Lipoprotein glomerulopathy caused by mutation of apolipoprotein E gene in children: a report of two cases / 中华肾脏病杂志

The paper reports two cases of lipoprotein glomerulopathy (LPG) in children. The Sanger sequencing results in 2 cases indicated apolipoprotein E gene mutation[c.127 (exon3) C>T, p.R43C (p.Arg43Cys); c.494 (exon4) G>C, p.R165P (p.Arg165Pro),respectively]. Renal pathological presentation of two children showed that a large number of lipoprotein emboli were formed in the glomerular capillary loop, and the diagnosis of LPG was confirmed. The onset of LPG has no specific clinical manifestation, which is easy to be undiagnosed or misdiagnosed. Renal biopsy is a diagnostic means, glucocorticoid treatment is ineffective, and long-term lipid-lowering treatment may be required for LPG.

Interaction between apolipoprotein E genotypes, excessive daytime sleepiness, and cognitive function in obstructive sleep apnea patients / Interação entre genótipos da apolipoproteína E, sonolência excessiva diurna e função cognitiva em pacientes com apneia obstrutiva do sono

Abstract Background Some studies show an association between the apolipoprotein E ε4 allele (ApoEε4) and obstructive sleep apnea syndrome (OSAS), and other studies, an association between ApoEε4 and excessive daytime sleepiness (EDS), but there are no data in the literature on the interaction between EDS, cognitive function, and ApoEε4 in patients with OSA. Objective To examine the cognitive function of adults with and without EDS and with and without ApoEε4. Methods A total of 21 male and female patients aged between 33 and 79 years, underwent a clinical interview, ApoE genotyping, neuropsychological evaluation, polysomnography, and the application of the Epworth Sleepiness Scale. Results Excessive daytime sleepiness was associated with lower intelligence quotient (IQ; total performance) and worse immediate visual memory, regardless of the ApoE genotype. Patients carrying the ApoEε3/ε4 genotype had a worse performance in divided attention, constructional praxis, perceptual organization, and cognitive flexibility. A combination of the ε4 allele and EDS potentiates the negative effect on cognition, except for immediate visual memory. In this case, patients had a worse performance in terms of processing speed, selective attention, and visuomotor coordination. Conclusions Excessive daytime sleepiness and the ApoEε3/ε4 genotype are associated with worse cognitive performance in OSA patients. The combination of EDS and ε4 allele potentiates cognitive impairment.

Resumo Antecedentes Alguns estudos mostram uma associação entre o alelo ε4 da apolipoproteina E (ApoEε4) e a síndrome da apneia obstrutiva do sono (SAOS), e outros, entre ApoEε4 e a sonolência excessiva diurna (SED), mas não há dados na literatura sobre a interação entre SED, função cognitiva e ApoEε4 em pacientes com SAOS. Objetivo Avaliar a função cognitiva em adultos com SAOS com e sem SED e com e sem ApoEε4. Métodos Ao todo, 21 pacientes, de 33 a 79 anos, homens e mulheres, foram avaliados clinicamente, e submetidos a genotipagem ApoE, avaliação neuropsicológica, polissonografia, e aplicação da Escala de Sonolência de Epworth. Resultados A SED esteve associada com menor quociente de inteligência (QI; desempenho geral) e pior memória visual imediata, independentemente do genótipo ApoE. Pacientes com genótipo ApoEε3/ε4 apresentaram pior desempenho na atenção dividida, praxe construcional, organização perceptiva e flexibilidade cognitiva. A combinação do alelo ε4 com a SED potencializa esse efeito deletério na cognição, exceto na memória visual imediata. Nesse caso, os pacientes tiveram uma menor velocidade de processamento cognitivo, e piores atenção seletiva e coordenação visiomotora. Conclusões A SED e o genótipo ApoEε3/ε4 estão associados a um pior desempenho cognitivo em pacientes com SAOS. A combinação de SED e do alelo ε4 potencializa esse efeito.

