Objective: Current treatment and prognosis of Parkinson's disease (PD) are not ideal. This study explored the mechanism of long non-coding RNA (lncRNA) rhabdomyosarcoma 2-associated transcript (RMST) in dopaminergic (DA) neuron damage in PD rats. Methods: PD rats were modeled and injected with RMST silence or overexpression vectors to figure out its roles in oxidative stress, the apoptosis of DA neurons in brain substantia nigra (SN), and neurobehavioral activities of PD rats. Tyrosine hydroxylase (TH), synaptophysin (SYN), glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule (Iba-1) in SN were detected. RMST and Toll-like receptor (TLR)/nuclear factor kappa B (NF-kappa B) pathway-related factors were detected. Results: RMST expression in brain SN of rats, TLR2, TLR4 expression in neurons and NF-kappa B expression in cell nucleus were increased. Silenced RMST improved the neurobehavioral activities, depressed oxidative stress and neuronal apoptosis, increased TH and SYN expression, and reduced the activation degree of glial cells in SN and the inflammatory response via reducing GFAP and Iba-1. Moreover, reduced RMST reduced TLR2 and TLR4 expression in neurons and NF-kappa B expression in cell nucleus in PD rats. Conclusion: Inhibited RMST attenuates DA neuron damage in PD rats, which may be implicated with TLR/NF-kappa B signaling pathway.

目的 评估细胞间黏附分子-1(Intercellular adhesion molecule-1,ICAM-1)基因启动子区甲基化水平与脑梗死的相关性.方法 对2017年9月-2018年9月于解放军第960医院就诊患者进行回顾性分析,根据诊断标准挑选152例脑梗死患者为病例组,同期于该院体检健康者152例为对照组,采用酶联免疫吸附法(Enzyme linked immunosorbent assay,ELISA)检测2组受试者外周血ICAM-1水平,使用荧光定量甲基化特异性聚合酶链反应(Quantitative Methylation Specific PCR,qMSP)法测定2组受试者ICAM-1甲基化程度.结果 病例组外周血ICAM-1水平显著高于对照组(T=20.27,P<0.001);病例组ICAM-1基因甲基化程度显著低于对照组(Z=-3.158,P=0.002);病例组亚组分析发现有吸烟史者甲基化程度更低(Z=-3.305,P=0.001);2组ICAM-1甲基化程度均与ICAM-1水平呈显著负相关(病例组r=-0.756,P<0.001;对照组r=-0.823,P<0.001).结论 ICAM-1低甲基化通过促进ICAM-1的高表达,参与脑梗死的病理过程,可能通过调节基因表达水平来影响脑梗死的患病风险.IC A M-1启动子区甲基化程度升高可作为脑梗死的保护因素.

Parkinson's disease (PD) is a neurodegenerative disease that occurs mostly in middle-aged and older adults. Its main pathological feature is the progressive death of substantia nigra dopaminergic neurons. As the world's population ages, the number of PD patients is increasing. In this study, we explored the relationship between PD and the cell cycle. In this study, we collected two independent PD transcriptomic datasets, GSE54536 and GSE6613, from the Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was used to identify dysregulated pathways in PD samples. Gene expression was verified by qPCR in PD patients. Nineteen pathways were negatively enriched in both the GSE54536 and GSE6613 datasets. Seven of these 19 pathways were cell cycle-related pathways, including the M/G1 transition, S phase, G1/S transition, mitotic G1-G1/S phases, CDT1 association with the CDC6 ORC origin complex, cell cycle checkpoints and synthesis of DNA. Next, we found that eight genes (PSMA4, PSMB1, PSMC5, PSMD11, MCM4, RPA1, POLE, and PSME4) were mainly enriched in the GSE54536 and GSE6613 datasets. In GSE54536, PSMA4, PSMB1, PSMC5, and PSME4 could significantly predict the occurrence of PD, whereas, in GSE6613, RPA1 and PSME4 could significantly predict the occurrence of PD. Only PSME4 showed significant results in both datasets. Finally, we assessed blood samples from PD patients and controls. Compared with the control samples, the PD samples had lower mRNA levels of PSME4. In summary,these findings can significantly enhance our understanding of the causes and potential molecular mechanisms of PD; the cell cycle signaling pathways and PSME4 may be therapeutic targets for PD.

