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BACKGROUND: The effect of a combination of a goal-directed fluid protocol and preoperative carbohydrate loading on postoperative complications in elderly patients still remains unknown. Therefore, we designed this trial to evaluate the relative impact of preoperative carbohydrate loading and intraoperative goal-directed fluid therapy versus conventional fluid therapy (CFT) on clinical outcomes in elderly patients following gastrointestinal surgery. METHODS: This prospective randomized controlled trial with 120 patients over 65 years undergoing gastrointestinal surgery were randomized into a CFT group (n = 60) with traditional methods of fasting and water-deprivation, and a GDFT group (n = 60) with carbohydrate (200 ml) loading 2 h before surgery. The CFT group underwent routine monitoring during surgery, however, the GDFT group was conducted by a Vigileo/FloTrac monitor with cardiac index (CI), stroke volume variation (SVV), and mean arterial pressure (MAP). For all patients, demographic data, intraoperative parameters and postoperative outcomes were recorded. RESULTS: Patients in the GDFT group received significantly less crystalloids fluid (1111 ± 442.9 ml vs 1411 ± 412.6 ml; p < 0.001) and produced significantly less urine output (200 ml [150-300] vs 400 ml [290-500]; p < 0.001) as compared to the CFT group. Moreover, GDFT was associated with a shorter average time to first flatus (56 ± 14.1 h vs 64 ± 22.3 h; p = 0.002) and oral intake (72 ± 16.9 h vs 85 ± 26.8 h; p = 0.011), as well as a reduction in the rate of postoperative complications (15 (25.0%) vs 29 (48.3%) patients; p = 0.013). However, postoperative hospitalization or hospitalization expenses were similar between groups (p > 0.05). CONCLUSIONS: Focused on elderly patients undergoing open gastrointestinal surgery, we found perioperative fluid optimisation may be associated with improvement of bowel function and a lower incidence of postoperative complications. TRIAL REGISTRATION: ChiCTR, ChiCTR1800018227 . Registered 6 September 2018 - Retrospectively registered.
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Dieta da Carga de Carboidratos/métodos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Hidratação/métodos , Cuidados Intraoperatórios/métodos , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Idoso , Feminino , Avaliação Geriátrica/métodos , Objetivos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Estudos Prospectivos , Resultado do TratamentoRESUMO
Drug resistance is one characteristic of hepatocellular carcinoma (HCC) and can affect the prognosis of patients directly. To explore drug resistance well, we established an oxaliplatin (OXA)-resistant cell line Bel-7402/OXA by exposure to gradually increased concentration of OXA. Some biological characters, such as proliferation, migration, and invasion, were studied. Drug sensitivity and the mechanisms of drug resistance were also investigated. We found that the resistant index of Bel-7402/OXA was 8.3. In comparison with Bel-7402, the percentages of cells in S and G2/M phase were increased. The nature apoptosis rate and drug-after apoptosis rate were all decreased in Bel-7402/OXA, as compared to Bel-7402. Bel-7402/OXA acquired increased migration and invasion ability with epithelial-mesenchymal transition (EMT) phenotype. Knockdown of EMT transcription factor Snail could reverse EMT and sensitized Bel-7402/OXA cells to OXA. EMT was one mechanism of drug resistance and may be a novel target of treatment for drug resistance.
