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World Journal of Gastroenterology 2006年第36期12卷 5875-5877页

作者： Jrg Bojunga Christoph Sarrazin Georg Hess Stefan Zeuzem Internal Medicine Ⅱ Saarland University Hospital 66421 Homburg/Saar Germany roche diagnostics 68305 Mannheim Germany

AIM: To investigate plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), an established marker of cardiac function, in patients with chronic hepatitis C during interferon-based antiviral therapy. METHODS: Using a sandwich immunoassay, plasma levels of NT-proBNP were determined in 48 patients with chronic hepatitis C at baseline, wk 24 and 48 during antiviral therapy and at wk 72 during ***: Plasma NT-proBNP concentrations were significantly increased (P < 0.05) at wk 24, 48 and 72 compared to the baseline values. NT-proBNP concentrations at baseline and wk 24 were closely correlated (r = 0.8; P < 0.001). At wk 24, 7 (14.6%) patients had NT-proBNP concentrations above 200 ng/L compared to 1 (2%) patient at baseline (P = 0.059). Six of these 7 patients had been treated with high-dose IFN-α induction therapy. In multiple regression analysis, NT-proBNP was not related to other clinical parameters, biochemical parameters of liver disease or virus load and response to ***: Elevated levels of NT-proBNP during and after interferon-based antiviral therapy of chronic hepatitis C may indicate the presence of cardiac dysfunction, which may contribute to the clinical symptoms observed in patients during therapy. Plasma levels of NT-proBNP may be used as a diagnostic tool and for guiding therapy in patients during interferon-based antiviral therapy.

关键词：等离子体尿钠排泄慢性丙型肝炎抗病毒治疗

Tumor necrosis factor-alpha -308G/A polymorphism and risk of hepatocellular carcinoma in hepatitis C virus-infected patients

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Chinese Journal of Cancer 2012年第1期31卷 29-35页

作者： Roba M.Talaat Ahmed A.Esmail Reda Elwakil Adel A.Gurgis Mahmoud I.Nasr Molecular Biology Departments Genetic Engineering and Biotechnology Research Institute(GEBRI)Menofia UniversitySadat 22857Egypt roche diagnostics Ain Shams UniversityCairo 11522Egypt Department of Tropical Medicine Ain Shams UniversityCairo 11522Egypt

Tumor necrosis factor-alpha (TNF-α) is an important cytokine in generating an immune response against infection with hepatitis C virus (HCV). The functions of TNF-α may be altered by single-nucleotide polymorphisms (SNPs) in its gene structure. We hypothesized that SNPs in TNF-α may be important in determining the outcome of an HCV infection. To test this hypothesis, we investigated the role of the polymorphism -308G/A, which is located in the promoter region of the TNF-α gene, in the progression of HCV infection in Egyptian patients using a quantitative real-time polymerase chain reaction (qRT-PCR). The distribution of this polymorphism and its impact on the serum level of TNF-α was compared between 90 HCV-infected patients [45 with HCV-induced cirrhosis and 45 with HCV-related hepatocellular carcinoma (HCC)] and 45 healthy Egyptian volunteers without any history of liver disease. Our results showed that at the TNF-α -308 position, the G/G allele was most common (78.5% ) in the study population, with the G/A and A/A alleles occurring less frequently (13.3% and 8.1% , respectively). Frequencies of G/G, G/A, and A/A genotypes were 87%, 7%, and 6% in patients with liver cirrhosis and were 94% , 4% , and 2% in patients with HCC, respectively. Serum levels of TNF-α were significantly higher in HCV-infected patients than in healthy controls, indicating that the TNF-α -308 polymorphism does not influence the production of TNF-α. The serum level of TNF-α was positively correlated with HCV infection. Taken together, these findings suggest that the TNF-α -308 polymorphism may not be a host genetic factor associated with the severity of HCV infection, but may be an independent risk factor for HCC.

