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One hundred Alzheimer′s disease (AD) patients with behavioral and psychological symptoms of dementia (BPSD) treated with donepezil+risperidone group ( n=50, group 1) or hydrochloride memantine+risperidone group ( n=50, group 2) in geriatric departments of Hangzhou Seventh People′s Hospital were enrolled in the study. Montreal cognitive assessment scale (MoCA), positive and negative syndrome scale (PANSS), treatment emergent symptom scale (TESS) were applied for evaluation; and blood routine examination, blood biochemistry, eletrocardiogram were performed in two groups before and after treatment. After treatment, MoCA score in group 2 (16.10±3.90) was significantly higher than that in group 1 (18.14±3.71)( t=-3.99, P<0.01), and PANSS score in group 2 (86.66±6.62) was significantly lower than that in group 1 (109.50±11.51; t=12.67, P<0.01). The incidence rates of dry mouth (16%,8/50), extrapyramidal side effects (10%,5/50) and the total score of TESS (3.92±2.02) in group 2 were markedly lower than those of group 1 [44%(22/50), 36%(18/50), (12.49±1.45);χ 2=9.33,9.54, t=17.90,all P<0.01]. Meanwhile, group 2 had significantly lower influences on the levels of blood lipids and fasting blood glucose (all P<0.01). The risperidone dose used in group 2 was significantly lower than that in group 1 [(2.06±0.50) vs. (3.85±0.89)mg, t=14.40, P=0.04].The results suggest that hydrochloridememantine combined with risperidone is more effective with less side effects compared to donepezil combined with risperidone for AD patients with BPSD.
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Objective To investigate the expression and mechanism of miR-1470 in plasma of diabetic retinopathy (DR) patients.Methods Thirty patients with DR (DR group),30 patients with diabetes (DM group) and 30 normal healthy subjects (normal group) were enrolled in the study.Three groups of subjects were taken 5 ml of venous blood,and total plasma RNA was extracted and purified.The differentially expressed miRNAs in the plasma of DR patients were screened by gene chip,and the results of gene chip detection were verified by reverse transcription polymerase chain reaction (RT-PCR).Bioinformatics was used to predict potential target genes for miRNA regulation,and miR-1470 and its target gene epidermal growth factor receptor (EGFR) were screened.Human retinal microvascular endothelial cells (hREC) were divided into normal group (sugar concentration 5.5 mmol/L) and high glucose group (sugar concentration 25.0 mmol/L).hREC was transfected into miR-1470 mimics to establish a miR-1470 high expression cell model,which was divided into blank control group,high expression group and negative control group.The expression of miR-1470 was detected by RT-PCR.The expression of EGFR protein was detected by Western blot.The measurement data of the two groups were compared using the independent sample t test.The comparison of the measurement data between the two groups was analyzed by ANOVA.The comparison between the measurement data of the groups was compared by multiple comparisons.Results The results of RT-PCR were consistent with those of the gene chip.The expression of miR-1470 in the plasma of the DR group,the DM group and the normal group was statistically significant (F=63.486,P=0.049).Compared with the DM group and the normal group,the expression of miR-1470 in the DR group was significantly decreased,and the difference was statistically significant (q=l 11.2,73.9;P＜0.05).The expression of miR-1470 in hREC in the high glucose group was significantly lower than that in the normal group (t=42.082,P=0.015).The expression of EGFR protein in hREC of high glucose group was significantly higher than that of normal group (t=-39.939,P=0.016).The expression of miR-1470 (F=637.069,P=0.000) and EGFR (F=122.908,P=0.000) protein expression in hREC of blank control group,negative control group and high expression group were statistically significant.Compared with the blank control group and the negative control group,the expression of miR-1470 in hREC of high expression group was significantly increased (q=329.7,328.8;P＜0.05),and the expression of EGFR protein was significantly decreased (q=242.5,234.6;P＜0.05).There was no significant difference in the expression of miR-1470 and EGFR protein in hREC between the negative control group and the blank control group (q=1.5,7.9;P＞0.05).Conclusion The expression ofmiR-1470 in the plasma of patients with DR is significantly down-regulated,and the increase of EGFR expression may be related to it.
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Objective To explore repressive effects of transthyretitin (TTR) on the growth of human retinal endothelial cells (hREC) under high glucose and hypoxia environment. Methods hRECs were divided into 8 groups, including normal glucose group (5.5 mmol/L glucose), hypoxia group, high glucose group (25.0 mmol/L glucose), high glucose and hypoxia group, normal glucose group+TTR, normal glucose and hypoxia group+TTR, high glucose group+TTR, high glucose and hypoxia group+TTR. Flow cytometry was used to analyze cellular apoptosis. The expression level of Akt, p-Akt, eNOS, Bcl-2 and Bax protein were measured by Western blot. Results Hypoxia could induce apoptosis as the apoptosis rate of normal and hypoxia group was higher than normal group (χ2=25.360, P<0.05), high glucose and hypoxia group was higher that high glucose group (χ2=17.400, P<0.05). The cell apoptosis rate of high glucose and hypoxia group+TTR were increased significantly as compared with high glucose and hypoxia group (χ2=9.900, P<0.05). There was no statistically significant difference on the cell apoptosis rate between normal group and high glucose group, normal group+TTR and normal group, high glucose group+TTR and high glucose group, normal and hypoxia group+TTR and normal and hypoxia group (P>0.05). Western blot showed that the expression of Akt did not change significantly in all eight groups(F=2.450, P>0.05). Compared to normal group, the expression of p-Akt, eNOS, Bcl-2 in normal and hypoxia group were decreased (t=9.406, 5.306, 4.819), and the expression of Bax (t=-4.503) was increased (P<0.05). Compared to high glucose group, same trend was found in high glucose and hypoxia group (t=8.877, 7.723, 6.500, -14.646; P<0.05). The expression of p-Akt in normal and hypoxia group+TTR was higher than normal and hypoxia group (t=-5.024, P<0.05) ,but there was no difference on the expression of eNOS, Bcl-2, Bax between these two groups (t=-2.235, -2.656, -0.272;P>0.05). Compared to high glucose and hypoxia group, the expression of p-Akt and Bcl-2 in high glucose and hypoxia group+TTR were decreased (t=4.355, 4.308; P<0.05), the expression of Bax was increased (t=-4.311, P<0.05), and there was no difference on the expression of eNOS between these two groups (t=-1.590, P>0.05). There was no statistically significant difference in the expression of p-Akt, eNOS, Bcl-2, Bax between high glucose group and normal group (t=-3.407, -4.228, -4.302, -2.076; P>0.05), normal group+TTR and normal group (t=-4.245, -4.298, -2.816, -1.326; P>0.05), high glucose group+TTR and high glucose group (t=4.016, -0.784, 0.707, -0.328; P>0.05). Conclusion Under high glucose and hypoxia, transthyretitin suppress the growth of hREC through Akt/Bcl-2/Bax, but not Akt/eNOS signaling pathway.
