RESUMO
Objective: To screen and analyze the differentially-expressed genes (DEGs) in primary hepatocellular carcinoma tissues and adjacent tissues using bioinformatics methods to explore the molecular mechanism of the occurrence and prognosis of primary hepatocellular carcinoma. Methods: GSE76427 data set was collected through GEO database, and DEGs were identified using GEO2R online analysis. Go and KEGG databases were used for enrichment and functional annotation of DEGs. Protein interaction network was built based on the STRING database and Cytoscape software to analyze the key genes of hepatocellular carcinoma, and the survival curve of these key genes were analyzed using the GEPIA database. Results: A total of 74 hepatocellular carcinoma DEGs were screened, of which 3 and 71 were up-and-down-regulated genes. The results of GO enrichment analysis showed that the down-regulated DEGs were mainly involved in cell response to cadmium and zinc ions, negative growth regulation, heterologous metabolic processes and hormone-mediated signaling pathways. KEGG pathway enrichment analysis results showed that the down-regulated DEGs pathway were mainly involved in retinol metabolism, chemical carcinogenesis, drug metabolism-cytochrome P450, cytochrome P450 metabolizing xenobiotics, tryptophan metabolism and caffeine metabolism. Protein interaction network had screened out 10 down-regulated core genes: MT1G, MT1F, MT1X, MT1E, MT1H, insulin-like growth factor 1, FOS, CXCL12, EGR1, and BGN. Among them, the insulin-like growth factor 1 was related to the prognosis of primary hepatocellular carcinoma. Conclusion: Bioinformatics analysis results of HCC chip data showed that 10 key genes may play a key role in the occurrence and development of HCC and the insulin like growth factor 1 is associated with the prognosis of primary hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular , Biologia Computacional , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , PrognósticoRESUMO
Objective: This study analyzes the expression level of miR-1180-3p and constructs the regulatory network of relevant ceRNA by integrating the DNA methylation and gene expression profile of hepatocellular carcinoma from the Cancer Genome Atlas (TCGA). Methods: Firstly, the expression level of miR-1180-3p in hepatocellular carcinoma and adjacent tissues was analyzed by TCGA database, and the differential expression of lncrna and mRNA was screened. Secondly, the LncBase database and the TargetScan database were used to predict the relationship between miR-1180-3p and lncRNA and mRNA, and the DNA methylation-mediated lncRNA was screened by the DNA methylation profile of lncRNA. Finally, Cytoscape software was used to construct miR-1180-3p relevant ceRNA network, and WebGestalt website was used to perform GO and KEGG analysis of related mRNA in ceRNA. Results: Compared with patients with low expression of miR-1180-3p (mean overall survival duration, 5.69 ± 0.35 years), patients with high expression of miR-1180-3p had shorter overall survival time (mean overall survival duration, 3.99 ± 0.47 years), indicating that the high expression of miR-1180-3p was hepatocellular carcinoma risk factor affecting the prognosis (HR = 1.28, 95% CI = 1.1 ~ 1.5, P < 0.01). A miR-1180-3p related ceRNA regulatory network was constructed in this study, which contained 2 lncRNAs (F11-AS1 and LINC01511) and 37 mRNAs. Conclusion: This study has successfully constructed miR-1180-3p relevant ceRNA regulatory network, and DNA methylation-mediated F11-AS1 and F11-AS1/miR-1180-3p/C11of54 ceRNA regulatory axis has played an important role in the occurrence and development of hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs , TranscriptomaRESUMO
BACKGROUND AND AIM: Current chemoradiotherapy doesn't usually effectively control oesophageal cancer progression. This study assessed the efficacy and toxicity profiles of paclitaxel/lobaplatin (TL)- and cisplatin/5-fluorouracil (PF)-based concurrent chemoradiotherapy (CCRT) in patients with advanced inoperable oesophageal cancer. METHODS: A total of such 68 patients was recruited and randomised to receive TL or PF-based CCRT. Radiotherapy was given at a total dose of 60-70 Gy over 6 weeks. In the TL group of patients, paclitaxel 60 mg/m(2) was administered intravenously on day 1, 8 and 15 and lobaplatin 30 mg/m(2) was administered on day 2 in two cycles at 3-week intervals. In the PF group, cisplatin 75 mg/m(2) was administered intravenously on