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ACE Score Identifies HBeAg-negative Inactive Carriers at a Single-point Evaluation,regardless of HBV Genotype

Journal of Clinical and Translational Hepatology 2022年第6期10卷 1068-1076页

作者： Luisa roade Mar riveiro-Barciela Adriana Palom Francisco r.dr.guez-Frías Marta Bes Ariadna rando María Teresa Salcedo rosario Casillas Elena Vargas-Accarino David Tabernero Silvia Sauleda rafael esteban María Buti Liver Unit Internal Medicine DepartmentHospital Universitari Vall d’HebronVall d’Hebron Barcelona Hospital CampusBarcelonaSpain Universitat Autònoma de Barcelona(UAB) Department of MedicineBarcelonaSpain Universitat Au-tònoma de Barcelona(UAB) Department of Biochemistry and Molecular BiologyBarcelonaSpain Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas(CIBErehd) Instituto de Salud Carlos IIIMadridSpain Liver Pathology Lab Biochemistry and Microbiology Departments(Clinical Laboratories)Hospital Universitari Vall d’HebronVall d’Hebron Barcelona Hospital CampusBarcelonaSpain Vall d’Hebron Institut de recerca(VHIr) Liver Diseases GroupBarcelonaSpain Transfusion Safety Laboratory Banc de Sang i TeixitsServei Catalàde la SalutBarcelonaSpain De-partment of Pathology Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelonaSpain

Background and Aims:Hepatitis B virus(HBV)biomark-ers have been used for a better categorization of patients,even though the lack of simple algorithms and the impact of genotypes limit their *** aim was to assess the usefulness of noninvasive markers for the identification of HBV inactive carriers(ICs)in a single-point evaluation and to design a predictive model for their ***-ods:This retrospective-prospective study included 343 consecutive HBeAg-negative ***,analytical,and virological data were collected,and a liver biopsy was performed if *** were classified at the end of follow-up as ICs,chronic hepatitis B and gray zone.A pre-dictive model was constructed,and validated by 1000-boot-strap ***:After 39 months of follow-up,298 subjects were ICs,36 were chronic hepatitis B CHB,and nine were gray ***-nine(25.9%)individuals re-quired a liver *** HBV DNA hazard ratio(Hr)6.0,pre-related antigen(HBcrAg)(Hr 6.5,praphy(Hr 4.6,pre inde-pendently associated with the IC *** ACE score(HBV DNA,HBcrAg,elastography),obtained by bootstrapping,yielded an area under the receiver operating characteris-tics(AUrOC)of 0.925(95%CI:0.880-0.970,pr identification of *** AUrOC for genotype D was 0.95,0.96 for A,0.90 for E,and 0.88 for H/*** ACE score ofredictive value of 99.5%,and a score≤12 points had a diagnostic accuracy of 93.8%.Conclusions:Low baseline HBV DNA,HBcrAg,and liver stiffness were in-dependently associated with the IC phase.A score including those variables identified ICs at a single-point evaluation,and might be applied to implement less intensive follow-up strategies.

关键词： Hepatitis B virus Inactive carrier Liver stiffness HBV DNA Quan-titative HBsAg Core-related antigen.

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Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population

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World Journal of Gastroenterology 2018年第6期24卷 680-692页

作者： rosario Casillas David Tabernero Josep Gregori Irene Belmonte Maria Francesca Cortese Carolina González Mar riveiro-Barciela rosa Maria López Josep Quer rafael esteban Maria Buti Francisco r.dr.guez-Frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d’Hebron Institut Recerca-Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas(CIBErehd) Instituto de Salud Carlos IIIMadrid 28029Spain roche Diagnostics SL Sant Cugat del Vallès 08174Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain

AIM To determine the variability/conservation of the domain of hepatitis B virus(HBV) pre S1 region that interacts with sodium-taurocholate cotransporting polypeptide(hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism(S267 F, NTCP variant) in a Spanish population. METHODS Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection(CHB)(n = 41, 73% Caucasians), patients with resolved HBV infection(n = 100, 100% Caucasians) and an HBV-uninfected control group(n = 105, 100% Caucasians). Variability/conservation of the amino acid(aa) sequences of the NTCPinteracting domain,(aa 2-48 in viral genotype D) and a highly conserved pre S1 domain associated with virion morphogenesis(aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCr melting curve *** The HBV pre S1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21(in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCPinteracting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies(25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms(34% vs 27.3%), according to consensus sequences from Gen Bank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable(limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any ***

