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Clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer

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Cancer Biology & Medicine 2020年第2期17卷 444-457页

作者： Juan Moreno-Rubio Santiago Ponce rosa Alvarez maria Eugenia Olmedo Sandra Falagan Xabier Mielgo Fatima Navarro Patricia Cruz Luis Cabezon-Gutierrez Carlos Aguado Gonzalo Colmenarejo Marta Munoz-Fernandez de Leglaria Ana Belen Enguita maria Cebollero Amparo Benito Isabel Alemany Carolina del Castillo Ricardo Ramos Ana Ramirez de Molina Enrique Casado maria Sereno Ana Ramirez de Molina1 Enrique Casado5Maria Sereno5 XIMDEA Food InstituteCEI UAM+CSICMadrid 28702Spain 12 de Octubre University Hospital Madrid 28041Spain Gregorio Maranon University Hospital Madrid 28009Spain Ramon y Cajal University Hospital Madrid 28034Spain Infanta Sofia University Hospital San Sebastian De Los ReyesMadrid 28702Spain Fundacion Alcorcon University Hospital AlcorconMadrid 28922Spain Prlncipe de Asturias University Hospital Alcala De HenaresMadrid 28805Spain La Paz University Hospital Madrid 28046Spain University Hospital of Torrejon Torrejon De ArdozMadrid 28850Spain Clinico San Carlos University Hospital Madrid 28040Spain Parque Cientifico de Madrid Foundation Madrid 28049Spain

Objective:Long-term survivors(LS)of non-small cell lung cancer(NSCLC)without driver alterations,displaying an overall survival(OS)of more than 3 years,comprise around 10%of cases in several series treated with *** are classical prognosis factors for these cases[stage,Eastern Cooperative Oncology Group(ECOG),etc.],but more data are required in the *** this multi-center study,we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular ***:In the first step,we conducted a clinical-pathological characterization of the ***,we carried out a genetic analysis by comparing LS to a sample of short-term survivors(SS)(with an OS less than 9 months).We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS,and later confirmed these with reverse transcription-polymerase chain reaction(RT-PCR)for the rest of the ***:A total of 94 patients were included,who were mainly men,former smokers,having adenocarcinoma(AC)-type NSCLC with an ECOG of *** obtained an initial differential transcriptome expression,displaying 5 over-and 33 under-expressed genes involved in different pathways:namely,the secretin receptor,surfactant protein,trefoil factor 1(T FF1),serpin,Ca-channels,and Tolllike receptor(TLRs)***,RT-PCR analysis of 40(20 LS/20 SS)samples confirmed that four genes(surfactant proteins and SFTP)were significantly down-regulated in SS compared to LS by using an analysis of covariance(ANCOVA)model:SFTPA1(P=0.023),SFTPA2(P=0.027),SFTPB{P=0.02),and SFT PC(P=0.047).Conclusions:We present a sequential genetic analysis of a sample of NSCLCLS with no driver alterations,obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

关键词： Long-term survivors non-small cell lung cancer surfactant proteins

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

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 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 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(P<0.05).Some group-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

Muscle fatigue in women with primary biliary cirrhosis:Spectral analysis of surface electromyography

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World Journal of Gastroenterology 2006年第32期12卷 5186-5190页

作者： maria rosa Biagini Alessandro Tozzi Antonello Grippo Andrea Galli Stefano Milani Aldo Amantini Department of Clinical Pathophysiology Gastroenterology Unit University of FlorenceAOU CareggiFirenzeItaly Department of Neurological Science Neurophysiological Unit University of FlorenceAOU CareggiFirenzeItaly

瞄准：与健康题目相比与主要胆汁性肝硬变在病人评估外部易疲性的肌电表明。方法：有没有 comorbidity 的主要胆汁性肝硬变的十六个女人和好久匹配的 13 个健康女人和身体团索引(BMI ) 完成了自我报导的问询表疲劳影响规模。所有题目经... 详细信息

瞄准：与健康题目相比与主要胆汁性肝硬变在病人评估外部易疲性的肌电表明。方法：有没有 comorbidity 的主要胆汁性肝硬变的十六个女人和好久匹配的 13 个健康女人和身体团索引(BMI ) 完成了自我报导的问询表疲劳影响规模。所有题目经历了对外部易疲性的表面肌电描记法评价。前面的胫骨的肌肉等轴的随意收缩在 80% 最大的自愿的等长收缩为 20 s 被执行。在锻练 electromyographic 信号期间，系列象 electromyographic 信号频率光谱(肌肉易疲性的估计) 的平均数和 median 一样被记录，根意味着平方(中央开车的表达式) 被计算。每个题目执行了试用 two times。EMG 参数被规范的、然后线性的回归被使用，斜坡是计算的。结果：七个病人被使疲劳(中部的疲劳影响规模分数：38，变化：26-66 ) 并且 9 没被使疲劳(中部的疲劳影响规模分数：7，变化：0-17 ) 。最大的自愿的等长收缩在病人是类似的(82， 54-115 N ) 并且控制(87， 74-101 N ) ，并且在有高度的病人(81， 54-115 N ) 并且低疲劳影响规模分数(86， 65-106 N ) 。方形以及频率光谱斜坡吝啬、中部的根平均数与 Mann-Whitney U 测试相比，并且没有有效差量被发现在之间使疲劳并且非使 \O 疲劳的病人和控制。结论：外部易疲性的仪器的证据都不能与主要胆汁性肝硬变而是没有 comorbidity 在女人被发现，建议在如此的病人的那疲劳可能具有中央起源。

