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sTING regulates BcR signaling in normal and malignant B cells

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cellular & Molecular Immunology 2021年第4期18卷 1016-1031页

作者： chih-Hang Anthony Tang Avery c.Lee shiun chang Qin Xu Andong shao Yun lo Walker T.spalek Javier A.Pinilla-lbarz Juan R.Del Valle chih-chi Andrew Hu The Wistar Institute 3601 Spruce StreetPhiladelphiaPA 19104USA Department of malignant Hematology H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Department of chemistry&Biochemistry University of Notre DameNotre DameIN 46556USA

sTING is an endoplasmic reticulum(ER)-resident protein critical for sensing cytoplasmic DNA and promoting the production of type Ⅰ interferons;however,the role of sTING in B cell receptor(BcR)signaling remains *** generated sTING V154M knock-in mice and showed that B cells carrying constitutively activated sTING specifically degraded membrane-bound IgM,Ig a and Igβ via sEL1L/HRD1-mediated ER-associated degradation(ERAD).B cells with activated sTING were thus less capable of responding to BcR activation by phosphorylating Igα and syk than those without activated *** immunized with T-independent antigens,sTING V154M mice produced significantly fewer antigen-specific plasma cells and antibodies than immunized wild-type(WT)*** further generated B cell-specific sTING^(KO) mice and showed that sTING^(KO) B cells indeed responded to activation by transducing stronger BcR signals than their sTING-proficient *** B cell-specific sTING^(KO) mice were T-independently immunized,they produced significantly more antigen-specific plasma cells and antibodies than immunized sTIN^(WT)*** both human and m ouse IGHV-unmutated malignant chronic lymphocytic leukemia(cLL)cells downregulated the expression of sTING,we explored whether sTING downregulation could contribute to the well-established robust BcR signaling phenotype in malignant cLL *** generated a sTING-deficient cLL mouse model and showed that sTING-deficient cLL cells were indeed more responsive to BcR activation than their sTING-proficient *** results revealed a novel B cell-intrinsic role of sTING in negatively regulating BcR signaling in both normal and malignant B cells.

关键词： sTING BcR ER-associated degradation cLL Plasma cells

Acute pancreatitis induced by transarterial chemoembolization:a single-center experience of over 1500 cases

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Hepatobiliary & pancreatic Diseases International 2016年第1期15卷 93-98页

作者： Wong Hoi she Albert cY chan Tan To cheung Kenneth sH chok see ching chan Ronnie TP Poon chung mau lo Division of Hepatobiliary & pancreatic surgery and Liver Transplantation Department of SurgeryThe University of Hong Kong

BAcKGROUND： Acute pancreatitis is a relatively rare but po- tentially lethal complication after transarterial chemotherapy. This study aimed to review the complications such as acute pancreatitis after transarterial chemotherapy with or without embolization for hepatocellular carcinoma. METHODs： A total of 1632 patients with hepatocellular car- cinoma who had undergone transarterial chemoembolization from ]anuary 2000 to February 2014 in a single-center were reviewed retrospectively. We investigated the potential com- plications of transarterial chemoembolization, such as acute pancreatitis and acute pancreatitis-related complications. REsULTs： Of the 1632 patients with hepatocellular carcinoma who had undergone 5434 transarterial chemoembolizations, 1328 were male and 304 female. The median age of these pa- tients was 61 years. Most （79.6%） of the patients suffered from HBV-related hepatoceUular carcinoma. The median tumor size was 5.2 cm. Of the 1632 patients, 145 patients underwent transarterial chemoembolization with doxorubicin elut- ing bead, making up a total of 538 episodes. The remaining patients underwent transarterial chemoembolization with cisplatin. seven （0.4%） patients suffered from acute pancre- atitis post-chemoembolization. six patients had chemoembo- lization with doxorubicin and one had chemoembolization with cisplatin. patients who received doxornbicin eluting bead had a higher risk of acute pancreatitis [6/145 （4.1%） vs 1/1487 （0.1%）, P〈0.0001]. Two patients had anatomical arterial variations. Four patients developed acute pancreatitis- related complications including necrotizing pancreatitis （n=3） and pseudocyst formation （n=1）. All of the 4 patients resolved after the use of antibiotics and other conservative treatment. Three patients had further transarterial chemoembolization without any complication. cONcLUsIONs： Acute pancreatitis after transarterial chemo- embolization could result in serious complications, especially after treatment wit

