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Translational pancreatic cancer research:a comparative study on patient-derived xenograft models

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World Journal of Gastroenterology 2018年第7期24卷 794-809页

作者： Mercedes Rubio-Manzanares Dorado Luis Miguel Marín Gómez Daniel Aparicio Sánchez Sheila Pereira Arenas juan Manuel Praena-Fernández juan jose borrero martín Francisco Farfán López Miguel ángel Gómez Bravo Jordi Muntané Relat Javier Padillo Ruiz Department of Hepatobiliary and Pancreatic Surgery Virgen del Rocio University Hospital Oncology Surgery Cell Therapy and Organ Transplantation Group Institute of Biomedicine of Seville (IBiS) Virgen del Rocio University Hospital University of Seville Statistics Methodology and Evaluation of Research Unit Virgen del Rocio University Hospital Pathology Department Virgen del Rocio University Hospital

AIM To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude *** This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations(intraperitoneal, subcutaneous and pancreatic). Histological analysis(haematoxylin-eosin and Masson's trichrome staining) and immunohistochemical assessment of apoptosis(TUnEL), proliferation(Ki-67), angiogenesis(CD31) and fibrogenesis(α-SMA) were performed. When a tumour xenograft reached the target size, it was reimplanted in a new nude mouse. Three sequential tumour xenograft generations were generated(F1, F2 and F3).RESULTS The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth(69.9%), followed by intraperitoneal(57.6%) and pancreatic(55%) models. Tumour development was faster in the subcutaneous model(17.7 ± 2.6 wk) compared with the pancreatic(23.1 ± 2.3 wk) and intraperitoneal(25.0 ± 2.7 wk) models(P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models(F1 28.1% vs F2 71.4% vs F3 80.9%, P no significant differences in tumour xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical *** In our experie

关键词： Immunohistological analysis Pancreatic cancer Patient-derived xenograft Animal model nude mice

Impact of diff erent waves of COVID-19 on emergency medical services and out-of-hospital cardiopulmonary arrest in Madrid, Spain

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World Journal of Emergency Medicine 2022年第5期13卷 386-389页

作者： jose-María navalpotro-Pascual Diana Monge martín Manuel-José González León Fernando neria Serrano Carlos Alonso Blas Belén Muñoz Isabel Yago Muñecas Cuesta Alfredo Carrillo Moya juan Les González Alonso Mateos Rodríguez Madrid Emergency Medical Services SUMMA 112Madrid 28045Spain School of Medicine Francisco de Vitoria UniversityMadrid 28223Spain(School of MedicineUniversidad Francisco de VitoriaMadrid 28223Spain)

Out-of-hospital cardiac arrest(OHCA)is one of the three leading causes of death in industrialized countries.[1,2]Some studies have described the impact of the first COVID-19 pandemic wave in terms of the number of cases and OHCA survival rates in various regions,[3-5]but few have addressed the relationship between the successive phases and how they affected OHCA.[6,7]The 14-d cumulative incidence peaked at more than 990 cases,with these rates remaining above 200 for an eight-month period between 15 March 2020 and 15 March 2021 in Madrid,Spain.

关键词： cardiac services successive

Prospective application of a bleeding and ischemic risks-adjusted antithrombotic protocol in elderly patients revascularized with everolimus-eluting stents:EPIC05-Sierra75 study

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Journal of Geriatric Cardiology 2022年第5期19卷 354-366页

