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1.
Eur Spine J ; 32(2): 395-407, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36109389

RESUMO

PURPOSE: Although numerous publications on three-dimensional printing (3DP) in spine surgery have been published, bibliometric analysis studies are scarce. Thus, this study aimed to present a bibliometric analysis of the status, hot spots, and frontiers of 3DP in spine surgery and associated research disciplines. METHODS: All publications relating to the utilization of 3DP in spine surgery from 1999 to May 9, 2022, were retrieved from the Web of Science. The bibliometric analysis was performed using CiteSpace software, and information on the country, institution, author, journal, and keywords for each publication was collected. RESULTS: A total of 270 articles were identified. From 2016 onward, a significant increase in publications on spinal surgery was observed. China was the most productive and influential country (98 publications) and H-index (22), followed by the USA and Australia. The most productive institution was Capital Medical University (9 publications). P. S. D'urso (8 publications, 46 citations) and R. J. Mobbs (8 publications, 39 citations) were the most prolific authors. European Spine Journal contributed the highest number of publications. The eight main clusters were: "rapid prototyping" #0, "3D printed" #1, "spine fusion" #2, "scoliosis" #3, "spine surgery" #4, "patient-specific" #5, "nervous system" #6, and "neuronavigation" #7. The strongest keyword bursts in 3DP in spine surgery were "fixation," "drill template," "instrumentation," "fusion," "complication," and "atlantoaxial instability." CONCLUSION: This analysis provides information on research trends and frontiers in the application of 3DP in spine surgery, as well as research and collaboration partners, institutions, and countries.


Assuntos
Impressão Tridimensional , Escoliose , Humanos , Austrália , Bibliometria , China
2.
J Labelled Comp Radiopharm ; 66(12): 384-392, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37615234

RESUMO

The vesicular acetylcholine transporter (VAChT) in the brain is an important presynaptic cholinergic biomarker, and neuroimaging studies of VAChT may provide in vivo information about psychiatric and neurologic conditions including Alzheimer's disease that are not accessible by other methods. The 18 F-labeled radiotracer, ((-)-(1-(-8-(2-[18 F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone ([18 F]VAT, 1), was reported as a selective and high affinity ligand for the in vivo imaging of VAChT. The synthesis of [18 F]VAT has been reported in a two-step procedure with total 140 min, which includes preparation of 2-[18 F]fluoroethyltosylate and alkylation of benzovesamicol (-)-5 precursor with this radiosynthon using two different automated production modules consecutively. A multiple step synthetic route was employed for the synthesis of stereospecific precursor benzovesamicol (-)-5, which is difficult to be adapted for scale-up. To make the production of this tracer more amenable for clinical imaging, we present an improved total synthesis protocol to attain [18 F]VAT: (1) a tosylethoxy group being pre-installed tosylate precursor (-)-8 is synthesized to render a simple one-step radiofluorination under mild conditions; (2) The key optically active intermediate benzovesamicol (-)-5 was obtained via the regio- and enantio-enriched ring-opening amination of meso-epoxide 3 with 4-phenylpiperidine derivative 2 under catalysis of a chiral salenCo(III) catalyst 4b, which dramatically simplifies the synthetic route of the tosylate precursor (-)-8. [18 F]VAT 1 was prepared within ~65 min with desired chemical and radiochemical purities, via a fully automated procedure, using a commercial PET tracer production module. The final drug product was obtained as a sterile, pyrogen-free solution that conforms United States Pharmacopeia (USP) <823> requirements.