关键词： transarterial chemoembolization acute pancreatitis hepatocellular carcinoma

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胫骨骨髓炎骨缺损骨搬移软组织并发症的处理

中国矫形外科杂志 2024年第18期32卷 1703-1707页

作者：范丛亮马海龙窦浚峰张景义海雯海国栋郑州市骨科医院骨病骨肿瘤科河南郑州450000 谢菲尔德大学英国谢菲尔德S102TN

[目的]介绍胫骨骨髓炎骨缺损骨搬移软组织并发症的处理的手术技术和初步临床结果。[方法]2017年1月—2022年12月笔者采用骨搬移治疗54例胫骨慢性骨髓炎骨缺损。对会合端周围皮肤感染或坏死,分别采用局部清创植皮或皮瓣移植修复,或清创... 详细信息

[目的]介绍胫骨骨髓炎骨缺损骨搬移软组织并发症的处理的手术技术和初步临床结果。[方法]2017年1月—2022年12月笔者采用骨搬移治疗54例胫骨慢性骨髓炎骨缺损。对会合端周围皮肤感染或坏死,分别采用局部清创植皮或皮瓣移植修复,或清创并皮肤牵张器牵张。对会合端软组织嵌顿采用局部软组织松解。会合端软组织嵌顿合并骨不愈合,行会合端清理植骨,更换锁定板外固定。晚期再次软组织缺损并骨外露,给予局部清创皮肤牵张。[结果]54例患者骨搬运长度3~14cm,外固定指数为1.2~2.5个月/cm。30例患者会合端顺利愈合,无软组织并发症,其余24例出现会合端周围软组织相关并发症,占44.4%。经上述方法给予相应处理后,局部软组织并发症均有效解决。[结论]胫骨骨髓炎骨缺损应用Ilizarov骨搬移早期软组织再次感染、单纯软组织嵌顿、软组织嵌顿伴对合端骨不愈合、晚期再次软组织缺损并骨外露等并发症发生率较高。虽然最终均可通过后期的治疗解决相关并发症,但是明显延长治疗过程,增加患者负担,应引起骨科医生的高度重视。

关键词：骨搬运胫骨慢性骨髓炎会合端并发症 Ilizarov技术

clinical significance of NOD2/cARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease

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World Journal of Gastroenterology 2008年第28期14卷 4454-4461页

作者： Luciana Rigoli claudio Romano Rosario Alberto caruso maria A lo Presti chiara Di Bella Vincenzo Procopio Giuseppina lo Giudice maria Amorini Giuseppe costantino maria D sergi caterina cuppari Giovanna Elisa calabrò Romina Gallizzi carmelo Damiano salpietro Walter Fries Dipartimento di scienze Pediatriche Mediche e chirurgiche Università di MessinaMessina 98125Italy Dipartimento di patologia Umana Università di MessinaMessina 98125Italy Dipartimento di Medicina Interna e Terapia Medica Università di MessinaMessina 98125Italy

AIM： To evaluate the role of genetic factors in the pathogenesis of crohn＇s disease （cD） and ulcerative colitis （Uc）, we investigated the single nucleotide polymorphisms （sNPs） of NOD2/cARD15 （R702W, Gg08R and L1007finsc）, and Toll-like receptor 4 （TLR4） genes （D299G and T399I） in a selected inflammatory bowel disease （IBD） population coming from southern Italy. METHODs： Allele and genotype frequencies of NOD2/ cARD15 （R702W, Gg08R and L1007finsc） and TLR4 （D299G and T399I） sNPs were examined in 133 cD patients, in 45 Uc patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. REsULTs： NOD2/cARD15 R702W mutation was significantly more frequent in cD （9.8%） than in controls （2.4%, P = 0.001） and in Uc （2.3%, P = 0.03）. No significant difference was found between Uc patients and control group （P 〉 0.05）. In cD and Uc patients, no significant association with G908R variant was found. L1007finsc sNP showed an association with cD （9.8%） compared with controls （2.9%, P = 0.002） and Uc patients （2.3%, P = 0.01）. Moreover, in cD patients, G908R and L1007finsc mutations were significantly associated with different phenotypes compared to cD wild-type patients. No association of IBD with the TLR4 sNPs was found in either cohort （allele frequencies： D299G-controls 3.9%, cD 3.7%, Uc 3.4%, P 〉 0.05; T399I-controls 2.9%, cD 3.0%, Uc 3.4%, P 〉 0.05）. cONcLUsION： These findings confirm that, in our IBD patients selected from southern Italy, the NOD2/ cARD15, but not TLR4 sNPs, are associated with increased risk of cD.