Analysis of solute carrier organic anion transporter family member 1b1 and apolipoprotein E genes in a population from southern Yunnan / 中国基层医药

Objective:To analyze the distribution of solute carrier organic anion transporter family member 1b1 ( SLCO1B1) and apolipoprotein E ( ApoE) genes in a population from southern Yunnan. Methods:The data of 104 patients who received treatment in Southern Central Hospital of Yunnan Province (The First People's Hospital of Honghe State) between May 2019 and June 2020 were collected. The distribution of SLCO1B1 and ApoE genes and their relationship with nationality, sex, and age were analyzed and compared between different regions. Results:The percentage of patients carrying *1a/*1a, *1a/*1b, *1b/*1b, *1a/*15, *1b/*15, five phenotypes of SLCO1B1 gene, in the population from southern Yunnan was 4.81%, 32.69%, 42.31%, 12.50% and 7.69% respectively. Phenotypes *1a/*5, *5/*5, *5/*15 and *15/*15 were not detected. Normal metabolic phenotype of SLCO1B1 accounted for 79.81%, and intermediate metabolic phenotype of SLCO1B1 accounted for 20.19%. Weak metabolic phenotype was not detected. The percentage of patients carrying E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, five phenotypes of ApoE gene in the population from southern Yunnan was 0.96%, 16.35%, 70.19%, 11.54% and 0.96% respectively. E2/E4 phenotype was not detected. The percentage of patients with ApoE protective phenotype, ApoE normal phenotype, and ApoE risk phenotype was 17.31%, 70.19% and 12.50% respectively. The observed polymorphism mutation frequency of SLCO1B1 and ApoE genes was consistent with the Hardy-Weinberg equilibrium ( P > 0.05), suggesting constancy and a population representation. The Fisher test showed that SLCO1B1 gene distribution differed significantly between ethnic minorities and Han nationality in southern Yunnan ( P = 0.013). There was no significant difference in SLCO1B1 gene distribution between different sexes and between different ages (all P > 0.05). There was no significant difference in ApoE gene distribution between ethnic minorities and Han nationality, between different sexes, and between different ages in the population from southern Yunnan (all P > 0.05). Conclusion:SLCO1B1 gene distribution is related to nationality in the population from southern Yunnan, but it is unrelated to sex and age. ApoE gene distribution is unrelated to nationality, sex and age.

Vascular mild cognitive impairment and its relationship to hemoglobin A1c levels and apolipoprotein E genotypes in the Dominican Republic / Comprometimento cognitivo leve vascular e sua relação com os níveis de hemoglobina a1c e genótipos apolipoproteína e na república dominicana

ABSTRACT. Dementia and vascular mild cognitive impairment (VaMCI) currently impose a tremendous human and economic burden on patients from aging populations and their families worldwide. Understanding the interplay of cardiometabolic risk factors and apolipoprotein E (APOE) may direct us to a more personalized medicine and preventative care in MCI and dementia. Objective: To evaluate the relationship of cardiometabolic risk factors with MCI and assess the APOE genotype's role in an elderly cohort in the Dominican Republic. Methods: We studied a cohort of 180 participants 65 years of age and older using a combined assessment of cardiometabolic risk factors, neuropsychological battery tests, and APOE genotyping. We used the number of failed tests as a proxy to predict MCI. Results: We found that patients with the ε3-ε4 APOE genotype had 2.91 higher number of failed cognitive tests (p=0.027) compared to patients with the ε3-ε3 genotyped. The rate of test failures increased 10% (p=0.025) per unit increase in HbA1c percentage. Conclusions: Increased Hemoglobin A1c levels and ε3-ε4 APOE genotypes seem to have an association with the development of VaMCI.

RESUMO. A demência e o comprometimento cognitivo leve vascular (VaMCI) atualmente impõem uma enorme carga humana e econômica aos pacientes de populações envelhecidas e suas famílias em todo o mundo. Compreender a interação dos fatores de risco cardiometabólicos e apolipoproteína E (APOE) pode nos direcionar para uma medicina mais personalizada e de cuidados preventivos em MCI e demência. Objetivo: Avaliar a relação dos fatores de risco cardiometabólicos com o MCI e o papel do genótipo APOE em uma coorte de idosos na República Dominicana. Métodos: Estudamos uma coorte de 180 participantes com 65 anos de idade ou mais, utilizando uma avaliação combinada de fatores de risco cardiometabólicos, uma bateria de testes neuropsicológicos e genotipagem APOE. Adotou-se o número de testes com mau desempenho para o diagnóstico de MCI. Resultados: Verificou-se que os pacientes com o genótipo ε3-ε4 do APOE apresentaram 2,91 vezes mais testes cognitivos com mau desempenho (p=0,027) em comparação com os pacientes com o genótipo ε3-ε3. A taxa de falhas de teste aumentou 10% (p=0,025) por aumento de unidade na porcentagem de HbA1c. Conclusões: Níveis mais altos de HbA1c e os genótipos ε3-ε4 do APOE parecem estar associados ao desenvolvimento de VaMCI.

