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OBJECTIVE@#To investigate the efficacy, prognosis and safety of decitabine combined with low-dose CAG regimen in the treatment of elderly patients with acute myeloid leukemia （AML）.@*METHODS@#The clinical data of 40 elderly patients with relapsed/refractory AML （69-85 years old） admitted to our hospital from January 2014 to August 2016 were analyzed retrospectively. 40 patients were divided into combination therapy group and CAG group according to different treatment methods. 20 patients of the combination therepy group were treated with decitabine combined with low-dose CAG （decitabine, 15 mg/m, d 1; aclarithromycin, 10 mg/m, d 3-6; Cytidine, 10 mg/m, d 1-14; recombinant human granulocyte macrophage colony-stimulating factor （G-CSF） for injection, 200 μg/（m·d）, d 1-14）. 20 patients of CAG group were treated by the standard CAG protocol （acralmycin 20 mg/m, d 1-4; cytarabine for injection, 15 mg/m, d 1-14; G-CSF 400 μg/（m·d）, d 1-14）. One course of treatment lasted for 2 weeks, after 2 courses of continuous medication, the complete remission rate （CR）, overall remission rate （ORR）, overall survival （OS）, 1-year survival rate, hemoglobin, white blood cells, platelets improvement, and incidence of adverse reactions were compared.@*RESULTS@#In combination therapy group the CR was 55.00% （11/20）, OR was 85.00% （17/20）, but in the CAG group CR was 30.00% （6/20）, and OR was 50.00% （10/20）. Till to February 2018, out of 40 patients 17 survived, 20 died, and 3 failed to be followed-up. The median follow-up time was 12 （2 to 35） months; the median survival time in the comtination therapy group was 13 （2-35） months, and the 1-year OS rate was 70.00%, and the median survival time of the CAG group was 10 （2-31） months, and the 1-year OS rate was 50.00%, without staistical significance between the 2 groups （P>0.05）. After treatment, the WBC and Plt counts in the combination therapy group were higher than those in the CAG group, but the Hb level was lower than that in the CAG group with statistically significant difference （P<0.05）. In the combination therapy group, the incidence of lung infection, nausea and vomiting was higher than that of the CAG group （65.00% vs 25.00%, 50.00% vs 20.00%）, with statistically significant difference （P<0.05）.@*CONCLUSION@#Decitabine combined with low-dose CAG regimen is effective for the treatment of relapsed/refractory AML in the elderly. Compared with the standard CAG regimen, the long-term efficacy of this regimen is not different significantly, but its adverse reactions are increase, thus the preventive treatment should be given in time.
Subject(s)
Aged , Aged, 80 and over , Humans , Antineoplastic Combined Chemotherapy Protocols , Cytarabine , Decitabine , Granulocyte Colony-Stimulating Factor , Leukemia, Myeloid, Acute , Drug Therapy , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To study the effects of intrahippocampal injection of cellular prion protein (PrP) antibody on cognitive deficits of APPswe/PSEN1 transgenic mice.</p><p><b>METHODS</b>Eight-month-old male APPswe/PSEN1 transgenic mice were subjected to bilateral intrahippocampal injection of a single dose (2 µL) of anti-PrP monoclonal antibody (EP1802Y) or PBS, with wild-type C57Bl/6J mice serving as the control group. After two months, the mice were tested for cognitive behaviors using open filed (OF) test, Morris water maze (MWM) test, fear conditioning (FC) test, and novel object recognition (NOR) test, and immunohistochemistry was used to examine the changes in hippocampal expression of Aβ.</p><p><b>RESULTS</b>The EP1802Y-treated and PBS-treated mice showed no significantly differences in the performance in OF test in terms of central activity time or total distance of activity (P>0.05), nor in NOR test in terms of novel object recognition index (P>0.05). In MWM test, the EP1802Y-treated and PBS-treated mice showed significantly reduced crossings of the hidden platform as compared with the wild-type mice (P<0.05), but EP1802Y-treated mice had a significantly shorter swimming distance to find the platform than PBS-treated mice (P<0.05). No significant differences were found in the results of FC test among the 3 groups. Immunohistochemistry revealed a significantly reduced expression of Aβ in the hippocampus of EP1802Y-treated mice.</p><p><b>CONCLUSION</b>Intrahippocampal injection of PrP antibody can improve cognitive deficits of APPswe/PSEN1 transgenic mice, which sheds light on a novel therapeutic approach for Alzheimer's disease that targets PrP to lower the toxicity of Aβ oligomer.</p>