关键词：肿瘤坏死因子-α 单核苷酸多态性丙型肝炎病毒病毒感染患者肝癌风险聚合酶链反应

1A6/DRIM, the human UTP20 functions in 28S and 5.8S rRNA processing

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Chinese Science Bulletin 2010年第17期55卷 1770-1776页

作者： KONG RuiRui HAN Wei ULRICH H. Weidle NING Tao DU XiaoJuan KE Yang Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Genetics Laboratory Peking University School of Oncology Beijing Cancer Hospital & Institute Beijing 100142 China Cancer Research Center Peking University Health Science Center Beijing 100191 China roche diagnostics GmbH Division Pharma 82372 Penzberg Germany Department of Cell Biology Peking University Health Science Center Beijing 100191 China

1A6/DRIM has been identified as UTP20, a small subunit processome component, functioning in 18S rRNA processing. In the present study, the maturation of 28S rRNA and 5.8S rRNA was inhibited when 1A6/DRIM was silenced in HeLa cells; and coincidently, an accumulation of 32S rRNA precursor was observed. Immunoprecipitation was performed with the anti-1A6/DRIM antibody, followed by Northern blot with the ITS2 probe. The results showed that 1A6/DRIM was associated with both 32S and 12S rRNA precursors in vivo. The expression profile of 1A6/DRIM during rRNA processing was investigated by sucrose density gradient fractionation in combination with Western blot analysis. The results demonstrated that 1A6/DRIM was involved in the pre-60S particles in addition to the pre-40S particles and co-sediment with the 32S and 12S rRNA precursors in the nucleolus. Furthermore, the interaction of U8 snoRNA with 1A6/DRIM was revealed by immunoprecipitation. These results demonstrated that 1A6/DRIM interacted with both 32S rRNA and U8 snoRNA, being involved in 28S rRNA and 5.8S rRNA processing.

关键词： rRNA基因加工过程 snoRNA 职能人类 HeLa细胞免疫印迹分析免疫沉淀

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全球日晒行为调查研究

中华皮肤科杂志 2024年第7期57卷 672-673页

作者： Thierry Passeron Henry W. Lim Chee Leok Goh Hee Young Kang Fatimata Ly Akimichi Morita Jorge Ocampo-Candiani Susana Puig Sergio Schalka Wei Liu Anne-Laure Demessant-Flavigny Caroline Le Floc’h Delphine Kerob Brigitte Dreno Jean Krutmann Department of Dermatology Côte d'Azur University Nice University Hospital Center Nice France INSERM U1065 C3M Côte d'Azur University Nice France Department of Dermatology Henry Ford Health Detroit Michigan USA National Skin Centre Singapore City Singapore Department of Dermatology Ajou University School of Medicine Suwon South Korea Department of Dermatology Cheikh Anta Diop Dakar University EPS Institute of Social Hygiene Dakar Senegal Department of Geriatric and Environmental Dermatology Nagoya City University Graduate School of Medical Sciences Nagoya Japan Universidad Autonoma de Nuevo León Facultad de Medicina University Hospital “Dr. Jose E. González” Monterrey Mexico Dermatology Department Hospital Clinic de Barcelona Barcelona University Barcelona Spain Medcin Skin Research Center and Biochemistry Department Chemistry Institute of Sao Paulo University Sao Paulo Brazil Department of Dermatology The General Hospital of Air Force PLA Beijing China La roche-Posay International Levallois-Perret France Nantes University Univ Angers INSERM Immunology and New Concepts in ImmunoTherapy INCIT UMR 1302 Nantes France IUF Leibniz Research Institute for Environmental Medicine Duesseldorf Germany Medical Faculty Heinrich-Heine-University Duesseldorf Germany

适量的日光照射有益于维生素D合成和情绪调节,但日光中的紫外线可能引发多种机体损伤,包括红斑、晒伤、光免疫抑制和光变态反应等急性损伤,以及皮肤癌、黄褐斑、炎症后色素沉着和光老化等慢性损伤。近期研究还显示,可见光(紫色至红色,40... 详细信息

适量的日光照射有益于维生素D合成和情绪调节,但日光中的紫外线可能引发多种机体损伤,包括红斑、晒伤、光免疫抑制和光变态反应等急性损伤,以及皮肤癌、黄褐斑、炎症后色素沉着和光老化等慢性损伤。近期研究还显示,可见光(紫色至红色,400~700nm)和红外线(700nm~1mm)也是皮肤光老化和光损伤的影响因素,可见光会导致黄褐斑等色素性疾病加重。

关键词：色素性疾病皮肤光老化光变态反应慢性损伤日光照射黄褐斑机体损伤维生素D

Pseudomonas exotoxin antisense RNA selectively kills hepatitis B virus infected cells

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World Journal of Gastroenterology 2008年第18期14卷 2810-2817页

作者： Peter Hafkemeyer Ulrich Brinkmann Elizabeth Brinkmann Ira Pastan Hubert E Blum Thomas F Baumert Department of Medicine Ⅱ University Hospital Freiburg Hugstetterstrasse 55 Freiburg D-79106 Germany roche diagnostics Nonnenwald 2 Penzberg D-82377 Germany National Cancer Institute National Institutes of Health Bethesda United States Inserm unit 748 Université Louis Pasteur 3 Rue Koeberle Strasbourg F-67000 France