关键词：肌肉疲劳胆硬化光谱分析肌电图

Laboratory markers in ulcerative colitis: Current insights and future advances

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World Journal of Gastrointestinal Pathophysiology 2015年第1期6卷 13-22页

作者： Michele Cioffi Antonella De rosa rosalba Serao Ilaria Picone maria Teresa Vietri Department of Biochemistry Biophysics and General PathologySecond Medical School Naples

Ulcerative colitis(UC)and Crohn’s disease(CD)are the major forms of inflammatory bowel diseases(IBD)in *** some common features,these forms can be distinguished by different genetic predisposition,risk factors and clinical,endoscopic and histological *** aetiology of both CD and UC remains unknown,but several evidences suggest that CD and perhaps UC are due to an excessive immuneresponse directed against normal constituents of the intestinal bacterial *** sometimes invasive are routine for the diagnosis and care of patients with *** of UC is based on clinical symptoms combined with radiological and endoscopic *** employment of non-invasive biomarkers is *** biomarkers have the potential to avoid invasive diagnostic tests that may result in discomfort and potential *** ability to determine the type,severity,prognosis and response to therapy of UC,using biomarkers has long been a goal of clinical *** describe the biomarkers assessed in UC,with special reference to acute-phase proteins and serologic markers and thereafter,we describe the new biological markers and the biological markers could be developed in the future:(1)serum markers of acute phase response:The laboratory tests most used to measure the acute-phase proteins in clinical practice are the serum concentration of C-reactive protein and the erythrocyte sedimentation *** biomarkers of inflammation in UC include platelet count,leukocyte count,and serum albumin and serum orosomucoid concentrations;(2)serologic markers/antibodies:In the last decades serological and immunologic biomarkers have been studied extensively in immunology and have been used in clinical practice to detect specific *** UC,the presence of these antibodies can aid as surrogate markers for the aberrant host immune response;and(3)future biomarkers:The development of biomarkers in UC will be very important in the *** progress of

关键词： Inflammatory bowel diseases Ulcerative colitis Crohn’s disease Serologic markers Acute phase response

Beneficial effects of saffron(Crocus sativus L.) in ocular pathologies, particularly neurodegenerative retinal diseases

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Neural Regeneration Research 2020年第8期15卷 1408-1416页

作者： Jose A.Fernandez-Albarral rosa de Hoz Ana I.Ramirez Ines Lopez-Cuenca Elena Salobrar-Garcia maria D.Pinazo-Duran Jose M.Ramirez Juan J.Salazar Instituto de Investigaciones Oftalmologicas Ramon Castroviejo MadridSpain Departamento de Inmunologia Oftalmologia y ORLFacultad de Optica y OptometriaMadridSpain Departamento de Inmunologia Oftalmologia y ORLFacultad de MedicinaMadridSpain Unidad de Investigacion Oftalmologica Santiago Grisolia Universidad de ValenciaValenciaSpain

Saffron(Crocus sativus L.)has been traditionally used in food preparation and as a medicinal *** currently has numerous therapeutic properties attributed to it,such as protection against ischemia,as well as anticonvulsant,antidepressant,anxiolytic,hypolipidemic,anti-atherogenic,anti-hypertensive,antidiabetic,and anti-cancer *** addition,saffron has remarkable beneficial properties,such as anti-apoptotic,anti-inflammatory and antioxidant activities,due to its main metabolites,among which crocin and crocetin stand ***,increasing evidence underwrites the possible neuroprotective role of the main bioactive saffron constituents in neurodegenerative diseases,such as Parkinson’s and Alzheimer’s diseases,both in experimental models and in clinical studies in ***,saffron supplementation is being tested for ocular neurodegenerative pathologies,such as diabetic retinopathy,retinitis pigmentosa,age-related macular degeneration and glaucoma,among others,and shows beneficial *** present article provides a comprehensive and up to date report of the investigations on the beneficial effects of saffron extracts on the main neurodegenerative ocular pathologies and other ocular *** review showed that saffron extracts could be considered promising therapeutic agents to help in the treatment of ocular neurodegenerative diseases.