作者： jose M de la Torre Hernandez Ramon Lopez Palop Jesus M Jimenez Mazuecos Pilar Carrillo Sáez Alejandro Gutierez-Barrios Eduardo Pinar Belen Cid Luis Fernandez Tamara Garcia Camarero Cristóbal Urbano-Carrillo juan F Oteo Dominguez Victor A Jimenez Diaz Antonio EGomez Menchero Eladio Galindo Fernández juan GCórdoba Soriano Raymundo Ocaranza Eduardo ArroyoÚcar Koldobika Garcia San Roman Silvio Leal Ginés martínez Cáceres jose A Linares Vicente Georgina Fuertes Ferre Xavier Carrillo juan CRama Merchán Catia Costa juan Sanchis Renato Fernandes Alberto Rodrigues jose M Vegas Valle Hélder Pereira Armando Perez de Prado Cardiology Department Hospital Universitario Marqués de ValdecillaIDIVALSantanderSpain Cardiology Department Hospital Universitario San JuanAlicanteSpain Cardiology Department Complejo Hospitalario Universitario de AlbaceteAlbaceteSpain Cardiology Department Hospital Universitario Puerta del MarCadizSpain Cardiology Department Hospital Clínico Universitario Virgen de la ArrixacaMurciaSpain Cardiology Department Hospital Clinico Universitario de SantiagoCIBERCVSantiago de CompostelaSpain Cardiology Department Hospital Universitario de CrucesBilbaoSpain Cardiology Department Hospital Regional Universitario de MálagaMalagaSpain Cardiology Department Hospital Universitario Puerta de HierroMadridSpain Cardiology Department Hospital Alvaro CunqueiroVigoSpain Cardiology Department Hospital Juan Ramon JimenezHuelvaSpain Cardiology Department Hospital Universitario de BadajozBadajozSpain Cardiology Department Hospital Universitario Lucus AugustiLugoSpain Cardiology Department Hospital de Torrevieja/VinalopóRibera SaludTorreviejaSpain Cardiology Department Hospital Santa CruzLisboaPortugal Cardiology Department Hospital Clínico Universitario Lozano BlesaZaragozaSpain Cardiology Department Hospital Universitario Miguel ServetZaragozaSpain Cardiology Department Hospital Germans Trias i PujolBadalonaSpain Cardiology Department Hospital de MeridaMeridaSpain Cardiology Department Hospital São BernardoSetúbalPortugal Cardiology Department Hospital Clinico Universitario de ValenciaUniversidad de ValenciaCIBERCVValenciaSpain Cardiology Department Hospital do Espirito SantoEvoraPortugal Cardiology Department Centro Hospitalar de Vilanova de GaiaVilanova de GaiaPortugal Cardiology Department Hospital de CabueñesGijonSpain Cardiology Department Hospital Garcia de OrtaAlmadaPortugal Cardiology Department Complejo Asistencial Universitario de LeónLeonSpain

OBJECTIVES Elderly patients show a higher incidence of ischemic and bleeding events after percutaneous transluminal coron-ary intervention(PCI).We sought to investigate outcomes in elderly patients treated with antithrombotic strategy guided by bleeding and ischemic risks after revascularization with last generation everolimus-eluting stent(EES).METHODS Prospective multicenter registry including patients over 75 years revascularized with EES and antithrombotic ther-apy guided by clinical presentation,PCI complexity and PRECISE DAPT ***-primary safety endpoints were:(1)composite of cardiac death,myocardial infarction and stent thrombosis and;(2)bleeding(BARC 2-5).Primary efficacy endpoint was target lesion revascularization.A matched group of patients revascularized with current drug-eluting stents and no such tailored antith-rombotic therapy was used as *** Finally,1064 patients were included in SIERRA-75 cohort,80.8±4.2 years,36.6%women,71%acute coronary syn-dromes(ACS)and 53.6%complex ***-primary safety endpoint of major adverse cardiovascular events was met in 6.2%,co-primary safety endpoint of bleeding in 7.8%and primary efficacy endpoint of TKLR in 1.5%.The multivariable adjusted model showed no significant association of the prescribed short/long dual antiplatelet therapy(DAPT)durations with any endpoint suggesting a well tailored *** stent thrombosis reported in the subgroup with 1-3 months DAPT *** compared to control group,bleeding BARC 2-5 was significantly lower in SIERRA-75 group(7.4%vs.10.2%,P=0.04)as well as the net safety-efficacy endpoint(14.3%vs.18.5%,P=0.02).COnCLUSIOnS In elderly population,the application of this risks-adjusted antithrombotic protocol after revascularization with last generation EES seems to be associated with an improved prognosis in terms of ischemic and bleeding outcomes.