Interaction between physical exercise and APOE gene polymorphism on cognitive function in older people

We aimed to present an overview of the literature regarding the interaction between physical exercise and APOE gene polymorphism on cognitive function, particularly in patients with Alzheimer's disease (AD). Firstly, this review focused on the effect of the physical exercise on cognitive function, regardless of APOE gene polymorphism. Some studies have shown that a high level of cardiorespiratory fitness is associated with less neuronal damage with an improvement in memory score tests whereas other studies failed to detect any association between physical exercise and cognitive improvement either in healthy individuals or patients with AD. Taken together, standardized protocols and more longitudinal studies are required to provide a better insight into the effects of physical exercise on cognitive function. Although there is no agreement in the literature regarding the effects of physical exercise on cognitive function, it is well established that it improves social interaction and the feeling of well-being, thereby positively contributing to the quality of life of the elderly. Regarding the influence of physical exercise on cognitive function in APOE ε4 allele carriers, the data trend shows that the carriers of allele ε4 for APOE gene were more responsive to the beneficial effects of physical exercise on cognitive function compared with non-carriers. Nevertheless, studies with larger sample sizes will provide more accuracy about this relationship.

Association between apolipoprotein E polymorphism and myocardial infarction in patients with type 2 diabetes mellitus / 中华检验医学杂志

Objective:To investigate the relationship between the E2 and E4 alleles of apolipoprotein E (apoE) gene and myocardial infarction (MI) in type 2 diabetes Mellitus (T2DM) patients, and to explore the relationship between apoE polymorphism and blood lipid metabolism.Methods:This case control study was conducted from August 2016 to March 2020 in China-Japan Friendship Hospital, 3 459 inpatients with T2DM were included including 3 044 patients without MI (T2DM group) and 415 patients with MI (T2DM+MI group). Real time fluorescent quantitative PCR was used to detect apoE polymorphism. Automatic biochemical analyzer was used to detect lipid levels. Logistic regression analyses were performed to determine the association of apoE with risk of MI in patients with T2DM.Results:(1) The frequency of E4 allele in T2DM+MI group (12.29%, 102/830) was significantly higher than in T2DM group (9.13%,556/6 088), while the frequency of E2 allele in T2DM+MI group (7.35%,61/830) was significantly lower than that in T2DM group (8.21%,500/6 088), P=0.012. Logistic regression analyses showed that E4 allele carrier (E3/E4+E4/E4) faced a higher risk for MI in T2DM patients ( OR=1.48, 95% CI 1.14-1.92, P=0.003), while E2 allele carrier(E2/E3+E2/E2)did not face a higher risk of MI in T2DM patients ( OR=0.88, P=0.642). (2) The levels of apoE polymorphism and blood lipid: The levels of TC, LDL-C and apoB increased in the order of E4 allele, wild type and E2 allele ( P<0.05). The levels of HDL-C, apoA1 and apoE decreased in the order of E4 allele, Wild type and E2 allele ( P<0.05). Conclusion:The E4 allele is a risk factor for MI in T2DM patients, and apoE polymorphism can affect blood lipid level in this patent cohort.

Mechanism of neuronal damage induced by sevoflurane: the relationship between phosphorylation of Tau protein and apolipoprotein E containing 18 kDa fragments / 中华麻醉学杂志