Background The goal of our study is to investigate whether the methylation levels of AHCY and CBS promoters are related to the risk of cerebral infarction by detecting the methylation level of AHCY and CBS genes. Methods We extracted peripheral venous blood from 152 patients with cerebral infarction and 152 gender- and age-matched healthy controls, and determined methylation levels of AHCY and CBS promoters using quantitative methylation-specific polymerase chain reaction. We used the percentage of methylation reference (PMR) to indicate gene methylation level. Results We compared the promoter methylation levels of two genes (AHCY and CBS) in peripheral blood DNA between the cerebral infarction case group and the control group. Our study showed no significant difference in AHCY promoter methylation between case and control. Subgroup analysis by gender showed that the methylation level of AHCY in males in the case group was lower than that in the control group, but the difference was not statistically significant in females. In a subgroup analysis by age, there was no significant difference in the AHCY methylation level between the case and control in the young group (≤44 years old). However, the level of AHCY gene methylation in the middle-aged group (45–59 years old) was significantly higher and the aged group (≥60 years old) was significantly lower than that in the control groups. However, CBS promoter methylation levels were significantly lower in the case group than in the control group (median PMR: 70.20% vs 104.10%, P = 3.71E-10). In addition, the CBS methylation levels of males and females in the case group were significantly lower than those in the control group (male: 64.33% vs 105%, P = 2.667E-08; female: 78.05% vs 102.8%, P = 0.003). We also found that the CBS levels in the young (23–44), middle-aged (45–59), and older (60–90) groups were significantly lower than those in the control group (young group: 69.97% vs 114.71%; P = 0.015; middle-aged group: 56.04% vs 91.71%; P = 6.744E-06; older group: 81.6% vs 119.35%; P = 2.644E-04). Our ROC curve analysis of CBS hypomethylation showed an area under the curve of 0.713, a sensitivity of 67.4%, and a specificity of 74.0%. Conclusion Our study suggests that hypomethylation of the CBS promoter may be closely related to the risk of cerebral infarction and may be used as a non-invasive diagnostic biomarker for cerebral infarction.

外泌体是一种内吞起源的纳米级细胞外囊泡(EV),可以由真核生物在生理和病理条件下分泌,它含有神经退行性疾病(NDs)发病相关的蛋白,有作为生物标志物的潜力,并可穿过血脑屏障,有助于将药物和其他治疗分子输送到大脑治疗NDs.所以,在本文中,我们将对外泌体在不同NDs发病机制中所起的作用,以及将它们作为疾病诊断生物标志物和治疗手段的相关研究进行综述.

Objective Paraoxonase (PON) family genes are closely related to the etiology and prognosis of cerebral infarction. This study explored the association of the promoter methylation of PON family genes (PON1, PON2 and PON3) with the risk of cerebral infarction. Materials and Methods In this study, 152 patients with confirmed cerebral infarction were selected as the case group, and 152 healthy controls were selected as the control group. The quantitative methylation-specific PCR (qMSP) was used to determine the promoter methylation levels of PON1, PON2 and PON3 genes. The methylation level was expressed as a methylation reference percentage (PMR). Results Our results indicated that PON1 methylation was significantly higher in the case group than in the control group (P = 0.0001). On the contrary, PON3 methylation was significantly lower in the case group than in the control group(P = 0.002). In addition, we found that PON2 gene had a very low level of methylation in both case and control groups (PMR = 0). Subgroup analysis showed that PON1 and PON3 methylation were associated with cerebral infarction only in males (PON1, P = 0.0002; PON3, P = 0.007). Interestingly, the methylation levels of PON1 and PON3 were correlated with each other (case: r = 0.418, P = 0.0001; control: r = 0.3, P = 0.0002). Further multiple regression analysis suggested that elevated methylation levels of PON3 were a protective factor for cerebral infarction [OR (95% CI) = 0.979 (0.96, 0.999), β = -0.021,P = 0.035)], high- density lipoprotein (HDL) and uric acid (UA) also were protective factors for cerebral infarction [HDL, OR (95% CI) = 0.01 (0.003, 0.033), P < 0.0001); UA, OR (95% CI) = 0.995 (0.991, 0.998), P = 0.003)]. The ROC curve analysis found that the combination of PON3, HDL, and UA had a good predictive power for cerebral infarction (AUC=0.878, 95% CI=0.839-0.918, sensitivity 73.7%, specificity 89.7%, P < 0.0001). Conclusion PON1 and PON3 promoter methylation levels in peripheral blood were closely related. PON1 and PON3 methylation were associated with the risk of cerebral infarction in men. PON3 promoter methylation combined with HDL and UA could be used as potential biomarkers for the diagnosis of cerebral infarction.