关键词： Hepatitis B virus Hepatitis B virus preS1 region sodium-taurocholate co-transporting polypeptide NTCP-interacting domain virion morphogenesis domain SNP rs2296651 next-generation sequencing real-time PCr melting curves

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Effects of Chemical Products on Fire Blight Suppression,and Fruit Production and Quality in Apple(Malus domestica Borkh.)*** Glory

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Phyton-International Journal of Experimental Botany 2022年第7期91卷 1341-1351页

作者： Álvaro r.dr.guez-Peña Ana C.Gonzalez-Franco Jared Hernández-Huerta Nora A.Salas-Salazar Dámaris L.Ojeda-Barrios esteban Sánchez Loreto robles-Hernández Facultad de Ciencias Agrotecnológicas Universidad Autónoma de ChihuahuaPascual OrozcoChihuahua31350México Centro de Investigación y Desarrollo A.C. DeliciasChihuahua33089México

Antibiotics are widely used in fire blight management programs,yet there are no studies that demonstrate the evaluation of their efficacy in ***,the present study was conducted to investigate the effects of the active ingredients in five commercial products(Kasumin■2L,Agrygent Plus■,Agricultural Terramycin■,Agrimicin100,and Actigard■)on fire blight suppression,and fruit yield and quality of apple(Malus domestica Borkh.)*** *** experiment was conducted in a commercial orchard using a completely randomized block design,with six treatments:(1)Oxytetracycline[Ox],110 mg L^(−1);(2)Kasugamycin[Kas],4.7 mL L^(−1);(3)Oxytetracycline+Gentamicin[Ox+Gen],48 mg L^(−1)+12 mg L^(−1);(4)Streptomycin+Oxytetracycline[Str+Ox],90 mg L^(−1)+9 mg L^(−1);(5)Acibenzolar-S-methyl[ASM],70 mg L^(−1);and(6)Control,only water,with four replications,and three 11-year-old trees as an experimental *** of infection including flowers,shoots and fruits,yield and fruit quality were *** treatments suppressed infection in flowers,shoots,and *** provided the highest levels of reduction of flower and shoot infection,while Kas had the least effect on the reduction of infection in these *** Ox+Gen treatment had the greatest suppression of fruit infection,and the best results on fruit yield and quality,followed by Ox and *** is the first study conducted to evaluate the efficacy of the active ingredients of five commercial products used for the management of fire blight in apple trees in Mexico.

关键词： Erwinia amylovora oxytetracycline gentamicin kasugamycin streptomycin Acibenzolar-S-methyl

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Paclobutrazol and Its Use in Fruit Production:A review

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Phyton-International Journal of Experimental Botany 2022年第1期91卷 1-12页

作者： Laura raquel Orozco-Meléndez Ofelia Adriana Hernández-r.dr.guez Oscar Cruz-Álvarez Loreto robles-Hernández Graciela Dolores Avila-Quezada esteban Sánchez Chavez DamiánAarón Porras-Flores Dámaris Leopoldina Ojeda-Barrios Facultad de Ciencias Agrotecnológicas Universidad Autónoma de ChihuahuaAvenida Pascual OrozcoChihuahua31350México Centro de Investigación y Desarrollo A.C. DeliciasChihuahua33089México

There are documentary records referring to paclobutrazol(PBZ)as a growth bioregulator that inhibits the gibberellin synthesis and its application increases yields in fruit and vegetable crop *** agronomic management includes it as an emerging technology to reduce vigour,promote flower induction and flower development in fruit trees with increased economic *** use is banned in some countries because of concerns about residues that can cause harmful effects on the ***,the aim of this article was to collect,analyse and summarise relevant information on the use of PBZ in fruit tree production and its possible risks to the *** results obtained indicated that the application of PBZ can be effective in solving some problems related to flowering if it is applied in the right amount and at the right ***,it is necessary to elucidate the physiological processes with which it is associated and its response to be taken into account to increase *** is currently used in fruit trees such as mango,lime,apple and guava,increasing their ***,some studies have shown its residual effect on the ***,PBZ is a viable strategy,because it presents a series of advantages in the production of fruit ***,it is vital to generate protocols that seek its regulation with a rational and sustainable approach.

