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1.
Phytomedicine ; 72: 153236, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32464544

RESUMO

BACKGROUND: Intestinal obstruction (IO) is a kind of acute abdomen with high morbidity and mortality. Patients suffer from poor quality of life and tremendous financial pressure. Da-Cheng-Qi decoction (DCQD), a classical purgation prescription, has clinically been proven to be an effective treatment for IO. PURPOSE: Network pharmacology integrated with bioactive equivalence assessment was used to discover the quality marker (Q-marker) of DCQD against IO. METHODS: As there is hardly any targets recorded in database, thus the collection of IO targets was conducted by searching those of alternative diseases which have similar pathological symptoms with IO. In order to improve the reliability of the obtained targets, IO metabolomics data was introduced. Active compounds combination (ACC) was focused as potential Q-markers via component-target network analysis and function query from the identified components corresponding to the common targets. Bioequivalence between ACC and DCQD was assessed from the aspects of intestine motility (somatostatin secretion), inflammation (IL-6 secretion) and injury (wound healing assay) in vitro and was further validated in ileus rat model. PPI network analysis of core targets followed by gene pedigree classification and experimental validation confirmed the potential intervention pathway. RESULTS: A combination of 11 ingredients, including emodin, physcion, aloe-emodin, rhein, chrysophanol, gallic acid, magnolol, honokiol, naringenin, tangeretin, and nobiletin was finally confirmed bioequivalence with DQCD to some extent and could serve as Q-markers for DCQD to attenuate IO. PI3K/AKT was verified as a possible affected pathway that DCQD exerted the effectiveness against IO. CONCLUSION: For the disease with few recorded targets, searching those of alternative diseases which have similar pathological symptoms could be a feasible and effective approach. The proposed network pharmacology integrated bioactive equivalence evaluation paradigm is efficient to discover Q-marker of herbal formulae.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Obstrução Intestinal/tratamento farmacológico , Algoritmos , Animais , Antraquinonas/análise , Antraquinonas/farmacocinética , Biomarcadores Farmacológicos/análise , Compostos de Bifenilo/análise , Compostos de Bifenilo/farmacocinética , Mineração de Dados , Flavanonas/análise , Flavanonas/farmacocinética , Células HT29 , Humanos , Lignanas/análise , Lignanas/farmacocinética , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Equivalência Terapêutica
2.
Ann Oncol ; 10(9): 1035-41, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10572600

RESUMO

BACKGROUND: The objective was to locate, appraise and summarise evidence from scientific studies on intestinal obstruction due to advanced gynaecological and gastrointestinal cancers, in order to assess the efficacy of corticosteroids. MATERIALS AND METHODS. DATA SOURCES: A comprehensive list of studies was provided by an extensive search of electronic databases, relevant journals, bibliographic databases, conference proceedings, reference lists, the grey literature, personal contact and the world wide web. DATA SYNTHESIS: Two researchers extracted the data independently. A qualitative analysis was performed of the dichotomous data of resolution of obstruction and death at one month. Both fixed and random effect models were used. Number needed to treat (with corticosteroids to resolve one episode of bowel obstruction) was derived from the odds ratio. Kaplan-Meier survival curves from individual patient data were also analysed. Studies of lower methodological quality were assessed in a qualitative manner. RESULTS: There is a trend towards resolution of bowel obstruction using corticosteroids but this result does not achieve statistical significance. There is no statistically significant difference in mortality at one month, nor in the Kaplan Meier survival curves. Number needed to treat is 6, though with wide confidence intervals (3-infinity). The results are robust to fixed and random effects models and to 'best' and 'worst case' scenarios on the data from missing patients. The morbidity associated with corticosteroids appears to be very low. CONCLUSIONS: The role of corticosteroids needs further elucidation. More patients need to be recruited in order to obtain more precise results. Further trials should include quality of life measures as primary outcomes as well as most effective type of corticosteroid, dose or dosing regime, route of administration and morbidity.


Assuntos
Corticosteroides/uso terapêutico , Neoplasias Gastrointestinais/complicações , Neoplasias dos Genitais Femininos/complicações , Obstrução Intestinal/tratamento farmacológico , Análise Custo-Benefício , Feminino , Humanos , Obstrução Intestinal/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Sensibilidade e Especificidade , Taxa de Sobrevida , Fatores de Tempo
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