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1.
BMC Psychiatry ; 20(1): 133, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32204700

RESUMO

BACKGROUND: Accurate diagnosis of delirium is very important for prevention and treatment. Present study was designed to validate the 3-Minute Diagnostic Interview for CAM-defined Delirium Chinese version (3D-CAM-CN) in surgical ICU patients. METHODS: In this prospective diagnostic study, the 3D-CAM was translated into Chinese with culture adaption. Two interviewers (Roles A and B) independently administrated 3D-CAM-CN assessment in adult patients from postoperative days 1 to day 3. At the meantime, a panel of psychiatrists diagnosed delirium according to the Diagnostic and Statistical Manual of Mental Disorders-fifth edition as the reference standard. The sensitivity and specificity were calculated to analyze the diagnostic character of the 3D-CAM-CN. Kappa coefficient was used to evaluate interrater reliability. RESULTS: Two hundred forty-five adult patients were assessed for at least 2 days, resulting a total of 647 paired-assessments. When compared with the reference standard, the sensitivity and specificity of the 3D-CAM-CN assessment were 87.2 and 96.7%, respectively, by Role A and 84.6 and 97.4%, respectively, by Role B, with good interrater reliability (Kappa coefficient = 0.82, P < 0.001). It also performed well in patients with mild cognitive impairment, with the sensitivity from 85.7 to 100% and the specificity from 95.7 to 96.4%. CONCLUSION: Our results showed that the 3D-CAM-CN can be used as a reliable and accurate instrument for delirium assessment in surgical patients. TRIAL REGISTRATION: This trail was approved by the Clinical Research Ethic Committee of Peking University First Hospital (No. 2017-1321) and registered on Chinese clinical trial registry on July 6, 2017 (ChiCTR-OOC-17011887).


Assuntos
Comparação Transcultural , Delírio , Complicações Cognitivas Pós-Operatórias , Idoso , Delírio/diagnóstico , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Complicações Cognitivas Pós-Operatórias/diagnóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
2.
Eur J Med Chem ; 127: 137-146, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-28039772

RESUMO

Two new platinum(II) complexes 7a and 7b with methyl hydrazinecarbodithioate derivatives of indolin-2-one have been prepared and characterized by single-crystal X-ray diffraction, NMR spectroscopy and mass spectrometry. Antiproliferative activity of the two complexes and their ligands 6a and 6b against HCT-116, MCF-7 and MDA-MB-231 cell lines was determined by the MTS assay. Complexes 7a and 7b exhibited stronger antiproliferative activity against three cell lines than compounds 6a and 6b (IC50, 1.89-5.60 versus 6.52-35.13 µM). Moreover, treatment of HCT-116 cells with the complexes resulted in an obvious sub-G1 peak by cell cycle profile analysis, and an increase of cleaved PARP1 and caspases 3, 7, and 9 by immunoblotting analysis. Live cell imaging showed that nucleus shrinkage and condensation started to appear when MCF-7 cells were treated with 7a for 8 h. Fluorescent spectrophotometric analysis revealed that the complexes physically associated with calf thymus DNA. Competitive DNA binding assays uncovered that the complexes non-covalently bind to DNA. Taken together, our results indicated that the two new platinum(II) complexes 7a and 7b non-covalently bind to DNA with high affinity and exhibit cytotoxicity against cancer cells by inducing apoptosis.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Hidrazinas/química , Indóis/química , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Bovinos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Cristalografia por Raios X , DNA/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Células MCF-7 , Modelos Moleculares , Conformação Molecular , Compostos Organoplatínicos/química , Compostos Organoplatínicos/metabolismo , Relação Estrutura-Atividade
3.
Eur J Med Chem ; 108: 364-373, 2016 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-26703795

RESUMO

A series of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at the C2-position were synthesized and evaluated for their antiproliferative activities against A549, MCF-7, HeLa, HT29 and HCT-116 cell lines. Most of the synthesized compounds exhibited broad spectrum antitproliferative activity against five cell lines, of which 5c was the most potent against HT29 cell line with an IC50 value of 5.53 µM, inducing a G2/M phase arrest in HT29 cells. Treatment of HT29 cells with 5c resulted in BubR1 phosphorylation and an increase of mitotic index in a time-dependent manner. Furthermore, 5c promoted tubulin polymerization in vitro. These results demonstrate that quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position may be potentially novel antitumor agents targeting tubulin to activate the spindle assembly checkpoint.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Quinazolinonas/química , Quinazolinonas/farmacologia , Tiocarbamatos/química , Tiocarbamatos/farmacologia , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Quinazolinonas/síntese química , Relação Estrutura-Atividade , Tiocarbamatos/síntese química
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