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Ages of celiac disease: From changing environment to improved diagnostics

World Journal of Gastroenterology 2011年第32期17卷 3665-3671页

作者： Alberto Tommasini Tarcisio Not Alessandro Ventura Laboratory of Immunopathology Institute for Maternal and Child Health Scientific Institute for Research and Care Burlo Garofolo and University of Trieste Department of Pediatrics Institute for Maternal and Child Health Scientific Institute for Research and Care Burlo Garofolo and University of Trieste

From the time of Gee's landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat gliadin, leading to typical mucosal changes in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten (AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic "gluten infection". The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of autoantibodies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed.

关键词： Antibodies Autoimmunity Celiac disease Diagnostics History Intestinal mucosa

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ntestinal-mucosa anti-transglutaminase antibody assays to test for genetic gluten intolerance

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Cellular & Molecular Immunology 2014年第6期11卷 617-620页

作者： Sara Quaglia Luigina De Leo Fabiana Ziberna Serena Vatta Vincenzo Villanacci Marilena Granzotto Vincenzo Petix Stefano Martelossi Grazia Di Leo Lucio Torelli Tarcisio Not institute for maternal and child health - irccs 'burlo garofolo' Trieste Italy Department of Pathology Spedali Civili University of Brescia Brescia Italy University of Trieste Trieste Italy These two authors contributed equally to the study

Celiac disease （CD） is an autoimmune enteropathy character- ized by gluten-triggered intestinal mucosa lesions in genetically susceptible individuals carrying the HLA DQ2 or DQ8. CD diagnosis is based on the concentration of IgA serum anti- transglutaminase （anti-tTG） antibodies together with mucosal damage at intestinal biopsy.

关键词： Intestinal-mucosa antibody assays genetic gluten intolerance

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The Uptake and Distribution Evidence of Nano-and Microplastics in vivo after a Single High Dose of Oral Exposure

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Biomedical and Environmental Sciences 2024年第1期37卷 31-41页

作者： HONG Tao SUN Wei DENG Yuan LYU Jian Da JIN Cui Hong BAI Ying Long NA Jun ZHANG Rui GAO Yuan PAN Guo Wei YANG Zuo Sen YAN Ling Jun Research Center for Universal health School of Public HealthChina Medical UniversityShenyang 110122LiaoningChina Department of Pain Management Shengjing Hospital of China Medical UniversityShenyang 110004LiaoningChina Department of Toxicology School of Public HealthChina Medical UniversityShenyang 110122LiaoningChina Department of maternal and child health School of Public HealthChina Medical UniversityShenyang 110122LiaoningChina institute of Preventive Medicine China Medical UniversityShenyang 110122LiaoningChina institute of Chronic Diseases Liaoning Provincial Center for Disease Control and PreventionShenyang 110000LiaoningChina

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in *** Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body weight).The fluorescence intensity(FI)in observed organs was measured using the IVIS Spectrum at 0.5,1,2,and 4 h after *** was performed to corroborate these *** In the 100 nm group,the FI of the stomach and small intestine were highest at 0.5 h,and the FI of the large intestine,excrement,lung,kidney,liver,and skeletal muscles were highest at 4 h compared with the control group(P<0.05).In the 3μm group,the FI only increased in the lung at 2 h(P<0.05).In the 10μm group,the FI increased in the large intestine and excrement at 2 h,and in the kidney at 4 h(P<0.05).The presence of nano-/microplastics in tissues was further verified by *** peak time of nanoplastic absorption in blood was *** Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however,only small amounts of MPs could penetrate the organs.

