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Objective:To explore abnormal microstructural changes of white matter in patients with white matter lesions(WML) using diffusion tensor imaging(DTI), and to determine the association of such abnormalities of DTI parameters with executive function.Methods:Totally 34 patients with WML were recruited from the department of Neurology, Beijing Tiantan Hospital, Capital Medical University from March 2012 to May 2019.All patients with WML were scored with Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA), and assessed with Montreal cognitive assessment (MoCA) and clinical dementia rating(CDR). They were divided into WML-cognitive normal group, WML-vascular cognitive impairment-non dementia group and WML-Dementia group.The Stroop color and word test (SCWT), trail making test-A (TMTA), digit symbol test and verbal fluency test were carried out to evaluate executive function.In addition, the healthy elderly without WML lesions were selected as the control group after they were examined by MRI, and all brains of the subjects went through DTI with Siemens 3.0 T MR.The data were collected and analyzed by voxel based analysis (VBA). The anisotropy and mean diffusion coefficient of DTI in the region of interest (ROI) and other regions in the brain were studied in the four groups, and their correlation with scores of executive function in WML patients was analyzed.Results:(1)In these executive function test, there were significant differences between the patients with cognitive impairment (WML-VAD group, WML-VCIND group) and normal cognition group(WML-CN group, NC group), such as SCWT(B)(65.54±6.24 vs 43.67±0.95, 76.75±2.13 vs 43.67±0. 95, 65.54±6.24 vs 43.66±1.81, 76.75±2.13 vs 43.66±1.81), SCWT(C)(88.58±6.76 vs 61.63±1.31, 96.37±1.47 vs 61 63±1.31, 88.58±6.76 vs 66.31±8.19, 96.37±1.47 vs 66.31±8.19), TMTA(40.47±2.76 vs 30.92±0.47, 44.24±1.43 vs 30.92±0.47, 44.24±1.43 vs 31.99±2.07, 40.47±2.76 vs 31.99±2.07), TMTB(88.66±6.55 vs 80.34±0.61, 96.70±1.72 vs 80.34±0.61, 88.66±6.55 vs 83.10±5.91, 96.70±1.72 vs 83. 10±5.91), Digit Symbol Test(39.25±5.63 vs 47.00±2.55, 31.27±3.93 vs 47.00±2.5, 39.25±5.63 vs 48.86±4.34, 31.27±3.93 vs 48.86±4.34) and Verbal Fluency Test(8.94±1.00 vs 11.71±0.47, 6.64±0.81 vs 11.71±0.47, 8.94±1.00 vs 10.86±0.69, 6.64±0.81 vs 10.86±0.69) scores ( P<0.05); In the patients with cognitive impairment, there were significant differences between WML-VAD group and WML-VCIND group, such as SCWT(B), SCWT(C), TMTA, TMTB, digit symbol test and verbal fluency test scores ( P<0.05); There were significant differences between WML-CN patients and NC group in the scores of SCWT (C), verbal fluency test( P<0.05). (2)FA values in the genu of corpus callosum and the inferior longitudinal fasciculus were negatively correlated with the time of SCWT (B), SCWT (C) and the TMTA( r=-0.436--0.471), but positively correlated with the scores of digit symbol test and verbal fluency test( r=0.428-0.573). MD values in the genu of corpus callosum, the superior/inferior longitudinal fasciculus and the inferior fronto-occipital fasciculus were positively correlated with the time of SCWT (B), SCWT (C) and TMTA( r=0.432~0.609), but negatively correlated with the scores of digit symbol test and verbal fluency test( r=-0.424--0.630, all P<0.003125 after emendation). Conclusion:The executive function of patients with WML-Dementia decreases significantly.The more serious the damage of white matter microstructure, the more serious the damage of executive of function.