关键词： crohn's disease Ulcerative colitis NOD2/ cARD15 gene Toll-like receptor 4 gene single nucleotide polymorphisms

Incidence,predictors and treatment strategies of inadequate defibrillation safety margin of implantable cardioverter defibrillator or cardiac resynchronization therapy defibrillator

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Incidence,predictors and treatment strategies of inadequate ...

中华医学会第11次心血管病学术会议

作者：程中伟 Ronald lo Anurag Gupta paul c Zei Henry H Hsia Amin Al-Almad paul J Wang 北京协和医院 stanford University Medical center

Objective The purpose of this study is to ascertain the incIdence and predictors of inadequate DsM and the treatment strategies for inadequate DsM in IcD or cRTD *** consecutive IcD or cRTD recIpients from Jan 2006 to may 2008 who underwent DsM test at the time of implantation were *** DsM patients were defined as patients who had a DsM within 10 Joules of the maximum delivered energy of the device and compared to patients who had adequate *** 243 pa-

关键词：

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城市污水厂污泥快速高效堆肥技术研究

农业环境科学学报 2005年第2期24卷 380-383页

作者：李宇庆陈玲赵建夫许民 c.paullo 同济大学污染控制与资源化研究国家重点实验室上海200092 school of Public Healthand Tropical Medicine Department of Environmental Health sciences Tulane University New OrleansLA

采用好氧发酵仓式堆肥系统,研究了城市污泥处理过程中温度、含水率、pH、有机质、水溶性有机碳和发芽指数等指标参数的变化规律。结果表明,当物料初始含水率控制在60%左右时,在强制通风量为300L·m in-1,搅拌频率为5m in·8h-1～5m in·... 详细信息

采用好氧发酵仓式堆肥系统,研究了城市污泥处理过程中温度、含水率、pH、有机质、水溶性有机碳和发芽指数等指标参数的变化规律。结果表明,当物料初始含水率控制在60%左右时,在强制通风量为300L·m in-1,搅拌频率为5m in·8h-1～5m in·12h-1的工艺条件下,堆肥过程可以实现顺利升温并在55℃以上维持4d,满足杀灭致病菌要求的条件;14d反应周期结束时,物料含水率、水溶性有机碳和有机质含量显著降低,堆肥产品腐熟,卫生学指标达到了美国E pa污泥产品A类标准;得到的污泥产品成为性质优良的土壤质量调节剂。

关键词：污泥堆肥调理剂强制通风

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上海经济适用房与商品房关联性研究

上海经济研究 2018年第12期30卷 66-80页

作者：罗佳朱赋斌上海财经大学金融学院 200433 上海海事大学经济管理学院 201306

本文利用2013至2018年上海市共计964个住宅小区的面板数据,应用双向固定效应模型与倍差法(DID)实证检验经济适用房和商品房市场之间的关联性。以商品房住宅小区到最近的经适房小区的直径距离为核心解释变量,并选取了小区所属区域、周边... 详细信息

本文利用2013至2018年上海市共计964个住宅小区的面板数据,应用双向固定效应模型与倍差法(DID)实证检验经济适用房和商品房市场之间的关联性。以商品房住宅小区到最近的经适房小区的直径距离为核心解释变量,并选取了小区所属区域、周边地铁情况、小区绿化率与容积率等因素,将住宅小区进行分组。实证结果显示,经适房周边的商品房房价显著低于非周边的。商品房房价:离经适房0.5公里内的商品房房价较3.5公里之外的商品房房价低8.6%,并且这种效应呈现出“波纹效应”,即经适房对其周边商品房房价的负向影响随着远离中心而减弱。此外,本文以首批经适房产权满五年期的时间(2017年)为转折点,考察“经转商”政策的影响,当经适房获准进入二手房市场后,并未对周边商品房市场产生显著性影响,即二手房市场的房价无显著波动。结果表明,通过制定合理的经适房政策,可以有效地缓解其对商品房市场的短期冲击,并推动住房市场的长期发展。

关键词：经济适用房商品房市场房地产价格固定效应模型倍差法

Bacteroides fragilis supernatant Extracts Enriched in Phenylacetic Acid Induce a cytotoxic Effect in mammalian cells

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Advances in Microbiology 2015年第10期5卷 730-736页

作者： Laís s.Falcao Eduardo N.F.Antunes Eliane O.Ferreira Heidi pauer maria Teresa V.Romanos Rossiane c.Vommaro sérgio H.seabra Daniela s.Alviano celuta s.Alviano Antonio Jorge R.da silva Leandro A.lobo Regina maria c.P.Domingues Departamento de ciências Básicas Pólo Universitário de Nova FriburgoUniversidade Federal FluminenseNova FriburgoBrasil Instituto de Microbiologia Prof.pa.lo de Góes Universidade Federal do Rio de JaneiroRio de JaneiroBrasil Instituto de Biofísica carlos chagas Filho Universidade Federal do Rio de JaneiroRio de JaneiroBrasil centro Universitário Estadual da Zona Oeste—UEZO Rio de JaneiroBrasil Instituto de Pesquisa Produtos Naturais Universidade Federal do Rio de JaneiroRio de JaneiroBrasil

