33 results on '"W. Xin"'
Search Results
2. [A case of acute osteomyelitis with pulmonary embolism in children]
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W, Wang, Y J, Wang, X W, Xin, Y, Yin, X R, Wang, C, Zhao, Z Y, Sun, and Y P, Jin
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Acute Disease ,Humans ,Osteomyelitis ,Child ,Pulmonary Embolism - Abstract
患儿 男,11岁,因“急性髂骨骨髓炎”于2020年1月入住山东第一医科大学附属省立医院小儿骨科,手术后出现呼吸困难急转入小儿重症医学科,因体循环高压行超声心动图检查发现肺动脉高压,进一步行心脏大血管CT造影(CTA)发现右下肺动脉栓塞,给予积极抗感染,依诺肝素皮下注射及口服利伐沙班序贯抗凝治疗,1个月后复查CTA示肺栓塞消失,随访1年患儿恢复良好。儿童急性骨髓炎合并肺栓塞临床特征不典型,临床上极易误诊,临床医师亟需提高对该病的认知和诊疗水平。.
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- 2022
3. Dendritic cell biology and its role in tumor immunotherapy
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Shuzhong Cui, Na Li, Ying-Ying Wang, Ying Xiang, Xiao-Qin Liu, Qing Zhang, Xian-Wang Wang, Zhaowu Ma, Yan-Ning Lyv, Dong Wang, Victoria W. Xin, Hong-Wu Xin, Jun-Ting Cheng, and Xiao-Chun Peng
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0301 basic medicine ,Cancer Research ,Protein Conformation ,medicine.medical_treatment ,Receptors, Fc ,Review ,Exosomes ,Lymphocyte Activation ,Mice ,0302 clinical medicine ,Neoplasms ,Tumor Microenvironment ,Receptors, Immunologic ,Immunologic Surveillance ,Antigen Presentation ,Clinical Trials as Topic ,Tumor immunotherapy ,Immune cells ,Hematology ,lcsh:Diseases of the blood and blood-forming organs ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Immunotherapy ,T cell ,Antigen presentation ,Receptors, Antigen, T-Cell ,Biology ,lcsh:RC254-282 ,03 medical and health sciences ,Immune system ,Antigen ,Antigens, Neoplasm ,Dendritic cells (DCs) ,medicine ,Autophagy ,Animals ,Humans ,Lectins, C-Type ,Antigen-presenting cell ,Molecular Biology ,Tumor microenvironment ,lcsh:RC633-647.5 ,Histocompatibility Antigens Class I ,Models, Immunological ,Dendritic cell ,Dendritic Cells ,Lymphocyte Subsets ,030104 developmental biology ,Cancer research ,MHC ,Immunologic Memory - Abstract
As crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4+ and CD8+ T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovered to participate in antigen presentation. T cell microvillar dynamics and TCR conformational changes were demonstrated upon DC antigen presentation. Caspase-11-driven hyperactive DCs were recently reported to convert effectors into memory T cells. DCs were also reported to crosstalk with NK cells. Additionally, DCs are the most important sentinel cells for immune surveillance in the tumor microenvironment. Alongside DC biology, we review the latest developments for DC-based tumor immunotherapy in preclinical studies and clinical trials. Personalized DC vaccine-induced T cell immunity, which targets tumor-specific antigens, has been demonstrated to be a promising form of tumor immunotherapy in patients with melanoma. Importantly, allogeneic-IgG-loaded and HLA-restricted neoantigen DC vaccines were discovered to have robust anti-tumor effects in mice. Our comprehensive review of DC biology and its role in tumor immunotherapy aids in the understanding of DCs as the mentors of T cells and as novel tumor immunotherapy cells with immense potential.
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- 2020
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4. Blocking the CGRP Pathway for Acute and Preventive Treatment of Migraine: The Evolution of Success
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Charles M. Conway, Gene M. Dubowchik, and Alison W Xin
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medicine.drug_class ,Calcitonin Gene-Related Peptide ,Migraine Disorders ,Pharmacology ,Calcitonin gene-related peptide ,Monoclonal antibody ,01 natural sciences ,03 medical and health sciences ,Calcitonin Gene-Related Peptide Receptor Antagonists ,Drug Discovery ,medicine ,Animals ,Humans ,Receptor ,030304 developmental biology ,0303 health sciences ,Chemistry ,medicine.disease ,0104 chemical sciences ,Blockade ,010404 medicinal & biomolecular chemistry ,Rimegepant ,Migraine ,Calcitonin ,Molecular Medicine ,Nasal administration ,Receptors, Calcitonin Gene-Related Peptide ,Signal Transduction - Abstract
The pivotal role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology was identified over 30 years ago, but the successful clinical development of targeted therapies has only recently been realized. This Perspective traces the decades long evolution of medicinal chemistry required to advance small molecule CGRP receptor antagonists, also called gepants, including the current clinical agents rimegepant, vazegepant, ubrogepant, and atogepant. Providing clinically effective blockade of CGRP signaling required surmounting multiple challenging hurdles, including defeating a sizable ligand with subnanomolar affinity for its receptor, designing antagonists with an extended confirmation and multiple pharmacophores while retaining solubility and oral bioavailability, and achieving circulating free plasma levels that provided near maximal CGRP receptor coverage. The clinical efficacy of oral and intranasal gepants and the injectable CGRP monoclonal antibodies (mAbs) are described, as are recent synthetic developments that have benefited from new structural biology data. The first oral gepant was recently approved and heralds a new era in the treatment of migraine.
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- 2020
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5. [Effect and influence factors of cardiopulmonary resuscitation in children with congenital heart disease in pediatric intensive care unit]
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G, Liu, J P, Chu, J L, Chen, S Y, Qian, D Q, Jin, X L, Lu, M X, Xu, Y B, Cheng, Z Y, Sun, H J, Miao, J, Li, S Y, Dong, X, Ding, Y, Wang, Q, Chen, Y Y, Duan, J T, Huang, Y M, Guo, X N, Shi, J, Su, Y, Yin, X W, Xin, S D, Zhao, Z X, Lou, J H, Jiang, and J S, Zeng
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Heart Defects, Congenital ,Male ,Child, Preschool ,Humans ,Female ,Child ,Intensive Care Units, Pediatric ,Cardiopulmonary Resuscitation ,Heart Arrest ,Retrospective Studies - Published
- 2022
6. [ACTG2 associated visceral myopathy with intestinal pseudoobstruction]
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M X, Shen, C, Zhao, Y J, Wang, X W, Xin, Y, Yin, and Y P, Jin
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Phenotype ,Intestinal Pseudo-Obstruction ,Humans ,Actins - Abstract
1岁11月龄患儿以腹胀、呕吐起病,临床表现为腹腔高压综合征、重度营养不良,腹部影像学检查提示肠梗阻,剖腹探查见所有肠道严重扩张,未见机械性梗阻,回肠造瘘术后仍有腹胀,后全外显子组基因检测提示为ACTG2基因c.769CT; p.Arg257Cys突变,诊断为原发性内脏肌病致假性肠梗阻。该病临床罕见,预后差,目前以对症支持治疗为主。当患儿出现顽固性难治性腹胀且排除机械性肠梗阻时,需考虑此病,早期基因检测可明确诊断。.
- Published
- 2021
7. Notch2 blockade enhances hematopoietic stem cell mobilization and homing
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Jay Myers, Shuiliang Yu, Christian W. Siebel, Ming Li, Wei Xin, Weihuan Wang, William W. Xin, Alex Yee-Chen Huang, Hillard M. Lazarus, Lan Zhou, Yiwei Wang, Marwah Albakri, and Alison W. Xin
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0301 basic medicine ,Receptors, CXCR4 ,endocrine system ,endocrine system diseases ,medicine.medical_treatment ,Notch signaling pathway ,Antineoplastic Agents ,Bone Marrow Cells ,Mice, Transgenic ,Hematopoietic stem cell transplantation ,Biology ,CXCR4 ,Article ,Mice ,03 medical and health sciences ,Cell Therapy & Immunotherapy ,Cell Movement ,medicine ,Animals ,Humans ,Receptor, Notch2 ,Cell Self Renewal ,Progenitor cell ,Hematopoietic Stem Cell Mobilization ,Cell Cycle ,Hematopoietic Stem Cell Transplantation ,Cell Differentiation ,Hematology ,Hematopoietic Stem Cells ,Endothelial stem cell ,030104 developmental biology ,Gene Expression Regulation ,Immunology ,Cancer research ,Stem cell ,Signal Transduction ,Homing (hematopoietic) - Abstract
Despite use of newer approaches, some patients being considered for autologous hematopoietic cell transplantation (HCT) may only mobilize limited numbers of hematopoietic progenitor cells (HPCs) into blood, precluding use of the procedure, or being placed at increased risk of complications due to slow hematopoietic reconstitution. Developing more efficacious HPC mobilization regimens and strategies may enhance the mobilization process and improve patient outcome. Although Notch signaling is not essential for homeostasis of adult hematopoietic stem cells (HSCs), Notch-ligand adhesive interaction maintains HSC quiescence and niche retention. Using Notch receptor blocking antibodies, we report that Notch2 blockade, but not Notch1 blockade, sensitizes hematopoietic stem cells and progenitors (HSPCs) to mobilization stimuli and leads to enhanced egress from marrow to the periphery. Notch2 blockade leads to transient myeloid progenitor expansion without affecting HSC homeostasis and self-renewal. We show that transient Notch2 blockade or Notch2-loss in mice lacking Notch2 receptor lead to decreased CXCR4 expression by HSC but increased cell cycling with CXCR4 transcription being directly regulated by the Notch transcriptional protein RBPJ. In addition, we found that Notch2-blocked or Notch2-deficient marrow HSPCs show an increased homing to the marrow, while mobilized Notch2-blocked, but not Notch2-deficient stem cells and progenitors, displayed a competitive repopulating advantage and enhanced hematopoietic reconstitution. These findings suggest that blocking Notch2 combined with the current clinical regimen may further enhance HPC mobilization and improve engraftment during HCT.