Objective:To evaluate the relationship between phosphorylation of Tau protein and apolipoprotein E (ApoE) containing 18 kDa fragments and investigate the mechanism of neuronal damage induced by sevoflurane.Methods:Primary neurons (ApoE3 and ApoE2 genotypes, 24 dishes for each genotype) of fetal mice cultured until the 5th day were divided into 4 groups ( n=12 each) using a random number table method: ApoE3 control group (A3C group), ApoE3 sevoflurane group (A3S group), ApoE2 control group (A2C group) and ApoE2 sevoflurane group (A2S group). Neurons were treated with 21% oxygen + 5% carbon dioxide + 4.1% sevoflurane for 4 h in A3S and A2S groups, while the neurons were only treated with 21% oxygen + 5% carbon dioxide in A3C and A2C groups.The cell proteins were then extracted to detect the expression of full-length ApoE and ApoE, AT8 and PHF1 containing 18 kDa fragments (by Western blot), expression of ApoE mRNA (by real-time polymerase chain reaction), and concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the supernatant (by enzyme-linked immunosorbent assay). Results:Compared with A2C group, the expression of ApoE mRNA and full-length ApoE in neurons was up-regulated ( P<0.05), and no significant change was found in the expression of AT8 and PHF1 and concentrations of TNF-α and IL-6 in the supernatant in A2S group ( P>0.05). Compared with A3C group, the expression of ApoE mRNA, full-length ApoE, and ApoE, AT8 and PHF1 containing 18 kDa fragments was up-regulated, and the concentrations of TNF-α and IL-6 in the supernatant were increased in A3S group ( P<0.05). Conclusion:Sevoflurane may promote phosphorylation of Tau proteins and increase inflammatory responses through up-regulating the expression of ApoE containing 18 kDa fragments, thus leading to neuronal damage.

Apolipoprotein E genotypes and vascular cognitive impairment / 国际脑血管病杂志

Vascular cognitive impairment is the only cognitive impairment disease that can be intervened at present. In recent years, the research on its genetic factors has attracted much attention. Among them, apolipoprotein E (ApoE) and its genotypes are closely associated with lipid metabolism, β-amyloid aggregation and deposition, the changes of brain structure and function, and are closely correlated with the pathogenesis of dementia. This article discusses some possible mechanisms of ApoE and its genotypes affecting cognitive function, in order to provide reference for the management of cognitive function in patients with vascular cognitive impairment.

Herpes virus and Alzheimer's disease: the debate and new evidence / 中华神经科杂志

Alzheimer's disease is a chronic progressive neurodegeneration disease,currently the pathogenesis of which is not fully elucidated and no disease-modifying therapies are available.The amyloid-beta cascade hypothesis is still predominant in the field.Although has been proposed for decades,the herpes virus hypothesis remains controversial due to lack of solid evidence.New evidence supporting the hypothesis is emerging while debates remain,which would be the focus of this paper.

A case-control study of the association between the polymorphisms of APOE and SLCO1B1 and the severity of coronary artery disease / 中华检验医学杂志

Objective The single nucleotide polymorphisms (SNPs) of APOE and SLCO1B1 were examined to explore their association with the risk and severity of coronary heart disease(CAD). Methods A total of 1267 cases of consecutive coronary heart disease (CAD)-suspected inpatients visiting department of Cardiology in Peking University Peoples' Hospital from March 2017 to november were recruited into this case-control study, and then 391 CAD cases and 223 non-CAD controls were enrolled for final analysis after screening by coronary angiography and exclusion criteria. The severity of the CAD cases were evaluated according to Gensini scores. The SNPs of APOE(388T>C, 526C>T) and SLCO1B1(388A>G, 521T>C) were detected using Real-time PCR and further verified using Sanger sequencing. Environmental risk factors were collected, and the correlations between SNPs of APOE and SLCO1B1 and the risk and severity of CAD were performed by SPSS version 16.0. Results The SNPs of all the subjects included in CAD group and non-CAD group were successfully detected, with an accordance of 100％ to Sanger sequencing. The distribution of APOE and SLCO1B1 gene were subjected to Hardy-Weinberg. The distributions of APOE gene ε3/ε3 genotypes and ε3 allele were most commonly found in both CAD group and non-CAD group (ε3/ε3: 70.8％,73.1％;ε3: 83.5％,85.2％;respectively). APOE genotypes and alleles were comparable between the CAD cases and non-CAD controls (P>0.05). The frequencies of APOE gene ε4+genotype were more likely to be found in the subgroup of CAD with Gensini score≥72 (P<0.05). The distributions of SLCO1B1 gene *1b/*1b genotypes and *1b allele were most commonly found in both CAD group and non-CAD group (*1b/*1b: 37.3％, 36.8％; *1b: 60.1％, 61.7％; respectively). There was no significant difference in genotype and allele frequencies of SLCO1B1 between the two groups and among subgroups with different severity of CAD (P>0.05). Conclusion This study observed no association between SNPs of APOE, SLCO1B1 and the risk of CAD in this population. However, APOE gene ε4 +genotype may increase the severity of CAD.