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Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/patologia , Compostos Organoplatínicos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/genética , Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Camundongos , Oxaliplatina , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND AND AIMS: This study investigated the feasibility, safety, and efficacy of transarterial chemoembolization (TACE) combined with CT-guided 125iodine seed implantation for treatment of hepatocellular carcinoma (HCC) with first-branch portal vein tumor thrombosis (PVTT). METHODS: This prospective, controlled, multicenter study included HCC patients with Barcelona Clinic Liver Cancer stage C disease and PVTT in the right and/or left portal veins. Patients were treated with either TACE and sorafenib or TACE and CT-guided 125iodine seed implantation and regularly evaluated for clinical response and adverse events, with treatment termination resulting from declining clinical status, loss to follow-up, or death. RESULTS: This study demonstrated a significant between-group difference in median overall survival (OS); therefore, it was terminated early. A total of 123 patients were included in this study, with 52 patients in the TACE-sorafenib group and 71 patients in the TACE-125iodine group, without significant differences in baseline characteristics between groups. The median OS was 8.3 months (95% CI: 6.105-10.495) in the TACE-sorafenib group and 13.8 months (95% CI: 9.519-18.081) in the TACE-125iodine group. In a subgroup analysis of type IIa versus type IIb PVTT, the median OS was 17.5 months for type IIa and 7.1 months for IIb in the TACE-125iodine group. The median OS was 9.3 months for IIa and 4.0 months for IIb in the TACE-sorafenib group. Univariate and multivariate analyses confirmed that the PVTT type and treatment strategy were significant independent factors affecting OS. The objective response rates (ORR) for intrahepatic lesions and PVTT showed significant differences between groups. Most patients in both groups experienced minor adverse events related to TACE. The overall incidence of sorafenib-related adverse events or toxic effects was 90.4% in TACE-sorafenib group. In the TACE-125iodine group, the incidence of pneumothorax and minor hepatic subcapsular hemorrhage were 7.04% and 9.86%, respectively. CONCLUSIONS: This study showed that TACE-125iodine treatment significantly enhanced survival of patients with HCC and type II PVTT, especially subtype IIa, with minimal adverse events. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trials Database, identifier ChiCTR-ONN-16007929.
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Graphene-based strain sensors have attracted tremendous interest due to their potential application as intelligent wearable sensing devices. However, for graphene-based strain sensors, it is found that the sensing property at the beginning of the tensile cycle is not stable. Concretely, the peak resistance value gradually declines in the first dozens of cycles in every cyclic test. This is a problem that obviously affects the measurement accuracy but is rarely investigated so far. In this paper, this phenomenon is for the first time systematically studied. According to the reliable experimental results, it can be concluded that the decline of resistance is caused by the evolution of wrinkle morphologies in the graphene layer, which is essentially attributed to the temporary slippage of the graphene sheets under external stress. Based on the analyzed mechanism, a targeted improvement solution was proposed and verified. By the combined effects of polydopamine and Ni2+, the slippage among the rGO sheets was suppressed and a strain sensor with excellent sensing stability was obtained as expected. Furthermore, the sensitivity of the modified sensor was six times higher than that of the pristine one due to the change in the crack form, demonstrating it to be an effective method to obtain a graphene-based strain sensor with comprehensively high performance.
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Voltage-gated outward K(+) currents from pancreatic islet beta-cells are known to repolarize the action potential during a glucose stimulus, and consequently to modulate Ca(2+) entry and insulin secretion. The voltage gated K(+) (Kv) channel, Kv2.1, which is expressed in rat islet beta-cells, mediates over 60% of the Kv outward K(+) currents. A novel peptidyl inhibitor of Kv2.1/Kv2.2 channels, guangxitoxin (GxTX)-1, has been shown to enhance glucose-stimulated insulin secretion. Here, we show that SNAP-25(1-180) (S180), an N-terminal SNAP-25 domain, but not SNAP-25(1-206) (S206), inhibits Kv current and enhances glucose-dependent insulin secretion from rat pancreatic islet beta-cells, and furthermore, this enhancement was induced by the blockade of the Kv2.1 current. This study indicates that the Kv2.1 channel is a potential target for novel therapeutic agent design for the treatment of type 2 diabetes. This target may possess advantages over currently-used therapies, which modulate insulin secretion in a glucose-independent manner.