关键词： Microplastics Nanoplastics IVIS Spectrum small-animal imaging system Tissue distribution Blood

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Human CD56+CD39+ dNK cells support fetal survival through controlling trophoblastic cell fate:immune mechanisms of recurrent early pregnancy loss

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National Science Review 2024年第6期11卷 129-145页

作者： Wentong Jia Liyang Ma Xin Yu Feiyang Wang Qian Yang Xiaoye Wang Mengjie Fan Yan Gu Ran Meng Jian Wang Yuxia Li Rong Li Xuan Shao Yan-Ling Wang State Key Laboratory of Stem cell and Reproductive Biology Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of Sciences Beijing institute for Stem Cell and Regenerative Medicine University of the Chinese Academy of Sciences NHC Key Lab of Reproduction Regulation Shanghai Engineering Research Center of Reproductive Health Drug and Devices Shanghai Institute for Biomedical and Pharmaceutical Technologies National Clinical Center for Obstetrics and Gynecology Peking University Third Hospital Department of Family Planning The Second Hospital of Tianjin Medical University Department of Prenatal Screening Haidian Maternal and Child Health Hospital

Decidual natural killer（dNK） cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss（RPL） at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG（NOD/Shi-scid/IL-2Rγnull） mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients（dNK-RPL）remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+dNK *** studies revealed that CD56+CD39+dNK subset facilitates early differentiation of mouse trophoblast stem cells（m TSCs） towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor（M-CSF）. Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.

关键词： recurrent pregnancy loss CD56+CD39+ dNK subset NOG mice adoptive transfer placental trophoblast cell fate M-CSF

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Proficiency score as a predictor of early trifecta achievement during the learning curve of robot-assisted radical prostatectomy for high-risk prostate cancer:Results of a multicentric series

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Current Urology 2024年第2期18卷 110-114页

作者： Umberto Anceschi Rocco Simone Flammia Antonio Tufano Michele Morelli Antonio Galfano Lorenzo Giuseppe Luciani Leonardo Misuraca Paolo Dell’Oglio Gabriele Tuderti Aldo Brassetti Maria Consiglia Ferriero Alfredo Maria Bove Riccardo Mastroianni Francesco Prata Isabella Sperduti Giovanni Petralia SilviaSecco Ettore Di Trapani DanieleMattevi Tommaso Cai Aldo Massimo Bocciardi Giuseppe Simone Department of Urology IRCCS“Regina Elena”National Cancer InstituteRomeItaly Urologic Clinic Department of Maternal-Child and Urologic SciencesSapienza University of RomeItaly Ospedale Niguarda Ca’Granda Department of UrologyMilanItaly Department of Urology APSS Santa Chiara Regional HospitalTrentoItaly Department of Biostatistical Unit IRCCS Regina Elena National Cancer InstituteRomeItaly

Background:Recently,an innovative tool called“proficiency score”was introduced to assess the learning curve for robot-assisted radical prostatectomy(RARP).However,the initial study only focused on patients with low-risk prostate cancer forwhompelvic lymph node dissection(PLND)was not *** address this issue,we aimed to validate proficiency scores of a contemporarymulticenter cohort of patients with high-risk prostate cancer treated with RARP plus extended PLND by trainee *** andmethods:Between 2010 and 2020,4 Italian institutional prostate-cancer datasets weremerged and queried for“RARP”and“high-risk prostate cancer.”High-risk prostate cancer was defined according to the most recent European Association of Urology guidelines as follows:prostate-specific antigen>20 ng/mL,International Society ofUrological Pathology≥4,and/or clinical stage(cT)≥2c on preoperative *** selected cohort(n=144)included clinical cases performed by trainee surgeons(n=4)after completing their RARP learning curve(50 procedures for low-risk prostate cancer).The outcome of interest,the proficiency score,was defined as the coexistence of all the following criteria:a comparable operation time to the interquartile range of the mentor surgeon at each center,absence of any significant perioperative complications Clavien-Dindo Grade 3–5,no perioperative blood transfusions,and negative surgical margins.A logistic binary regression model was built to identify the predictors of 1-year trifecta achievement in the trainee *** all statistical analyses,a 2-sided p<0.05 was considered ***:A proficiency score was achieved in 42.3%*** univariable level,proficiency score was associated with 1-year trifecta achievement(odds ratio,8.77;95%confidence interval,2.42–31.7;p=0.001).After multivariable adjustments for age,nerve-sparing,and surgical technique,the proficiency score independently predicted 1-year trifecta achievement(odds ratio,9.58;95%confidence i

关键词： Trifecta Learning curve Robot-assisted radical prostatectomy High-risk prostate cancer

