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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

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Contribution of extracellular vesicles to steatosis-related liver disease and their therapeutic potential

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World Journal of Hepatology 2024年第9期16卷 1211-1228页

作者： Margarita Montoya-Buelna Inocencia G ramirez-Lopez Cesar A San Juan-Garcia Jose J Garcia-Regalado Mariana S Millan-Sanchez Ulises de la Cruz-Mosso Jesse Haramati ana L Pereira-Suarez Jose Macias-Barragan Laboratorio de Inmunología Departamento de FisiologíaUniversidad de GuadalajaraGuadalajara 44340JaliscoMexico departamento de Ciencias de la Salud Centro Universitario de los VallesUniversidad de GuadalajaraAmeca 46600JaliscoMexico Doctorado en Ciencias Biomédicas Centro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340JaliscoMexico Laboratorio de Inmunología Departamento de FisiologíaCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340JaliscoMexico Red de Inmunonutrición y Genómica Nutricional en las Enfermedades Autoinmunes Departamento de NeurocienciasCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340JaliscoMexico Laboratorio de Inmunobiología Departamento de Biología Celular y MolecularCentro Universitario de Ciencias Biológicas y AgropecuariasUniversidad de GuadalajaraZapopan 45200JaliscoMexico Instituto de Investigación en Ciencias Biomédicas Departamento de Microbiología y PatologíaCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340JaliscoMexico

Extracellular vesicles(EVs)are small particles released by many cell types in different tissues,including the liver,and transfer specific cargo molecules from originating cells to receptor *** process generally culminates in activation of distant cells and inflammation and progression of certain *** global chronic liver disease(CLD)epidemic is estimated at 1.5 billion patients *** and liver cancer are the most common risk factors for ***,hepatitis C and B virus infection and obesity are also highly associated with ***,the etiology of many CLD pathophysiological,cellular,and molecular events are *** in hepatic lipid metabolism can lead to lipotoxicity events that induce EV ***,we aimed to present an overview of EV features,from definition to types and biogenesis,with particular focus on the molecules related to steatosis-related liver disease,diagnosis,and therapy.

关键词： Extracellular vesicles Exosomes Chronic liver disease Hepatocellular carcinoma Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis

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deciphering the role of PGC-1α in neurological disorders: from mitochondrial dysfunction to synaptic failure

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Neural Regeneration Research 2022年第2期17卷 237-245页

作者： Jessica D.Panes Aline Wendt Oscar ramirez-molina Patricio A.Castro Jorge Fuentealba Laboratorio de Screening de Compuestos Neuroactivos(LSCN) Departamento de FisiologiaFacultad de Ciencias BiologicasUniversidad de ConcepcionConcepcionChile Centro de Investigaciones Avanzadas en Biomedicina(CIAB-UdeC) Facultad de Ciencias BiologicasUniversidad de ConcepcionConcepcionChile departamento de Fisiologia Facultad de Ciencias BiologicasUniversidad de ConcepcionConcepcionChile

The onset and mechanisms underlying neurodegenerative diseases remain uncertain. The main features of neurodegenerative diseases have been related with cellular and molecular events like neuronal loss, mitochondrial dysfunction and aberrant accumulation of misfolded proteins or peptides in specific areas of the brain. The most prevalent neurodegenerative diseases belonging to age-related pathologies are Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. Interestingly, mitochondrial dysfunction has been observed to occur during the early onset of several neuropathological events associated to neurodegenerative diseases. The master regulator of mitochondrial quality control and energetic metabolism is the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α). Additionally, it has been observed that PGC-1α appears to be a key factor in maintaining neuronal survival and synaptic transmission. In fact, PGC-1α downregulation in different brain areas(hippocampus, substantia nigra, cortex, striatum and spinal cord) that occurs in function of neurological damage including oxidative stress, neuronal loss, and motor disorders has been seen in several animal and cellular models of neurodegenerative diseases. Current evidence indicates that PGC-1α upregulation may serve as a potent therapeutic approach against development and progression of neuronal damage. Remarkably, increasing evidence shows that PGC-1α deficient mice have neurodegenerative diseases-like features, as well as neurological abnormalities. Finally, we discuss recent studies showing novel specific PGC-1α isoforms in the central nervous system that appear to exert a key role in the age of onset of neurodegenerative diseases and have a neuroprotective function in the central nervous system, thus opening a new molecular strategy for treatment of neurodegenerative diseases. The purpose of this review is to provide an up-t