Quantification of serum apolipoprotein E and patient phenotyping using isotope dilution liquid chromatography-tandem mass spectrometry / 中华检验医学杂志

Objective To establish an isotope dilution liquid chromatography tandem mass spectrometry method (ID-LC-MS) for quantification of serum apolipoprotein E and phenotyping. Methods Method establishment. Samples underwent denaturing, alkylation and trypsin digestion with addition of internal standards as isotope labelling arginine. SB-C18 column was used for the liquid chromatographic separation and mass spectrometry positive ion mode and multiple reaction monitoring were employed for quantification and phenotyping. Precision, accuracy and linearity were investigated for method evaluation. 40 serum samples from Shanghai Dongfang Hospital during Oct. to Dec., 2018 were used for method comparison between ID-LC-MS and immunoassay. Deming regression and Bland-Altman were used for method comparison analysis and SPSS 24 for linearity. Results Target peptides reached their releasing maximum within 4 hours and SE did at 3 hours. 3 phenotyping of ApoE were observed, such as E3/E3, E2/E3 and E3 / E4. The imprecision of IQC was 5.2 ％ . The relative bias for low and high levels of accuracy-based samples was 7.6 ％ and 3.6 ％, respectively. Deming regression showed the intercept with 95 ％ confidence interval (CI) was 6.44-11.44 (P<0.05 and the 95％ confidence interval for the slopewas 0.77-0.89 (P<0.05). The coefficient was r=0.97. The mean difference was - 2.95 mg / L with 95 ％ CI-4.26--1.65 mg/L. The linearity covered from 16.9 to 58.5 mg/L. Conclusion ID-LC-MS can be used to quantify serum apolipoprotein E and simultaneously detect its phenotyping.

Correlation analysis of ApoE gene polymorphism in patients with mild cognitive impairment / 中国医师杂志

Objective To investigate the association of apolipoprotein E (ApoE) gene polymorphism in patients with mild cognitive impairment.Methods The patients aged 60-85 years were randomly selected from the outpatient,hospital or community age of Xinjiang Medical University Affiliated Hospital of traditional Chinese medicine in January 2015-June 2016,and cognitive function assessment for the patients.A total of 100 cases of mild cognitive impairment (MCI) patients were selected as case group,and 139 cases with normal cognitive function were the control group.The polymorphism of ApoE gene was analyzed in all patients.The final data were analyzed by Pearson chi square test.Results Compared to the control group,the proportion of genotype T/T in the genotype distribution of rs429358 loci was lower than that of the control group,T/C and C/C were higher than those in the control group,Allele C was a risk factor for MCI disease (OR value =2.100).The epsilon 4 allele was significantly higher than that of the control group,and the epsilon 3 allele was significantly higher than that of the control group (P ＜ 0.05).Conclusions The polymorphism of the ApoE gene is associated with the pathogenesis of MCI,in which the ApoE-E4 allele may be a risk gene for MCI.This suggests that the detection of ApoE gene polymorphism may provide useful information for the early diagnosis of MCI.

Case-control study on the influencing factors related to cognitive impairment in the elderly population of China / 中华预防医学杂志