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maternal weight and its association with risk of overweight in offspring:a trajectory analysis from a birth cohort in China

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World Journal of Pediatrics 2024年第5期20卷 496-505页

作者： Rui Deng Wei-Qin Li Xing-Xiu Li Liu-Mei Wei Jie Hu Jun-Hong Leng Bin Dong institute of child and Adolescent health School of Public HealthPeking University Health Science CenterNo.38 Xueyuan RdHaidian DistrictBeijing100191China Tianjin Women and children’s health Center No.96 Guizhou RdHeping DistrictTianjin300070China Menzies health institute Queensland Griffith UniversityNathanQLD4111Australia

Background Most studies on the association of maternal pregnancy weight with offspring weight trajectory have a short follow-up *** study aimed to explore the associations of maternal prepregnancy body mass index(BMI)and gestational weight gain(GWG)with childhood weight trajectories in a 7-year birth *** A total of 946 mother–child pairs(467 boys and 479 girls)from a longitudinal birth cohort in Tianjin City,China,were included in this study,ranging from pregnancy to offspring at 7 *** outcome variable was defined as overweight or not overweight in offspring at the last round.A group-based trajectory model was applied to identify childhood BMI trajectory *** Five discrete BMI trajectory groups were identified and characterized as constant underweight(25.2%),constant normal weight(42.8%),and high or increasing trajectory[at risk of overweight(16.9%),progressive overweight(11.0%)and progressive obesity(4.1%)].maternal prepregnancy overweight was associated with 1.72(95%CI 1.14–2.60,P=0.01)to 4.02(95%CI 1.94–8.36,Pchildren in all high or increasing trajectory groups were associated with greater overweight risk at the last round[risk ratios(RRs)ranged from 3.54(95%CI 2.53–4.95,Pmaternal prepregnancy overweight and excessive gestational weight gain were associated with increasing or high-level childhood body mass index trajectories as well as a greater risk of overweight at 7 years.

关键词： Body-weight trajectory child Gestational weight gain Overweight Pregnancy

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Molecular mechMolecular mechanism of glucocorticoid resistance in inflammatory bowel disease

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World Journal of Gastroenterology 2011年第9期17卷 1095-1108页

作者： Sara De Iudicibus Raffaella Franca Stefano Martelossi Alessandro Ventura Giuliana Decorti Department of Reproduction and Development University of Trieste institute for maternal and child health irccs burlo garofolo Department of Life Sciences University of Trieste

Natural and synthetic glucocorticoids (GCs) are widely employed in a number of inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for inducing remission in moderate to severe active Crohn’s disease and ulcerative colitis. Despite their extensive therapeutic use and the proven effectiveness, considerable clinical evidence of wide inter-individual differences in GC efficacy among patients has been reported, in particular when these agents are used in inflammatory diseases. In recent years, a detailed knowledge of the GC mechanism of action and of the genetic variants affecting GC activity at the molecular level has arisen from several studies. GCs interact with their cytoplasmic receptor, and are able to repress inflammatory gene expression through several distinct mechanisms. The glucocorticoid receptor (GR) is therefore crucial for the effects of these agents: mutations in the GR gene (NR3C1, nuclear receptor subfamily 3, group C, member 1) are the primary cause of a rare, inherited form of GC resistance; in addition, several polymorphisms of this gene have been described and associated with GC response and ***, the GR is not self-standing in the cell and the receptor-mediated functions are the result of a complex interplay of GR and many other cellular partners. The latter comprise several chaperonins of the large cooperative hetero-oligomeric complex that binds the hormonefree GR in the cytosol, and several factors involved in the transcriptional machinery and chromatin remodeling, that are critical for the hormonal control of target genes transcription in the nucleus. Furthermore, variants in the principal effectors of GCs (e.g. cytokines and their regulators) have also to be taken into account for a comprehensive evaluation of the variability in GC response. Polymorphisms in genes involved in the transport and/or metabolism of these hormones have also been suggested as

关键词： Glucocorticoids Inflammatory bowel disease Pharmacogenomics

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Induced pluripotent stem cells as an innovative model to study drug induced pancreatitis

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World Journal of Gastroenterology 2021年第35期27卷 5796-5802页