关键词： Alzheimer's disease amyotrophic lateral sclerosis Huntington's disease mitochondrial dysfunction Parkinson's disease PGC-1α synaptic function vascular dementia

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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

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Pharmacogenomics in colorectal cancer: The first step for individualized-therapy

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World Journal of Gastroenterology 2007年第44期13卷 5888-5901页

作者： Eva Bandrés Ruth Zárate Natalia ramirez ana Abajo Nerea Bitarte Jesus García-Foncillas Laboratory of Pharma-cogenomics Cancer Research Program (Center for Applied Medical Research) University of Navarra Navarra Spain

Interindividual differences in the toxicity and response to anticancer therapies are currently observed in practically all available treatment regimens. A goal of cancer therapy is to predict patient response and toxicity to drugs in order to facilitate the individualization of patient treatment. Identification of subgroups of patients that differ in their prognosis and response to treatment could help to identify the best available drug therapy according the genetic profile. Several mechanisms have been suggested to contribute to chemo-therapeutic drug resistance: amplification or overexpression of membrane transporters, changes in cellular proteins involved in detoxification or in DNA repair, apoptosis and activation of oncogenes or tumor suppressor genes. Colorectal cancer (CRC) is regarded as intrinsically resistant to chemotherapy. Several molecular markers predictive of CRC therapy have been included during the last decade but their results in different studies complicate their application in practical clinical. The simultaneous testing of multiple markers predictive of response could help to identify more accurately the true role of these polymorphisms in CRC therapy. This review analyzes the role of genetic variants in genes involved in the action mechanisms of the drugs used at present in colorectal cancer.

关键词： Colorectal cancer Pharmacogenomics Chemotherapy Polymorphisms Markers

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Dog sperm head morphometry： its diversity and .=volution

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Asian Journal of Andrology 2017年第2期19卷 149-153页

作者： Caries Soler ana Alambiaga Maria A Marti Almudena Garcia-molina Anthony Valverde Jesus Contell Marcos Campos department of Functional Biology and Physical Anthropology University of Valencia 46100 Burjassot Spain R+D department Proiser R+D Scientific Park University of Valencia 46980 Paterna Spain 3Technological Institute of Costa Rica San Carlos Campus School of Agronomy 223-21001 Alajuela Costa Rica department of Medicine and Animal Surgery University CardenaI-Herrera-CEU 46113 Moncada Valencia Spain Global Veterinaria (Reprovalcan) 46500 Sagunto Valencia Spain Clinica Veterinaria Sangueso 46009 Valencia Spain

Dogs have been under strong artificial selection as a consequence of their relationship with man. Differences between breeds are evident that could be reflected in seminal characteristics. The present study was to evaluate differences in sperm head morphometry between seven well-defined breeds of dog： the British Bulldog, Chihuahua, German Shepherd, Labrador Retriever, Spanish Mastiff, Staffordshire Terrier, and Valencian Rat Hunting dog. Semen samples were obtained by masturbation and smears stained with Diff-Quik. Morphometric analysis （CASA-Morph） produced four size and four shape parameters. Length, Ellipticity, and Elongation showed higher differences between breeds. MANOVA revealed differences among all breeds. Considering the whole dataset, principal component analysis （PCA） showed that PC1 was related to head shape and PC2 to size. Procluster analysis showed the British Bulldog to be the most isolated breed, followed by the German Shepherd. The PCA breed by breed showed the Chihuahua, Labrador Retriever, Spanish Mastiff, and Staffordshire Terrier to have PC1 related to shape and PC2 to size, whereas the British Bulldog, Valencia Rat Hunting dog, and German Shepherd had PC1 related to size and PC2 to shape. The dendrogram for cluster groupings and the distance between them showed the British Bulldog to be separated from the rest of the breeds. Future work on dog semen must take into account the large differences in the breeds＇ sperm characteristics. The results provide a base for future work on phylogenetic and evolutionary studies of dogs, based on their seminal characteristics.