Objective@#To explore the influencing factors affecting the cognitive impairment of the elderly population in China.@*Methods@#A stratified multi-stage cluster sampling was used in 6 provinces (autonomous administrative regions and municipalities) to select the sample. A total 24 000 urban and rural residents aged 60 years and above received a set of standardized questionnaire interview, physical examinations, laboratory test of lipid and glucose levels of blood and apolipoprotein E (APOE) genotype. The primary screening of cognitive function was assessed by using the Chinese Version of Ascertain Dementia 8, and then suspicious cognitive impairment cases with more than two abnormal results would receive the further cognitive function assessment by using the Mini-Mental State Examination (MMSE). 1 300 cases with cognitive impairment and 2 600 controls without cognitive impairment were recruited and matched according to their age, gender and resident area in a 1∶2 case-control study. The conditional logistic regression model was used to analyze the association between relevant factors and cognitive impairment.@*Results@#Factors negatively associated with cognitive impairment and their OR (95%CI) values were primary or middle school as 0.63 (0.51-0.77), high school and above as 0.59 (0.39-0.88), daily neighborhood communication as 0.61 (0.50-0.75), weekly participating in social activities 0.59 (0.44-0.79), daily tea drinking as 0.71 (0.58-0.88) and doing regular exercise as 0.71 (0.57-0.88), reading newspaper (occasional: 0.50 (0.37-0.67); frequent: 0.40 (0.28-0.57)), playing majiang or cards (occasional: 0.51 (0.34-0.74); frequent: 0.50 (0.36-0.68)) respectively. Factors positively associated with cognitive impairment and their OR (95%CI) values were APOE-ε4 heterozygote as 1.31 (1.08-1.58), homozygote as 2.74 (1.52-5.00), diabetes onset before 50 years of age and after as 9.03 (3.07-33.60) and 4.40 (3.18-6.17), stroke as 1.90 (1.35-2.69), asthma as 1.95 (1.11-3.42) respectively.@*Conclusion@#APOE-ε4 alleles, lower educational level, stroke, asthma, diabetes are risk factors of cognitive impairment in the elderly. Keeping a healthy lifestyle and preventing chronic diseases in the whole life course could significantly reduce the incidence of cognitive impairment in the elderly.

Correlation between apolipoprotein E gene polymorphism and the urine level of Alzheimer-associated neuronal thread protein in patients with Alzheimer's disease and mild cognitive impairment / 中华神经科杂志

Objective To explore the correlation between apolipoprotein E (ApoE) gene polymorphism and urine Alzheimer-associated neuronal thread protein (AD7c-NTP) level in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI).Methods The cognitive function of 30 AD patients (AD group),30 MCI patients (MCI group) and 30 normal controls (NC group) was evaluated by neuropsychological batteries like MMSE,the Cambridge Cognitive Examination-Chinese Version (CAMCOG-C),etc.ELISA was used to test the urine level of AD7c-NTP.The genotypes of ApoE were analyzed by the high-resolution melting assay in blood samples.Results Compared with the NC group (0.59 (0.40,0.66) ng/ml),the urine level of AD7c-NTP in the AD group (1.03(0.80,1.41) ng/ml) and the MCI group (0.69(0.53,0.91) ng/ml) was increased (Z =33.727,P ＜0.01).The urine level of AD7c-NTP in the AD group was higher than that in the MCI group (Z =8.232,P ＜ 0.05).The level of AD7c-NTP in urine was negatively correlated with MMSE and CAMCOG-C scores (rMMSE =-0.604,P ＜ 0.01;rCAMCOG-C =-0.486,P ＜ 0.01).According to receiver operating characteristic curve,the optimal cutoff point of AD7c-NTP in urine for diagnosis of patients including AD and MCI was 0.70 ng/ml,with sensitivity of 71.7％ and specificity of 83.3％,and area under the curve of 0.82 (95％ CI 0.73-0.90,P ＜0.05).There were four genotypes comprising ε2/3,ε3/3,ε3/4 and ε4/4 for ApoE gene.The frequencies of ε4 carriers were 46.7％ (14/30),23.3％ (7/30) and 23.3％ (7/30) in the AD,MCI and NC groups,respectively.There was a notable increase in urine AD7c-NTP and a significant decrease in CAMCOG-C scores in MCI patients who harbored the ApoE ε4 allele (ZAD7c-NTP =4.857,P ＜ 0.05;ZCAMCOG-C =4.284,P ＜0.05).Conclusions The urine level of AD7c-NTP was significantly increased in AD and MCI patients,the higher the level of AD7c-NTP,the more serious the cognitive impairment.The ε4 carriers exhibited higher urine level of AD7c-NTP,but worse cognitive function compared to ε4 non-carriers in the MCI group.