关键词： Environment flower induction gibberellin biosynthesis growth bioregulator vegetative growth

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renal function and choroidal thickness using swept-source optical coherence tomography in diabetic patients

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International Journal of Ophthalmology(English edition) 2019年第6期12卷 985-989页

作者： Antonio Manuel Garrido-Hermosilla Mariola Méndez-Muros Estanislao Gutiérrez-Sánchez Cristóbal Morales-Portillo María Jesús Díaz-GrANDa Eduardo esteban-González Isabel relimpio-López María Asunción Martínez-Brocca Enrique r.dr.guez-de-la-rúa-Franch Department of Ophthalmology Virgen Macarena University HospitalSeville 41009Spain Oftared Institute of Health Carlos IIIMadridSpain Department of Endocrinology and Nutrition Virgen Macarena University HospitalSeville 41009Spain

AIM: To assess the relationship between choroidal thickness and renal function in diabetic patients. METHODS: Cross-sectional retrospective clinical study of 42 eyes of 21 ocular treatment-na?ve diabetic patients. Demographic data included: age, sex, type and course of diabetes. Ocular data included: severity of diabetic retinopathy;retinal thickness at the central macular region, as well as choroidal thickness at the central and paracentral quadrants, using automatically generated maps by swept-source optical coherence tomography;presence of cystic macular edema;and ocular axial length(AXL). Lab-test parameters included: glycated hemoglobin(HbA1c), albuminuria, albumin/creatinine ratio in urine, and glomerular filtration rate. rESULTS: A significant negative correlation was mainly observed between several choroidal thicknesses, age(Pr AXL(Prary, a significant positive correlation was found between all choroidal thicknesses, HbA1 c(Pria(Proidal thickness can represent an additional tool to help clinicians predicting the renal status in ocular treatment-na?ve diabetic patients.

关键词： choroidal thickness renal function swept-source optical coherence tomography spectral-domain optical coherence tomography diabetes mellitus

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Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy

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World Journal of Gastroenterology 2018年第19期24卷 2095-2107页

作者： Carolina González David Tabernero Maria Francesca Cortese Josep Gregori rosario Casillas Mar riveiro-Barciela Cristina Godoy Sara Sopena Ariadna rando Marcal Yll rosa Lopez-Martinez Josep Quer rafael esteban Maria Buti Francisco r.dr.guez-Frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d’Hebron Institut Recerca-Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas(CIBErehd) Instituto de Salud Carlos IIIMadrid 28029Spain roche Diagnostics SL Sant Cugat del Vallès 08174Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain

AIM To detect hyper-conserved regions in the hepatitis B virus(HBV) X gene(HBX) 5' region that could be candidates for gene *** The study included 27 chronic hepatitis B treatmentnaive patients in various clinical stages(from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeA g-negative and HBeA g-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/m L, the HBX 5' end region [nucleotide(nt) 1255-1611] was PCramplified and submitted to next-generation sequencing(NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide position in a multiple alignment of all unique sequences(haplotypes) obtained by NGS. Conservation at the HBx protein amino acid(aa) level was also *** NGS yielded 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample(2487-9279, IQr 2817). In 14/27 patients(51.8%), phylogenetic analysis of viral nucleotide haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments detected 2 hyper-conserved nucleotide regions, one in the HBX upstream non-coding region(nt 1255-1286) and the other in the 5' end coding region(nt 1519-1603). This last region coded for a conserved amino acid region(aa 63-76) that partially overlaps a Kunitz-like *** Two hyper-conserved regions detected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype.