Assuntos
Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Encéfalo/metabolismo , Neuroimagem , Proteínas Vesiculares de Transporte de Acetilcolina/metabolismo
3.
Eur J Orthop Surg Traumatol ; 33(4): 1439-1440, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35031849

RESUMO

A recent article entitled "Full­endoscopic (bi­portal or uni­portal) versus microscopic lumbar decompression laminectomy in patients with spinal stenosis: systematic review and meta­analysis" written by Pairuchvej et al. (Eur J Orthop Surg Traumatol 30(4):595-611, 2019) published in "European Journal of Orthopaedic Surgery & Traumatology" has aroused our great interest. The authors concluded that compared with minimally invasive decompression surgery, full endoscopic spinal surgery had better pain relief (back pain and leg pain) in the treatment of lumbar spinal stenosis and had a lower complication rate, but no statistical difference in oswestry disability index score and operative time between both groups. Comparing to minimally invasive spinal surgery, bi-portal endoscopic spinal surgery had better back pain relief in the early stage, while uni-portal full endoscopic spinal surgery had better pain relief in the leg and a lower rate of complications.


Assuntos
Laminectomia , Estenose Espinal , Humanos , Descompressão Cirúrgica , Estenose Espinal/cirurgia , Vértebras Lombares/cirurgia , Resultado do Tratamento , Endoscopia , Dor/complicações
4.
Int Orthop ; 46(7): 1597-1608, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35099577

RESUMO

PURPOSE: To determine trends and hot subjects in the field of oblique lumbar interbody fusion (OLIF) research during the last decade using bibliometric analysis and visualization tools, in order to assist researchers in exploring new directions for future research in that field. METHODS: Articles published from January 1, 2012, to August 15, 2021, were screened in the Web of Science database. The data were analyzed with CiteSpace software, which generated visualization knowledge maps. All literature was assessed for the following parameters: the number of total publications, distribution, h-index, institutions, journals, authors, co-occurrence state, and research hotspots. RESULTS: A total of 173 articles were identified. The country with the largest number of articles was China (41.04%), followed by South Korea (20.81%), the USA (15.61%), Japan (9.83%), and Thailand (2.89%). South Korea and the USA had the highest h-index (9), followed by China (8), Japan (7), and Thailand (2). Catholic University of Korea was the organization that produced the most literature. World Neurosurgery published the most papers about OLIF (12.50%), but articles in Spine were most frequently cited (151). Kim JS was the most productive author, whereas Silvestre C was the most cited author. The main research hotspots are anatomy, discectomy, approach, injure, and diseases. CONCLUSIONS: The number of publications in the field of OLIF has increased considerably in recent years. The USA, China, South Korea, and Japan have made substantial contributions to this field. Anatomy, complications, decompression surgery, and application in various degenerative lumbar diseases have been the research hotspots in recent years.


Assuntos
Bibliometria , Publicações , Humanos , Região Lombossacral , Procedimentos Neurocirúrgicos , Coluna Vertebral/cirurgia
5.
Medicina (Kaunas) ; 58(12)2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36557019

RESUMO

Background: Surgical incision pain, rebound pain, and recurrence can manifest themselves in different forms of postoperative pain after full endoscopic lumbar discectomy (FELD). This study aims to evaluate various postoperative pains after FELD and summarize their characteristics. Methods: Data about the demographic characteristics of patients, pain intensity, and functional assessment results were collected from January 2016 to September 2019. Clinical outcomes including Oswestry Disability Index (ODI) and visual analog scale (VAS) scores, were obtained. Results: A total of 206 patients were enrolled. ODI and VAS of the patients significantly decreased after FELD at 12-month follow-up. A total of 193 (93.7%) patients had mild surgical incision pain after FELD and generally a VAS < 4, and it mostly resolved on its own within 3 days. A total of 12 (5.8%) patients experienced rebound pain, which was typically characterized by pain (mainly leg pain with or without back pain), generally occurring within 2 weeks after FELD and lasting < 3 weeks. The pain levels of rebound pain were equal to or less than those of preoperative pain, and generally scored a VAS of < 6. The recurrence rate was 4.4%. Recurrence often occurs within three months after surgery, with the pain level of the recurrence being greater than or equal to the preoperative pain. Conclusions: Different types of postoperative pain have their own unique characteristics and durations, and treatment options are also distinct. Conservative treatment and analgesia may be indicated for rebound pain and surgical incision pain, but recurrence usually requires surgical treatment.


