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| 1 | 抗结核药物肝毒性反应的危险因素及其影响显示文摘背景:肝毒性反应是抗结核药物(下简称ATD)最严重的不良反应之一。虽然已有许多关于肝毒性反应危险因素的报道,但关于肝毒性反应严重程度的影响尚无系统研究。目的:评估肝毒性反应的危险因素(包括高龄、慢性肝病、酗酒或滥用药物或营养不良)对ATD所致肝毒性反应严重性的影响。设计:对1998年1月至2002年7月期间在结核科门诊接受异烟肼、利福平、吡嗪酰胺治疗的471例活动性结核病人进行前瞻性队列分析。根据ATD所致肝毒性反应危险因素的暴露情况评价肝毒性反应的发生率及其严重性。结果:危险因素暴露组ATD所致肝毒性反应(血清转氨酶>3倍的正常上限值)的发生率为18.2%(42/231例),而对照组为5.8%(14/240例),(OR=3.5;95%CI:1.9-6.7;P<0.001)。暴露组的严重肝毒性反应(血清转氨酶>10倍的正常上限值)发生率为6.9%(16/231),而对照组为0.4%(1/240)(OR=17.7;95%CI:2.3-135;P<0.001)。结论:肝毒性反应危险因素暴露组病人的ATD所致肝炎显著多见且较为严重。 | A. Fernández-Villar B. Sopena J. Fernández-Villar R. Vázquez-Gallardo F. Ulloa V. Leiro M. Mosteiro L. Pineiro 马玙 | 2005 | 结核与肺部疾病杂志2005，8，1： | 13 |
| 2 | Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis delta virus superinfection显示文摘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 viruses.AIM To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis delta(CHD) and chronic HBV mono-infected patients.METHODS 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 levels.The 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 complexity.RESULTS 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 statistically significant differences(CHB2.81, IQR 1.11-4.57 vs CHD 8.87, 6.56-11.18, P = 0.038). There were no significant differences in the functional indices, but CI and CHD patients also showed a trend towards greater complexity than CHB. No differences were found for any HBV quasispecies complexity indices between CHD and CI patients. G-to-A and C-to-T nucleotide changes, characteristic of APOBEC3 G, were higher in CHD and CI than in CHB in genotype A haplotypes, but not in genotype D. The proportion of nt G-to-A vs A-to-G changes and C-to-T vs T-to-C changes in genotype A and D haplotypes in CHD patients showed no significant differences. In CHB and CI the results of these comparisons were dependent on HBV genotype.CONCLUSION The lower-replication CHD and CI groups show a trend to higher quasispecies complexity than the higher-replication CHB group. The mechanisms associated with this greater complexity require elucidation. | 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 | 2019 | World Journal of Gastroenterology2019，25，13： | 6 |
| 3 | Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy显示文摘AIM To detect hyper-conserved regions in the hepatitis B virus(HBV) X gene(HBX) 5' region that could be candidates for gene therapy.METHODS 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 analyzed.RESULTS 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 domain.CONCLUSION 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. | 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 | 2018 | World Journal of Gastroenterology2018，24，19： | 6 |
| 4 | Multimodality imaging techniques显示文摘 | Martí-Bonmatí L Sopena R Bartumeus P | | 0，，： | 1 |
| 5 | A survey of ratoon stunting disease (Leifsonia xyli subsp, xyli) in commercial sugarcane fields at Tucuman(Argentina) 显示文摘 | Rago A M Acreche M M Sopena R A | 2004 | Sugar Cane International2004，22，6： | 1 |
| 6 | Disseminated verruciform xanthoma显示文摘 | Sopena J Gamo R Iglesias L | 2004 | Br J Dermatol2004，151，3： | 1 |
| 7 | Persistence of Legionella in hospital water supplies and nosocomial Legionnaires' disease显示文摘 | Garcia-Nunez M Sopena N Ragull S | 2008 | FEMS Immunol Med Microbiol2008，52，2： | 1 |
| 8 | Muhicenter study of hospital acquired pneumonia in non - ICU patients 显示文摘 | SOPENA N SABRIA M Neunos 2000 study Group | 2005 | Chest2005，127，1： | 1 |
| 9 | Prospective study of community-acquired pneumonia of bacterial etiology in adults显示文摘 | Sopena N Sabria M Pedro-Botet ML | 1999 | Eur J Clin Microbiol Infect Dis1999，18，12： | 1 |
| 10 | Argument structure and association preferences in Spanish and English complex NPs显示文摘 | SOPENA J M CLIFTON C | 1995 | Cognition1995，54，2： | 1 |
| 11 | Coloring the square of the Cartesian product of two cycles显示文摘 | Sopena t Wu J | 2010 | Discrete Mathematics2010，310，17： | 1 |
| 12 | Experimental use of polyamide bands in combination with intramedullary pinning for repair of oblique femoral fractures in rabbits显示文摘 | Carrillo JM Sopena JJ Rubio M | 2005 | Vet Surg2005，34，4： | 1 |
| 13 | The influence of risk factors on the severity of anti-tuberculosis drug-induced hepatotoxicity显示文摘 | Fernandez-Villar A Sopena B Fernandez-Villar J | 2004 | Int J Tubere Lung Dis2004，8，12： | 1 |
| 14 | Ibuprofen versus indomethacin in the preterm persistent patent ductus arteriosus therapy: review and meta-analysis 显示文摘 | Gimeno Navarro A Modesto Alapont V Morcillo Sopena F | 2007 | An Pediatr2007，67，4： | 1 |
| 15 | Ibuprofeno frente a indometacina para el tratamiento de la persistencia del conducto arterioso del prematuro: revisión sistemática y metaanálisis显示文摘 | A. Gimeno Navarro V. Modesto Alapont F. Morcillo Sopena C. Fernández Gilino I. Izquierdo Macián A. Gutiérrez Laso | 2007 | Anales de Pediatria2007，，4： | 1 |
| 16 | Controlled release of the herbicide norflurazon into water from ethylcellulose formulations显示文摘 | Sopena F Cabrera A Maqueda C | 2005 | J Agric Food Chem2005，53，9： | 1 |
| 17 | Auto- immune manifestations of Kikuchi disease显示文摘 | Sopena B Rivera A Vazquez Trinanes C | 2012 | Semin Ar- thritis Rheum2012，41，6： | 1 |
| 18 | Assessing the chemical and biological accessibility of the herbicide isoproturon in soil amended with biochar 显示文摘 | Sopena F Semple K Bending G | 2012 | Chemosphere2012，88，1： | 1 |
| 19 | Risk factors for hospitalacquired pneumonia outside the intensive care unit:a casecontrol study显示文摘 | Sopena N Heras E Casas I | 2014 | Am J Infect Control2014，42，1： | 1 |
| 20 | Persistence of Legionella in hospital water supplies and nosocomial Legionnaires' disease 显示文摘 | Garcia-Nufiez M Sopena N Ragull S | 2008 | FEMSlmmunolMedMicrobiol2008，52，2： | 1 |
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