day 1, and 5-fluorouracil 500 mg/m(2) and leucovorin 200 mg/m(2) were administered intravenously daily for 5 days in two cycles at 3-week intervals. Adverse events, treatment response and follow-up data were collected. RESULTS: The treatment response rates were 73.53% and 50.00% in the TL and PF groups respectively (P = 0.040). The median tumour progression-free survival (PFS) was 13.0 and 6.5 months in the TL and PF groups respectively (P = 0.034). Compared with PF group, the TL group demonstrated decreased grade 3/4 nausea and vomiting (5.88% vs 35.29%, P = 0.003), decreased granulocytopenia (11.76% vs 32.35%, P = 0.041) and platelet count reduction (32.5% vs 8.8%, P = 0.016). CONCLUSIONS: The TL treatment regimen demonstrated higher efficacy with less overall toxicity in patients with advanced inoperable oesophageal cancer compared with the PF regimen. Further study is warranted to validate our current observations.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Neoplasias Esofágicas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Ciclobutanos/administração & dosagem , Ciclobutanos/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversosRESUMO
A rapid, sensitive, and reliable high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the analysis of decoquinate in chicken tissues. The compounds were extracted using acetonitrile by liquid-liquid extraction (LLE) and purified with an Oasis(™) HLB solid-phase extraction (SPE) cartridge. Chromatographic separation was performed on an XTerra C18 reversed-phase column with a mobile phase of water containing 0.1% formic acid and acetonitrile. The analyte was detected by tandem quadrupole mass spectrometry after positive electrospray ionization by multiple reaction monitoring. The detection and quantitation limits were 1 and 2.5 µg/kg, respectively. The recoveries of edible tissues ranged from 85.3% to 104.9%, with relative standard deviations (RSD) lower than 10.4%. The depletion profile of decoquinate was studied in healthy chickens after oral administration of feed containing 27.2 mg/kg decoquinate for 10 consecutive days. The residue concentrations of decoquinate in chicken muscle and liver were detected using the developed method. The highest residue concentrations were attained 0.25 day post-treatment, and decoquinate residues were still detected 5 days postmedication in the tissues examined. The developed method has been successfully applied to the depletion study of decoquinate in chicken tissues. The recommended withdrawal period with oral administration based on our research is 3 days.
Assuntos
Galinhas/metabolismo , Coccidiostáticos/farmacocinética , Decoquinato/farmacocinética , Resíduos de Drogas/farmacocinética , Administração Oral , Animais , Cromatografia Líquida/métodos , Cromatografia Líquida/veterinária , Coccidiostáticos/administração & dosagem , Coccidiostáticos/química , Decoquinato/administração & dosagem , Decoquinato/química , Fígado/química , Estrutura Molecular , Músculo Esquelético/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massas em Tandem/veterinária , Fatores de TempoRESUMO
BACKGROUND: The incidence of Clostridium difficile-associated diarrhoea (CDAD) in hospitalized children and adolescents has been increasing year-on-year. Paediatric CDAD places a significant economic burden on healthcare systems. Probiotics are live organisms thought to improve the microbial balance of the host, counteract disturbances in intestinal flora, and reduce the risk of colonization by pathogenic bacteria. AIM: A cost-effectiveness analysis was conducted to assess the economy of probiotics for the prevention of CDAD in children and adolescents receiving antibiotics. METHODS: A decision tree model combining clinical effectiveness, utility and cost data was used. Sensitivity analyses were conducted to determine the robustness of the model outcomes. FINDING: The 'oral probiotics' strategy and 'no probiotics' strategy offered patients 0.05876 and 0.056 quality-adjusted life years (QALYs) at a cost of $16,668.70 and $20,355.28, respectively. The oral probiotics strategy exhibited higher QALY and lower cost, and represents the cost-saving strategy. The results were robust for sensitivity analyses. CONCLUSION: From the perspective of the medical system, oral probiotics as a preventive strategy for CDAD in hospitalized children and adolescents receiving a therapeutic course of antibiotics reduced the risk of CDAD and represents a cost-saving strategy.