关键词： Canis familiaris cluster analysis diversity sperm morphometry

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Forensic Sciences Research 2019年第3期4卷 257-266页

作者： Benito Morentin M.Paz Suárez-Mier ana Monzó Pilar molina Joaquín S.Lucena Section of Forensic Pathology Basque Institute of Legal MedicineBilbaoSpain Histopathology Service Department of MadridNational Institute of Toxicology and Forensic SciencesSpain Forensic Pathology Service Institute of Legal Medicine and Forensic SciencesValenciaSpain Forensic Pathology Service Institute of Legal Medicine and Forensic SciencesSevilleSpain

This is a multicentre forensic study that identifies all sports-related sudden deaths (SRSDs) in young people,due to myocardial diseases (MDs) that occurred in a large area of *** aim of the study is to assess the epidemiology,causes of death,and sport activities associated with these *** is a retrospective study based on forensic autopsies performed in the provinces of Biscay,Seville,Valencia and in the jurisdiction covered by the National Institute of Toxicology and Forensic Sciences in Madrid (Spain).The retrospective study encompasses from 2010 to *** sudden cardiac deaths (SCDs) in persons 1-35years old were *** total number of SCDs were divided into death occurred during exercise (SRSD) and death during rest,sleep or normal activities (non-SRSD).Each of these two groups was subdivided according to the cause of death into MD (primary cardiomyopathies and myocarditis) and ***-pathological,toxicological and genetic characteristics of SRSD due to MD were *** the 8-year study period,we identified 645 cases of SCD in the young: 75 SRSD (11.6%) and 570 non-SRSD (88.4%).MD was diagnosed in 33 (44.0%) of the SRSD and in 112 (19.6%) of the non-SRSD *** cases of SRSD due to MD were males (mean age (24.0±7.6) years) practicing recreational sports (85%).SRSDs were more frequent in arrhythmogenic cardiomyopathy (ACM) (37%) and hypertrophic cardiomyopathy (HCM) (24%),followed by myocarditis (15%) and idiopathic left ventricular hypertrophy (ILVH) (9%).Only in five cases of SRSD the MD responsible of death (HCM) had been diagnosed in *** symptoms related to the disease were present in other seven patients (six of them with ACM).Postmortem genetic studies were performed in 15/28 (54%) primary cardiomyopathies with positive results in 12 (80%) *** most frequent sports disciplines were football (49%) followed by gymnastics (15%) and running (12%).In Spain,SRSD in young people due to MDs occurs in mal

关键词： Forensic sciences forensic pathology sudden cardiac death sports myocardial diseases autopsy young

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Overlap of reflux and eosinophilic esophagitis in two patients requiring different therapies:A review of the literature

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World Journal of Gastroenterology 2008年第9期14卷 1463-1466页

作者： Javier molina-Infante Lucía Ferrando-Lamana Jose María Mateos-Rodríguez Belén Pérez-Gallardo ana Beatriz Prieto-Bermejo Unit of Gastroenterology Hospital San Pedro de Alcantara Avda. Pablo Naranjo s/n 10003 Caceres Spain department of Pathology. Hospital San Pedro de Alcantara Avda. Pablo Naranjo s/n 10003 Caceres Spain

Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) have overlapping clinical, manometric, endoscopic and histopathologic features. The diagnosis of EE is nowadays based upon the presence of 15 or more eosinophils per high power field (eo/HPF) in esophageal biopsies. We report the cases of two young males suffering from dysphagia and recurrent food impaction with reflux esophagitis and more than 20 eo/HPF in upper-mid esophagus biopsies, both of which became asymptomatic on proton pump inhibitor (PPI) therapy. The first patient also achieved a histologic response, while EE remained in the other patient after effective PPI treatment, as shown by 24-h esophageal pH monitoring. Topical steroid therapy combined with PPI led to complete remission in this latter patient. GERD and EE may be undistinguishable, even by histology, so diagnosis of EE should only be established after a careful correlation of clinical, endoscopic and pathologic data obtained under vigorous acid suppression. These diagnostic difficulties are maximal when both diseases overlap. Limited data are available about this topic, and the interaction between EE and GERD is a matter of debate. In this setting, upper-mid esophagus step biopsies and esophageal pH monitoring of patients on PPI therapy are pivotal to evaluate the role of each disease. A PPI trial is mandatory in patients with a histopathologic diagnosis of EE; in those unresponsive to PPI treatment, EE should be suggested. However, a clinical response to PPI may not rule out quiescent EE, as shown in this report.