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- 2017
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8. [Advances in the research of the relationship between skin regulatory T cells and wound healing and immune diseases]
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Y W, Xin, Y F, Chai, and Y M, Yao
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Wound Healing ,Immune System Diseases ,T-Lymphocyte Subsets ,Humans ,T-Lymphocytes, Regulatory ,Skin - Abstract
As the body's largest organ, skin harbors a large amount of immune cells to regulate both innate and adaptive immune responses. Regulatory T cells (Tregs), as a subset of T lymphocytes with negative regulatory functions, play an important role in maintaining the immune homeostasis of different tissue. However, researches of skin Tregs are largely limited and uncompleted as compared with other tissue. In recent years, a comprehensive understanding is increasingly showing the specialized functions of Tregs in skin, including the orchestration of tissue wound healing, involvement in hair follicle recycling, and modulation of proper immune homeostasis. In this review, we outline the classification and characteristics of Tregs in skin, distribution, migration routes, immune effects, and relationship with wound healing, which aims to deepening our understanding towards the immunological effects of T lymphocytes subsets in skin and its regulatory pathways.作为机体最大的器官,皮肤中聚集了大量免疫细胞调节先天性和获得性免疫反应。调节性T细胞(Treg)作为具有负性调节功能的T淋巴细胞亚群,对维持不同组织免疫动态平衡发挥着重要作用。但是,相比于其他组织,有关Treg在皮肤组织中的研究相对较少,且不完善。近年来,随着研究的逐渐深入,研究者们认识到Treg在皮肤中具有特征性免疫效应,包括调控组织损伤修复、参与毛囊生长周期循环、诱导适当的免疫平衡等。本文就Treg在皮肤中的分类与特性、分布特点、迁移途径、免疫效应以及与创面愈合的关系进行综述,旨在深化对皮肤T淋巴细胞亚群免疫学效应及其调控途径的新认识。.
- Published
- 2020
9. CRISPR/Cas9 genome editing technology significantly accelerated herpes simplex virus research
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Shi-Bao Song, Ying-Ying Wang, Xian-Wang Wang, Xiao-Chun Peng, Yan-Ning Lyu, Hong-Wu Xin, Lin Chen, Cheng-Bin Li, Ying Xiang, Zhaowu Ma, Jiafu Ji, Victoria W. Xin, and Dong Wang
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Gene Editing ,0301 basic medicine ,Cancer Research ,Cas9 ,Genetic enhancement ,Genome, Viral ,Computational biology ,Biology ,medicine.disease_cause ,Genome ,Virus ,03 medical and health sciences ,030104 developmental biology ,Herpes simplex virus ,Genome editing ,medicine ,Animals ,Humans ,Simplexvirus ,Molecular Medicine ,CRISPR ,CRISPR-Cas Systems ,Molecular Biology ,Genome size - Abstract
Herpes simplex viruses (HSVs) are important pathogens and ideal for gene therapy due to its large genome size. Previous researches on HSVs were hampered because the technology to construct recombinant HSVs were based on DNA homology-dependent repair (HDR) and plaque assay, which are inefficient, laborious, and time-consuming. Fortunately, clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9 (CRISPR/Cas9) recently provided the possibility to precisely, efficiently, and rapidly edit genomes and indeed is successfully being used in HSVs. Importantly, CRISPR/Cas9 technology increased HSV HDR efficiency exponentially by a 10,000-1,000,000 times when making recombinant HSVs, and its combination with flow cytometric technology made HSV recombination practically automatic. These may have a significant impact on virus and gene therapy researches. This review will summarize the latest development and molecular mechanisms of CRISPR/Cas9 genome editing technology and its recent application in HSVs.
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- 2018
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10. Study on diagnostic value of P1NP and β-CTX in bone metastasis of patients with breast cancer and the correlation between them
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C-T, Zuo, D-C, Yin, H-X, Fan, M, Lin, Z, Meng, G-W, Xin, Y-C, Zhang, and L, Cheng
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Adult ,Biopsy ,Bone Neoplasms ,Breast Neoplasms ,Middle Aged ,Bone and Bones ,Collagen Type I ,Healthy Volunteers ,Peptide Fragments ,Bone Density ,Case-Control Studies ,Biomarkers, Tumor ,Humans ,Female ,Peptides ,Procollagen ,Retrospective Studies - Abstract
This study aimed to investigate the diagnostic value of the total amino-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of β-I collagen (β-CTX) in bone metastasis of patients with breast cancer and the correlation between them.The medical records of 73 patients were retrospectively analyzed. These patients with breast cancer were treated in Oncology, General Surgery, and Orthopedic Departments in The Third People's Hospital of Qingdao from March 2014 to April 2017, including 40 patients with bone metastasis (bone metastasis group) and 33 patients with no bone metastasis (non-bone metastasis group). Other 40 healthy people who received physical examination in the same period were selected as the control group. The expression of P1NP and β-CTX in plasma were detected by the Enzyme-linked immunosorbent assay, and the correlation between them was analyzed.There were significant differences in P1NP and β-CTX concentrations among the three groups (p0.05). The concentrations of P1NP in the control group and the non-bone metastasis group were significantly lower than that in the bone metastasis group (p0.05); the concentrations of β-CTX in the control group and the non-bone metastasis group were significantly lower than that in the bone metastasis group (p0.05). P1NP: AUC=0.852, sensitivity: 72.5%, specificity: 93.9%, CUT OFF=66.44. β-CTX: AUC=0.883, sensitivity: 85.0%, specificity: 84.8%, CUT OFF=69.8. Joint detection: AUC=0.952, sensitivity: 84.8%, specificity: 99.5%, CUT OFF=99.5. The results of the concentrations of P1NP and β-CTX in the bone metastasis group detected by the Pearson correlation analysis showed that their concentrations were positively correlated in the bone metastasis group (r=0.764, p0.05).P1NP and β-CTX in plasma have a high diagnostic value for bone metastasis of breast cancer and have important significance in the diagnosis of bone metastasis and disease monitoring.
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- 2019
11. [Differences in anterior segment structure between Chinese Han people and American Caucasians]
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N, He, L L, Wu, M, Qi, S, Lin, and W, Xin
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Adult ,Aged, 80 and over ,China ,Anterior Chamber ,Gonioscopy ,Iris ,Middle Aged ,United States ,Cross-Sectional Studies ,Asian People ,Anterior Eye Segment ,Humans ,Glaucoma, Angle-Closure ,Intraocular Pressure ,Tomography, Optical Coherence ,Aged - Published
- 2018
12. [Safety of atypical antipsychotics in the treatment of behavioral and psychological symptoms in dementia: a meta-analysis]
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X J, Xue, R L, He, W X, Li, J W, Xin, Q Y, Ye, X C, Chen, and X D, Pan
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Europe ,Schizophrenia ,Humans ,Dementia ,Risperidone ,Antipsychotic Agents - Published
- 2018
13. [Effect of simplified and traditional Chinese character on accommodative microfluctuation in young adult myopes and emmetropes]
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W, Xin, P C, Shen, C C, Zheng, Y, Liu, and D, Xu
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Adult ,China ,Young Adult ,Reading ,Myopia ,Accommodation, Ocular ,Humans ,Prospective Studies ,Emmetropia ,Language - Published
- 2018
14. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