Assuntos
Deslocamento do Disco Intervertebral , Ferida Cirúrgica , Humanos , Deslocamento do Disco Intervertebral/cirurgia , Resultado do Tratamento , Vértebras Lombares/cirurgia , Discotomia/efeitos adversos , Discotomia/métodos , Endoscopia/efeitos adversos , Endoscopia/métodos , Dor nas Costas , Dor Pós-Operatória/etiologia , Estudos Retrospectivos
6.
BMC Gastroenterol ; 20(1): 262, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770945

RESUMO

BACKGROUND: Delayed bowel obstruction due to seat belt injury is extremely rare. The delayed onset of nonspecific symptoms makes a timely diagnosis difficult. A deep understanding of the characteristics of this condition is helpful for early diagnosis and treatment. CASE PRESENTATION: A 39-year-old male was transferred to our hospital from another hospital complaints of progressive abdominal distension and severe weakness. In the previous hospital, he was diagnosed with "adult megacolon" and was recommended for surgical treatment. In our hospital, he was diagnosed with delayed bowel obstruction due to seat belt injury and underwent surgical intervention. Following laparoscopic adhesiolysis and resection of the narrow small intestine, his symptoms improved rapidly, and he was discharged. CONCLUSION: Delayed bowel obstruction due to seat belt injury may present clinical symptoms any time after the injury. Imaging examination, ileus tube and small colonoscopy may provide us with valuable cues for the diagnosis and treatment of delayed bowel obstruction, and laparoscopy may be an alternative approach in surgical intervention.


Assuntos
Traumatismos Abdominais , Íleus , Obstrução Intestinal , Traumatismos Abdominais/complicações , Traumatismos Abdominais/cirurgia , Adulto , Humanos , Íleus/etiologia , Íleus/cirurgia , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Intestino Delgado , Masculino , Cintos de Segurança/efeitos adversos
7.
Proc Natl Acad Sci U S A ; 114(45): 11974-11979, 2017 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-29078333

RESUMO

Pluripotency of embryonic stem cells (ESCs) can be functionally assessed according to the developmental potency. Tetraploid complementation, through which an entire organism is produced from the pluripotent donor cells, is taken as the most stringent test for pluripotency. It remains unclear whether ESCs of other species besides mice can pass this test. Here we show that the rat ESCs derived under 2i (two small molecule inhibitors) conditions at very early passages are able to produce fertile offspring by tetraploid complementation. However, they lose this capacity rapidly during culture due to a nearly complete loss of genomic imprinting. Our findings support that the naïve ground state pluripotency can be captured in rat ESCs but also point to the species-specific differences in its regulation and maintenance, which have implications for the derivation and application of naïve pluripotent stem cells in other species including human.


Assuntos
Embrião de Mamíferos/citologia , Desenvolvimento Embrionário/fisiologia , Células-Tronco Embrionárias/citologia , Células-Tronco Pluripotentes/citologia , Animais , Diferenciação Celular , Células Cultivadas , Feminino , Teste de Complementação Genética , Camundongos , Ratos , Ratos Endogâmicos F344 , Tetraploidia
9.
J Labelled Comp Radiopharm ; 61(14): 1069-1080, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30289176

RESUMO

6-[18 F]Fluorodopamine ([18 F]F-DA) is taken into cells via the norepinephrine transporter (NET). Recent [18 F]F-DA positron emission tomography-computed tomography (PET-CT) imaging of adult neuroendocrine tumors shows a dramatic improvement in sensitivity over the standard-of-care, meta-iodobenzylguanidine (MIBG) single-photon emission computed tomography (SPECT)-CT. A new precursor (ALPdopamine™) allows no-carrier-added synthesis resulting in high-molar activity [18 F]F-DA. Automated synthesis of [18 F]F-DA was performed in a single reactor using a two-step procedure: 1) fluorination via thermolysis of a diaryliodonium salt precursor, followed by 2) acid hydrolysis. Phase transfer agents, Kryptofix 222 and two tetraalkylammonium salts, were investigated. Optimized synthesis of [18 F]F-DA was achieved in 56 to 60 minutes (26% end of synthesis [EOS], nondecay corrected). The product passed all Food and Drug Administration (FDA)-required quality control testing for human use. Accumulation of [18 F]F-DA in SK-N-BE(2)-C (high NET expression) cells was significantly higher than in SH-EP (minimal NET expression) cells (P < 0.0001). ALPdopamine provides an effective scaffold for the routine production of [18 F]F-DA for human use. Validation of uptake by neuroblastoma (NB) cell lines supports the use of [18 F]F-DA for imaging NB patients. A pediatric NB imaging trial using [18 F]F-DA PET has been approved (Investigational New Drug application (IND) no. 138638) based on the methods reported here. We expect [18 F]F-DA will be localized in NB tumors and that high-quality functional images will be obtained within minutes after injection.