Assuntos
Infecções por Clostridium/economia , Infecções por Clostridium/prevenção & controle , Análise Custo-Benefício , Diarreia/economia , Diarreia/prevenção & controle , Probióticos/administração & dosagem , Probióticos/economia , Administração Oral , Adolescente , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Anos de Vida Ajustados por Qualidade de VidaRESUMO
PURPOSE: This study evaluated the efficacy and safety of the combination drug tegafur, gimeracil, and oteracil potassium (S-1) concurrent with 3-dimensional conformal radiotherapy for newly diagnosed squamous cell carcinoma of the lung in elderly patients. PATIENTS AND METHODS: Patients with pathologically or cytologically newly diagnosed lung squamous cell carcinoma (n=106) were randomly assigned to receive the combination of tegafur, gimeracil, and oteracil potassium (40mg/m(2), BID, d1-28, repeated every 6 weeks for 4 cycles) and concurrent 3D-conformal radiotherapy (60Gy; experimental group), or gemcitabine (800-1000mg/m(2), d1 and d8) repeated every 21 days for 4 cycles as well as 3D-conformal radiotherapy (control group). RESULTS: The overall response rate (complete and partial responses) of the experimental group was 68.6%, which was significantly higher than that of the control group (38.5%; P=0.002). The median progression-free survival rates of the experimental and control groups were 11.8 months (95% confidence interval [CI]: 8.0-22.4) and 7.8 months (95% CI, 6.9-9.2), respectively (P=0.017). Adverse reactions included grade I/II radiation esophagitis and pneumonitis, with good tolerance. Grade III/IV adverse reactions of the experimental and control groups were leucopenia (20% cf. 56.6%, respectively; P=0.027), thrombocytopenia (3.9% cf. 25%; P=0.037), and gastrointestinal reaction (1.9% cf. 3.5%; P=0.35). CONCLUSION: The efficacy of concurrent combination chemotherapy with tegafur, gimeracil, and oteracil potassium (S-1) and 3D-conformal radiotherapy for newly diagnosed squamous cell carcinoma of the lung in elderly patients was excellent, and all toxicities were well tolerated. This treatment might be considered a main regimen in the management of squamous cell carcinoma of the lung in elderly patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Radioterapia Conformacional , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Combinação de Medicamentos , Feminino , Humanos , Masculino , Ácido Oxônico/efeitos adversos , Ácido Oxônico/uso terapêutico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Radioterapia Conformacional/efeitos adversos , Tegafur/efeitos adversos , Tegafur/uso terapêutico , Resultado do TratamentoRESUMO
Patterned carbon nanotubes arrays (PCNTA) with reduced density and length were developed with polystyrene sphere masked catalyst dots followed by plasma enhanced chemical vapor deposition method. The nanotubes were then uniformly coated with electropolymerized polypyrrole (PPy). The coating thickness was conformally adjustable. Gold nanoparticles (AuNP) together with glucose oxidase (Gox) were doped into the PPy film on the nanotubes to develop a high performance PCNTA glucose sensor. The sensitivity of the sensor was improved by the co-existence of Gox and AuNP on the carbon nanotube. Moreover, in contrast to previous reported PCNTA glucose sensors, the design herein utilized the entire surface of nanotubes as active sensing areas in order to maximize the Faradic currents. This research outlines a practical avenue to fabricate high performance PCNTA sensor chips with multiple molecules and functional nano-architectures.