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Aude Nicolas, Kevin P. Kenna, Alan E. Renton, Nicola Ticozzi, Faraz Faghri, Ruth Chia, Janice A. Dominov, Brendan J. Kenna, Mike A. Nalls, Pamela Keagle, Alberto M. Rivera, Wouter van Rheenen, Natalie A. Murphy, Joke J.F.A. van Vugt, Joshua T. Geiger, Rick A. Van der Spek, Hannah A. Pliner, null Shankaracharya, Bradley N. Smith, Giuseppe Marangi, Simon D. Topp, Yevgeniya Abramzon, Athina Soragia Gkazi, John D. Eicher, Aoife Kenna, Gabriele Mora, Andrea Calvo, Letizia Mazzini, Nilo Riva, Jessica Mandrioli, Claudia Caponnetto, Stefania Battistini, Paolo Volanti, Vincenzo La Bella, Francesca L. Conforti, Giuseppe Borghero, Sonia Messina, Isabella L. Simone, Francesca Trojsi, Fabrizio Salvi, Francesco O. Logullo, Sandra D’Alfonso, Lucia Corrado, Margherita Capasso, Luigi Ferrucci, Cristiane de Araujo Martins Moreno, Sitharthan Kamalakaran, David B. Goldstein, Aaron D. Gitler, Tim Harris, Richard M. Myers, Hemali Phatnani, Rajeeva Lochan Musunuri, Uday Shankar Evani, Avinash Abhyankar, Michael C. Zody, Julia Kaye, Steven Finkbeiner, Stacia K. Wyman, Alex LeNail, Leandro Lima, Ernest Fraenkel, Clive N. Svendsen, Leslie M. Thompson, Jennifer E. Van Eyk, James D. Berry, Timothy M. Miller, Stephen J. Kolb, Merit Cudkowicz, Emily Baxi, Michael Benatar, J. Paul Taylor, Evadnie Rampersaud, Gang Wu, Joanne Wuu, Giuseppe Lauria, Federico Verde, Isabella Fogh, Cinzia Tiloca, Giacomo P. Comi, Gianni Sorarù, Cristina Cereda, Philippe Corcia, Hannu Laaksovirta, Liisa Myllykangas, Lilja Jansson, Miko Valori, John Ealing, Hisham Hamdalla, Sara Rollinson, Stuart Pickering-Brown, Richard W. Orrell, Katie C. Sidle, Andrea Malaspina, John Hardy, Andrew B. Singleton, Janel O. Johnson, Sampath Arepalli, Peter C. Sapp, Diane McKenna-Yasek, Meraida Polak, Seneshaw Asress, Safa Al-Sarraj, Andrew King, Claire Troakes, Caroline Vance, Jacqueline de Belleroche, Frank Baas, Anneloor L.M.A. ten Asbroek, José Luis Muñoz-Blanco, Dena G. Hernandez, Jinhui Ding, J. Raphael Gibbs, Sonja W. Scholz, Mary Kay Floeter, Roy H. Campbell, Francesco Landi, Robert Bowser, Stefan M. Pulst, John M. Ravits, Daniel J.L. MacGowan, Janine Kirby, Erik P. Pioro, Roger Pamphlett, James Broach, Glenn Gerhard, Travis L. Dunckley, Christopher B. Brady, Neil W. Kowall, Juan C. Troncoso, Isabelle Le Ber, Kevin Mouzat, Serge Lumbroso, Terry D. Heiman-Patterson, Freya Kamel, Ludo Van Den Bosch, Robert H. Baloh, Tim M. Strom, Thomas Meitinger, Aleksey Shatunov, Kristel R. Van Eijk, Mamede de Carvalho, Maarten Kooyman, Bas Middelkoop, Matthieu Moisse, Russell L. McLaughlin, Michael A. Van Es, Markus Weber, Kevin B. Boylan, Marka Van Blitterswijk, Rosa Rademakers, Karen E. Morrison, A. Nazli Basak, Jesús S. Mora, Vivian E. Drory, Pamela J. Shaw, Martin R. Turner, Kevin Talbot, Orla Hardiman, Kelly L. Williams, Jennifer A. Fifita, Garth A. Nicholson, Ian P. Blair, Guy A. Rouleau, Jesús Esteban-Pérez, Alberto García-Redondo, Ammar Al-Chalabi, Ekaterina Rogaeva, Lorne Zinman, Lyle W. Ostrow, Nicholas J. Maragakis, Jeffrey D. Rothstein, Zachary Simmons, Johnathan Cooper-Knock, Alexis Brice, Stephen A. Goutman, Eva L. Feldman, Summer B. Gibson, Franco Taroni, Antonia Ratti, Cinzia Gellera, Philip Van Damme, Wim Robberecht, Pietro Fratta, Mario Sabatelli, Christian Lunetta, Albert C. Ludolph, Peter M. Andersen, Jochen H. Weishaupt, William Camu, John Q. Trojanowski, Vivianna M. Van Deerlin, Robert H. Brown, Leonard H. van den Berg, Jan H. Veldink, Matthew B. Harms, Jonathan D. Glass, David J. Stone, Pentti Tienari, Vincenzo Silani, Adriano Chiò, Christopher E. Shaw, Bryan J. Traynor, John E. Landers, Isabella Simone, Giancarlo Logroscino, Ilaria Bartolomei, Maria Rita Murru, Emanuela Costantino, Carla Pani, Roberta Puddu, Carla Caredda, Valeria Piras, Stefania Tranquilli, Stefania Cuccu, Daniela Corongiu, Maurizio Melis, Antonio Milia, Francesco Marrosu, Maria Giovanna Marrosu, Gianluca Floris, Antonino Cannas, Gianluigi Mancardi, Paola Origone, Paola Mandich, Sebastiano Cavallaro, Kalliopi Marinou, Riccardo Sideri, Silvana Penco, Lorena Mosca, Giuseppe Lauria Pinter, Massimo Corbo, Paola Carrera, Nicola Fini, Antonio Fasano, Lucio Tremolizzo, Alessandro Arosio, Carlo Ferrarese, Gioacchino Tedeschi, Maria Rosaria Monsurrò, Giovanni Piccirillo, Cinzia Femiano, Anna Ticca, Enzo Ortu, Rossella Spataro, Tiziana Colletti, Marcella Zollino, Amelia Conte, Marco Luigetti, Serena Lattante, Marialuisa Santarelli, Antonio Petrucci, Maura Pugliatti, Angelo Pirisi, Leslie D. Parish, Patrizia Occhineri, Fabio Giannini, Claudia Ricci, Michele Benigni, Tea B. Cau, Daniela Loi, Cristina Moglia, Maura Brunetti, Marco Barberis, Gabriella Restagno, Federico Casale, Giuseppe Marrali, Giuseppe Fuda, Irene Ossola, Stefania Cammarosano, Antonio Canosa, Antonio Ilardi, Umberto Manera, Maurizio Grassano, Raffaella Tanel, Fabrizio Pisano, Neil A. Shneider, Stephen Goutman, Siddharthan Chandran, Suvankar Pal, George Manousakis, Stanley H. Appel, Ericka Simpson, Leo Wang, Summer Gibson, Richard Bedlack, David Lacomis, Dhruv Sareen, Alexander Sherman, Lucie Bruijn, Michelle Penny, Andrew S. Allen, Stanley Appel, Richard S. Bedlack, Braden E. Boone, Robert Brown, John P. Carulli, Alessandra Chesi, Wendy K. Chung, Elizabeth T. Cirulli, Gregory M. Cooper, Julien Couthouis, Aaron G. Day-Williams, Patrick A. Dion, Yujun Han, Sebastian D. Hayes, Angela L. Jones, Jonathan Keebler, Brian J. Krueger, Brittany N. Lasseigne, Shawn E. Levy, Yi-Fan Lu, Tom Maniatis, Slavé Petrovski, Alya R. Raphael, Zhong Ren, Katherine B. Sims, John F. Staropoli, Lindsay L. Waite, Quanli Wang, Jack R. Wimbish, Winnie W. Xin, Justin Kwan, James R. Broach, Ximena Arcila-Londono, Edward B. Lee, Noah Zaitlen, Gregory A. Cox, Steve Finkbeiner, Efthimios Dardiotis, Eran Hornstein, Daniel J. MacGowan, Terry Heiman-Patterson, Molly G. Hammell, Nikolaos A. Patsopoulos, Joshua Dubnau, Avindra Nath, Stacia Wyman, Alexander LeNail, Jenny Van Eyk, Stephan Züchner, Rebecca Schule, Jacob McCauley, Sumaira Hussain, Anne Cooley, Marielle Wallace, Christine Clayman, Richard Barohn, Jeffrey Statland, John Ravits, Andrea Swenson, Carlayne Jackson, Jaya Trivedi, Shaida Khan, Jonathan Katz, Liberty Jenkins, Ted Burns, Kelly Gwathmey, James Caress, Corey McMillan, Lauren Elman, Erik Pioro, Jeannine Heckmann, Yuen So, David Walk, Samuel Maiser, Jinghui Zhang, Fabiola De Marchi, Stefania Corti, Mauro Ceroni, Gabriele Siciliano, Massimiliano Filosto, Maurizio Inghilleri, Silvia Peverelli, Claudia Colombrita, Barbara Poletti, Luca Maderna, Roberto Del Bo, Stella Gagliardi, Giorgia Querin, Cinzia Bertolin, Viviana Pensato, Barbara Castellotti, Vincent Meininger, Gérard Besson, Emmeline Lagrange, Pierre Clavelou, Nathalie Guy, Philippe Couratier, Patrick Vourch, Véronique Danel, Emilien Bernard, Gwendal Lemasson, Ahmad Al Kheifat, Peter Andersen, Adriano Chio, Jonathan Cooper-Knock, Annelot Dekker, Vivian Drory, Alberto Garcia Redondo, Marc Gotkine, Winston Hide, Alfredo Iacoangeli, Jonathan Glass, Kevin Kenna, Matthew Kiernan, John Landers, Russell McLaughlin, Jonathan Mill, Miguel Mitne Neto, Mattieu Moisse, Jesus Mora Pardina, Karen Morrison, Stephen Newhouse, Susana Pinto, Sara Pulit, Pamela Shaw, Chris Shaw, William Sproviero, Gijs Tazelaar, Philip van Damme, Leonard van den Berg, Rick van der Spek, Kristel van Eijk, Michael van Es, Joke van Vugt, Jan Veldink, Mayana Zatz, Denis C. Bauer, Natalie A. Twine, Department of Neurosciences, Pentti Tienari / Principal Investigator, Neurologian yksikkö, Research Programs Unit, Clinicum, Research Programme for Molecular Neurology, University of Helsinki, Medicum, Department of Pathology, HUS Neurocenter, Nicolas A., Kenna K.P., Renton A.E., Ticozzi N., Faghri F., Chia R., Dominov J.A., Kenna B.J., Nalls M.A., Keagle P., Rivera A.M., van Rheenen W., Murphy N.A., van Vugt J.J.F.A., Geiger J.T., Van der Spek R.A., Pliner H.A., Shankaracharya, Smith B.N., Marangi G., Topp S.D., Abramzon Y., Gkazi A.S., Eicher J.D., Kenna A., Logullo F.O., Simone I.L., Logroscino G., Salvi F., Bartolomei I., Borghero G., Murru M.R., Costantino E., Pani C., Puddu R., Caredda C., Piras V., Tranquilli S., Cuccu S., Corongiu D., Melis M., Milia A., Marrosu F., Marrosu M.G., Floris G., Cannas A., Capasso M., Caponnetto C., Mancardi G., Origone P., Mandich P., Conforti F.L., Cavallaro S., Mora G., Marinou K., Sideri R., Penco S., Mosca L., Lunetta C., Pinter G.L., Corbo M., Riva N., Carrera P., Volanti P., Mandrioli J., Fini N., Fasano A., Tremolizzo L., Arosio A., Ferrarese C., Trojsi F., Tedeschi G., Monsurro M.R., Piccirillo G., Femiano C., Ticca A., Ortu E., La Bella V., Spataro R., Colletti T., Sabatelli M., Zollino M., Conte A., Luigetti M., Lattante S., Santarelli M., Petrucci A., Pugliatti M., Pirisi A., Parish L.D., Occhineri P., Giannini F., Battistini S., Ricci C., Benigni M., Cau T.B., Loi D., Calvo A., Moglia C., Brunetti M., Barberis M., Restagno G., Casale F., Marrali G., Fuda G., Ossola I., Cammarosano S., Canosa A., Ilardi A., Manera U., Grassano M., Tanel R., Pisano F., Mazzini L., Messina S., D'Alfonso S., Corrado L., Ferrucci L., Harms M.B., Goldstein D.B., Shneider N.A., Goutman S.A., Simmons Z., Miller T.M., Chandran S., Pal S., Manousakis G., Appel S.H., Simpson E., Wang L., Baloh R.H., Gibson S.B., Bedlack R., Lacomis D., Sareen D., Sherman A., Bruijn L., Penny M., Moreno C.D.A.M., Kamalakaran S., Allen A.S., Boone B.E., Brown R.H., Carulli J.P., Chesi A., Chung W.K., Cirulli E.T., Cooper G.M., Couthouis J., Day-Williams A.G., Dion P.A., Gitler A.D., Glass J.D., Han Y., Harris T., Hayes S.D., Jones A.L., Keebler J., Krueger B.J., Lasseigne B.N., Levy S.E., Lu Y.