目的:探讨对氧磷酶1(paraoxonase1,PON1)基因启动子区甲基化水平和端粒长度与中国山东地区汉族人群脑梗死发病的相关性.方法:选取152例确诊脑梗死患者为病例组,152例健康人为对照组,提取外周静脉血基因组DNA,使用荧光定量甲基化特异性PCR(quantitative methylationspecific PCR,qMSP)测定受试者的血液PON1基因启动子甲基化水平及端粒长度.每个样本的甲基化程度以甲基化参考百分比(PMR)来表示.结果:病例组中PON1甲基化程度显著高于对照组(Z=-3.898,P=0.0001),性别亚组显示差异主要在男性中更为显著(Z=-3.786,P=0.0002).病例组患者的端粒长度显著低于对照组(Z=-11.843,P＜0.0001),且男女亚组中端粒长度均显著低于对照组(P＜0.05).然而,并没有发现PON1甲基化水平与端粒长度的相关性(病例组r=0.023,P=0.775;对照组r=-0.157,P=0.054).结论:PON1启动子区高甲基化和端粒长度变短与脑梗死发病相关,是中国山东地区汉族人群脑梗死发病的危险因素.

There is growing evidence of the position of microRNAs (miRs) in Alzheimer's disease (AD), thus our objective was to discuss the impact of miR-129-5p regulating nerve injury and inflammatory response in AD rats by modulating SOX6 expression. The AD rat model was established by injecting Aβ25-35 into the brain. The pathological changes, ultrastructure, number of neurons, cell degeneration and apoptosis of hippocampal tissue were observed in vivo. MiR-129-5p, SOX6, IL-1β, TNF-α, Bcl-2 and Bax expression in serum and hippocampal tissues were detected by ELISA, RT-qPCR or western blot analysis. The successfully modeled hippocampal neuronal cells of AD were transfected with miR-129-5p mimic, SOX6-siRNA or their controls to figure out their roles in proliferation, apoptosis and inflammatory reaction in vitro. Low expression of SOX6 and high expression of miR-129-5p in vivo of rats would shorten the escape latent period and increase the times of crossing platforms, alleviate the pathological injury, inhibit neuronal apoptosis and reduce the inflammatory reaction. Up-regulation of miR-129-5p and down-regulation of SOX6 promoted proliferation, suppressed apoptosis and degraded the inflammatory reaction of neuronal cells in vitro. Up-regulation of SOX6 reversed the expression of miR-129-5p to reduce the damage and inflammatory response of the cell model of AD. Our study presents that up-regulation of miR-129-5p or down-regulation of SOX6 can reduce nerve injury and inflammatory response in rats with AD. Thus, miR-129-5p may be a potential candidate for the treatment of AD.

