTCD),in type 1 AIH they remain to be ***-1 predisposition is conferred by possession of the MHC class II HLA DRB1*03 at all ages,while DRB1*04 predisposes to late onset disease;AIH-2 is associated with possession of DRB1*07 and DRB1**** majority of patients responds well to standard immunosuppressive treatment,based on steroid and azathioprine;second-and third-line drugs should be considered in case of intolerance or insufficient *** review offers a comprehensive overview of pathophysiological and clinical aspects of AIH.

关键词： Autoimmune Hepatitis Immunopathophysiology Treatment genetic Predisposition

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Autoimmune hepatitis: standard treatment and systematic review of alternative treatments

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World Journal of gastroenterology 2017年第33期23卷 6030-6048页

作者： Benedetta Terziroli Beretta-Piccoli giorgina mieli-vergani Diego vergani Epatocentro Ticino Paediatric Liver GI and Nutrition CentreMowat LabsKing’s College Hospital Institute of Liver Studies Mowat LabsKing’s College Hospital

Autoimmune hepatitis is a rare chronic inflammatory liver disease,affecting all ages,characterised by elevated transaminase and immunoglobulin g levels,positive autoantibodies,interface hepatitis at liver histology and good response to immunosuppressive treatment. If untreated,it has a poor prognosis. The aim of this review is to summarize the evidence for standard treatment and to provide a systematic review on alternative treatments for adults and children. Standard treatment is based on steroids and azathioprine,and leads to disease remission in 80%-90% of patients. Alternative first line treatment has been attempted with budesonide or cyclosporine,but their superiority compared to standard treatment remains to be demonstrated. Second-line treatments are needed for patients not responding or intolerant to standard treatment. No randomized controlled trials have been performed for second-line options. Mycophenolate mofetil is the most widely used second-line drug,and has good efficacy particularly for patients intolerant to azathioprine,but has the major disadvantage of being teratogenic. Only few and heterogeneous data on cyclosporine,tacrolimus,everolimus and sirolimus are available. More recently,experience with the anti-tumour necrosis factoralpha infliximab and the anti-CD20 rituximab has been published,with ambivalent results; these agents may have severe side-effects and their use should be restricted to specialized centres. Clinical trials with new therapeutic options are ongoing.

关键词： Autoimmune hepatitis Standard treatment Second-line treatment Adults Children

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Update on Autoimmune Hepatitis

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Journal of Clinical and Translational Hepatology 2015年第1期3卷 42-52页

作者： Rodrigo Liberal Diego vergani giorgina mieli-vergani Paediatric Liver GI & Nutrition Centre and Institute of Liver Studies King's College London School of Medicine at King's College Hospital London UK

Autoimmune hepatitis (AIH),a liver disorder affecting both children and adults,is characterized by inflammatory liver histology,elevated transaminase levels,circulating nonorgan-specific autoantibodies,and increased levels of immunoglobulin g,in the absence of a known *** types of AIH are recognized according to seropositivity:smooth muscle antibody and/or antinuclear antibody define AIH type 1 and antibodies to liver-kidney microsome type 1 and/or liver cytosol type 1 define AIH type *** type 1 affects both adults and children,while AIH type 2 is mainly a paediatric disease,though it does occasionally affects young *** should be considered during the diagnostic workup of any patient with increased liver enzyme *** is exquisitely responsive to immunosuppressive treatment with prednisolone with or without azathioprine,with symptom free longterm survival for the majority of *** those who do not respond to standard treatment,or who are difficult-totreat,mycophenolate mofetil and,in the absence of a response,calcineurin inhibitors should be tried in addition to *** pathogenesis of AIH is not fully understood,although there is mounting evidence that genetic susceptibility,molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune *** damage is thought to be mediated primarily by CD4 T-cells,although recent studies support the involvement of diverse populations,including Th17 cells.A deeper understanding of the pathogenesis of AIH is likely to contribute to the development of novel treatments,such as the adoptive transfer of autologous expanded antigenspecific regulatory T-cells,which ultimately aim at restoring tolerance to liver-derived antigens.

关键词： Autoimmune hepatitis Autoantibodies Immunogenetics Regulatory T cells Immunosuppresion

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Challenges and opportunities in the production of magnesium parts by directed energy deposition processes

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Journal of Magnesium and Alloys 2024年第5期12卷 1663-1686页

作者： gürel Cam Ali günen Iskenderun Technical University Faculty of Engineering and Natural SciencesDepartment of Mechanical Engineering31200 Iskenderun-HatayTurkey Iskenderun Technical University Faculty of Engineering and Natural SciencesDepartment of Metallurgy and Materials Engineering31200 Iskenderun-HatayTurkey

Mg-alloys have gained considerable attention in recent years for their outstanding properties such as lightweight,high specific strength,and corrosion resistance,making them attractive for applications in medical,aerospace,automotive,and other transport ***,their widespread application is hindered by their low formability at room temperature due to limited slip *** Mg-alloys have low mechanical properties due to the presence of casting defects such as porosity and anisotropy in addition to the high *** casting methods benefit from established process optimization techniques for these problems,additive manufacturing methods are increasingly replacing casting methods in Mg alloys as they provide more precise control over the microstructure and allow specific grain orientations,potentially enabling easier optimization of anisotropy properties in certain *** metal additive manufacturing(MAM)technology also results in some manufacturing defects such as inhomogeneous microstructural evolution and porosity and additively manufactured Mg alloy parts exhibit lower properties than the wrought parts,they in general exhibit superior properties than the cast ***,MAM is a promising technique to produce Mg alloy *** energy deposition processes,particularly wire arc directed energy deposition(WA-DED),have emerged as an advantageous additive manufacturing(AM)technique for metallic materials including magnesium alloys,offering advantages such as high deposition rates,improved material efficiency,and reduced production costs compared to subtractive ***,the inherent challenges associated with magnesium,such as its high reactivity and susceptibility to oxidation,pose unique hurdles in the application of this *** review paper delves into the progress made in the application of DED technology to Mg-alloys,its challenges,and ***,the predominant imperfections,notably inhomo