关键词： patients bleeding antithrombotic

Classification of anemia for gastroenterologists

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World Journal of Gastroenterology 2009年第37期15卷 4627-4637页

作者： jose Antonio Moreno Chulilla Maria Soledad Romero Colás martín Gutiérrez martín Department of Hematology University Hospital "Lozano Blesa" University of Zaragoza C/San Juan Bosco 15 Zaragoza 50009 Spain

Most anemia is related to the digestive system by dietary deficiency, malabsorption, or chronic bleeding. We review the World Health Organization definition of anemia, its morphological classifi cation (microcytic, macrocytic and normocytic) and pathogenic classi-fication (regenerative and hypo regenerative), and integration of these classifications. Interpretation of laboratory tests is included, from the simplest (blood count, routine biochemistry) to the more specific (iron metabolism, vitamin B12, folic acid, reticulocytes, erythropoietin, bone marrow examination and Schilling test). In the text and various algorithms, we propose a hierarchical and logical way to reach a diagnosis as quickly as possible, by properly managing the medical interview, physical examination, appropriate laboratory tests, bone marrow examination, and other comple-mentary tests. The prevalence is emphasized in all sections so that the gastroenterologist can direct the diagnosis to the most common diseases, although the tables also include rare diseases. Digestive diseases potentially causing anemia have been studied in preference, but other causes of anemia have been included in the text and tables. Primitive hematological diseases that cause anemia are only listed, but are not discussed in depth. The last section is dedicated to simplifying all items discussed above, using practical rules to guide diagnosis and medical care with the greatest economy of resources and time.

关键词： Anemia Microcytic anemia Iron Deficiency diseases Macrocytic anemia normocytic anemia

Direct-fed microbes: A tool for improving the utilization of low quality roughages in ruminants

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Journal of Integrative Agriculture 2015年第3期14卷 526-533页

作者： Mona M Y Elghandour Abdelfattah Z M Salem jose S martínez Castaeda Luis M Camacho Ahmed E Kholif juan C Vázquez Chagoyán Faculty of Veterinary Medicine and Animal Science Autonomous University of the State of Mexico Faculty of Veterinary Medicine and Animal Science Autonomous University of Guerrero Dairy Science Department National Research Centre

For many years, ruminant nutritionists and microbiologists have been interested in manipulating the microbial ecosystem of the rumen to improve production efficiency of different ruminant species. Removal and restriction of antibiotics subtherapeutic uses from ruminant diets has amplified interest in improving nutrient utilization and animal performance and search for more safe alternatives. Some bacterial and fungal microorganisms as a direct-fed microbial（DFM） can be the most suitable solutions. Microorganisms that are commonly used in DFM for ruminants may be classified mainly as lactic acid producing bacteria（LAB）, lactic acid utilizing bacteria（LUB）, or other microorganism＇s species like Lactobacillus, Bifidobacterium, Enterococcus, Streptococcus, Bacillus, Propionibacterium, Megasphaera elsdenii and Prevotellabryantii, in addition to some fungal species of yeast such as Saccharomyces and Aspergillus. A definitive mode of action for bacterial or fungal DFM has not been established; although a variety of mechanisms have been suggested. Bacterial DFM potentially moderate rumen conditions, and improve weight gain and feed efficiency. Fungal DFM may reduce harmful oxygen from the rumen, prevent excess lactate production, increase feed digestibility, and alter rumen fermentation patterns. DFM may also compete with and inhibit the growth of pathogens, immune system modulation, and modulate microbial balance in the gastrointestinal tract. Improved dry matter intake, milk yield, fat corrected milk yield and milk fat content were obtained with DFM administration. However, the response to DFM is not constant; depending on dosages, feeding times and frequencies, and strains of DFM. nonetheless, recent studies have supported the positive effects of DFM on ruminant performance.