-F., Maniatis T., McKenna-Yasek D., Myers R.M., Petrovski S., Pulst S.M., Raphael A.R., Ravits J.M., Ren Z., Rouleau G.A., Sapp P.C., Sims K.B., Staropoli J.F., Waite L.L., Wang Q., Wimbish J.R., Xin W.W., Phatnani H., Kwan J., Broach J., Arcila-Londono X., Lee E.B., Van Deerlin V.M., Fraenkel E., Ostrow L.W., Baas F., Zaitlen N., Berry J.D., Malaspina A., Fratta P., Cox G.A., Thompson L.M., Finkbeiner S., Dardiotis E., Hornstein E., MacGowan D.J.L., Heiman-Patterson T., Hammell M.G., Patsopoulos N.A., Dubnau J., Nath A., Musunuri R.L., Evani U.S., Abhyankar A., Zody M.C., Kaye J., Wyman S.K., LeNail A., Lima L., Rothstein J.D., Svendsen C.N., Van Eyk J.E., Maragakis N.J., Kolb S.J., Cudkowicz M., Baxi E., Benatar M., Taylor J.P., Wu G., Rampersaud E., Wuu J., Rademakers R., Zuchner S., Schule R., McCauley J., Hussain S., Cooley A., Wallace M., Clayman C., Barohn R., Statland J., Swenson A., Jackson C., Trivedi J., Khan S., Katz J., Jenkins L., Burns T., Gwathmey K., Caress J., McMillan C., Elman L., Pioro E.P., Heckmann J., So Y., Walk D., Maiser S., Zhang J., Silani V., Gellera C., Ratti A., Taroni F., Lauria G., Verde F., Fogh I., Tiloca C., Comi G.P., Soraru G., Cereda C., De Marchi F., Corti S., Ceroni M., Siciliano G., Filosto M., Inghilleri M., Peverelli S., Colombrita C., Poletti B., Maderna L., Del Bo R., Gagliardi S., Querin G., Bertolin C., Pensato V., Castellotti B., Camu W., Mouzat K., Lumbroso S., Corcia P., Meininger V., Besson G., Lagrange E., Clavelou P., Guy N., Couratier P., Vourch P., Danel V., Bernard E., Lemasson G., Laaksovirta H., Myllykangas L., Jansson L., Valori M., Ealing J., Hamdalla H., Rollinson S., Pickering-Brown S., Orrell R.W., Sidle K.C., Hardy J., Singleton A.B., Johnson J.O., Arepalli S., Polak M., Asress S., Al-Sarraj S., King A., Troakes C., Vance C., de Belleroche J., ten Asbroek A.L.M.A., Munoz-Blanco J.L., Hernandez D.G., Ding J., Gibbs J.R., Scholz S.W., Floeter M.K., Campbell R.H., Landi F., Bowser R., Kirby J., Pamphlett R., Gerhard G., Dunckley T.L., Brady C.B., Kowall N.W., Troncoso J.C., Le Ber I., Heiman-Patterson T.D., Kamel F., Van Den Bosch L., Strom T.M., Meitinger T., Shatunov A., Van Eijk K.R., de Carvalho M., Kooyman M., Middelkoop B., Moisse M., McLaughlin R.L., Van Es M.A., Weber M., Boylan K.B., Van Blitterswijk M., Morrison K.E., Basak A.N., Mora J.S., Drory V.E., Shaw P.J., Turner M.R., Talbot K., Hardiman O., Williams K.L., Fifita J.A., Nicholson G.A., Blair I.P., Esteban-Perez J., Garcia-Redondo A., Al-Chalabi A., Al Kheifat A., Andersen P.M., Chio A., Cooper-Knock J., Dekker A., Redondo A.G., Gotkine M., Hide W., Iacoangeli A., Kiernan M., Landers J.E., Mill J., Neto M.M., Pardina J.M., Newhouse S., Pinto S., Pulit S., Robberecht W., Shaw C., Sproviero W., Tazelaar G., Van Damme P., van den Berg L.H., van Vugt J., Veldink J.H., Zatz M., Bauer D.C., Twine N.A., Rogaeva E., Zinman L., Brice A., Feldman E.L., Ludolph A.C., Weishaupt J.H., Trojanowski J.Q., Stone D.J., Tienari P., Shaw C.E., Traynor B.J., ITALSGEN Consortium, Genomic Translation ALS Care GTAC, ALS Sequencing Consortium, NYGC ALS Consortium, Answer ALS Fdn, Clinical Res ALS Related Disorders, SLAGEN Consortium, French ALS Consortium, Project MinE ALS Sequencing Consor, Medical Research Council (MRC), ANS - Complex Trait Genetics, Human Genetics, ARD - Amsterdam Reproduction and Development, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Università cattolica del Sacro Cuore [Roma] (Unicatt), Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1), Lunar and Planetary Laboratory [Tucson] (LPL), University of Arizona, Università degli studi di Torino (UNITO), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), New York Genome Center [New York], New York Genome Center, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), St Jude Children's Research Hospital, Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), Centre de compétence de la Sclérose Latérale Amyotrophique [CHRU Tours] (SLA CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), University College of London [London] (UCL), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), King‘s College London, University of New Haven [Connecticut], Princeton University, Laboratoire de Biochimie [CHRU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Helmholtz-Zentrum München (HZM), University Medical Center [Utrecht], Deutsches Forschungszentrum für Künstliche Intelligenz GmbH = German Research Center for Artificial Intelligence (DFKI), Mayo Clinic [Jacksonville], Trinity College Dublin, Maurice Wohl Clinical Neuroscience Institut, Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Repositório da Universidade de Lisboa, Nicolas, A, Kenna, K, Renton, A, Ticozzi, N, Faghri, F, Chia, R, Dominov, J, Kenna, B, Nalls, M, Keagle, P, Rivera, A, van Rheenen, W, Murphy, N, van Vugt, J, Geiger, J, van der Spek, R, Pliner, H, Shankaracharya, N, Smith, B, Marangi, G, Topp, S, Abramzon, Y, Gkazi, A, Eicher, J, Kenna, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Borghero, G, Murru, M, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Capasso, M, Caponnetto, C, Mancardi, G, Origone, P, Mandich, P, Conforti, F, Cavallaro, S, Mora, G, Marinou, K, Sideri, R, Penco, S, Mosca, L, Lunetta, C, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Mandrioli, J, Fini, N, Fasano, A, Tremolizzo, L, Arosio, A, Ferrarese, C, Trojsi, F, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Ticca, A, Ortu, E, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Santarelli, M, Petrucci, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Cau, T, Loi, D, Calvo, A, Moglia, C, Brunetti, M, Barberis, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Canosa, A, Ilardi, A, Manera, U, Grassano, M, Tanel, R, Pisano, F, Mazzini, L, Messina, S, D'Alfonso, S, Corrado, L, Ferrucci, L, Harms, M, Goldstein, D, Shneider, N, Goutman, S, Simmons, Z, Miller, T, Chandran, S, Pal, S, Manousakis, G, Appel, S, Simpson, E, Wang, L, Baloh, R, Gibson, S, Bedlack, R, Lacomis, D, Sareen, D, Sherman, A, Bruijn, L, Penny, M, Moreno, C, Kamalakaran, S, Allen, A, Boone, B, Brown, R, Carulli, J, Chesi, A, Chung, W, Cirulli, E, Cooper, G, Couthouis, J, Day-Williams, A, Dion, P, Gitler, A, Glass, J, Han, Y, Harris, T, Hayes, S, Jones, A, Keebler, J, Krueger, B, Lasseigne, B, Levy, S, Lu, Y, Maniatis, T, McKenna-Yasek, D, Myers, R, Petrovski, S, Pulst, S, Raphael, A, Ravits, J, Ren, Z, Rouleau, G, Sapp, P, Sims, K, Staropoli, J, Waite, L, Wang, Q, Wimbish, J, Xin, W, Phatnani, H, Kwan, J, Broach, J, Arcila-Londono, X, Lee, E, Van Deerlin, V, Fraenkel, E, Ostrow, L, Baas, F, Zaitlen, N, Berry, J, Malaspina, A, Fratta, P, Cox, G, Thompson, L, Finkbeiner, S, Dardiotis, E, Hornstein, E, Macgowan, D, Heiman-Patterson, T, Hammell, M, Patsopoulos, N, Dubnau, J, Nath, A, Musunuri, R, Evani, U, Abhyankar, A, Zody, M, Kaye, J, Wyman, S, Lenail, A, Lima, L, Rothstein, J, Svendsen, C, Van Eyk, J, Maragakis, N, Kolb, S, Cudkowicz, M, Baxi, E, Benatar, M, Taylor, J, Wu, G, Rampersaud, E, Wuu, J, Rademakers, R, Züchner, S, Schule, R, Mccauley, J, Hussain, S, Cooley, A, Wallace, M, Clayman, C, Barohn, R, Statland, J, Swenson, A, Jackson, C, Trivedi, J, Khan, S, Katz, J, Jenkins, L, Burns, T, Gwathmey, K, Caress, J, Mcmillan, C, Elman, L, Pioro, E, Heckmann, J, So, Y, Walk, D, Maiser, S, Zhang, J, Silani, V, Gellera, C, Ratti, A, Taroni, F, Lauria, G, Verde, F, Fogh, I, Tiloca, C, Comi, G, Sorarù, G, Cereda, C, De Marchi, F, Corti, S, Ceroni, M, Siciliano, G, Filosto, M, Inghilleri, M, Peverelli, S, Colombrita, C, Poletti, B, Maderna, L, Del Bo, R, Gagliardi, S, Querin, G, Bertolin, C, Pensato, V, Castellotti, B, Camu, W, Mouzat, K, Lumbroso, S, Corcia, P, Meininger, V, Besson, G, Lagrange, E, Clavelou, P, Guy, N, Couratier, P, Vourch, P, Danel, V, Bernard, E, Lemasson, G, Laaksovirta, H, Myllykangas, L, Jansson, L, Valori, M, Ealing, J, Hamdalla, H, Rollinson, S, Pickering-Brown, S, Orrell, R, Sidle, K, Hardy, J, Singleton, A, Johnson, J, Arepalli, S, Polak, M, Asress, S, Al-Sarraj, S, King, A, Troakes, C, Vance, C, de Belleroche, J, ten Asbroek, A, Muñoz-Blanco, J, Hernandez, D, Ding, J, Gibbs, J, Scholz, S, Floeter, M, Campbell, R, Landi, F, Bowser, R, Kirby, J, Pamphlett, R, Gerhard, G, Dunckley, T, Brady, C, Kowall, N, Troncoso, J, Le Ber, I, Kamel, F, Van Den Bosch, L, Strom, T, Meitinger, T, Shatunov, A, Van Eijk, K, de Carvalho, M, Kooyman, M, Middelkoop, B, Moisse, M, Mclaughlin, R, Van Es, M, Weber, M, Boylan, K, Van Blitterswijk, M, Morrison, K, Basak, A, Mora, J, Drory, V, Shaw, P, Turner, M, Talbot, K, Hardiman, O, Williams, K, Fifita, J, Nicholson, G, Blair, I, Esteban-Pérez, J, García-Redondo, A, Al-Chalabi, A, Al