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Polymorphism AGT2(rs4762)is involved in the development of dermatologic events:Proof-of-concept in hepatocellular carcinoma patients treated with sorafenib

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World Journal of Hepatology 2022年第7期14卷 1438-1458页

作者： Víctor Sapena Massimo Iavarone loreto Boix Floriana Facchetti Maria Guarino Marco Sanduzzi Zamparelli Alessandro Granito Esther Samper Mario Scartozzi Josep Corominas Giorgia Marisi Alba Díaz Andrea Casadei-Gardini Laura Gramantieri Pietro Lampertico Filomena Morisco Ferran Torres Jordi Bruix María reig Barcelona Clinic Liver Cancer Group Liver UnitHospital Clínic de BarcelonaInstitut d'Investigacions Biomèdiques August Pi SunyerCentro de Investigación Biomédica en Red Enfermedades Hepáticas y DigestivasBarcelona 08036Spain Universidad de Barcelona Barcelona 08036Spain Division of Gastroenterology and Hepatology Foundation Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Ca’Granda Ospedale Maggiore PoliclinicoMilano 20122Italy Department of Clinical Medicine and Surgery Gastroenterology UnitUniversity of Naples Federico IINaples 80131Italy Gastroenterology and Hepatology Unit Fondazione Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica CàGranda Ospedale Maggiore PoliclinicoUniversity of MilanMilan 20100Italy Department of Clinical Medicine and Surgery Gastroenterology UnitUniversity of Naples"Federico II"Napoli 80100Italy Department of Clinical Medicine and Surgery Gastroenterology and HepatologyFederico II University of NaplesNaples 80131Italy Division of Internal Medicine Hepatobiliary and Immunoallergic DiseasesIstituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Azienda Ospedaliero-Universitaria di BolognaBologna 40139Italy Department of Medical and Surgical Sciences University of BolognaBologna 40139Italy Department of Medical Oncology University of CagliariCagliari 45698Italy Biosciences Laboratory Istituto di Ricovero e Cura a Carattere Scientifico di Natura PubblicaIstituto Romagnolo per lo Studio dei Tumori“Dino Amadori”Meldola 47014Italy Department of pathology Hospital Clínic de BarcelonaUniversitat de BarcelonaBarcelona 08036Spain School of Medicine Vita-Salute San Raffaele UniversityMilan 20132Italy Unit of Oncology UniversitàVita-SaluteIstituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica-San Raffaele Scientific InstituteMilan 20132Italy Division of Internal Medicine Hepatobiliary and Immunoallergic DiseasesIstituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Aziend

BACKGROUND Dermatologic adverse events(DAEs)are associated with a better outcome in patients with hepatocellular carcinoma(HCC)irrespective of the therapeutic agent *** exact mechanisms associated with the development of DAEs are unknown although several studies point to direct toxicity of tyrosine kinase inhibitors(TKIs)to the skin or an immune-mediated reaction triggered by the oncologic *** is the case in other conditions,individual genetic variants may partially explain a higher risk of *** To evaluate the contribution of several gene variants to the risk of developing DAEs in HCC patients treated with *** We first analyzed 27 single-nucleotide polymorphisms(SNPs)from 12 genes selected as potential predictors of adverse event(AE)development in HCC patients treated with sorafenib[Barcelona Clinic Liver Cancer 1(BCLC1)cohort].Three additional cohorts were analyzed for AGT1(rs699)and AGT2(rs4762)polymorphisms-initially identified as predictors of DAEs:BCLC2(n=79),Northern Italy(n=221)and Naples(n=69)cohorts,*** relation between SNPs and DAEs and death were assessed by univariate and multivariate Cox regression models,and presented with hazard ratios and their 95%confidence intervals(95%CI).RESULTS The BCLC1 cohort showed that patients with arterial hypertension(AHT)(HR=1.61;P value=0.007)and/or AGT SNPs had an increased risk of ***,AGT2(rs4762)AA genotype was found to be linked to a statistically significant increased probability of DAEs(HR=5.97;P value=0.0201,AA vs GG)in the Northern Italy cohort by multivariate analysis adjusted for BCLC stage,ECOG-PS,diabetes and *** value of this genetic marker was externally validated in the cohort combining the BCLC1,BCLC2 and Naples cohorts[HR=3.12(95%CI:1.2-8.14),P value=0.0199,AGT2(rs4762)AA vs AG genotype and HR=2.73(95%CI:1.18-6.32)P value=0.0188,AGT2(rs4762)AA vs GG genotype].None of the other gene variants tested were found to be associated with the risk of D

关键词： HCC Early DAE Single-nucleotide polymorphisms AGT1(rs699) AGT2(rs4762),Tyrosine kinase inhibitors

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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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

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 poly- morphisms (SNPs) of NOD2/CARD15 (R702W, G908R and L1007fi nsC), 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, G908R and L1007finsC) and TLR4 (D299G and T399I) SNPs were examined in 133 CD pa-tients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS: NOD2/CARD15 R702W mutation was sig-nificantly more frequent in CD (9.8%) than in controls (2.4%, P = 0.001) and in UC (2.3%, P = 0.03). No sig-nificant difference was found between UC patients and control group (P > 0.05). In CD and UC patients, no signifi cant association with G908R variant was found. L1007f insC 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 in-creased risk of CD.

关键词：结肠疾病肠溃疡核苷酸治疗方法

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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

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急相蛋白对新生儿感染性疾病的诊断意义

中华儿科杂志 1988年第5期26卷 280-282+317页

作者：罗小平刘皖君王珊同济医科大学附属同济医院儿科

本文采用免疫扩散技术测定新生儿期血清C-反应蛋白(CRP),α-酸性糖蛋白(α-AGP)、α-抗胰蛋白酶(α-AT)和前白蛋白(pa)4种急相蛋白,并观察其在几种常见新生儿疾病病程中的动态变化。结果显示败血症、肺炎组新生儿血清CRP,α-AGP和α-AT... 详细信息

本文采用免疫扩散技术测定新生儿期血清C-反应蛋白(CRP),α-酸性糖蛋白(α-AGP)、α-抗胰蛋白酶(α-AT)和前白蛋白(pa)4种急相蛋白,并观察其在几种常见新生儿疾病病程中的动态变化。结果显示败血症、肺炎组新生儿血清CRP,α-AGP和α-AT含量显著增高。上感、窒息和黄疸组仅α-AGP和α-AT稍高于正常,且很快恢复。动态观察表明:CRP、pa变化迅速,有助于感染性疾病早期诊断,反映抗生素即时效果;α-AGP、α-AT变化相对慢,与感染病程平行,对指导抗生素疗程及预后判断更有意义。本文还对α-AGP、α-AT和pa的测定与Behring药盒进行了方法学比较。

关键词：急相蛋白新生儿感染抗生素免疫扩散

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 ...

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

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-

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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

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俄译师洛丹西饶所著《简明正字法》

青海民族大学学报（藏文版） 2016年第3期 44-51页

作者：才航多杰