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Objective To explore the applied value of electroencephalogram (EEG) in assessment of psychiatric impairment among patients with mental disorders due to traumatic brain injury.Methods According to the ICD-10,a total of 271 subjects were enrolled and assessed with the criterion of mental disorders due to traumatic brain injury.Activity of Daily Living Scale (ADL),Functional Activities Questionnaire (FAQ) and Social Disability Screening Schedule (SDSS) were used to evaluate the severity of patients.All the participants were tested by Wechsler Adult Intelligence Scale (WAIS) and examined by EEG.Results Totally 215 patients accomplished the study.The results of Glasgow Coma Scale (GCS),the severity of craniocerebral injury and the scores of FAQ,SDSS and ADL showed significant difference among the patients with different severity of EEG (P＜0.05).The grades of psychiatric impairment showed significant difference among the patients with different abnormal EEG (P＜0.05).Conclusion EEG can reflect the severity of craniocerebral injury,assist evaluate the social function and activity of daily living of patients with mental disorders due to traumatic brain injury,and distinguish the mild psychiatric impairment grades,which suggest that EEG has a certain reference value in the assessment of psychiatric impairment.
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The internal ribosome entry site (IRES) sequence was derived from encephalomyocarditis virus. It allows to translate two open reading frames at one mRNA, so two genes conjoined by IRES have the same expression rate. K(DfGC) and K(DfGd) cell lines, stably expressing D-amino acid oxidase (DAAO) gene and green fluorescence protein (GFP) genes, were obtained by transfection of K562e cells with retroviral vector pLDfG containing IRES sequence, DAAO cDNA and GFP gene. Fluorescence positive rate and fluorescence intensity of the two cell lines were measured with flow cytometry. H(2)O(2) production by K(DfGC) and K(DfGd) cells treated with D-alanine was measured by the phenol red oxidation assay. The fluorescence positive rate and fluorescence intensity in K(DfGC) and K(DfGd) cell were 94.64% and 96.31% and 202 units and 174 units per 2 x 10(4) cells, respectively. There was exponential correlation between fluorescence intensity and H(2)O(2) level. The above-mentioned results demonstrate that DAAO gene and GFP gene were simultaneously expressed in K562e cell line by the regulation of IRES sequence, and DAAO level was correlated with fluorescence intensity of GFP.
Subject(s)
Humans , Binding Sites , Genetics , D-Amino-Acid Oxidase , Genetics , Metabolism , Gene Expression , Gene Expression Regulation, Enzymologic , Genetic Vectors , Genetics , Green Fluorescent Proteins , Hydrogen Peroxide , Metabolism , K562 Cells , Luminescent Proteins , Genetics , Metabolism , Retroviridae , Genetics , Ribosomes , Metabolism , TransfectionABSTRACT
Objective:To investigate the m echanism of D- amino acid oxidase/D- Alanine system in killing K5 6 2 e cells in vitro.Methods:The killing effects of D- Ala on K5 6 2 e cells stably expressing DAAO and GFP were observed.H2 O2 production by DAAO+ cells were m easured by the phenol red oxidation assay.L owry method was used to determ ine the protein quantities of cells and fluorescent intensities of GFP+ cells were assayed by flow cytom eter.Results:KDf Gd cells were killed completely after treated with 2 5 mm ol/L D- Ala for 2 4 h.The effect of D - Ala at 2 0 m mol/L on KDf Gd cells increased apparently within 4 8h,but the same effect was not observed if D - Ala was below 15 m mol/L .The cytotoxicity of D- Ala in KDf Gd cells was more sensitive than in parental K 5 6 2 e cells.The H2 O2 levels in the medium were consistent with the killing effects of D- Ala.Conclusion:The killing effects of DAAO/D- Ala system is m ediated by H2 O2 . [