Kheifat, A, Andersen, P, Chio, A, Cooper-Knock, J, Dekker, A, Redondo, A, Gotkine, M, Hide, W, Iacoangeli, A, Kiernan, M, Landers, J, Mill, J, Neto, M, Pardina, J, Newhouse, S, Pinto, S, Pulit, S, Robberecht, W, Shaw, C, Sproviero, W, Tazelaar, G, van Damme, P, van den Berg, L, van Eijk, K, van Es, M, Veldink, J, Zatz, M, Bauer, D, Twine, N, Rogaeva, E, Zinman, L, Brice, A, Feldman, E, Ludolph, A, Weishaupt, J, Trojanowski, J, Stone, D, Tienari, P, Chiò, A, Traynor, B, Nicolas, Aude, Kenna, Kevin P, Renton, Alan E, Ticozzi, Nicola, Faghri, Faraz, Chia, Ruth, Dominov, Janice A, Kenna, Brendan J, Nalls, Mike A, Keagle, Pamela, Rivera, Alberto M, van Rheenen, Wouter, Murphy, Natalie A, van Vugt, Joke J F A, Geiger, Joshua T, Van der Spek, Rick A, Pliner, Hannah A, Shankaracharya, Null, Smith, Bradley N, Marangi, Giuseppe, Topp, Simon D, Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D, Kenna, Aoife, Mora, Gabriele, Calvo, Andrea, Mazzini, Letizia, Riva, Nilo, Mandrioli, Jessica, Caponnetto, Claudia, Battistini, Stefania, Volanti, Paolo, La Bella, Vincenzo, Conforti, Francesca L, Borghero, Giuseppe, Messina, Sonia, Simone, Isabella L, Trojsi, Francesca, Salvi, Fabrizio, Logullo, Francesco O, D'Alfonso, Sandra, Corrado, Lucia, Capasso, Margherita, Ferrucci, Luigi, Logullo, Fo, Murru, Mr, Marrosu, Mg, Conforti, Fl, Pinter, Gl, Tedeschi, Gioacchino, Monsurrò, Maria Rosaria, Parish, Ld, Cau, Tb, Moreno, Cristiane de Araujo Martin, Kamalakaran, Sitharthan, Goldstein, David B, Gitler, Aaron D, Harris, Tim, Myers, Richard M, Phatnani, Hemali, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C, Kaye, Julia, Finkbeiner, Steven, Wyman, Stacia K, Lenail, Alex, Lima, Leandro, Fraenkel, Ernest, Svendsen, Clive N, Thompson, Leslie M, Van Eyk, Jennifer E, Berry, James D, Miller, Timothy M, Kolb, Stephen J, Cudkowicz, Merit, Baxi, Emily, Benatar, Michael, Taylor, J Paul, Rampersaud, Evadnie, Wu, Gang, Wuu, Joanne, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P, Sorarù, Gianni, Cereda, Cristina, Corcia, Philippe, Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W, Sidle, Katie C, Malaspina, Andrea, Hardy, John, Singleton, Andrew B, Johnson, Janel O, Arepalli, Sampath, Sapp, Peter C, McKenna-Yasek, Diane, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, Baas, Frank, Ten Asbroek, Anneloor L M A, Muñoz-Blanco, José Lui, Hernandez, Dena G, Ding, Jinhui, Gibbs, J Raphael, Scholz, Sonja W, Floeter, Mary Kay, Campbell, Roy H, Landi, Francesco, Bowser, Robert, Pulst, Stefan M, Ravits, John M, Macgowan, Daniel J L, Kirby, Janine, Pioro, Erik P, Pamphlett, Roger, Broach, Jame, Gerhard, Glenn, Dunckley, Travis L, Brady, Christopher B, Kowall, Neil W, Troncoso, Juan C, Le Ber, Isabelle, Mouzat, Kevin, Lumbroso, Serge, Heiman-Patterson, Terry D, Kamel, Freya, Van Den Bosch, Ludo, Baloh, Robert H, Strom, Tim M, Meitinger, Thoma, Shatunov, Aleksey, Van Eijk, Kristel R, de Carvalho, Mamede, Kooyman, Maarten, Middelkoop, Ba, Moisse, Matthieu, Mclaughlin, Russell L, Van Es, Michael A, Weber, Marku, Boylan, Kevin B, Van Blitterswijk, Marka, Rademakers, Rosa, Morrison, Karen E, Basak, A Nazli, Mora, Jesús S, Drory, Vivian E, Shaw, Pamela J, Turner, Martin R, Talbot, Kevin, Hardiman, Orla, Williams, Kelly L, Fifita, Jennifer A, Nicholson, Garth A, Blair, Ian P, Rouleau, Guy A, Esteban-Pérez, Jesú, García-Redondo, Alberto, Al-Chalabi, Ammar, Rogaeva, Ekaterina, Zinman, Lorne, Ostrow, Lyle W, Maragakis, Nicholas J, Rothstein, Jeffrey D, Simmons, Zachary, Cooper-Knock, Johnathan, Brice, Alexi, Goutman, Stephen A, Feldman, Eva L, Gibson, Summer B, Taroni, Franco, Ratti, Antonia, Gellera, Cinzia, Van Damme, Philip, Robberecht, Wim, Fratta, Pietro, Sabatelli, Mario, Lunetta, Christian, Ludolph, Albert C, Andersen, Peter M, Weishaupt, Jochen H, Camu, William, Trojanowski, John Q, Van Deerlin, Vivianna M, Brown, Robert H, van den Berg, Leonard H, Veldink, Jan H, Harms, Matthew B, Glass, Jonathan D, Stone, David J, Tienari, Pentti, Silani, Vincenzo, Chiò, Adriano, Shaw, Christopher E, Traynor, Bryan J, Landers, John E, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
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Male ,Als gene ,Genome-wide association study ,FAMILIAL ALS ,ALS ,axonal transport ,cargo ,GWAS ,KIF5A ,WES ,WGS ,0302 clinical medicine ,80 and over ,Psychology ,Aetiology ,Aged, 80 and over ,0303 health sciences ,French ALS Consortium ,Kinesin ,KINESIN HEAVY-CHAIN ,Cognitive Sciences ,Human ,Hereditary spastic paraplegia ,Neuroscience(all) ,Single-nucleotide polymorphism ,TARGETED DISRUPTION ,Article ,03 medical and health sciences ,Genetics ,Humans ,Amino Acid Sequence ,Loss function ,Aged ,HEXANUCLEOTIDE REPEAT ,Neuroscience (all) ,MUTATIONS ,Amyotrophic Lateral Sclerosis ,3112 Neurosciences ,1702 Cognitive Science ,medicine.disease ,ITALSGEN Consortium ,Answer ALS Foundation ,030104 developmental biology ,ALS Sequencing Consortium ,Human medicine ,1109 Neurosciences ,030217 neurology & neurosurgery ,0301 basic medicine ,[SDV]Life Sciences [q-bio] ,Kinesins ,Neurodegenerative ,Genetic analysis ,Genome ,AMYOTROPHIC-LATERAL-SCLEROSIS ,3124 Neurology and psychiatry ,Cohort Studies ,Pathogenesis ,Loss of Function Mutation ,Missense mutation ,2.1 Biological and endogenous factors ,Amyotrophic lateral sclerosis ,NYGC ALS Consortium ,General Neuroscience ,ALS, axonal transport, cargo, GWAS, KIF5A, WES, WGS ,Middle Aged ,Phenotype ,Settore MED/26 - NEUROLOGIA ,Neurological ,Project MinE ALS Sequencing Consortium ,Female ,Adult ,Biology ,GENOTYPE IMPUTATION ,Genome-Wide Association Study ,Young Adult ,NO ,Rare Diseases ,medicine ,SLAGEN Consortium ,Gene ,030304 developmental biology ,Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium ,Neurology & Neurosurgery ,Human Genome ,Neurosciences ,AXONAL-TRANSPORT ,Brain Disorders ,Family member ,DNA-DAMAGE ,MOTOR-NEURONS ,3111 Biomedicine ,Cohort Studie ,Genomic Translation for ALS Care (GTAC) Consortium ,Amyotrophic Lateral Sclerosi - Abstract
© 2018 Elsevier Inc., To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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- 2018
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15. Notch Receptor-Ligand Engagement Maintains Hematopoietic Stem Cell Quiescence and Niche Retention
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Yiwei Wang, Alex Yee-Chen Huang, Peter Qiao, Lan Zhou, Jeongsup Shim, Jay Myers, Grant Zimmerman, Dan Huang, John B. Lowe, David T. Scadden, Weihuan Wang, Vionnie W.C. Yu, Yuanshuai Huang, Pamela Stanley, William W. Xin, Wei Xin, Minhong Yan, Xiaoran Huang, Shuiliang Yu, and Christian W. Siebel
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Stromal cell ,Receptors, Notch ,Notch signaling pathway ,Wild type ,Hematopoietic stem cell ,Cell Biology ,Biology ,Hematopoietic Stem Cells ,Article ,Cell biology ,Mice ,Haematopoiesis ,medicine.anatomical_structure ,medicine ,Animals ,Humans ,Molecular Medicine ,Stem Cell Niche ,Stromal Cells ,Progenitor cell ,Stem cell ,Signal transduction ,Signal Transduction ,Developmental Biology - Abstract
Notch is long recognized as a signaling molecule important for stem cell self-renewal and fate determination. Here, we reveal a novel adhesive role of Notch-ligand engagement in hematopoietic stem and progenitor cells (HSPCs). Using mice with conditional loss of O-fucosylglycans on Notch EGF-like repeats important for the binding of Notch ligands, we report that HSPCs with faulty ligand binding ability display enhanced cycling accompanied by increased egress from the marrow, a phenotype mainly attributed to their reduced adhesion to Notch ligand-expressing stromal cells and osteoblastic cells and their altered occupation in osteoblastic niches. Adhesion to Notch ligand-bearing osteoblastic or stromal cells inhibits wild type but not O-fucosylglycan-deficient HSPC cycling, independent of RBP-JK-mediated canonical Notch signaling. Furthermore, Notch-ligand neutralizing antibodies induce RBP-JK-independent HSPC egress and enhanced HSPC mobilization. We, therefore, conclude that Notch receptor–ligand engagement controls HSPC quiescence and retention in the marrow niche that is dependent on O-fucosylglycans on Notch. Stem Cells 2015;33:2280–2293
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- 2015
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16. [Application of Chinese version of ACE-Ⅲ in type 2 diabetes mellitus patients with mild cognitive impairment]
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J W, Xin, X L, Xiao, X C, Chen, and X D, Pan
- Subjects
Diabetes Mellitus, Type 2 ,ROC Curve ,Humans ,Reproducibility of Results ,Cognitive Dysfunction ,Neuropsychological Tests ,Cognition Disorders - Published
- 2017