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Hipoglicemiantes/farmacologia , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Canais de Potássio Shab/antagonistas & inibidores , Proteína 25 Associada a Sinaptossoma/farmacologia , Animais , Glucose/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Masculino , Estrutura Terciária de Proteína , Ratos , Ratos Wistar , Canais de Potássio Shab/metabolismo , Proteína 25 Associada a Sinaptossoma/químicaRESUMO
BACKGROUND: Several epidemiology studies have explored the association between dietary B vitamins' intake and the risk of esophageal cancer (EC). However, the results remain inconclusive. Thus, we conducted a systematic review with meta-analysis to evaluate such association. METHODS: Literature retrieval was performed using PubMed (Medline), ScienceDirect, and Cochrane Library electronic databases for all studies published from database inception to December 2017. RESULTS: The meta-analysis included 19 studies and showed an overall decreased risk of EC (OR=0.77, 95% CI: 0.68-0.87) in association with multivitamin B (ie, B1, B2, B3, B5, B6, B9, and B12) dietary intake. In a subgroup analysis based on vitamin B subclass, B1, B3, B6, and B9 vitamins were associated with decreased EC risk (vitamin B1: OR=0.68, 95% CI: 0.56-0.82; vitamin B3: OR=0.70, 95% CI: 0.53-0.94; vitamin B6: OR=0.64, 95% CI: 0.49-0.83; and vitamin B9: OR=0.69, 95% CI: 0.55-0.86). By contrast, no association was detected between dietary vitamin B2 and vitamin B5 intake and EC risk (vitamin B2: OR=0.86, 95% CI: 0.64-1.16; vitamin B5: OR=0.49, 95% CI: 0.20-1.20), whereas a potential non-linear dose-response association was found between dietary vitamin B12 intake and EC risk. A statistically significant, inverse association was observed for an increase of 100 µg/day in supplemental vitamin B6 and B9 and EC risk (vitamin B6: OR=0.98, 95% CI: 0.98-0.99; vitamin B9: OR= 0.89; 95% CI: 0.86-0.94). CONCLUSION: These findings support that vitamin B may have an influence on carcinogenesis of the esophagus. Vitamin B1, B3, B6, B9 showed a decreased risk of EC, and vitamin B12 showed an increased risk of EC.
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AIM: To investigate the effect of integrin-linked kinase (ILK) on proliferation, metastasis, and invasion of the colorectal cancer cell line SW480. METHODS: In this study, the colorectal cancer cell line SW480 was stably transfected with ILK plasmids, and small interfering RNA (siRNA) was used to knockdown expression of nuclear factor (NF)-κB/p65. Methylthiazole tetrazolium (MTT) assay was performed to measure proliferation, and the wound healing migration assay and matrigel invasion assay were used to test the metastasis and invasion ability of SW480 cells. To explore the epithelial-mesenchymal transition (EMT) process, embryonic development, and the invasion and metastasis of tumors, the protein level of E-cadherin, vimentin, snail, and slug was detected by western blot. Immunofluorescence was also used to detect E-cadherin expression. Western blot was used to determine the level of phosphorylated-inhibitor of kappa B (IκB)a, inhibitor of gamma B (IγB)a, and nuclear factor kappa B (NF-κB) expressions and to explore the ILK signaling pathway. RESULTS: Western blot results revealed that ILK expression significantly increased when ILK was overexpressed in SW480 cells (P < 0.05). Proliferation, metastasis, and invasion ability were improved in the vector-ILK group compared to the vector group (P < 0.05). Immunofluorescence results revealed that E-cadherin fluorescence intensity decreased after ILK was overexpressed (P < 0.05). Western blot results revealed that the protein expression of E-cadherin was reduced, while vimentin, snail, and slug were upregulated when ILK was overexpressed in SW480 cells (P < 0.05). In order to determine the role of the NF-κB signaling pathway in ILK overexpression promoted EMT occurrence, we overexpressed ILK in SW480 cells and found that levels of NF-κB/p65 and cytoplasmic phosphorylated-IκBa were increased and that cytoplasmic IкBa levels were decreased compared to the control group (P < 0.05). Furthermore, NF-κB/p65 knockout revealed that E-cadherin was increased in the overexpressed ILK group. CONCLUSION: ILK overexpression improved the proliferation, metastasis, and invasion ability of SW480 cells, and this effect may be mediated by the NF-κB signaling pathway.