关键词： AMD crocetin crocin Crocus sativus L. diabetic retinopathy glaucoma neuroprotection ocular diseases retinitis pigmentosa saffron safranal

On an Exact Cylindrically Symmetric Solution in a Born-Infeld Type Theory of Gravity

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Journal of High Energy Physics, Gravitation and Cosmology 2019年第3期5卷 711-718页

作者： Tiago de Oliveira rosa maria Emilia Xavier Guimarã es Joaquim Lopes Neto Instituto Federal Goiano Campus Uruta&#237 Rodovia Geraldo Silva Nascimento Uruta&#237 Brazil Instituto de Fí sica Universidade Federal Fluminense Niter&#243 i Brazil Instituto de Fí sica Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil

In this work, we derive an exact vacuum solution for a cylindrically symmetric metric in an extended gravity theory developed by Novello, De Lorenci and Luciane (hereafter referred to as the NDL theory) which is inspired in the Born-Infeld theory. The main goal of this paper is to nd a cosmic string solution for the NDL theory. However, a careful analysis of the metric shows that it is asymptotically singular and therefore does not represent a cosmic string solution.

关键词： Modi ed Theories of Gravity Topological Defects

The cross-talk between family and pediatrician: The case of bronchial asthma

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Health 2013年第2期5卷 307-312页

作者： Salvatore Leonardi Rossella Pecoraro maria Teresa Garozzo Alfina Coco Mario La rosa Department of Pediatrics Bronchopneumoallergology and Cystic Fibrosis Unit University of Catania Catania Italy

Today the most important challenge facing the pediatrician is the increasing prevalence of chronic diseases. With this regard, pediatricians play a key role in the management of these conditions. The closeness with the family, the knowledge of the clinical case and the care continuity allow the pediatrician to acquire a position of director of every case. When pathological events have a chronic feature, suddenly the quality of life of the whole family changes. For this reason the first communication of chronic disease is very important and the task of the pediatrician should be to provide a positive message to help the family in facing the difficulty of this new challenge. The bronchial asthma is the most common chronic disease worldwide. The incidence, the prevalence, and the mortality of the disease have increased in children over the past decades. These trends are particularly marked above all in preschool children. The success reached by Pediatricians is closely related to the compliance and the implementation of the therapy followed by the little patient and his family. With this regard authors, in this review, focus on the illustration of several strategies, based on the pediatrician’ skills and medicine documents, that can be used for the improvement of communication among pedia- trician-family and child, never forgetting the hu- man aspect of the same doctor, that should con- ciliate with the scientific knowledge in the taking care of a specific chronic disease.

关键词： Cross-Talk Bronchial Asthma Children

Sleep Quality in Non Dialysis Chronic Kidney Disease: Associated Factors and Influence on Prognosis

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International Journal of Clinical Medicine 2016年第7期7卷 481-486页

作者： Jesús calviño Lourdes Gonzalez-Tabarés Secundino Cigarrán Beatriz Millán Monica Guijarro Carmen Cobelo maria-Jesús Sobrido Department of Nephrology Hospital Lucus Augusti EOXI Lugo-Cervo-Monforte Lugo Spain Department of Nephrology Hospital da Costa EOXI Lugo-Cervo-Monforte Burela Lugo Spain Department of Neurology Hospital Lucus Augusti EOXI Lugo-Cervo-Monforte Lugo Spain Department of Neurology Fundación Pública Galega de Medicina Xenómica-SERGAS Instituto de Investigación Sanitaria Santiago de Compostela Spain Department of Neurology Hospital San Rafael A Coru&ntildea Spain

Deficient sleep quality (SQ) has been linked with a higher hospitalization rate and mortality in dialysis patients, however the prevalence of sleep disorders and their influence on prognosis in non-dialysis chronic kidney disease (CKD) has been poorly investigated. The aim of this study was to assess factors related with SQ in CKD patients (stages I-IV) followed in a nephrology outpatient clinic as well as the long-term impact of SQ on patient’s outcome. Between January and May 2008, Pittsburgh Sleep Quality Index (PSQI) was self-administered by 122 patients (68 males and 54 females) with a mean age of 65 years. Patients were classified as “good” (global PSQI < 6) and “poor” sleepers (global PSQI ≥ 6). We identified 66 (54%) poor sleepers (PS), characterized by an older age (66 ± 14.2 vs 57 ± 17.0, p < 0.01), female predominance (59% vs 26%, p < 0.01) and worse renal function (49 ± 19.1 vs 57 ± 23.2 ml/min, p < 0.05). There was a significant correlation between phosphate and PSQI score (r = 0.234, p = 0.01), however no correlation with calcium or PTH. Vitamin D was also lower in PS (17 ± 7.2 vs 23 ± 15.1 ng/ml, p < 0.05). Until June 2015, hospitalization rate was higher among PS (64% vs 44%, p < 0.05). In this period, there was also a trend towards higher mortality for PS (18% vs 16%). In summary, over 50% of CKD patients have poor SQ, which was associated with older age, female gender, worse renal function, lower vitamin D and higher phosphate levels. Deficient sleep was associated with a greater probability of hospitalization and might be a prognostic marker in CKD.

关键词： Chronic Kidney Disease Sleep Quality Hospitalization Pittsburgh Sleep Quality Index Vitamin D