Bacteroides species are nearly half of the fecal flora community and some are host symbionts crucial to host nutrition and systemic immunity. Among Bacteroides species B. fragilis strains are considered to be the opportunistic ones, being the most isolated anaerobic bacteria in clinical samples. cell-free supernatants of 65 B. fragilis strains were assayed and they were capable of inducing vacuolating phenotype on Vero cells lineage. The supernatant of the Bacteroides fragilis ATcc 23745 strain was elicited to have the strongest vacuolating effect on Vero cells monolayers and peritoneal macrophages. some drastic cell alterations were observed, such as a general disorganization of cytoplasm and chromatin condensation, evidencing cell death. By transmission electron microscopy it was confirmed that the vacuoles observed were, in fact, swollen mitochondria. An immunocytochemical assay, TUNEL, was used to confirm this hypothesis and showed that Vero cells and peritoneal macrophages were dying by apoptotic process after exposition of B. fragilis cell-free supernatant. Physical analysis of the apoptotic factor has revealed properties similar to short-chain fatty acids. After gas chromatography and mass spectrometry analysis, phenylacetic acid (pa) was characterized as the major compound present in the most purified active fraction. We believe that the pa is responsible for the pro-apoptotic effect elicited by the supernatant of B. fragilis cultures.

关键词： Bacteroides fragilis Vacuolization Apoptosis Vero cells Lineage Peritoneal macrophages Phenylacetic Acid

Initial Analysis of Lipid Metabolomic Profile Reveals Differential Expression Features in Myeloid malignancies

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Journal of cancer Therapy 2015年第15期6卷 1262-1272页

作者： Adriana Ramos de Oliveira Ismael Dale cotrim Guerreiro Da silva Edson G. lo Turco Helio Alves martins Júnior maria de lourdes L. Ferrari chauffaille chauffaille Department of clinical and Experimental Oncology Federal University of Sao Paulo Sao Paulo Brazil Gynecologic Department Federal University of Sao Paulo Sao Paulo Brazil

The purpose of this preliminary study was to determine the comparative lipid profile of blood plasma samples of healthy individuals and patients with Myeloproliferative Neoplasms. Methods: Untargeted shotgun Ms/Ms Analysis was performed to evaluate plasma samples from 153 participants, being 90 of the control Group, 43 Myeloproliferative Neoplasms (MPN), 11 Myelodysplastic syndromes (MDs) and 9 Acute Myeloid Leukemias (AML). Lipids were extracted from plasma using the Bligh-Dyer protocol. Data were acquired using the AB-sciex Analyst TF, processed using the AB-sciex LipidViewTM and the web-based analytical pipeline MetaboAnalyst 2.0 (***). Results: Untargeted analysis identified in negative and positive-modes a total of 658 features at 2 ppm resolution. PcA and PLs-DA analysis revealed clear discrimination among groups, in particular for AML patients. main lipid groups differentially expressed were: Monoacylglycerols (maG), Glucosylceramide E (GlcdE), Ethyl Esters (EE), Lysophosphatidic acid (Lpa), sulfoquinovosil diacylglycerols (sQDG), Monoglycerols (MG), Methyl Ethanolamines (ME), Lysophosphatidylcholines (LPc), Dimethyl Phosfatidyletanolamines (DMPE), Monometylphosphatidiletanolamines (MMPE), ceramide-1-phosphate (cerP), Glicerophosphoglycerols (GP), Lysomonomethyl-Phosphatidylethanolamines (LMMPE), Phosphatidic Acids (pa), Ergosterols (ERG), Glycerophosphoserine (Ps), Diacylglycerols (DAG), Hexocylceramides (Hexcer) and Lanosterol (Lan). ROc curve Analysis revealed Total LMMPE as the strongest discriminating marker between controls from patients. In addition, these lipids were also able to differentiate MDs and AML from NPM. conclusions: The Myeloproliferative Neoplasms from the point of view of global plasma lipidomics are accompanied by several modifications. In particular, the Lysomonomethyl-Phosphatidylethanolamines (LMMPE) seems to play important differentiating roles among them.

关键词： Lipids Lipidomics Myeloproliferative Neoplasms mass spectrometry