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Objective To explore the clinical characteristics of cognitive impairment in different age groups with the same severity of white matter lesions.Methods This study involved 110 consecutively recruited patients with white matter lesions(WMLs)from the Department of Neurology at Beijing Tiantan Hospital from August 2014 to March 2017.Patients were aged from 50 to 85 with a mean age of 63.1±9.7,and they were divided into an elderly group with a mean age of 71.6±5.2 (range:65-85 years)and a middle aged group with a mean age of 54.8 ± 3.4 (range:50-60 years).The severity of white matter lesions was evaluated with the Fazekas scale.MoCA was used to evaluate the cognitive function of patients.Results For Fazekas 1,the MoCA score was 25.5 ± 2.2 in the elderly group and 28.1 ± 1.4 in the middle aged group(t =6.946,P =0.000);the score for visuospatial and execution abilities was 3.8 ± 0.9 in the elderly group and 4.5 ± 0.6 in the middle aged group(t =3.7 2 6,P =0.0 2 3);the score for delayed memory was 2.7 ± 1.5 in the elderly group and 4.0 ± 1.0 in the middle aged group(t =4.365,P =0.018).For Fazekas 2,the MoCA score was 22.5±2.5 in the elderly group and 24.1 ± 1.5 in the middle aged group(t =3.361,P =0.034);the score for visuospatial and execution abilities was 2.8 ± 1.2 in the elderly group and 3.8 ± 0.8 in the middle aged group(t=6.473,P=0.007);the score for concentration was 4.6± 1.3 in the elderly group and 5.6±0.5 in the middle aged group(t=0.491,P=0.721).For Fazekas 3:the MoCA score was 15.2 ± 3.4 in the elderly group and 19.4 ± 2.8 in the middle aged group(t =4.709,P =0.001);the score for visuospatial and execution abilities was 1.8 ± 1.1 in the elderly group and 2.8± 1.4 in the middle aged group(t =1.563,P =0.043);the score for concentration was 3.3± 1.1 in the elderly group and 4.4± 1.4 in the middle aged group(t=2.231,P=0.026);the score for orientation was 4.2 ± 1.3 in the elderly group and 5.7 ± 0.5 in the middle aged group (t=3.255,P =0.000).Conclusions WMLs can increase the risk of vascular cognitive impairment and cause decline in multiple cognitive functions in both middle aged and elderly people.Cognitive dysfunction in age-related WMLs is mainly characterized by impairment in visuospatial and execution abilities.
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Objective To explore abnormal microstmctural changes of white matter in patients with white matter lesions using diffusion tensor imaging(DTI),and to determine the association of such abnormalities of DTI parameters with cognitive function.Methods The objects who have already confirmed with WML were collected from March 2012 to February 2018 through magnetic resonance imaging (MRI) scan from the neurology department of Beijing Tiantan Hospital.Use The hamilton depression scale(HAMD) and the hamilton anxiety scale (HAMA) to eliminate anxiety and depression,and divided into WML-CN group,WML-VCIND group and WML-VAD group with Mini-mental state examination (MMSE),Montreal Cognitive Assessment (MOCA)and clinical dementia rating(CDR).In addition,select the healthy elderly people without WML by MRI scan as the normal control group.All of the subjects were detected with the superconduct magnetic resonance imaging system (German SIEMENS 3.0T) for the DTI scanning.Original images were processed with VBA.Then explore the changes of FA and MD of DTI in whole brain and regions of interest in NC group,WML-CN group,WML-VCIND group and WWML-VAD group,and its correlation with the severity of cognitive impairment in patients with WML.Results The damage degree of the fiber microstructure of brain white matter was significantly correlated with the total grade point of MoCA (P＜0.01).In figure FA,the variance analysis of F test results showed that the significant brain areas were the splenium of the corpus callosum,the genu of corpus callosum,bilateral posterior internal capsule,retrolenticular part of internal capsule,anterior thalamic radiation,partial inferior longitudinal fasciculus and inferior fronto-occipital fasciculus,cingulate,external capsule,upper and posterior part of the radiation crowns,partial superior longitudinal fasciculus,etc.(P＜0.05 after FWE correction based on TFCE method).In Figure MD,the variance analysis of F test results showed that the statistically significant brain areas mainly included the left external capsule and hook,partial genu and splenium of corpus callosum,Bilateral,bilateral inferior fronto-occipital fasciculus,inferior longitudinal fasciculus,anterior thalamic radiation,retrolenticular part of internal capsule,cingulate,etc (P＜ 0.05 after FWE conection based on TFCE).Conclusion No matter whether cognitive impairment exists in patient with WML or not,all DTI parameters are different from those of normal people.The integrity of white matter fiber has been damaged with different degrees.The more severe the cognitive impairment in the external manifestations of patients with WML,the greater the damage to the intrinsic white matter microstructure.
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Objective To study the effect of bcl-2 antisense oligodexynucleotides on the apoptosis in human small-cell lung cancer cell line NCI-H69. Methods Cultured cells were divided into 4 groups: antisense oligodexynucleotides(ASODN), sense oligodexynucleotides (SODN), nonsense oligodexynucleotides (NSODN) and control.The different bcl-2 oligodexynucleotides was transfected into corresponding cells using oligofectamine.The expression of bcl-2 was examined by Western blot.The apoptosis rates were measured by flow cytometry (FCM).Results The bcl-2 expression in ASODN group was significantly inhibited compared to the control group, SODN and NSODN groups, but it was not obviously inhibited in SODN and NSODN groups.The apoptosis rate of ASODN group in different concentration was (9.97±1.54) %, (15.28±1.73) % and (21.41±1.85) % respectively, it was significantly higher than that of the control group (F = 7.19-15.48,q = 5.21-7.98, P ＜0.01). Conclusion The bcl-2 ASODN could enhance cell apoptosis rate in small-cell lung cancer by blocking bcl-2 gene effectively.