Effects of apolipoprotein E deficiency on neuromyelitis model in vitro / 中华神经科杂志

Objective To investigate the effects of apolipoprotein E (ApoE) deficiency on neuromyelitis optica (NMO) model of spinal cord sections induced by NMO-IgG and complement in vitro.Methods NMO-IgG was extracted from the patients with NMO,and complementary serum from healthy people.The spinal cord sections of seven days old C57BL / 6J mice with wild type (WT) or ApoE knockout (ApoE-/-) were cultured for seven days.The spinal cords of the two genotypes were randomly divided into experimental groups (NMO-ApoE-/-group,NMO-WT group) and control groups (C-AopE-/-group,C-WT group),respectively.The experimental groups were treated with NMO-IgG and complementary serum,and the control groups only with complementary serum.Then all the sections were continued incubating for 24 h before harvested.Immunofluorescence staining and modified thick tissue film immunofluorescence were used to detect the expression of aquaporin 4 (AQP4),glial fibrillary acidic protein (GFAP),ionic calcium fibronectin (IBA1),myelin basic protein (MBP) and human neurofilament protein L (NFL) respectively.The lesion score was calculated according to the areas percentage of AQP4 and GFAP deficiency in spinal cord sections.Results Compared with the respective control groups,the expressions of AQP4,GFAP,MBP and NFL were deficient in the experimental groups (The percentages of missing area in the NMO-ApoE-/-group were 83.88％ ± 5.01％,82.44％ ± 6.11％,45.02％ ± 5.11％ and 54.65％ ± 7.66％ respectively,while the percentages of missing area in the C-ApoE-/-group were 10.44％ ± 4.07％,5.73％ ±0.82％,9.12％ ±1.41％ and 5.72％ ±0.81％,t=34.143,37.269,20.300,19.051,allP ＜0.05;The percentages of missing area in the NMO-WT group were 77.74％ ± 6.75％,75.62％ ± 5.76％,37.60％ ± 4.88％ and 46.29％ ± 4.98％,while the percentages of missing area in the C-WT group were 9.31％ ± 2.97％,5.80％ ± 0.82％,9.10％ ± 1.63％,5.80％ ± 0.81％ respectively,t =27.828,35.934,16.613,24.057,all P ＜ 0.05).While IBA1 was up-regulated and the damage scores were higher in both the NMO-ApoE-/-group and the NMO-WT group.The percentages of missing area in the NMO-ApoE-/-group and the NMO-WT group showed statistically significant difference (t =2.194,2.436,3.149,2.746,all P ＜ 0.05).The expression level of IBA1 in the NMO-WT group was higher than that in the C-WT group (19.88 ± 1.11 vs 11.18 ±0.65,t =25.270,P ＜0.05),while the expression level of IBA1 in the NMO-ApoE-/-group was higher than that in the NMO-WT group (25.81 ± 1.61 vs 19.88 ± 1.11,t =9.101,P ＜0.05).The degree of deficiency or up-regulation of above-mentioned proteins was more obvious in the NMO-ApoE-/-group than that in the NMO-WT group.Conclusions NMO-IgG extracted from NMO patients can induce NMO-like damage in isolated tissue at the presence of complement.ApoE deficiency promotes the further activation of microglia,thereby aggravates the injury of astrocyte in the model of NMO.

Effect of oxymatrine on liver triglyceride metabolism enzymes of apolipoproteinE －/－ mice with fat-induced insulin resistance / 中华老年医学杂志

Objective To investigate the effect of oxymatrine on liver triglyceride metabolism enzymes of apolipoprotein E(ApoE)－/－mice with fat-induced insulin resistance. Methods A total of 72 ApoE－/－mice fed with a high-fat diet for 16 weeks were randomly assigned into a model group ,an oxymatrine 25 mg/kg group ,an oxymatrine 50 mg/kg group ,and an oxymatrine 100 mg/kg group , and oxymatrine was administered p.o.for 8 weeks.C57BL/6J mice were selected to serve as the control group.Serum biochemical parameters were assessed ;Insulin resistance was assessed with the Hyper insulinemic-euglycemic clamp test ;Pathological changes in the liver were visualized by hematoxylin ( HE ) staining ;levels of gene expression of triglyceride metabolism enzymes were examined by real-time polymerase chain reaction ( PCR ) and Western-blotting. Results Administration of oxymatrine reduced body weight ,fasting blood glucose , cholesterol ,and triglyceride to varying degrees and alleviated pathological changes in the liver.Glucose infusion rates were(18.5 ± 1.6)mU · kg －1· min－1,(20.1 ± 1.8)mU · kg －1· min－1,and(21.3 ± 2.3)mU · kg －1· min－1in the oxymatrine 25 ,50 ,and 100 mg/kg groups ,respectively ,and were significantly higher than that in the model group (16.5 ± 1.6)mU · kg －1· min－1(all P ＜ 0.05) .mRNA expression levels of hormone-sensitive lipase(HSL) ,adipose triglyceride lipase(ATGL) ,and peroxisome proliferator-activated receptor γ(PPARγ)were higher in the three oxymatrine groups than in the model group ,while levels of diacylglycerol acyltransferase (DGAT1 ) were lower in the oxymatrine groups(F＝53.81 ,21.06 ,23.67 ,35.37 ;all P＜0.05) ;Levels of HSL ,ATGL ,and PPARγ were higher ,while levels of DGAT1 were lower in the oxymatrine 50 and 100 mg·kg －1groups than in the model group ( F ＝ 53.62 ,22.87 ,28.13 ,33.54 ;all P ＜ 0.05 ). Conclusions Oxidative can mitigate insulin resistance in mice fed with a high fat diet through regulating the expression of liver triglyceride metabolism enzymes.