Assuntos
Dopamina/análogos & derivados , Neuroblastoma/diagnóstico por imagem , Transporte Biológico , Linhagem Celular Tumoral , Técnicas de Química Sintética , Dopamina/síntese química , Dopamina/química , Dopamina/metabolismo , Humanos , Neuroblastoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Controle de Qualidade , Radioquímica
10.
Neural Comput ; 29(5): 1151-1203, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28181880

RESUMO

This review examines the relevance of parameter identifiability for statistical models used in machine learning. In addition to defining main concepts, we address several issues of identifiability closely related to machine learning, showing the advantages and disadvantages of state-of-the-art research and demonstrating recent progress. First, we review criteria for determining the parameter structure of models from the literature. This has three related issues: parameter identifiability, parameter redundancy, and reparameterization. Second, we review the deep influence of identifiability on various aspects of machine learning from theoretical and application viewpoints. In addition to illustrating the utility and influence of identifiability, we emphasize the interplay among identifiability theory, machine learning, mathematical statistics, information theory, optimization theory, information geometry, Riemann geometry, symbolic computation, Bayesian inference, algebraic geometry, and others. Finally, we present a new perspective together with the associated challenges.

11.
Org Biomol Chem ; 15(10): 2246-2252, 2017 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-28230886

RESUMO

Aniline-derived diaryliodonium salts were synthesized and functionalized in good to excellent yields by judicious utilization of electron-withdrawing protecting groups. This simple approach opens another route to radiolabeling amino arenes in relatively complex molecules, such as flutemetamol.

12.
Proc Natl Acad Sci U S A ; 111(12): 4495-500, 2014 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-24616523

RESUMO

The process of nitrite-dependent anaerobic methane oxidation (n-damo) was recently discovered and shown to be mediated by "Candidatus Methylomirabilis oxyfera" (M. oxyfera). Here, evidence for n-damo in three different freshwater wetlands located in southeastern China was obtained using stable isotope measurements, quantitative PCR assays, and 16S rRNA and particulate methane monooxygenase gene clone library analyses. Stable isotope experiments confirmed the occurrence of n-damo in the examined wetlands, and the potential n-damo rates ranged from 0.31 to 5.43 nmol CO2 per gram of dry soil per day at different depths of soil cores. A combined analysis of 16S rRNA and particulate methane monooxygenase genes demonstrated that M. oxyfera-like bacteria were mainly present in the deep soil with a maximum abundance of 3.2 × 10(7) gene copies per gram of dry soil. It is estimated that ∼0.51 g of CH4 m(-2) per year could be linked to the n-damo process in the examined wetlands based on the measured potential n-damo rates. This study presents previously unidentified confirmation that the n-damo process is a previously overlooked microbial methane sink in wetlands, and n-damo has the potential to be a globally important methane sink due to increasing nitrogen pollution.