关键词： Hepatitis B virus Hepatitis B X gene Hepatitis B X protein Gene therapy Next-generation sequencing HBV conserved regions Small interference rNA

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紫茎泽兰入侵前后根部蜡样芽孢杆菌含量比较及其对化感物质处理的响应

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生物安全学报 2022年第1期31卷 27-33页

作者：赵云鹏杨子豪徐刚 esteban r.dr.guez-Leyva 杨国庆扬州大学园艺与植物保护学院江苏扬州225009 Posgrado en Fitosanidad Entomología y AcarologíaColegio de PostgraduadosTexcocoMexico

【目的】比较紫茎泽兰入侵地种群根部有益菌蜡样芽孢杆菌含量与原产地种群的差异,及其对化感物质的响应,为揭示紫茎泽兰与有益菌互作在入侵前后的变化及其机制提供参考。【方法】分别以紫茎泽兰原产地墨西哥的3个种群(M1、M2、M3)和入... 详细信息

【目的】比较紫茎泽兰入侵地种群根部有益菌蜡样芽孢杆菌含量与原产地种群的差异,及其对化感物质的响应,为揭示紫茎泽兰与有益菌互作在入侵前后的变化及其机制提供参考。【方法】分别以紫茎泽兰原产地墨西哥的3个种群(M1、M2、M3)和入侵地云南的3个种群(C1、C2、C3)为材料,采用同质园试验方法和蜡样芽孢杆菌分子定量的技术,检测原产地和入侵地紫茎泽兰种群植株根部(根系、根际土壤)蜡样芽孢杆菌的含量;使用不同种群紫茎泽兰植株叶片淋溶液和根系分泌液处理入侵地土壤,检测化感物质对土壤中蜡样芽孢杆菌含量的影响。【结果】紫茎泽兰入侵地种群根系蜡样芽孢杆菌含量高于原产地种群,其中入侵地种群C2的含量比原产地种群M1高1172%;在根际土壤中,2年生紫茎泽兰入侵地3个种群的蜡样芽孢杆菌含量显著高于原产地种群M1和M3。紫茎泽兰叶片淋溶液和根系分泌液处理均促进了土壤蜡样芽孢杆菌含量增加,入侵地种群叶片淋溶液处理的土壤的蜡样芽孢杆菌增加量高于原产地种群,根系分泌液处理的后期测定中也如此。【结论】与原产地相比,紫茎泽兰入侵后,根系与根际土壤蜡样芽孢杆菌含量均有所增加,增强了有益菌对入侵地种群的正反馈效应。

关键词：紫茎泽兰蜡样芽孢杆菌化感物质入侵

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A widely adaptable approach to generate integration-free iPSCs from non-invasively acquired human somatic cells

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Protein & Cell 2015年第5期6卷 386-389页

作者： Zhichao Ding Lina Sui ruotong ren Yanjun Liu Xiuling Xu Lina Fu ruijun Bai Tingting Yuan Ying Hao Weiqi Zhang Huize Pan Wensu Liu Han Yu concepcion r.dr.guez esteban Xiaobing Yu Ze Yang Jian Li Xiaomin Wang Juan Carlos Izpisua Belmonte Guang-Hui Liu Fei Yi Jing Qu National Laboratory of Biomacromolecules Institute of Biophysics University of the Chinese Academy of Sciences Chinese Acad- emy of Sciences Beijing 100101 China Department of Endocrinology 306th Hospital of PLA Beijing100101 China Science and Development Xtem Foshan 528000 China State Key Laboratory of reproductive Biology Institute of ZoologyChinese Academy of Sciences Beijing 100101 China Beijing Hospital of the Ministry of Health Beijing 100073 China Beijing Institute for Brain Disorders Beijing 100069 China Gene Expression Laboratory Salk Institute for Biological Studies10010 North Torrey Pines Road La Jolla CA 92037 USA Center for Molecular and Translational Medicine Beijing 100101China Department of Molecular and Cellular Physiology StanfordUniversity School of Medicine Stanford CA 94305 USA

Dear Editor Human pluripotent stem cells including human embryonic stem cells （ESCs） and induced pluripotent stem cells （iPSCs） are cells displaying abilities of unlimited self-renewal and differentiation into any somatic cell type. These unique properties make them increasingly attractive for novel applications in disease modeling, drug discovery, and cell therapy （Buganim et al., 2014; Liu et al., 2011; Liu et al., 2012; Sanchez Alvarado and Yamanaka, 2014）. Moreover, iPSCs hold great potential for personalized cell therapy as they avoid some of the ethical concerns as well as the immunological rejection issues ascribed to ESCs.