AIM: To present an approach for selectively killing retrovirus-infected cells that combines the toxicity of Pseudomonas exotoxin (PE) and the presence of reverse transcriptase (RT) in infected cells. METHODS: PE antisense toxin RNA has palindromic stem loops at its 5' and 3' ends enabling self-primed generation of cDNA in the presence of RT. The RT activity expressed in retrovirus-infected cells converts "antisense-toxin-RNA" into a lethal toxin gene exclusively in these cells. RESULTS: Using cotransfection studies with PE-expressing RNAs and β-gal expressing reporter plasmids, we show that, in HepG2 and HepG2.2.15 hepatoma cells as well as in duck hepatitis B virus (DHBV) infected cells, HBV or DHBV-polymerase reverse transcribe a lethal cDNA copy of an antisense toxin RNA, which is composed of sequences complementary to a PE gene and eukaryotic transcription and translation signals. CONCLUSION: This finding may have important implications as a novel therapeutic strategy aimed at the elimination of HBV infection.

关键词：假单胞菌外毒素基因治疗乙型肝炎病毒

Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis delta virus superinfection

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World Journal of Gastroenterology 2019年第13期25卷 1566-1579页

作者： Cristina Godoy David Tabernero Sara Sopena Josep Gregori Maria Francesca Cortese Carolina González Rosario Casillas Mar?al Yll Ariadna Rando Rosa López-Martínez Josep Quer Gloria González-Aseguinolaza Rafael Esteban Mar Riveiro-Barciela Maria Buti Francisco Rodríguez-Frías Liver Pathology Unit Departments of Biochemistry and Microbiology Hospital Universitari Vall d’Hebron Universitat Autònoma de Barcelona Liver Unit Liver Disease Laboratory-Viral Hepatitis Vall d’Hebron Institut Recerca-Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Instituto de Salud Carlos Ⅲ roche diagnostics SL Centro de Investigación Médica Aplicada (CIMA) Universidad de Navarra Liver Unit Department of Internal MedicineHospital Universitari Vall d’Hebron Universitat Autònoma de Barcelona (UAB)

Hepatitis delta virus(HDV) seems to strongly suppress hepatitis B virus(HBV)replication, although little is known about the mechanism of this interaction. Both these viruses show a dynamic distribution of mutants, resulting in viral quasispecies. Next-generation sequencing is a viable approach for analyzing the composition of these mutant spectra. As the regulatory hepatitis B X protein(HBx) is essential for HBV replication, determination of HBV X gene(HBX)quasispecies complexity in HBV/HDV infection compared to HBV monoinfection may provide information on the interactions between these two *** To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis delta(CHD) and chronic HBV mono-infected *** Twenty-four untreated patients were included: 7/24(29.2%) with HBeAgnegative chronic HBV infection(CI, previously termed inactive carriers), 8/24(33.3%) with HBeAg-negative chronic hepatitis B(CHB) and 9/24(37.5%) with CHD. A serum sample from each patient was first tested for HBV DNA *** HBX 5' region [nucleotides(nt) 1255-1611] was then PCR-amplified for subsequent next-generation sequencing(MiSeq, Illumina, United States). HBV quasispecies complexity in the region analyzed was evaluated using incidencebased indices(number of haplotypes and number of mutations), abundancebased indices(Hill numbers of order 1 and 2), and functional indices(mutation frequency and nucleotide diversity). We also evaluated the pattern of nucleotide changes to investigate which of them could be the cause of the quasispecies *** CHB patients showed higher median HBV-DNA levels [5.4 logIU/mL,interquartile range(IQR) 3.5-7.9] than CHD(3.4 logIU/mL, IQR 3-7.6)(P = n.s.)or CI(3.2 logIU/mL, IQR 2.3-3.5)(P < 0.01) patients. The incidence and abundance indices indicated that HBV quasispecies complexity was significantly greater in CI than CHB. A similar trend was observed in CHD patients, although only Hill numbers of order 2 showed

关键词： Hepatitis B virus Hepatitis delta virus Hepatitis B X gene Next-generation sequencing Viral quasispecies Hepatitis B virus-hepatitis delta virus interaction

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 Rodríguez-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

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 Rodríguez-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