Assuntos
Anaerobiose , Bactérias/metabolismo , Metano/metabolismo , Áreas Alagadas , Bactérias/classificação , Bactérias/genética , Genes Bacterianos , Dados de Sequência Molecular , Oxirredução , Filogenia , RNA Ribossômico 16S/genética
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(1): 44-48, 2017 Jan.
Artigo em Zh | MEDLINE | ID: mdl-28100321

RESUMO

OBJECTIVE: To study the clinical effect and mechanism of action of esmolol in the treatment of severe hand, foot, and mouth disease (HFMD). METHODS: A prospective randomized controlled trial was performed. A total of 102 children with severe HFMD were enrolled in the study and were randomly divided into conventional treatment and esmolol treatment groups (n=51 each). The children in the conventional treatment group were given conventional treatment according to the guidelines for the diagnosis and treatment of HFMD. Those in the esmolol treatment group were given esmolol in addition to the conventional treatment. The heart rate (HR), systolic blood pressure (SBP), and respiratory rate (RR) were continuously monitored for all children. Blood samples were collected from all children before treatment and 1, 3, and 5 days after treatment to measure the levels of norepinephrine (NE), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB) p65 in mononuclear cells. Serum levels of myocardial enzymes and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before treatment and after 5 days of treatment. RESULTS: There were no significant differences in HR, SBP, RR, NE, TNF-α, IL-6, NF-κB p65, serum myocardial enzymes, and NT-proBNP before treatment between the conventional treatment and esmolol treatment groups. Both groups had significant reductions in these parameters at each time point (P<0.05). Compared with the conventional treatment group, the esmolol treatment group had significant improvements in the above parameters after 1 and 3 days of treatment (P<0.05). After 5 days of treatment, the esmolol treatment group had significant improvements in serum levels of myocardial enzymes and NT-proBNP compared with the conventional treatment group (P<0.05). CONCLUSIONS: Early application of esmolol can effectively stabilize the vital signs of the children with severe HFMD. Its mechanism of action may be related to reducing serum catecholamine concentration, alleviating myocardial damage, improving cardiac function, and reducing inflammatory response.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Doença de Mão, Pé e Boca/tratamento farmacológico , Propanolaminas/uso terapêutico , Pré-Escolar , Feminino , Doença de Mão, Pé e Boca/sangue , Doença de Mão, Pé e Boca/fisiopatologia , Humanos , Lactente , Interleucina-6/sangue , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Propanolaminas/farmacologia , Estudos Prospectivos , Fator de Necrose Tumoral alfa/sangue
15.
Appl Microbiol Biotechnol ; 100(16): 7171-80, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27225473

RESUMO

In the current study, we investigated nitrite-dependent anaerobic methane oxidation (N-DAMO) as a potential methane sink in the Hangzhou Bay and the adjacent Zhoushan sea area. The potential activity of the N-DAMO process was primarily observed in Hangzhou Bay by means of (13)C-labeling experiments, whereas very low or no potential N-DAMO activity could be detected in the Zhoushan sea area. The measured potential N-DAMO rates ranged from 0.2 to 1.3 nmol (13)CO2 g(-1) (dry sediment) day(-1), and the N-DAMO potentially contributed 2.0-9.4 % to the total microbial methane oxidation in the examined sediments. This indicated that the N-DAMO process may be an alternative pathway in the coastal methane cycle. Phylogenetic analyses confirmed the presence of Candidatus Methylomirabilis oxyfera-like bacteria in all the examined sediments, while the group A members (the dominant bacteria responsible for N-DAMO) were found mainly in Hangzhou Bay. Quantitative PCR showed that the 16S rRNA gene abundance of Candidatus M. oxyfera-like bacteria varied from 5.4 × 10(6) to 5.0 × 10(7) copies g(-1) (dry sediment), with a higher abundance observed in Hangzhou Bay. In addition, the overlying water NO3 (-) concentration and salinity were identified as the most important factors influencing the abundance and potential activity of Candidatus M. oxyfera-like bacteria in the examined sediments. This study showed the evidence of N-DAMO in coastal environments and indicated the importance of N-DAMO as a potential methane sink in coastal environments.