关键词： Eosinophils Eosinophilic esophagitis Gastroesophageal reflux Proton pump inhibitors Overlap

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IKKβ overexpression together with a lack of tumour suppressor genes causes ameloblastic odontomas in mice

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International Journal of Oral Science 2020年第1期12卷 31-39页

作者： Angustias Page ana Bravo Cristian Suarez-Cabrera Raquel Sanchez-Baltasar Marta Oteo Miguel Angel Morcillo MLlanos Casanova Jose CSegovia Manuel Navarro Angel ramirez Molecular Oncology Unit.Centro de Investigaciones Energéticas Medioambientales y Tecnológicas(CIEMAT)MadridSpain Instituto de Investigación 12 de Octubre i+12 MadridSpain Centro de Investigación Biomédica en Red de Cáncer(CIBERONC) MadridSpain department of anatomy Animal Production and Veterinary Clinical SciencesLaboratory of Pathology Phenotyping of Genetically Engineered MiceFaculty of Veterinary MedicineUniversity of Santiago de CompostelaLugoSpain Biomedical Applications and Pharmacokinetics Unit Centro de Investigaciones EnergéticasMedioambientales y Tecnológicas(CIEMAT)MadridSpain Hematopoietic Innovative Therapies Division.Centro de Investigaciones Energéticas Medioambientales y Tecnológicas(CIEMAT).Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER)MadridSpain Unidad Mixta de Terapias Avanzadas Fundación Instituto de Investigaciones Sanitarias Fundación Jiménez DíazMadridSpain

Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their histopathological characteristics and clinical behaviour, the classification of these tumours is still under debate. Alterations in morphogenesis pathways such as the Hedgehog,MAPK and WNT/β-catenin pathways are implicated in the formation of odontogenic lesions, but the molecular bases of many of these lesions are still unknown. In this study, we used genetically modified mice to study the role of IKKβ(a fundamental regulator of NF-κB activity and many other proteins) in oral epithelial cells and odontogenic tissues. Transgenic mice overexpressing IKKβ in oral epithelial cells show a significant increase in immune cells in both the oral epithelia and oral submucosa. They also show changes in the expression of several proteins and mi RNAs that are important for cancer development. Interestingly, we found that overactivity of IKKβ in oral epithelia and odontogenic tissues, in conjunction with the loss of tumour suppressor proteins(p53, or p16 and p19), leads to the appearance of odontogenic tumours that can be classified as ameloblastic odontomas, sometimes accompanied by foci of secondary ameloblastic carcinomas. These tumours show NF-κB activation and increased β-catenin *** findings may help to elucidate the molecular determinants of odontogenic tumourigenesis and the role of IKKβ in the homoeostasis and tumoural transformation of oral and odontogenic epithelia.

关键词： IKKβ tumour suppressor

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analysis of the postoperative hemostatic profile of colorectal cancer patients subjected to liver metastasis resection surgery

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World Journal of Clinical Cases 2019年第17期7卷 2477-2486页

作者： Guillermo Perez Navarro ana Maria Pascual Bellosta Sonia María Ortega Lucea Mario Serradilla Martín Jose Manuel ramirez Rodriguez Javier Martinez Ubieto department of Anesthesiology University Hospital Miguel ServetZaragoza 50009Spain department of General Surgery University Hospital Miguel ServetZaragoza 50009Spain department of General Surgery University Hospital Lozano BlesaZaragoza 50009Spain

BACKGROUND Liver resection surgery has advanced greatly in recent years,and the adoption of fasttrack programs has yielded good *** anesthesia (general anesthesia associated to epidural analgesia) is an anesthetic-analgesic strategy commonly used for the perioperative management of patients undergoing surgery of this kind,though there is controversy regarding the coagulation alterations it may cause and which can favor the development of spinal *** To study the postoperative course of liver resection surgery,an analysis was made of the outcomes of liver resection surgery due to colorectal cancer metastases in our centre in terms of morbiditymortality and hospital stay according to the anesthetic technique used (general vs combination anesthesia).METHODS A prospective study was made of 61 colorectal cancer patients undergoing surgery due to liver metastases under general and combination anesthesia between January 2014 and October *** patient characteristics,intraoperative variables,postoperative complications,evolution of hemostatic parameters,and stay in intensive care and in hospital were *** A total of 61 patients were included in two homogeneous groups: general anesthesia (n = 30) and combination anesthesia (general anesthesia associated to epidural analgesia)(n = 31).All patients had normal coagulation values before *** international normalized ratio (INR) in both the general and combination anesthesia groups reached maximum values at 2448 h (mean 1.37 and 1.45 vs 1.39 and 1.41,respectively),followed by a gradual *** was less intraoperative bleeding in the combination anesthesia group (769 mL) than in the general anesthesia group (1200 mL)(P < 0.05).Of the 61 patients,38.8% in the general anesthesia group experienced some respiratory complication vs 6.6% in the combination anesthesia group (P < 0.001).The time to gastrointestinal tolerance was significantly correlated to the type of anesthesia,though

关键词： Hepatectomy Epidural analgesia Perioperative complications Epidural hematoma Multimodal rehabilitation Outcomes

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