关键词： direct-fed microbial(DFM) mode of action ruminants

Beta-blocker therapy in elderly patients with renal dysfunction and heart failure

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Journal of Geriatric Cardiology 2021年第1期18卷 20-29页

作者： juan martínez-Milla Marcelino Cortés García Julia Anna Palfy Mikel Taibo Urquía marta López Castillo Ana Devesa Arbiol Ana Lucía Rivero Monteagudo María Luisa martín Mariscal Inés Jiménez-Varas Sem Briongos Figuero juan Antonio Franco-Pelaéz JoséTuñón Department of Cardiology Hospital Universitario Fundación Jiménez Díaz-Quirónsalud Centro nacional de Investigaciones Cardiovasculares MadridSpain Department of Cardiology Hospital Central de Asturias Department of Cardiology Hospital Universitario Ruber-Quirónsalud Department of Cardiology Hospital Universitario Infanta Leonor Department of Endocrinology Hospital Clínico San Carlos Universidad Autónoma de Madrid CIBERCV MadridSpain

OBJECTIVE To assess the role of beta-blockers(BB)in patients with chronic kidney disease(CKD)aged≥75 *** AnD RESULTS From January 2008 to July 2014,we included 390 consecutive patients≥75 years of age with ejection fraction≤35%and glomerular filtration rate(GFR)≤60 m L/min per 1.73 m^*** analyzed the relationship between treatment with BB and mortality or cardiovascular *** mean age of our population was 82.6±4.1 *** ejection fraction was 27.9%±6.5%.GFR was 60-45 m L/min per 1.73 m^2 in 50.3%of patients,45-30 m L/min per 1.73 m^2 in 37.4%,andn per 1.73 m^2 in 12.3%.At the conclusion of follow-up,67.4%of patients were receiving *** median follow-up was28.04(IR:19.41-36.67)*** the study period,211 patients(54.1%)died and 257(65.9%)had a major cardiovascular event(death or hospitalization for heart failure).BB use was significantly associated with a reduced risk of death(HR=0.51,95%CI:0.35-0.74;Pnts receiving BB consistently showed a reduced risk of death across the different stages of CKD:stage IIIa(GFR=30-45 m L/min per 1.73 m^2;HR=0.47,95%CI:0.26-0.86,Pn per 1.73 m^2;HR=0.55,95%CI:0.26-1.06,P=0.007),and stages IV and V(GFRn per 1.73 m~2;HR=0.29,95%CI:0.11-0.76;P=0.047).COnCLUSIOnS The use of BB in elderly patients with HFr EF and renal impairment was associated with a better *** of BB should be encouraged when possible.

关键词： CKD GFR Beta-blocker therapy in elderly patients with renal dysfunction and heart failure

Tenofovir vs lamivudine plus adefovir in chronic hepatitis B:TEnOSIMP-B study

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World Journal of Gastroenterology 2017年第41期23卷 7459-7469页

作者： Manuel Rodríguez juan Manuel Pascasio Enrique Fraga Javier Fuentes martín Prieto Gloria Sánchez-Antolín jose Luis Calleja Esther Molina María Luisa García-Buey María Angeles Blanco Javier Salmerón María Lucía Bonet jose Antonio Pons jose Manuel González Miguel Angel Casado Francisco Jorquera 无 Division of Gastroenterology and Hepatology.Hospital Universitario Central de Asturias Unit for the Clinical Management of Digestive Diseases IBISHospital Universitario Virgen del Rocío Liver Transplantation and Hepatology Unit Gastroenterology ServiceHospital Universitario Reina Sofía Digestive Medicine Service Hospital Universitario Miguel Servet Hepatology Unit Digestive Medicine ServiceHospital Universitari i Politècnic La Fe Hepatology Unit Hospital Universitario Rio Hortega Liver Unit Hospital Universitario Puerta de Hierro de MajadahondaUniversidad Autónoma de Madrid Digestive Medicine Service Hospital Clínico de Santiago de Compostela Liver Unit Hospital Universitario de La Princesa Digestive Medicine Service Hospital General Universitario Gregorio Maranon Digestive Medicine Unit Complejo Hospitalario de Granada Digestive Medicine Service Hospital Universitario Son Espases Hepatology Unit IMIB Hospital Universitario Virgen de la Arrixaca Digestive Medicine Service Hospital Clínico Universitario de Valladolid Pharmacoeconomics and Outcomes Research Iberia Division of Gastroenterology and Hepatology Complejo Asistencial Universitario de León the TEnOSIMP-B Research Group