Assuntos
Bactérias/metabolismo , Baías/microbiologia , Sedimentos Geológicos/microbiologia , Metano/metabolismo , Nitratos/química , Nitritos/química , Anaerobiose , Sequência de Bases , DNA Bacteriano/genética , Marcação por Isótopo , Oxirredução , Filogenia , RNA Ribossômico 16S/genética , Salinidade , Análise de Sequência de DNA , Microbiologia do Solo
16.
Artigo em Zh | MEDLINE | ID: mdl-30120919

RESUMO

Objective: To clone and express the Tibetan Sheep-origin Echinococcus granulosus Antigen B8/2 Gene, and immunologically identify the encoded protein. Methods: The cDNA of EgAgB8/2 gene was amplified by RT-PCR. The prokaryotic expression vector pET-EgAgB8/2 was constructed and transformed into E. coli BL21(DE3) for expression. Proteins were extracted, separated in SDS-PAGE and identified by Western blotting. Results: The cloned EgAgB8/2 gene was 335 bp in length, and had a 98%-100% sequence homology with the reported cDNA sequence of EgAgB8/2, indicating the successful construction of the pET-EgAgB8/2 vector. SDS-PAGE revealed large amount of proteins in supernatant. Western blotting further confirmed the expression of the target protein. Conclusion: The EgAgB8/2 gene of Tibetan Sheep-origin in Qinghai is successfully cloned, and the constructed pET-EgAgB8/2 vector can be used to express the target protein.


Assuntos
Echinococcus granulosus , Animais , Antígenos de Helmintos , Western Blotting , Clonagem Molecular , DNA Complementar , Escherichia coli , Lipoproteínas , Ovinos , Tibet
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(11): 1065-1068, 2016 Nov.
Artigo em Zh | MEDLINE | ID: mdl-27817766

RESUMO

OBJECTIVE: To investigate the clinical effect and safety of somatostatin in the treatment of postoperative gastrointestinal bleeding in neonates. METHODS: A prospective randomized study was performed, and 126 neonates who underwent surgery for congenital gastrointestinal anomalies were randomly divided into control group, treatment group A, and treatment group B. The neonates in the control group were given routine postoperative hemostasis, and those in the treatment groups were given somatostatin in addition to the treatment for the control group. The neonates in treatment group A were given intravenous injection of somatostatin 0.25 mg as the initial dose and 0.25 mg/h for maintenance, and those in treatment group B were given continuous intravenous pumping of somatostatin at a dose of 3.5 µg/(kg·h). The clinical outcome and complications were compared between the three groups. RESULTS: Compared with the control group, the treatment groups had significantly shortened clearance time in occult blood test for gastrointestinal decompression drainage and a significantly lower degree of the reduction in 24-hour hemoglobin (P<0.05), while there were no significant differences between treatment groups A and B. Compared with the control group, treatment group A had significant reductions in heart rate (HR), respiratory rate (RR), blood pressure (BP), and SaO2 after one hour of treatment (P<0.05 ), but there were no significant differences at the other time points between the two groups (P>0.05). There were no significant differences in monitoring indices between the control group and treatment group B (P>0.05). No neonates in the control group experienced hypoglycemia reaction, and treatment group A had a significantly higher incidence rate of hypoglycemia (20%) than treatment group B (P<0.05). CONCLUSIONS: Somatostatin has a marked clinical effect and good safety in the treatment of neonates with postoperative gastrointestinal bleeding, and the administration of somatostatin by continuous intravenous pumping leads to fewer side effects.


Assuntos
Hemorragia Gastrointestinal/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Somatostatina/uso terapêutico , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Prospectivos , Somatostatina/efeitos adversos
18.
J Hepatol ; 63(4): 886-95, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26024833