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Neoplasias Colorretais/enzimologia , Transição Epitelial-Mesenquimal , Proteínas Serina-Treonina Quinases/biossíntese , Transdução de Sinais , Fator de Transcrição RelA/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Indução Enzimática , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Neoplásica , Proteínas Serina-Treonina Quinases/genética , Interferência de RNA , Fatores de Tempo , Fator de Transcrição RelA/genética , TransfecçãoRESUMO
This study evaluated the factors impacting overall survival (OS) and time to progression (TTP) in patients with unresectable hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE). HCC patients were grouped based on tumor vascularity and lipidiol deposition after TACE. Tumor vascularity was classified based on contrast enhancement on arterial phase baseline CT scans. Lipiodol deposition was evaluated using CT scans. The progression-free rate was significantly higher in patients with good blood supply + good lipiodol deposition compared to those with good blood supply + poor lipiodol deposition. In patients with poor lipidiol deposition, risk of death was significantly positively correlated with stage, and negatively correlated with number of TACE procedures and degree of lipidiol deposition after the first TACE. Risk of disease progression in these patients was positively correlated with tumor size, and negatively correlated with number of TACE procedures and degree of lipidiol deposition after the first TACE. Our data showed that tumor vascularity and lipiodol deposition can be used as early radiological markers to identify patients who do not respond to TACE, and who can be considered earlier for alternative combination treatment strategies. Our data also indicated that poor lipiodol retention may predict a poor TTP and OS despite the blood supply status.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica , Óleo Etiodado/uso terapêutico , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/tratamento farmacológico , Progressão da Doença , Feminino , Seguimentos , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Carga TumoralRESUMO
INTRODUCTION: The objective of the present study was to evaluate the capacity of a tissue-engineered complex of human osteoprotegerin (hOPG)-transfected periodontal ligament stem cells (PDLSCs) seeding on beta-tricalcium phosphate (ß-TCP) to regenerate alveolar bone defects in New Zealand rabbits. METHODS: PDLSCs were isolated from rabbit periodontal ligament tissues and expanded in vitro to enrich PDLSC numbers, and their proliferative activities and differentiation capability were evaluated under specific induction conditions. Lentiviral vector containing hOPG and enhanced green fluorescent protein (EGFP) was constructed by using Gateway technology and transfected into rabbit PDLSCs. The expression of hOPG was determined with quantitative real-time reverse transcription-polymerase chain reaction and Western blot. The PDLSCs with or without engineered hOPG were seeded on ß-TCP scaffolds prior to transplantation. Morphological characterization of cells and materials was done by scanning electron microscope. Twenty rabbits with alveolar bone defects were randomly allocated into four groups and transplanted with ß-TCP, PDLSCs/ß-TCP, and hOPG-transfected PDLSCs/ß-TCP or were left untreated as a control. Animals were sacrificed 12 weeks after operation for histological observation and histomorphometric analysis. RESULTS: PDLSCs expressed STRO-1 and vementin and favored osteogenesis and adipogenesis in conditioned media. Expressions of hOPG were significantly upregulated after transfection of the lentiviral vector into PDLSCs. PDLSCs attached and spread well on ß-TCP, and there was no significant difference in growth of PDLSCs on ß-TCP between the hOPG transfection group and the non-transfection group. The histological observation and histomorphometric analysis showed that the hOPG-transfected PDLSCs/ß-TCP complex exhibited an earlier mineralization and more bone formation inside the scaffold than control, ß-TCP, and PDLSCs/ß-TCP complexes. Implantation of hOPG-transfected PDLSCs contributed to new bone formation as determined by EGFP gene expression under circularly polarized light microscopy. CONCLUSIONS: The present study demonstrated the feasibility of ß-TCP scaffolds for primary PDLSC culture and expression of hOPG gene in vitro and in vivo, and hOPG-transfected PDLSCs could serve as a potential cell source for periodontal bone regeneration, which may shed light on the potential of systemic hOPG gene therapy in combination with PDLSC tissue engineering as a good candidate in periodontal tissue engineering for alveolar bone regeneration.