AIM To demonstrate the non-inferiority(15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate(TDF) vs the combination of lamivudine(LAM) plus adefovir dipivoxil(ADV) in the maintenance of virologic response in patients with chronic hepatitis B(CHB) and prior failure with *** This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups(TDF and LAM+ADV) of adult patients with hepatitis B e antigen(HBe Ag)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were *** Forty-six patients were evaluated [median age: 55.4 years(30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DnA(HBV-DnA) remained undetectable, all patients remained HBe Ag negative, and hepatitis B surface antigen(HBs Ag) positive. Alanine aminotransferase(ALT) values at the end of the study were similar in the 2 groups(25.1± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). no significant changes were observed in creatinine or serum phosphorus values in either group. no significant differences between the 2 groups were noted in the identification of adverse effects(AEs)(53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively(P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment(€4943 ± 1059 vs €5811 ± 1538, respectively, P nCLUSIOn TDF monotherapy proved to be safe

关键词： Tenofovir Lamivudine+Adefovir Efficacy Safety Adherence Costs Hepatitis B

Short-term effectiveness of high-and low-intensity percutaneous electrolysis in patients with patellofemoral pain syndrome:A pilot study

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World Journal of Orthopedics 2021年第10期12卷 781-790页

作者： juan Antonio Valera-Calero Alberto Sánchez-Mayoral-martín Umut Varol Department of Physiotherapy Camilo Jose Cela UniversityMadrid 28692Spain Business Analytics and Big Data IE School of Human Sciences and TechnologyMadrid 28006Spain

BACKGROUnD Unilateral patellofemoral pain syndrome(PFPS)is the most frequently diagnosed knee condition in populations aged0.05;tendon PPT immediate effects:F=0.15;η2=0.02;P>0.05 and tendon PPT 7-d effects:F=0.67;η2... 详细信息

BACKGROUnD Unilateral patellofemoral pain syndrome(PFPS)is the most frequently diagnosed knee condition in populations agednt of myofascial trigger points(MTrPs)is a common and effective tool for reducing pain,previous studies showed no additional benefits compared with placebo in populations with *** electrolysis is a minimally invasive approach frequently used in musculotendinous pathologies which consists of the application of a galvanic current through dry needling(Dn).AIM To evaluate changes in sensitivity,knee pain perception and perceived pain during the application of these three invasive *** A triple-blinded,pilot randomized controlled trial was conducted on fifteen patients with unilateral PFPS who were randomized to the high-intensity percutaneous electrolysis(HIPE)experimental group,low-intensity percutaneous electrolysis(LIPE)experimental group or Dn active control *** interventions were conducted in the most active MTrP,in the rectus femoris *** HIPE group received a 660 mA galvanic current for 10 s,the LIPE group 220 mA×30 s and the Dn group received no galvanic *** MTrP and patellar tendon pain pressure thresholds(PPTs)and subjective anterior knee pain perception(SAKPP)were assessed before,after and 7 d after the single *** addition,perceived pain during the intervention was also *** Both groups were comparable at baseline as no significant differences were found for age,height,weight,body mass index,PPTs or *** adverse events were reported during or after the interventions.A significant decrease in SAKPP(both HIPE and LIPE,Pnd increased patellar tendon PPT(all,Pnd,with no differences between the groups(VAS:F=0.30;η2=0.05;P>0.05;tendon PPT immediate effects:F=0.15;η2=0.02;P>0.05 and tendon PPT 7-d effects:F=0.67;η2=0.10;P>0.05).A significant PPT increase in rectus femoris MTrP was found at follow-up in both the HIPE

