Expression of multidrug resistance 1 gene and C3435T genetic polymorphism in peripheral blood of patients with intractable epilepsy

BACKGROUND： Increased expression of multidrug resistance 1 （MDR1） mRNA in peripheral blood of patients with intractable epilepsy is not due to epilepsy drugs, but epilepsy behavior. Monitoring MDR1 expression in peripheral blood is a target for MDR1 gene evaluation. OBJECTIVE： To investigate the influence of antiepileptic drugs and seizures on MDR expression in intractable epilepsy, and to analyze the genetic polymorphisms of C3435T in the MDRl gene. DESIGN, TIME AND SETTING： Factorial designs and comparative observations at the experimental center of the Affiliated Hospital of Qingdao Medical College, Qingdao University between October 2003 and October 2004. PARTICIPANTS： A total of 120 subjects were recruited from the epilepsy clinical department of the Affiliated Hospital of Qingdao Medical College. Four groups （n = 30） were classified according to statistical factorial design： intractable epilepsy, treatment response, no treatment, and normal control groups. METHODS： One-step semi-quantitative reverse-transcription polymerase chain reaction technology was used to test expressions of the MDR1 gene in 120 subjects. C3435T polymorphisms in intractable epilepsy group and normal control groups were analyzed by polymerase chain reaction-restriction fragment length polymorphism. MAIN OUTCOME MEASURES： Expression of MDR1 mRNA in the four groups, and C3435T genetic polymorphisms in intractable epilepsy and normal control groups. RESULTS： MDRl gene expression was increased in the intractable epilepsy group, due to the factor seizures, but not the antiepileptic drugs. However, the interaction between the two factors was not statistically significant. Of the 30 subjects in the intractable epilepsy group, the following genotypes were exhibited： 3 （10%） C/C genotype, 9 （30%） C/T genotype, and 18 （60%） T/T genotype at the site of C3435T, while 4 （13%）, 10 （33%）, and 16 （53%） subjects were determined to express these genotypes in the normal control group, respectively. C and T allele frequency were 25% and 75% in the intractable epilepsy group, and 30% and 70% in the normal control group, respectively. However, there was no statistical difference between the groups. CONCLUSION： Results demonstrated that seizures, not antiepileptic drugs, induced MDR1 gene expression in intractable epilepsy. Genetic polymorphisms of C3435T in the MDR1 gene did not contribute to the development of multidrug resistance in patients with intractable epilepsy.

如何避免夜景照明对城市环境的影响

笔者将根据我国城市夜景照明工程的发展历程和建管工作的重要性,分析我国城市夜景照明发展中存在的问题,探讨有效避免夜景灯光对城市环境影响的相关策略。

An elevated platelet-to-lymphocyte ratio is associated with a higher risk of intracranial atherosclerotic stenosis

Background:Previous studies have shown that inflammation plays an important role in intracranial atherosclerotic stenosis(ICAS).The platelet-to-lymphocyte ratio(PLR)has recently emerged as a potential inflammatory biomarker.This study aimed to explore the association of the PLR with ICAS in a Chinese Han population.Methods:A total of 2134 participants(518 with ICAS,1616 without ICAS)were enrolled in this study.ICAS was defined as atherosclerotic stenosis>50%or the occlusion of several main intracranial arteries.Multivariable logistic regression analyses were used to assess the association of the PLR with ICAS.Additional subgroup analyses were performed according to age(<60 vs.≥60 years)and acute ischemic stroke.Results:Multivariate regression analysis showed that a high PLR was associated with a higher risk of ICAS in all participants(P<0.001).Compared with the lowest quartile,the fourth PLR quartile was significantly associated with ICAS(OR 1.705,95%confidence interval 1.278–2.275,P<0.001).In the subgroups stratified by age,an association between the PLR and ICAS was found in the late-life group(P<0.001),but not in the mid-life group(P=0.650).In the subgroups stratified by acute ischemic stroke,the relationship between an elevated PLR and a higher risk of ICAS remained unchanged(stroke group,P<0.001;non-stroke group,P=0.027).Conclusions:An elevated PLR was associated with a higher risk of ICAS in a Chinese Han population.The PLR might serve as a potential biomarker for ICAS in the elderly population.