Relationship of TN-C, MMP-9 and TGF-β1 with aorta atherosclerotic plaues in mice / 中华老年心脑血管病杂志

Objective To study the relationship of TN-C,MMP-9 and TGF-β1 expression with aorta atherosclerotic plaue stability in mice on long-term high fat diet.Methods Fifty male apo E/ mice on high fat diet served as an experimental group and 50 male C57BL/6 mice on basic diet served as a control group.The morphology of plaques was observed with HE staining and the expression of TN-C,MMP-9 and TGF-β1 was detected with immunohistochemical staining.Results The serum TC and LDL-C levels were significantly higher in experimental group than in control group at weeks 16,24,32 and 40 (P＜0.05).The serum TG level was significantly higher in experimental group than in control group at week 16 (P＜0.05) and was significantly lower in experimental group than in control group at week 40 (P＜0.05).With the lengthening of the feeding time,the plaque area,the ratio of plaque to lumen area,and the expression of TN-C and MMP-9 increased gradually,but the expression of TGF-β1 decreased gradually (P＜0.05).Conclusion The expression of TN-C,MMP-9 and TGF-β1 can show the stability of atherosclerotic plaques.

ApoE genotyping and its clinical significance / 中华检验医学杂志

Apolipoprotein E has a dominant function in the metabolic process of triglyceride and cholesterol in multiple tissues of human .The allele of ApoE has three variants ε2,ε3,ε4 and six genotypesε2/ε2, ε3/ε3, ε4/ε4, ε2/ε3, ε2/ε4, ε3/ε4, due to polymorphisms of two common SNPs . These genotypes associated with kinds of diseases ,such as hyperlipidemia , ASCVD, and AD.In addition, they are also related to the treatment effect of statins .Thus, the detection of the ApoE genotypes is valuable and meaningful in the clinic.In this article, there is a simple discussion about the methodology of the ApoE genotypes, from the protein electrophoresis phenotyping to the rapid , precise and convenient genotyping methods, and its clinical significances.

The impact of astragaloside Ⅳ on the experimentally atherosclerotic formation in ApoE-deficient mice / 中国医师杂志

Objective To explore the impacts of astragalosideⅣ( AST-Ⅳ) on the experimentally atherosclerotic formation in ApoE-deficient mice. Methods ApoE-deficient mice were randomly divided into AST-Ⅳ and control groups, both groups were fed with high-fat diet, and were killed after 12 weeks of treatment. The plaque areas were measured; the percentage of CD4 +CD25 + T cells were determined by flow cytometry;the levels of supernatant cytokine such as interferon ( IFN )-γ, interleukin ( IL )-10 and transforming growth factor-β (TGF-β) were measured by enzyme-linked immunosorbent assay (ELISA). Results The plaque area of AST-Ⅳ group was ( 815. 78 ± 165. 43 )μm2 , which was smaller than that in control group of (2152. 13 ± 525. 47)μm2. The percentage of CD4 +CD25 +Treg accounted for (9. 86 ± 1. 78)％ of CD4 + cells, which was higher than that in control group (2. 52 ± 1. 43) ％. Compared to con-trol group, the supernatant levels of IL-10 and TGF-βwere significantly higher, and IFN-γwas significantly lower in AST-Ⅳ group (P<0. 05). Conclusions By influencing the regulatory T cell-mediated immune tolerance, AST-Ⅳ might inhibit atherosclerosis in mice.