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Objective To explore repressive effects of transthyretitin (TTR) on the growth of human retinal endothelial cells (hREC) under high glucose and hypoxia environment. Methods hRECs were divided into 8 groups, including normal glucose group (5.5 mmol/L glucose), hypoxia group, high glucose group (25.0 mmol/L glucose), high glucose and hypoxia group, normal glucose group+TTR, normal glucose and hypoxia group+TTR, high glucose group+TTR, high glucose and hypoxia group+TTR. Flow cytometry was used to analyze cellular apoptosis. The expression level of Akt, p-Akt, eNOS, Bcl-2 and Bax protein were measured by Western blot. Results Hypoxia could induce apoptosis as the apoptosis rate of normal and hypoxia group was higher than normal group (χ2=25.360, P<0.05), high glucose and hypoxia group was higher that high glucose group (χ2=17.400, P<0.05). The cell apoptosis rate of high glucose and hypoxia group+TTR were increased significantly as compared with high glucose and hypoxia group (χ2=9.900, P<0.05). There was no statistically significant difference on the cell apoptosis rate between normal group and high glucose group, normal group+TTR and normal group, high glucose group+TTR and high glucose group, normal and hypoxia group+TTR and normal and hypoxia group (P>0.05). Western blot showed that the expression of Akt did not change significantly in all eight groups(F=2.450, P>0.05). Compared to normal group, the expression of p-Akt, eNOS, Bcl-2 in normal and hypoxia group were decreased (t=9.406, 5.306, 4.819), and the expression of Bax (t=-4.503) was increased (P<0.05). Compared to high glucose group, same trend was found in high glucose and hypoxia group (t=8.877, 7.723, 6.500, -14.646; P<0.05). The expression of p-Akt in normal and hypoxia group+TTR was higher than normal and hypoxia group (t=-5.024, P<0.05) ,but there was no difference on the expression of eNOS, Bcl-2, Bax between these two groups (t=-2.235, -2.656, -0.272;P>0.05). Compared to high glucose and hypoxia group, the expression of p-Akt and Bcl-2 in high glucose and hypoxia group+TTR were decreased (t=4.355, 4.308; P<0.05), the expression of Bax was increased (t=-4.311, P<0.05), and there was no difference on the expression of eNOS between these two groups (t=-1.590, P>0.05). There was no statistically significant difference in the expression of p-Akt, eNOS, Bcl-2, Bax between high glucose group and normal group (t=-3.407, -4.228, -4.302, -2.076; P>0.05), normal group+TTR and normal group (t=-4.245, -4.298, -2.816, -1.326; P>0.05), high glucose group+TTR and high glucose group (t=4.016, -0.784, 0.707, -0.328; P>0.05). Conclusion Under high glucose and hypoxia, transthyretitin suppress the growth of hREC through Akt/Bcl-2/Bax, but not Akt/eNOS signaling pathway.
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Objective To explore the effect of gene mutations of epidermal growth factor receptor ( EGFR) on targeting therapy of advanced non-small cell lung cancer (NSCLC). Methods The 139 hospitalized patients who had been treated at least once with platinum-based chemotherapy and had tumor progression or recurrence after the last chemotherapy between December 2005 and December 2009, underwent EGFR gene test extracted from the pathological tissues. Based on the results of the test, the patients were divided into three groups: EGFR mutation per os (p.o.)Gefitinib (MPG) group, wild-type EGFR per os (p. o. ) Gefitinib (WpG) group and wild-type EGFR post-docetaxel chemotherapy (WpD) group. Clinical characteristics, pathology, treatment efficacy,survival time, performance status (PS) score, adverse reaction and quality of life of patients in the three groups were assessed. Results The EGFR mutation rate were higher in female, patients with adenocarcinoma and non-smokers than in male, smokers and those without adenocarcinoma. There were significant differences in median progression-free survival and median survival time among the three groups, which were 2.8 and 8. 9 months in MpG group, 2.0 and 7.1 months in WpG group,2.5 and 7. 8 months in WpD group(H=11. 198, 16. 991 ,all P＜0.01). The changes of PS score were significantly different between MpG group and WpG group (96. 8% vs. 62. 0%, x2 = 12. 583 ,P＜0. 01 ). However, there was no difference in changes of PS score between WpG group and WpD group (62. 0% vs. 66. 0%, x2 =0. 878,P＞0. 05). Conclusions The gene mutation of epidermal growth factor receptor may be served as an important indicator of advanced non-small cell cancer therapy.