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Perda do Osso Alveolar/terapia , Regeneração Óssea/fisiologia , Regeneração Tecidual Guiada Periodontal/métodos , Ligamento Periodontal/citologia , Transplante de Células-Tronco , Animais , Antígenos de Superfície/metabolismo , Fosfatos de Cálcio/uso terapêutico , Diferenciação Celular , Células Cultivadas , Proteínas de Fluorescência Verde/genética , Células HEK293 , Humanos , Masculino , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Osteoprotegerina/metabolismo , Doenças Periodontais/patologia , Doenças Periodontais/terapia , Periodonto/patologia , Coelhos , Células-Tronco/citologia , Engenharia Tecidual/métodos , Alicerces TeciduaisRESUMO
There were many causes for temporomandibular joint (TMJ) ankylosis including infection, trauma, degenerative changes and space-occupying lesion. This article reported a case of bilateral TMJ ankylosis caused by systemic (distal) infection. A 35-year old female patient complained of difficulty of opening mouth for about 20 years. She developed abscess in several places all over the body including bilateral TMJ 20 years ago. CT indicated that the condylar process was fused with the temporal bone. The patient was treated with resection of bilateral condylar/coracoid process and total joint prosthesis replacement. The maximal incisal opening was 2.5 cm 3 months post operation. The patient obtained a satisfied function of eating and speaking.
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Abscesso/complicações , Anquilose/etiologia , Transtornos da Articulação Temporomandibular/etiologia , Adulto , Feminino , HumanosRESUMO
PURPOSE: To evaluate the effects of hyperglycemia and glimepiride on proliferation, differentiation and mineralization of rat mandibular osteoblasts to verify the hypothesis of dental implant administration. METHODS: Primary osteoblasts were isolated and cultured. Then the cells were placed in an osteogenic medium, containing 2 different concentrations of glucose (5.5 mmol/L and 16.5 mmol/L), with or without glimepiride (10 µmol/L). Cell proliferation was evaluated through MTT assay. Alkaline phosphatase (ALP) activity was determined by biochemistric method. Col I protein levels were determined by Western blot. OCN mRNA levels were tested by RT-PCR. SPSS 13.0 software package was used for statistical analysis. RESULTS: Hyperglycemic conditions interfered with the proliferation, ALP activity and OCN mRNA expression of rat osteoblasts, but improved the expression of Col I on day 14. Glimepiride stimulated rat osteoblast proliferation, ALP activity and OCN mRNA expression. The addition of glimepiride to normoglycemic (5.5 mmol/L) cultures registered a significant increase of Col I expression at 7 d and 14 d. Glimepiride significantly increased Col I expression in cells cultured with 16.5 mmol/L glucose for 7 days, but failed to increase at 14 d. CONCLUSIONS: Hyperglycemic conditions interfered with the proliferation, differentiation and mineralization of osteoblasts in rats; however, glimepiride improved the proliferation, differentiation and mineralization of osteoblasts in rats.
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Diferenciação Celular , Osteoblastos , Animais , Proliferação de Células , Hiperglicemia , Mandíbula , RNA Mensageiro , Ratos , Compostos de SulfonilureiaRESUMO
AIM: To investigate the action and mechanism of Syn-1A in reversing the activation of K(ATP) channel induced by weak acidic pH. METHODS: The patches excised from Kir6.2/SUR2A expressing HEK-293 cells were used to establish inside-out configuration. To examine the actions of weak acidic pH in activation of the channel and the reverse action of Syn-1A on it, the inside-out patches were continuously perfused with the solution of pH from 7.4, 7.0, 6.8, 6.5 to 6.0 with or without Syn-1A. In vitro binding was employed to study the influence of different pH to the binding of Syn-1A to SUR2A subunit. RESULTS: Syn-1A blocked pH 6.5, 6.8 and 7.0 induced activation of the channel, and Syn-1A binding to SUR2A were increased by reducing pH from 7.4 to 6.0. CONCLUSION: Syn-1A would assert some inhibition of the KATP channels, which might temper the fluctuation of acidic pH-induced K(ATP) channel opening that could induce fatal re-entrant arrhythmias.