关键词： Additive manufacturing DED processes Arc-DED Wire arc additive manufacturing(WAAM) 3-D printing High deposition rate

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Recent research in mechanical properties of geopolymer-based ultrahigh-performance concrete:A review

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Defence Technology（防务技术） 2024年第2期32卷 67-88页

作者： g.Murali Division of Research&Innovation Uttaranchal UniversityDehradun 248007India

Due to the growing need for sustainable and ultra-high-strength construction materials,scientists have created an innovative ultra-high-performance concrete called geopolymer based ultra-highperformance concrete(gUHPC).Besides,in the last few decades,there have been a lot of explosions and ballistic attacks around the world,which have killed many civilians and fighters in border *** this context,this article reviews the fresh state and mechanical properties of ***,the ingredients of gUHPC and fresh properties such as setting time and flowability are briefly ***,the review of compressive strength,flexure strength,tensile strength and modulus of elasticity of fibrous ***,the blast and projectile impact resistance performance was ***,the microstructural characteristics were reviewed using the scanning electron microscope and X-ray Powder *** review outcome reveals that the mechanical properties were increased when 30%silica fume was added to a higher dose of steel fibre to improve the microstructure of *** is hypothesized that the brittleness of gUHPC was mitigated by adding 1.5%steel fibre reinforcement,which played a role in the decrease of contact explosion cratering and *** the need for cement in gUHPC was a key factor in the review,indicating a promising potential for lowering carbon ***,gUHPC research is still in its early stages,so more study is required before its full potential can be utilized.

关键词： Mechanical properties Blast Projectile impact Fibre geopolymer Silica fume Alkaline activators

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Nitrogen mineralization in the oldest climax communities in the eastern Mediterranean region

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Journal of Forestry Research 2024年第1期35卷 213-228页

作者： Fatma Selcen Sakar gürcan güleryüz Department of Biology Section Ecology GörükleGraduate School of Natural and Applied ScienceUniversity of Bursa Uludağ16059 NilüferBursaTurkey Department of Biology Section Ecology GörükleFaculty of Science and ArtsUniversity of Bursa Uludağ16059 NilüferBursaTurkey

In this study,we investigated how tree species affect N mineralization in connection to some soil properties and seconder metabolite levels of litter,in the soil of the old-est native forest *** the oldest pure communi-ties of Pinus nigra(PN),Fagus orientalis(FO),and Abies bornmuelleriana(AB)in the mountain range of Mount Uludağ,Bursa,Turkey,annual net yield and N mineraliza-tion in the 0-5-and 5-20-cm soil layers were determined in a field incubation study over 1 *** locations were chosen from 1300 to 1600 m a.s.l.,and moisture content(%),pH,water-holding capacity(%),organic C,total N,and C/N ratio,and annual net mineral N yield of the soil and hydro-lyzed tannic acid and total phenolic compounds in litter were compared for these forest *** had the highest annual net Nmin yield(43.9±4.8 kg ha^(-1) a^(-1)),*** the lowest(30.5±4.2 kg ha^(-1) a^(-1)).Our findings show that in the oldest forest ecosystems,the seasonal soil moisture content and tree species play an essential role in N cycling and that hydrolyzed tannic acids and total phenolic compounds effectively control N *** acid and total phenolics in the litter were found to inhibit nitrification,but total phenolics were found to stimulate ammonification.

关键词： Oldest forest communities Nitrogen mineralization Nitrification Tannic acid Total phenolic Litter

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Shell-model representations of the microscopic version of the Bohr-Mottelson collective model

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Communications in Theoretical Physics 2024年第8期76卷 79-90页

作者： H g ganev Joint Institute for Nuclear Research DubnaRussia Institute of Mechanics Bulgarian Academy of SciencesSofiaBulgaria

The structure of the irreducible collective spaces of the group Sp(12,R),which many-particle nuclear states are classified according to the chain Sp(12,R)⊃U(6)⊃SO(6)⊃SU_(pn)(3)⊗SO(2)⊃SO(3)of the proton-neutron symplectic model(PNSM),is considered in *** chain of the PNSM was recently shown to correspond to a microscopic shell-model version of the Bohr-Mottelson collective *** construction of the relevant shell-model representations of the Sp(12,R)group along this chain is considered for three nuclei with varying collective properties and from different mass *** is shown that the SU_(pn)(3)basis states of the Sp(12,R)representations belonging to the SO(6)irreps with seniorityυ≥υ0,withυ0 denoting the maximal seniority SO(6)irrep contained in the Sp(12,R)bandhead,are always Pauli allowed,but organized in a different way into different SO(6)*** is in contrast to the case of filling the levels of the standard three-dimensional harmonic oscillator and using the plethysm *** the SU_(pn)(3)multiplets withinυ<υ0 are not all Pauli forbidden,it is safe to discard *** results obtained in the present work are important for the practical application of the microscopic version of the Bohr-Mottelson collective model.

关键词： microscopic shell-model version of the Bohr-Mottelson model proton-neutron symplectic model Sp(12,R)dynamical algebra shell-model representations

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