一项在欧洲和中国进行的新型胃泌素释放肽前体(ProGRP)免疫检测多中心评估研究

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中国肺癌杂志 2017年第8期20卷 568-577页

作者： Catharina M.KORSE Stefan HOLDENRIEDER Xiuyi ZHI Xiaotong ZAHNG Ling QIU Andrea GEISTANGER Marcus-Rene LISY Birgit WEHNL Daan van den BROEK José M.ESCUDERO Jens STANDOP Mu HU Rafael MOLINA The Netherlands Cancer Institute Plesmanlaan 121Amsterdam 1066CXThe Netherlands University Hospital Bonn and Center of Integrative Oncology Cologne/Bonn Sigmund-Freud-StrasseBonn 25-53127Germany Xuanwu Hospital Capital Medical UniversityBeijing 100053China Peking Union Medical College Hospital (PUMCH) Beijing 100730China roche diagnostics GmbH Nonnenwald 2Penzberg 82377Germany Hospital Clinic University of BarcelonaCarrer Villarroel 170Barcelona 08036Spain

背景在欧洲和中国进行Elecsys?胃泌素释放肽前体(ProGRP)免疫检测的多中心评估研究。方法在欧洲的3个中心和中国的2个中心,在肺癌中,通过不精密度、稳定性、方法学比较和鉴别诊断能力来评价该检测法。结果 5个分析物浓度的中间不精密度... 详细信息

背景在欧洲和中国进行Elecsys?胃泌素释放肽前体(ProGRP)免疫检测的多中心评估研究。方法在欧洲的3个中心和中国的2个中心,在肺癌中,通过不精密度、稳定性、方法学比较和鉴别诊断能力来评价该检测法。结果 5个分析物浓度的中间不精密度范围为变异系数:2.2%-6.0%。在不同储存条件下,血浆和血清样本均显示出良好的稳定性。在血浆中Elecsys?和ARCHITECT检测(斜率1.02,截距-2.72 pg/m L)之间表现出良好的相关性。同时,Elecsys?检测在血清和血浆样本之间表现出良好的相关性(斜率0.93,截距2.35 pg/m L;相关系数0.97)。ProGRP作为不受种族、年龄、性别或吸烟史相关影响的检测手段,可鉴别小细胞和非小细胞肺癌(NSCLC);截断值为84pg/m L时,曲线下面积为0.90,95%CI:0.87-0.93;敏感性为78.3%,特异性为95%。ProGRP浓度中位数在良性病变(38pg/m L)、其他恶性肿瘤(40 pg/m L)或NSCLC(39 pg/m L)中较低,而在3期以上慢性肾脏疾病中浓度较高(>100pg/m L)。结论 Elecsys?ProGRP检测在血清和血浆中稳定性增加,较现有检测法明显更具优势。ProGRP检测在中国的首次评价在不同种族中显示出相当的鉴别能力。

关键词：鉴别诊断免疫检测促胃泌素释放肽前体 ProGRP SCLC 稳定性

Clinical application of intelligent technologies and integration in medical laboratories

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智能检验医学(英文) 2023年第1期1卷 82-91页

作者： Wenjie Huang Dongquan Huang Yeran Ding Cheng Yu Lei Wang Ning Lv Jiuxin Qu Hongzhou Lu Department of Clinical Laboratory National Clinical Research Center for Infectious DiseasesGuangdong Provincial Clinical Research Center for Infectious Diseases(Tuberculosis)Shenzhen Clinical Research Center for TuberculosisThe Third People's Hospital of ShenzhenSouthern University of Science and TechnologyShenzhenGuangdongChina Department of Centralized and Point of Care Solutions&Molecular diagnostics Roche Diagnostics(Shanghai)LtdShanghaiChina National Clinical Research Center for Infectious Diseases The Third People's Hospital of Shenzhen and the Second Hospital Affiliated to Southern University of Science and TechnologyShenzhenGuangdongChina

With the development of scientific technology,the transition to the intelligent era of digitalization and automation is an irresistible trend for medical *** diagnosis systems have undergone significant changes as a result of intelligent technologies,such as machine learning,artificial intelligence,and the Internet of Things,from the collection,transmission,and detection of test samples to the review of reports and the provision of clinical *** addition to significantly enhancing the efficiency,consistency,and accuracy of medical laboratory testing,these technologies also assist the improvement of individualized healthcare and medical expert systems,as well as the early detection and treatment of *** future development of medical laboratories will focus on integrating big data and diverse intelligent resources,cooperating more closely with clinical departments,and realizing the effective pathway of patient‐centered *** purpose of this review is to illustrate the current state of intelligent technology integration in medical laboratories and provide a preliminary discussion about the potential future influences of intelligent technology development on the evolution of medical laboratories.

关键词： AI/ML medical laboratory integration intelligence