17. [The efficacy and safety of testa triticum tricum purif in treatment of functional constipation in the late middle-aged and elderly patients: a multicenter randomized controlled clinical trial]
- Author
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X C, Fang, J, Zhang, S, Liu, H W, Xin, J, Wang, Y, Ba, W J, Fan, S M, Han, Z F, Wang, X P, Xie, X, Liu, and L M, Zhu
- Subjects
Adult ,Aged, 80 and over ,Dietary Fiber ,Feces ,Treatment Outcome ,Double-Blind Method ,Humans ,Middle Aged ,Defecation ,Gastrointestinal Motility ,Constipation ,Triticum ,Aged - Published
- 2017
18. [Associations of sigmoid colon mucosal mast cells with bowel symptoms and psychological status in patients with irritable bowel syndrome with diarrhea]
- Author
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D, Xu, W, Chen, W X, Zhou, C D, Wang, G J, Fei, L M, Zhu, H W, Xin, D R, Zhong, G, Sun, and X C, Fang
- Subjects
Adult ,Diarrhea ,Psychiatric Status Rating Scales ,Depression ,Biopsy ,Comorbidity ,Anxiety ,Abdominal Pain ,Irritable Bowel Syndrome ,Colon, Sigmoid ,Surveys and Questionnaires ,Humans ,Mast Cells ,Intestinal Mucosa ,Stress, Psychological - Abstract
To investigate the bowel symptoms and psychological status of patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D), and to verify whether sigmoid colon mucosal mast cells (MCs) and their activation have effect on the symptoms and psychological status of IBS-D patients.Patients meeting Rome Ⅲ diagnostic and subtyping criteria of IBS-D who visited the outpatient clinic of gastroenterology of Peking Union Medical College Hospital were consecutively enrolled between July 2009 and June 2012. IBS symptoms questionnaire was completed using face-to-face interview, and Hamilton Anxiety Scale (HAMA)/ Hamilton Depression Scale (HAMD) were administrated to evaluate psychological status, both by well-trained investigators. Mast cell tryptase monoclonal antibody was used for immunohistochemical staining to detect MCs and degranulated MCs in mucosal biopsy of sigmoid colon. MCs and degranulated MCs were blindly counted by a senior pathologist, and presented as number of cells in high power field (HPF) and percentage of activated MCs. Correlation analysis was performed using Spearman rank correlation analysis.Ninety-seven patients with IBS-D were enrolled in this study, with mean age of (44±11) years. 70.10%(68 cases) of the IBS-D patients had comorbid anxiety and/or depression. The median total numbers of MCs, activated MCs, and percentage of activated MCs in sigmoid mucosa were 11.60 (7.09)/HPF, 2.00 (1.40) /HPF, and 17.50% (10.90%), respectively. Patients having abdominal pain/discomfort before bowel movement "every day with intermediate to high severity" had significantly larger numbers of total MCs in sigmoid colon compared with those with pain or discomfort "not every day and mild" [13.80(4.85)vs 7.60(5.90)/HPF, P=0.019]; the patient having "frequent" urge to have a bowel movement and mushy stools showed significantly higher percentage of activated MCs in sigmoid colon mucosa compared to those having the symptoms "some of the time" [18.75%(9.12%) vs 14.50%(13.14%), P=0.031; 21.33%(7.43%)vs 11.51%(10.65%)vs 18.42%(8.61%), P=0.030]. There was a positive correlation between the bowel movement during IBS-D onset and the percentage of activated MCs (r=0.221, P=0.030). There were no statistically significant differences in the total number of MCs and percentage of activated MCs between the patients with anxiety/depression and those without anxiety/depression (P=0.255, P=0.315). Scores of HAMA and HAMD were found not correlated with either total MCs number or percentage of activated MCs in sigmoid colon mucosa(all P0.05).The majority of IBS-D patients had comorbid anxiety and/or depression. The total number and activation status of MCs in sigmoid colon mucosa might be related with some intestinal symptoms in IBS-D patients. Psychological disorders might influence the pathogenesis and regression of IBS-D through brain-gut axis other than MCs in sigmoid colon mucosa.
- Published
- 2016
19. [Epidemiological study on the relationship between the siesta and blood pressure]
- Author
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Y M, Cao, D, Li, K B, Li, H, Yu, W, Xin, D J, Miao, and Y, An
- Subjects
China ,Epidemiologic Studies ,Logistic Models ,Risk Factors ,Incidence ,Rest ,Surveys and Questionnaires ,Hypertension ,Humans ,Blood Pressure ,Sleep - Abstract
Use epidemiological approaches to investigate the correlation between the siesta and blood pressure.From March 1(st,) 2011 to June 30(th) 2013, a total of 950 people were collected from East Jiaozhou Qingdao region using variable sampling methods including stratified method, the entire group method, random and proportional methods. Medical professionals conducted a person-to-person survey, collecting the data and inputting it into computers, after which a database was established using STATA 12.0. We analyzed the correlation between the siesta time and blood pressure/hypertension by using rank correlation method (Spearman). Logistic regression method was used to analyze the relationship between high blood pressure and different time and habit of the siesta after adjusting age, sex and BMI.There was a negative correlation between the time of siesta and the systolic pressure with r=-0.18, P0.001; there was no relationship between the time of siesta and the diastolic pressure with r=-0.07, P=0.02; also, there is a negative correlation between the time of siesta and the hypertension morbidity, with r=-0.22, P0.001. In the Logistic regression analysis about the period of time to take a nap and the risk of hypertension, it was found that the relative risk factors for hypertension were more than 60-year-old, BMI25 kg/m(2) and no siesta habits.The time of siesta is negatively correlated to the systolic pressure, rather than the diastolic pressure, and it can generally reduce the incidence of hypertension. The relative risk factors of hypertension are more than 60-year-old, BMI25 kg/m(2) and no siesta habits in all four seasons. We recommend that take a nap a day, or it might be even better for systolic blood pressure to take longer siesta.
- Published
- 2016
20. Adiponectin Gene Polymorphisms Are Associated With Posttransplantation Diabetes Mellitus in Chinese Renal Allograft Recipients
- Author
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Guangyao Li, A.-R. Yu, H.-W. Xin, X. Fan, X.-C. Wu, H.-M. Liu, and Y. Bai
- Subjects
Adult ,Male ,China ,medicine.medical_specialty ,Single-nucleotide polymorphism ,Type 2 diabetes ,Polymorphism, Single Nucleotide ,Diabetes Complications ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Transplantation ,Adiponectin ,business.industry ,Odds ratio ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Endocrinology ,Female ,Surgery ,Gene polymorphism ,business ,Body mass index - Abstract
Background Posttransplantation diabetes mellitus (PTDM) is a well-recognized renal transplantation complication that is associated with increased graft loss, morbidity, and mortality. Adiponectin gene polymorphisms are associated with type 2 diabetes. However, it remains unknown whether these polymorphisms increase the risk for development of PTDM. Therefore, the aim of this study was to investigate the association between the adiponectin gene polymorphism and the risk of PTDM among Chinese renal allograft recipients. Methods We genotyped 398 unrelated renal allograft recipients without a prior diagnosis of diabetes, including 97 PTDM and 301 without PTDM, for adiponectin gene variants: single nucleotide polymorphisms at position 45 and 276, that is, SNP-45: T/G, SNP-276: G/T, using the polymerase chain reaction-restriction fragment length polymorphism assay. No prisoners or organs from prisoners were used in the study. Results The G allele of SNP-276 was significantly more frequent in PTDM than non-PTDM subjects (P = .041). For SNP-45 and SNP-276, the incidence of PTDM was significantly higher in patients with the GG genotype than those with the TG and TT genotypes (48.1% vs 21.5% and 23.6% and 30.7% vs 18.5% and 22.8%; (P = .011 and .024, respectively). Even after adjusting for age and sex, the effects of the SNP-45 genotypes for GG compared to TT (odds ratio [OR] = 3.108, P = .009) and GG compared to TG (OR = 3.620, P = .004) as well as for SNP-276 genotypes GG compared to TG (OR = 2.203, P = .002) and body mass index at transplantation (OR = 1.099, P = .024) remained significant. Conclusions These data suggested that SNP-45 and SNP-276 of the adiponectin gene were significantly associated with an increased risk for PTDM among Chinese renal allograft recipients.