Plasma neurofilament light as a longitudinal biomarker of neurodegeneration in Alzheimer’s disease

Objective:To examine whether plasma neurofilament light(NFL)might be a potential longitudinal biomarker for Alzheimer’s disease(AD).Methods:A total of 835 individuals from the Alzheimer’s Disease Neuroimaging Initiative were involved.Correlations of the rate of change in plasma NFL with cerebrospinal fluid biomarkers,cognition,and brain structure were investigated.Cox proportional hazards models were used to assess the associations between quartiles of plasma NFL and the risk of AD conversion.Results:Participants were further divided intoβamyloid-positive(Aβ+)versusβamyloid-negative(Aβ-),resulting in five biomarker group combinations,which are CN Aβ-,CN Aβ+,MCI Aβ-,MCI Aβ+and AD Aβ+.Plasma NFL concentration markedly increased in the five groups longitudinally(p<0.001)with the greatest rate of change in AD Aβ+group.The rate of change in plasma NFL was associated with cognitive deficits and neuroimaging hallmarks of AD over time(p<0.005).Compared with the bottom quartile,the top quartile of change rate was associated with a 5.41-fold increased risk of AD(95%CI=1.83-16.01)in the multivariate model.Conclusion:Our finding implies the potential of plasma NFL as a longitudinal noninvasive biomarker in AD.

Voxel-based meta-analysis of grey matter changes in Alzheimer’s disease

Background:Voxel-based morphometry(VBM)using structural brain MRI has been widely used for the assessment of impairment in Alzheimer’s disease(AD),but previous studies in VBM studies on AD remain inconsistent.Objective:We conducted meta-analyses to integrate the reported studies to determine the consistent grey matter alterations in AD based on VBM method.Methods:The PubMed,ISI Web of Science,EMBASE and Medline database were searched for articles between 1995 and June 2014.Manual searches were also conducted,and authors of studies were contacted for additional data.Coordinates were extracted from clusters with significant grey matter difference between AD patients and healthy controls(HC).Meta-analysis was performed using a new improved voxel-based meta-analytic method,Effect Size Signed Differential Mapping(ES-SDM).Results:Thirty data-sets comprising 960 subjects with AD and 1195 HC met inclusion criteria.Grey matter volume(GMV)reduction at 334 coordinates in AD and no GMV increase were found in the current meta-analysis.Significant reductions in GMV were robustly localized in the limbic regions(left parahippocampl gyrus and left posterior cingulate gyrus).In addition,there were GM decreases in right fusiform gyrus and right superior frontal gyrus.The findings remain largely unchanged in the jackknife sensitivity analyses.Conclusions:Our meta-analysis clearly identified GMV atrophy in AD.These findings confirm that the most prominent and replicable structural abnormalities in AD are in the limbic regions and contributes to the understanding of pathophysiology underlying AD.

Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders

Background:Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer's disease(AD).As the cerebrospinal fluid(CSF)α-synuclein has been suggested as a potential biomarker of AD,this study was set out to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders.Methods:The associations between CSF a-synuclein and other AD biomarkers were investigated at baseline in non-demented Chinese elders.The predictive values of CSF a-synuclein for longitudinal neuroimaging change and the conversion risk of non-demented elders were assessed using linear mixed effects models and multivariate Cox proportional hazard models,respectively,in the Alzheimer's disease Neuroimaging Initiative(ADNI)database.Results:The CSF α-synuclein levels correlated with AD-specific biomarkers,CSF total tau and phosphorylated tau levels,in 651 Chinese Han participants(training set).These positive correlations were replicated in the ADNI database(validation set).Using a longitudinal cohort from ADNI,the CSF α-synuclein concentrations were found to increase with disease severity.The CSF α-synuclein had high diagnostic accuracy for AD based on the"ATN"(amyloid,tau,neurodegeneration)system(A+T+versus A-T-control)(area under the receiver operating characteristic curve,0.84).Moreover,CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia.Conclusions:CSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders.This finding indicates that CSF α-synuclein is a potentially useful early biomarker for AD.

Cerebrospinal fluid heart fatty acid-binding protein as a predictive biomarker of neurodegeneration in Alzheimer's disease

Objective:This study aims to investigate whether the heart fatty acid-binding protein(HFABP)in the cerebrospinal fluid(CSF)was a potential predictive biomarker for Alzheimer’s disease(AD).Methods:We evaluated the associations of CSF HFABP levels with core biomarkers,cognition,and brain structure in a sample population(n=302)from the Alzheimer’s Disease Neuroimaging Initiative(ADNI)database.Multiple linear regression and mixed-effects models were employed in the analyses.AD progression was assessed using the Kaplan–Meier survival analysis.Results:CSF HFABP was higher in patients with mild cognitive impairment and AD than the normal controls(p<0.001)and was particularly higher in those with amyloid-β(Aβ)pathologic features.CSF HFABP was associated with higher baseline CSF t-tau(p<0.001),CSF p-tau(p<0.001),and CSF t-tau/Aβ42 and CSF p-tau/Aβ42(p<0.01).Moreover,CSF HFABP was found to play predictive roles in hippocampal atrophy(p<0.01),cognitive decline(p<0.05),and the risk of AD(p<0.001).Conclusion:Our findings suggest that CSF HFABP can be a predictive biomarker of AD.