关键词： Patellofemoral pain syndrome Electrolysis Myofascial pain syndromes Dry needling Clinical trial

Cerebral dopamine neurotrophic factor transfection in dopamine neurons using neurotensin-polyplex nanoparticles reverses 6-hydroxydopamine-induced nigrostriatal neurodegeneration

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neural Regeneration Research 2022年第4期17卷 854-866页

作者： Manuel A.Fernandez-Parrilla David Reyes-Corona Yazmin M.Flores-martinez Rasajna nadella Michael J.Bannon Lourdes Escobedo Minerva Maldonado-Berny Jaime Santoyo-Salazar Luis O.Soto-Rojas Claudia Luna-Herrera jose Ayala-Davila juan A.Gonzalez-Barrios Gonzalo Flores Maria E.Gutierrez-Castillo Armando JEspadas-Alvarez Irma A.martínez-Dávila Porfirio nava Daniel martinez-Fong Departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Programa Institucional de Biomedicina Molecular Escuela Nacional de Medicina y HomeopatíaInstituto Politécnico NacionalCiudad de MéxicoMéxico Department of Biosciences IIIT-SrikakulamRajiv Gandhi University of Knowledge Technologies(RGUKT)Andhra PradeshIndia Department of Pharmacology Wayne State University School of MedicineDetroitMIUSA Departamento de Física Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Facultad de Estudios Superiores Iztacala Universidad Nacional Autónoma de MéxicoTlalnepantla de BazEdo.de MéxicoMéxico Departamento de Fisiología Escuela Nacional de Ciencias BiológicasCiudad de MéxicoMéxico Laboratorio de Medicina Genómica Hospital Regional“1°de Octubre”ISSSTECiudad de MéxicoMéxico Laboratorio de neuropsiquiatría Instituto de FisiologíaBenemérita Universidad Autónoma de PueblaPueblaPueblaMéxico Departamento de Biociencias e Ingeniería Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y DesarrolloInstituto Politécnico NacionalCiudad de MéxicoMéxico Programa de nanociencias y nanotecnología Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico

Overexpression of neurotrophic factors in nigral dopamine neurons is a promising approach to reverse neurodegeneration of the nigrostriatal dopamine system,a hallmark in Parkinson's *** human cerebral dopamine neurotrophic factor(h CDnF)has recently emerged as a strong candidate for Parkinson's disease *** study shows that h CDnF expression in dopamine neurons using the neurotensinpolyplex nanoparticle system reverses 6-hydroxydopamine-induced morphological,biochemical,and behavioral *** independent electron microscopy techniques showed that the neurotensin-polyplex nanoparticles containing the h CDnF gene,ranging in size from 20 to 150 nm,enabled the expression of a secretable h CDnF in *** injection in the substantia nigra compacta on day 21 after the 6-hydroxydopamine lesion resulted in detectable h CDnF in dopamine neurons,whose levels remained constant throughout the study in the substantia nigra compacta and *** with the lesioned group,tyrosine hydroxylase-positive(TH^(+))nigral cell population and TH+fiber density rose in the substantia nigra compacta and striatum after h CDnF *** increase inβIII-tubulin and growth-associated protein 43 phospho-S41(GAP43 p)followed TH^(+)cell recovery,as well as dopamine and its catabolite *** reversal(80%)of drugactivated circling behavior and full recovery of spontaneous motor and non-motor behavior were ***-derived neurotrophic factor recovery in dopamine neurons that also occurred suggests its participation in the neurotrophic *** findings support the potential of nanoparticle-mediated h CDnF gene delivery to develop a disease-modifying treatment against Parkinson's *** Institutional Animal Care and Use Committee of Centro de Investigación y de Estudios Avanzados approved our experimental procedures for animal use(authorization no.162-15)on June 9,2019.

关键词： axonal growth brain-derived neurotrophic factor gene delivery nanoparticles neuritogenesis neuronal cytoskeleton neuroregeneration neurorestoration neurotrophic therapy Parkinson's disease reinnervation substantia nigra