作者： Elena Genova Gabriele Stocco Giuliana Decorti institute for maternal and child health IRCCS Burlo GarofoloTrieste 34137Italy Department of Life Sciences University of TriesteTrieste 34127Italy Department of Medical Surgical and Health SciencesUniversity of TriesteTrieste 34127Italy

Drug-induced pancreatitis is a gastrointestinal adverse effect concerning about 2%of *** majority of cases are mild to moderate but severe episodes can also occur,leading to hospitalization or even ***,the mechanisms of this adverse reaction are still not clear,hindering its prevention,and the majority of data available of this potentially life-threatening adverse effect are limited to case reports leading to a probable underestimation of this *** particular,in this editorial,special attention is given to thiopurine-induced pancreatitis(TIP),an idiosyncratic adverse reaction affecting around 5%of inflammatory bowel disease(IBD)patients taking thiopurines as immunosuppressants,with a higher incidence in the pediatric *** biomarkers are not available to assist clinicians in the prevention of TIP,also because of the inaccessibility of the pancreatic tissue,which limits the possibility to perform dedicated cellular and molecular *** this regard,induced pluripotent stem cells(iPSCs)and the exocrine pancreatic differentiated counterpart could be a great tool to investigate the cellular and molecular mechanisms underlying the development of this undesirable *** particular type of stem cells is obtained by reprogramming adult cells,including fibroblasts and leukocytes,with a set of transcription factors known as the Yamanaka’s *** unaltered the donors’genetic heritage,iPSCs represent an innovative model to study the mechanisms of adverse drug reactions in individual patients’tissues not easily obtainable from human ***,iPSCs can differentiate under adequate stimuli into almost any somatic lineage,opening a new world of opportunities for *** works are already available in the literature studying liver,central nervous system and cardiac cells derived from iPSCs and adverse drug ***,to our knowledge no studies have been performed on exocrine pancreas differentiated

关键词： Induced pluripotent stem cells Therapy personalization Patient-specific cells Drug-induced pancreatitis Thiopurines Inflammatory bowel disease

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Association between orofacial granulomatosis and Crohn's disease in children:Systematic review

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World Journal of Gastroenterology 2014年第23期20卷 7497-7504页

作者： Marzia Lazzerini Matteo Bramuzzo Alessro Ventura institute for maternal and child health IRCCS Burlo Garofolo34137 TriesteItaly University of Trieste 34137 TriesteItaly

AIM: To review pediatric cases of orofacial granulomatosis (OFG), report disease characteristics, and explore the association between OFG and Crohn’s disease.

关键词： Orofacial granulomatosis Melkersson-Rosenthal syndrome Cheilitis granulomatosa Crohn’ s disease children Systematic review

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Changes in the Non-targeted Metabolomic Profile of Three-year-old Toddlers with Elevated Exposure to Polycyclic Aromatic Hydrocarbons

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Biomedical and Environmental Sciences 2024年第5期37卷 479-493页

作者： LI Yang LIN Dan ZHANG Xiu Qin JU Guang Xiu SU Ya ZHANG Qian DUAN Hai Ping YU Wei Sen WANG Bing Ling PANG Shu Tao Department of Epidemiology and health Statistics School of Public HealthQingdao UniversityQingdao 266021ShandongChina Department of Environmental health Qingdao Municipal Center for Disease Control and PreventionQingdao Institute of Preventive MedicineQingdao 266033ShandongChina Physicochemical Laboratory Qingdao Municipal Center for Disease Control and PreventionQingdao Institute of Preventive MedicineQingdao 266033ShandongChina Section of child health Care Huangdao Maternity and Child Health Care Hospital of QingdaoQingdao 266499ShandongChina Qingdao Blood Center Qingdao 266071ShandongChina

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal *** Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old ***,37 children were categorized into low-and high-exposure groups based on the sum of the ten ***-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine ***,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina *** The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,Pchildren affected metabolic homeostasis,particularly that of certain gut microbiota-derived *** investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

关键词： child Gut microbiota Non-targeted metabolomics Polycyclic aromatic hydrocarbons Urinary metabolite profile

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