关键词： iPSC dbcAMP Definitive Endoderm Cell reprogram iPSC Line

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Mutations in foregut SOX2^+ cells induce efficient proliferation via CXCr2 pathway

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Protein & Cell 2019年第7期10卷 485-495页

作者： Tomoaki Hishida Eric Vazquez-Ferrer Yuriko Hishida-Nozaki Ignacio Sancho-Martinez Yuta Takahashi Fumiyuki Hatanaka Jun Wu Alejandro Ocampo Pradeep reddy Min-Zu Wu Laurie Gerken reuben J. Shaw concepcion r.dr.guez esteban Christopher Benner Hiroshi Nakagawa Pedro Guillen Garcia Estrella Nunez Delicado Antoni Castells Josep M. Campistol Guang-Hui Liu Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Advaneed Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical University Beijing 100053 China National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of the Chinese Academy of Sciences Beijing 100049 China Insitute for Stem Cell and regeneration Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Brain Disorder Beijing 100069 China Universidad Catolica San Antonio de Murcia Campus de los Jeronimos 135 Guadalupe 30107 Spain Molecular and Cell Biology Laboratory Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Howard Hughes Medical Institute Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Integrative Genomics Core Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Division of Gastroenterology Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA Abramson Cancer Center University of Pennsylvania Philadelphia PA 19104 USA Department of Traumatology and research Unit Clinica CEMTRO Av. Ventisquero de la Condesa 42 Madrid 28035 Spain Gastroenterology Department Hospital Clinic University of Barcelona IDIBAPS CIBEREHD Barcelona 08036 Spain

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2^+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras^G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2^+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KrAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras^G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KrAS and highlights a crucial role for the CXCr2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.

关键词： Sox2 tumor CXCr2 stratified epithelia

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Conservation and variability of hepatitis B core at different chronic hepatitis stages

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World Journal of Gastroenterology 2020年第20期26卷 2584-2598页

作者： Marcal Yll Maria Francesca Cortese Mercedes Guerrero-Murillo Gerard Orriols Josep Gregori rosario Casillas Carolina González Sara Sopena Cristina Godoy Marta Vila David Tabernero Josep Quer Ariadna rando rosa Lopez-Martinez rafael esteban Mar riveiro-Barciela Maria Buti Francisco r.dr.guez-Frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d'Hebron Institut Recerca-Hospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Department of Microbiology Hospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas Instituto de Salud Carlos ⅢMadrid 28029Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autónoma de BarcelonaBarcelona 08035Spain

BACKGrOUND Since it is currently not possible to eradicate hepatitis B virus(HBV)infection with existing treatments,research continues to uncover new therapeutic *** core protein,encoded by the HBV core gene(HBC),intervenes in both structural and functional processes,and is a key protein in the HBV life *** this reason,both the protein and the gene could be valuable targets for new therapeutic and diagnostic ***,alterations in the protein sequence could serve as potential markers of disease *** To detect,by next-generation sequencing,HBC hyper-conserved regions that could potentially be prognostic factors and targets for new *** Thirty-eight of 45 patients with chronic HBV initially selected were included and grouped according to liver disease stage[chronic hepatitis B infection without liver damage(CHB,n=16),liver cirrhosis(LC,n=5),and hepatocellular carcinoma(HCC,n=17)].HBV DNA was extracted from patients’plasma.A region between nucleotide(nt)1863 and 2483,which includes HBC,was amplified and analyzed by next-generation sequencing(Illumina Mi Seq platform).Sequences were genotyped by distance-based discriminant *** and intergroup nt and amino acid(aa)conservation was determined by sliding window *** presence of nt insertion and deletions and/or aa substitutions in the different groups was determined by aligning the sequences with genotype-specific consensus *** Three nt(nt 1900-1929,2249-2284,2364-2398)and 2 aa(aa 117-120,159-167)hyper-conserved regions were shared by all the clinical *** groups showed a similar pattern of conservation,except for five nt regions(nt 1946-1992,2060-2095,2145-2175,2230-2250,2270-2293)and one aa region(aa 140-160),where CHB and LC,respectively,were less conserved(Proup-specific conserved regions were also observed at both nt(2306-2334 in CHB and 1935-1976 and 2402-2435 in LC)and aa(between aa 98-103 in CHB and 28-30 and 5

关键词： Hepatitis B virus Hepatitis B core gene Next-generation sequencing Genetic conservation Amino acid substitution Gene therapy Small interfering rNA

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