RESUMO

BACKGROUND & AIMS: Long non-coding RNA Hotair has been considered as a pro-oncogene in multiple cancers. Although there is emerging evidence that reveals its biological function and the association with clinical prognosis, the precise mechanism remains largely elusive. METHODS: We investigated the function and mechanism of Hotair in hepatocellular carcinoma (HCC) cell models and a xenograft mouse model. The regulatory network between miR-218 and Hotair was elucidated by RNA immunoprecipitation and luciferase reporter assays. Finally, the correlation between Hotair, miR-218 and the target gene Bmi-1 were evaluated in 52 paired HCC specimens. RESULTS: In this study, we reported that Hotair negatively regulated miR-218 expression in HCC, which might be mediated through an EZH2-targeting-miR-218-2 promoter regulatory axis. Further investigation revealed that Hotair knockdown dramatically inhibited cell viability and induced G1-phase arrest in vitro and suppressed tumorigenicity in vivo by promoting miR-218 expression. Oncogene Bmi-1 was shown to be a functional target of miR-218, and the main downstream targets signaling, P16(Ink4a) and P14(ARF), were activated in Hotair-suppressed tumorigenesis. In primary human HCC specimens, Hotair and Bmi-1 were concordantly upregulated whereas miR-218 was downregulated in these tissues. Furthermore, Hotair was inversely associated with miR-218 expression and positively correlated with Bmi-1 expression in these clinical tissues. CONCLUSION: Hotair silence activates P16(Ink4a) and P14(ARF) signaling by enhancing miR-218 expression and suppressing Bmi-1 expression, resulting in the suppression of tumorigenesis in HCC.


Assuntos
Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas Experimentais/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Proteínas/genética , RNA Longo não Codificante/genética , Animais , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Inibidor p16 de Quinase Dependente de Ciclina , Humanos , Imunoprecipitação , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Camundongos , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , Regiões Promotoras Genéticas , Proteínas/metabolismo , RNA Longo não Codificante/biossíntese , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética
19.
Oncology ; 89(1): 23-30, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25613214

RESUMO

OBJECTIVES: It was the aim of this study to find an optimal therapeutic regimen of transarterial chemoembolization (TACE) by comparing the efficacy of chemoembolization with different anticancer agents in hepatocellular carcinoma (HCC) patients. METHODS: A single-blind, three-group parallel, randomized trial was conducted in Guangdong General Hospital, Guangzhou, China, with patients with biopsy-confirmed HCC. Group 1 received single-drug (doxorubicin) chemoembolization, while group 2 received double-drug (doxorubicin and mitomycin C) chemoembolization. Patients in group 3 were treated with triple-drug (doxorubicin, mitomycin C, and gemcitabine) chemoembolization. Lipiodol was used as embolization agent in all protocols. We compared the overall survival (OS), time to progression (TTP), and objective response rate (ORR) between groups. Response assessment was performed according to modified RECIST (Response Evaluation Criteria In Solid Tumors) criteria. RESULTS: Between January 2008 and January 2011, 162 patients (group 1, n = 50; group 2, n = 59; group 3, n = 53) were recruited. The OS and TTP in groups 1, 2, and 3 were 14.9 and 6.4, 13.2 and 6.4, and 20.5 and 6.8 months, respectively. OS and TTP were statistically significant among groups (p = 0.002 and p = 0.037). The ORR was 22.0, 40.7, and 56.6%, respectively. The ORR was significantly different across the three groups (p < 0.002). CONCLUSIONS: TACE with multiple chemotherapeutic agents might significantly increase survival and tumor response; additionally, gemcitabine was likely to have an advantage in improving the prognosis of HCC patients. © 2015 S. Karger AG, Basel.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/métodos , Doxorrubicina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/mortalidade , China , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Seguimentos , Artéria Hepática , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Método Simples-Cego , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Gencitabina
20.
Chemistry ; 21(17): 6394-8, 2015 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-25757054

RESUMO

Iodoarenes are important synthons for a wide range of organic transformations. Here we report a general strategy to prepare singly iodinated electron-rich aromatic compounds through the intermediacy of diaryliodonium salts. This process, which incorporates a phase separation that greatly simplifies product purification, is an attractive replacement for the Sandmeyer approach to iodoarenes that are otherwise difficult to access.


Assuntos
Hidrocarbonetos Iodados/síntese química , Hidrocarbonetos Iodados/química , Modelos Químicos , Estrutura Molecular , Sais
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