- Published
- 2011
- Full Text
- View/download PDF
21. Novel LIPA mutations in Mexican siblings with lysosomal acid lipase deficiency
- Author
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Aurea Vera-Loaiza, Kendrick Goss, María Teresa Gorráez-de la Mora, Raul E. Piña-Aguilar, Yuritzi Santillán-Hernández, Winnie W Xin, and Enory Almanza-Miranda
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Heterozygote ,Time Factors ,Biopsy ,DNA Mutational Analysis ,Case Report ,Lysosomal acid lipase deficiency ,Esophageal and Gastric Varices ,Internal medicine ,Hypertension, Portal ,medicine ,Humans ,Genetic Predisposition to Disease ,Sibling ,Ultrasonography, Doppler, Color ,Child ,Mexico ,medicine.diagnostic_test ,business.industry ,Siblings ,Fatty liver ,Gastroenterology ,Wolman Disease ,Infant ,General Medicine ,Exons ,Sterol Esterase ,medicine.disease ,Immunohistochemistry ,Pedigree ,Fatty Liver ,Diarrhea ,Endocrinology ,Phenotype ,Child, Preschool ,Mutation ,Disease Progression ,Elevated transaminases ,Female ,Esophagoscopy ,medicine.symptom ,business ,Dyslipidemia ,Lipoprotein ,Hepatomegaly - Abstract
Lysosomal acid lipase (LAL) deficiency is an under-recognized lysosomal disease caused by deficient enzymatic activity of LAL. In this report we describe two affected female Mexican siblings with early hepatic complications. At two months of age, the first sibling presented with alternating episodes of diarrhea and constipation, and later with hepatomegaly, elevated transaminases, high levels of total and low-density lipoprotein cholesterol, and low levels of high-density lipoprotein. Portal hypertension and grade 2 esophageal varices were detected at four years of age. The second sibling presented with hepatomegaly, elevated transaminases and mildly elevated low-density lipoprotein and low high-density lipoprotein at six months of age. LAL activity was deficient in both patients. Sequencing of LIPA revealed two previously unreported heterozygous mutations in exon 4: c.253C>A and c.294C>G. These cases highlight the clinical continuum between the so-called Wolman disease and cholesteryl ester storage disease, and underscore that LAL deficiency represents a single disease with a degree of clinical heterogeneity.
- Published
- 2015
22. Differentiation potential of an immortalized non-tumorigenic human liver epithelial cell line as liver progenitor cells
- Author
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W. Xin, T. Yamazaki, T. Tsukiyama, Masayuki Noguchi, N. Sugae, T. Tokiwa, and S. Enosawa
- Subjects
Cellular differentiation ,Cell ,Cell Culture Techniques ,Gene Expression ,Mice, SCID ,Biology ,Stem cell marker ,Cell Line ,Mice ,Cytochrome P-450 Enzyme System ,medicine ,Animals ,Cytochrome P-450 CYP3A ,Humans ,Progenitor cell ,Matrigel ,Stem Cells ,Cell Differentiation ,Epithelial Cells ,Cell Biology ,General Medicine ,Immunohistochemistry ,Epithelium ,Cell biology ,medicine.anatomical_structure ,Liver ,Cell culture ,Stem cell - Abstract
We report the differentiation potential of an immortalized non-tumorigenic human liver epithelial cell line, THLE-5b. Under basic culture conditions THLE-5b showed undifferentiated phenotypes. When grown as cell aggregates, THLE-5b exhibited a hepatocyte-like ultrastructure, ammonia metabolic activity and several other indicators that suggest hepatocytic maturation, including up-regulation or induction of liver-specific genes such as albumin and tryptophane 2,3-dioxygenase, and down-regulation of biliary cell markers such as gamma-glutamyl transpeptidase (GGT). Under these conditions, transcriptional factors such as HNF-1 and HNF-4alpha were also up-regulated or induced. In Matrigel culture, expression of GGT was up-regulated. THLE-5b expressed both albumin and alpha 1-antitrypsin, but lost expression of CK19 in severe combined immunodeficient mice. Thus, THLE-5b can be aligned with progenitor cells, which are committed to the hepatocytic or biliary epithelial cell lineage. These results imply that bipotent progenitor cell populations similar to THLE-5b cells may exist in adult human liver.
- Published
- 2006
- Full Text
- View/download PDF
23. Cost-effectiveness analysis of fulvestrant versus anastrozole as first-line treatment for hormone receptor-positive advanced breast cancer
- Author
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P. Huang, W. Xin, H. Ding, Y. Tong, Q. Zhou, and L. Fang
- Subjects
Oncology ,China ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,Cost-Benefit Analysis ,Advanced breast ,Anastrozole ,Breast Neoplasms ,Drug Costs ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Nitriles ,Humans ,Medicine ,030212 general & internal medicine ,Fulvestrant ,health care economics and organizations ,Gynecology ,Estradiol ,business.industry ,Cancer ,Cost-effectiveness analysis ,Triazoles ,medicine.disease ,Markov Chains ,First line treatment ,Receptors, Estrogen ,Hormone receptor ,030220 oncology & carcinogenesis ,Cohort ,Female ,Quality-Adjusted Life Years ,Receptors, Progesterone ,business ,medicine.drug - Abstract
Although recent studies demonstrated that fulvestrant is superior to anastrozole as first-line treatment for hormone receptor (HR)-positive advanced breast cancer, the cost-effectiveness of fulvestrant versus anastrozole remained uncertain. Thus, the current study aimed to evaluate the cost-effectiveness of fulvestrant compared with anastrozole in the first-line setting. A Markov model consisting of three health states (stable, progressive and dead) was constructed to simulate a hypothetical cohort of patients with HR-positive advanced breast cancer. Costs were calculated from a Chinese societal perspective. Health outcomes were measured in quality-adjusted life-year (QALY). The incremental cost-effectiveness ratio (ICER) was expressed as incremental cost per QALY gained. Model results suggested that fulvestrant provides an additional effectiveness gain of 0.11 QALYs at an incremental cost of $32,654 compared with anastrozole, resulting in an ICER of $296,855/QALY exceeding the willingness-to-pay threshold of $23,700/QALY. Hence, fulvestrant is not a cost-effective strategy compared with anastrozole as first-line treatment for HR-positive advanced breast cancer.
- Published
- 2017
- Full Text
- View/download PDF
24. Treatment of traumatically cutaneous necrosis of buttocks using vacuum sealing drainage combined with ileostomy
- Author
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W Xin, L Juan, and S Hao
- Subjects
Adult ,Male ,medicine.medical_specialty ,Soft Tissue Injuries ,medicine.medical_treatment ,Thigh ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,Ileostomy ,Fractures, Bone ,Necrosis ,Young Adult ,0302 clinical medicine ,Negative-pressure wound therapy ,medicine ,Humans ,Orthopedics and Sports Medicine ,030212 general & internal medicine ,Buttocks ,Pelvic Bones ,Skin ,Wound Healing ,Debridement ,Lumbar Vertebrae ,integumentary system ,business.industry ,Multiple Trauma ,Granulation tissue ,Skin Transplantation ,Middle Aged ,Anus ,Bandages ,Surgery ,body regions ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Emergency Medicine ,Granulation Tissue ,Defecation ,Drainage ,Spinal Fractures ,Female ,business ,Negative-Pressure Wound Therapy - Abstract
The purpose of this study is to evaluate the surgical technique and review the therapeutic effect of vacuum sealing drainage combined with ileostomy treating patients of traumatically buttock skin necrosis. 26 patients with buttock wounds were dressed and 6–12 days later, buttock skin necrosis boundaries were clear and debridement was performed. General surgeons were invited to perform the ileostomy. Thorough debridement was conducted and vacuum sealing drainage (VSD) devices were used to cover buttock wounds. Debridement and VSD were operated every 5–7 days until the granulation tissue of buttock wound was fresh. Then epidermal skin graft from thigh was performed to cover the granulation wound. About 3 months later after skin graft survival completely, the ileum was reversed by general surgeons and the patients recovered defecation using anus. The granulation tissues of all patients were fresh after debridement and VSD 2–3 times. In 20 cases, transplanted epidermal skin grew well. In six cases, necrosis was observed at the margins of the flap and further debridement and skin graft were conducted. During the follow-up period of approximate 6 months, the flaps grew well and the patients defecated normally from anus. Treating traumatically cutaneous necrosis of buttocks with vacuum sealing drainage and ileostomy can gain good therapeutic effect.
- Published
- 2014
25. Genetic imbalance and human papillomavirus states in vulvar squamous cell carcinomas
- Author
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O, Yangling, Z, Shulang, C, Rongli, L, Bo, C, Lili, and W, Xin
- Subjects
Base Sequence ,Vulvar Neoplasms ,Karyotyping ,Carcinoma, Squamous Cell ,Humans ,Nucleic Acid Hybridization ,Female ,Papillomaviridae ,Genomic Instability ,DNA Primers - Abstract
Vulvar squamous cell carcinoma (VSCC) is a disease of significant clinical importance, which arises in the presence or absence of human papillomavirus (HPV).We used comparative genomic hybridization (CGH) to document non-random chromosomal gains and losses with HPV positive and negative VSCCs.Gains of 3q and 12q were significantly more common in HPV-positive cancers compared to HPV-negative cancers where chromosome 8q was more commonly gained in HPV-negative compared to HPV-positive cancer chromosomes and, 4p and 3p were lost in both categories of VSCCs.The data indicate that one or more oncogenes important in the development and progression of HPV-induced carcinomas are located on 3q and 12q.
- Published
- 2008
26. A comparative study of Phyllanthus amarus compound and interferon in the treatment of chronic viral hepatitis B
- Author
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W, Xin-Hua, L, Chang-Qing, G, Xing-Bo, and F, Lin-Chun
- Subjects
Adult ,Male ,Phyllanthus ,Hepatitis B, Chronic ,Adolescent ,Liver Function Tests ,Humans ,Interferon-alpha ,Female ,Plant Preparations ,Middle Aged ,Phytotherapy - Abstract
Fifty-five patients with chronic viral hepatitis B were randomly divided into two groups. Thirty patients were treated with Phyllanthus amarus compound (PA Co) for three months in the treatment group, another 25 patients were treated with domestic recombinant human interferon alpha-1b (IFN-alpha 1b) for three months as controls. The total effective rate in the treatment group was 83.3%, showing no significant difference from the control (p0.05). The normalization rates of ALT, A/G and SB in the treatment group were 73.3%, 80.0% and 78.2% respectively, which were significantly higher than that in the control (p0.05). The negative conversion rates of HBeAg and HBV-DNA in the treatment group were 42.3% and 47.8%, showing no significant difference from the control (p0.005). It is indicated that PA Co has remarkable effect for chronic viral hepatitis B in recovery of liver function and inhibition of the replication of HBV.
- Published
- 2001
27. Free radical scavenging by green tea polyphenols
- Author
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B, Zhao, Q, Guo, and W, Xin
- Subjects
Flavonoids ,Tea ,Neutrophils ,Polymers ,Lipoxygenase ,Electron Spin Resonance Spectroscopy ,Polyphenols ,Free Radical Scavengers ,Hydrogen Peroxide ,Catalysis ,Neutrophil Activation ,Phenols ,Humans ,Tetradecanoylphorbol Acetate ,Lipid Peroxidation ,Synaptosomes - Published
- 2001
28. [Close injury of the tendon at wrist]
- Author
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L, Lu, Q, Li, and W, Xin
- Subjects
Adult ,Male ,Rupture ,Adolescent ,Colles' Fracture ,Middle Aged ,Plastic Surgery Procedures ,Wounds, Nonpenetrating ,Wrist Injuries ,Tendons ,Tendon Injuries ,Humans ,Female ,Aged ,Follow-Up Studies - Abstract
Because of the complicated causes and variable clinical signs, closed injury of tendons at wrist is difficult to diagnosis and treat. Twenty-six cases of tendon ruptur were reported. Among them, 11 cases were caused by bone fracture or dislocation, 8 cases were caused by rheumatoid synovitis, 5 cases were caused by synovial tuberculosis, and 2 cases caused by other. The pathogenesis and clinical signs were analyzed. Twenty-three cases were treated by tendon transfer and 3 cases were treated by tendon transplantation. By average follow-up of 16 months (ranged 6 months to 4 years), the results were as follows: the clip strength and both active and positive motion of fingers were restored in 19 caese, 75% of those were restored in 7 cases and 50% of those were restored in 2 cases. It was suggested that diagnosis, treatment and function rehabilitation should be carried out early, and tendon transfer or tendon transplatation were the method on priority.
- Published
- 1998
29. 37 patients with hepatic hydatid cyst rupturing into choledochus
- Author
-
X, Wu, W, Xin, and S Y, Zhao
- Subjects
Adult ,Common Bile Duct ,Male ,Echinococcosis, Hepatic ,Adolescent ,Rupture, Spontaneous ,Humans ,Female ,Middle Aged ,Child ,Aged - Abstract
2785 patients with hepatic hydatid cyst were treated operatively since 1965 to 1995, and the hydatid cyst rupturing into choledachus occurred in 37 patients (1.3%). Clinical manifestations, diagnosis and operation were described. In epidemic area the possibility of hepatic hydatic cyst rupturing into choledochus should be considered when the patient suffers from stiffness of abdominal muscles, Jaundice, right epigastric pain, hepatic mass and positive reaction of Casoni test. Ultrasound and CT are major means for the diagnosis of this disease. Early operation is the treatment of choice.
- Published
- 1997
30. Interaction between fulvic acids of different origins and active oxygen radicals
- Author
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C, Wang, Z, Wang, A, Peng, J, Hou, and W, Xin
- Subjects
Oxygen ,Selenium ,Free Radicals ,Hydroxyl Radical ,Neutrophils ,Humans ,Benzopyrans ,Free Radical Scavengers ,Spin Trapping ,Respiratory Burst - Abstract
Using the spin trapping technique, the interaction between fulvic acids (FAs) of different origins and the active oxygen radicals was studied. The active oxygen radicals under study included superoxide anion (O2.-) produced by xanthine oxidase (XOD) and stimulated polymorphonuclear leukocytes (PMN) of human being and hydroxyl radical (.OH) produced from Fenton's reaction. It has been found that the FAs from both Kaschin-Beck disease (KBD) region and non-KBD region can accelerate the production of .OH and scavenge O2.-. FA from peat can scavenge both O2.- and .OH. The results show that the behavior of KBD and non-KBD FAs differs clearly from peat FA. It has been concluded that the superoxidation damage of KBD induced by FA is mainly due to hydroxyl radical reaction initiated in biological system.
- Published
- 1996
31. Scavenging effects of baicalin on free radicals and its protection on erythrocyte membrane from free radical injury
- Author
-
H, Shi, B, Zhao, and W, Xin
- Subjects
Anions ,Flavonoids ,Binding Sites ,Free Radicals ,Hydroxyl Radical ,Protein Conformation ,Iron ,Erythrocyte Membrane ,Membrane Proteins ,Free Radical Scavengers ,Hydrogen Peroxide ,Antiviral Agents ,Hemolysis ,Kinetics ,Anti-Infective Agents ,Superoxides ,Reperfusion Injury ,Humans ,Sulfhydryl Compounds ,Drugs, Chinese Herbal - Abstract
Using electron spin resonance (ESR) spin trapping technique, we found that baicalin (B) could scavenge hydroxyl radicals generated from Fenton reaction. It also could scavenge superoxide radicals generated from the reaction system containing xanthine (X) and xanthine oxidase (XO), as was found by using chemiluminescence (CL) method. Kinetic studies on the competition between baicalin and a spin trap 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) in trapping OH showed that baicalin had a kinetic reactive rate constant of the order of 7.7 x 10(11) M-1 s-1 in its reaction with OH, and the studies on the competition between baicalin and ferricytochrome c (f.c.) in trapping O2- gave a kinetic reactive rate constant of 3.2 x 10(6) M-1 s-1 for baicalin in its reaction with O2-. Furthermore, we have investigated the protective effects of baicalin on erythrocyte membranes from hydroxyl free radical injuries. The results showed that baicalin could reduce hydrogen peroxide-induced hemolysis, protect the conformation of sulfhydryl groups (-SH) on membrane proteins and the membrane fluidity of erythrocytes incubated with hydrogen peroxide. The results indicated that baicalin could protect the membranes of erythrocytes from free radical injuries, and it was even more effective than alpha-tocopherol.
- Published
- 1995
32. Electron spin resonance determination and superoxide dismutase activity in polymorphonuclear leukocytes in congestive heart failure
- Author
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L, Chen, Y, Zang, B, Bai, M, Zhu, B, Zhao, J, Hou, and W, Xin
- Subjects
Adult ,Heart Failure ,Male ,Free Radicals ,Neutrophils ,Superoxide Dismutase ,Electron Spin Resonance Spectroscopy ,Humans ,Female ,Thiobarbituric Acid Reactive Substances ,Respiratory Burst - Abstract
Electron spin resonance spin trapping technique was used to measure the generation of active oxygen free radicals during the respiratory burst of phorbol myristate acetate-stimulated leukocytes, and the superoxide dismutase activity in healthy subjects and in patients with congestive heart failure. The authors also measured the concentration of peroxidation products (primarily malondialdehyde) by the thiobarbituric acid method. Experimental results showed that the electron spin resonance spectra obtained during the respiratory burst of polymorphonuclear leukocytes stimulated with phorbol myristate acetate primarily were those of the spin adduct of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) with the superoxide anion and to a lesser extent those of DMPO with hydroxyl radical. Compared with healthy subjects, the release of oxygen free radicals in the respiratory burst of polymorphonuclear leukocytes stimulated with phorbol myristate acetate and the concentration of thiobarbituric acid reactive product in plasma were significantly increased in patients with congestive heart failure while the activity of superoxide dismutase was markedly lower. The increased production of oxygen free radicals by polymorphonuclear leukocytes and the decreased capability of antioxidative defences might play an important role in the generation and development of cardiac failure.
- Published
- 1992
33. PGM1 subtype distribution in Chinese population of the Guangzhou area
- Author
-
W, Xin-Yao and K, Jing-Yuan
- Subjects
China ,Phenotype ,Gene Frequency ,Phosphoglucomutase ,Humans ,Alleles - Abstract
PGM1 subtypes of 275 Chinese living in the Guangzhou area were determined using isoelectric focusing. The allele frequencies of PGM1 were 1+ = 0.6036, 1- = 0.1018, 2+ = 0.2200, and 2- = 0.0673. A rare variant, named PGM1*8, was found with a gene frequency of 0.0073. The phenotype distribution was consistent with Hardy-Weinberg equilibrium.
- Published
- 1988
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