目的 探讨影响卒中后抑郁(PSD)患者院外抗抑郁药物服用依从性的影响因素.方法 收集251例PSD患者的年龄、性别、教育水平、婚姻状况、居住地、既往史、脑卒中亚型、NIHSS评分(评价神经功能受损的严重程度)、PHQ-9量表评分(评价患者抑郁症状的严重程度)、住院天数及服用的抗抑郁药物(艾司西酞普兰、氟西汀、黛力新、阿米替林等)等信息.随访出院后6个月时以调查问卷的形式了解患者的主要照顾人、抗抑郁药物的服用天数、服用效果(服用抗抑郁药物后抑郁症状对比服药前有无明显好转)、药物价格承担能力(患者或其主要照顾人对药物价格的主观感受),以及有无出现影响停止服药的不良反应.将服用抗抑郁药物天数≥总随访天数的50％纳入依从性好组,<50％纳入依从性差组.比较两组上述收集指标,并对有统计学意义的指标进行二元逐步Logistic回归分析.结果 出院后6个月,依从性好组96例(38.25％),依从性差组155例(61.75％).两组性别、教育水平、居住地、药物价格、药物服用效果、主要照顾人、酗酒史、住院和出院NIHSS评分、出院PHQ-9评分、住院天数比较差异有统计学意义(P<0.05或<0.01).Logistic回归分析结果显示,抗抑郁药物良好依从性与PHQ-9评分高(P<0.01,OR=1.475,95％CI=1.306～1.666)、药物效果自觉良好(P=0.013,OR=2.348,95％CI=1.194～4.616)、有家人陪伴(P=0.006,OR=0.147,95％CI=0.038～0.573)相关.结论 PSD患者院外抗抑郁药物服用依从性受多方面因素影响,PHQ-9量表评分高、抗抑郁药物自觉效果良好、有家人陪伴均能提高患者的抗抑郁药物服用依从性.

目的 观察米氮平治疗帕金森病抑郁的有效性和安全性.方法 选取2015-01 ～ 2018-01在武汉红桥脑科医院神经内科确诊为帕金森病抑郁的患者96例进行分析,按服药情况分为观察组和对照组,每组48例.观察组给予米氮平治疗,对照组给予舍曲林治疗,疗程均为12周,记录患者治疗前后汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)评分、日常生活能力量表(Activity of Daily Living Scale,ADL)评分、匹兹堡睡眠质量指数(Pittsburgh Sleep Quality Index,PSQI)评分及治疗期间的不良反应发生情况.结果 治疗前,两组年龄、性别、帕金森病程、帕金森抑郁病程、HAMD、ADL、PSQI评分差异均无统计学意义(P＞0.05).治疗12周后,两组HAMD、PSQI评分比治疗前均降低,ADL评分均升高;但观察组HAMD、PSQI评分低于对照组,而ADL评分高于对照组,差异均有统计学意义(P＜0.05).观察组胃肠道反应率低于对照组,差异有统计学意义(P＜0.05).结论 帕金森病抑郁选择药物治疗时,米氮平有较好的抗抑郁作用,且不良反应较舍曲林少,可作为帕金森病抑郁治疗的选择之一.

帕金森病(PD)是一种神经退行性疾病,主要的病理变化是黑质多巴胺能神经元变性死亡,表现出一系列运动症状和非运动症状,严重影响患者的生存质量,目前缺乏有效的早期诊断的生物标志物和治疗方法.miRNA是一种非编码RNA,参与体内众多生理和病理过程的调节,目前已经证实miRNA在PD的发病机制中起作用,并且还可能是PD诊断的生物标志物,本文就将目前miRNA与帕金森病关系的研究进展进行综述.

目的：探讨对氧磷酶1(paraoxonase1，PON1)基因启动子区甲基化水平和端粒长度与中国山东地区汉族人群脑梗死发病的相关性。方法：选取152例确诊脑梗死患者为病例组，152例健康人为对照组，提取外周静脉血基因组DNA，使用荧光定量甲基化特异性PCR(quantitative methylation-specific PCR，qMSP)测定受试者的血液PON1基因启动子甲基化水平及端粒长度。每个样本的甲基化程度以甲基化参考百分比(PMR)来表示。结果：病例组中PON1甲基化程度显著高于对照组(Z=−3.898，P=0.0001)，性别亚组显示差异主要在男性中更为显著(Z=−3.786，P=0.0002)。病例组患者的端粒长度显著低于对照组(Z=−11.843，P<0.0001)，且男女亚组中端粒长度均显著低于对照组(P<0.05)。然而，并没有发现PON1甲基化水平与端粒长度的相关性(病例组r=0.023，P=0.775；对照组r=−0.157，P=0.054)。结论：PON1启动子区高甲基化和端粒长度变短与脑梗死发病相关，是中国山东地区汉族人群脑梗死发病的危险因素。

目的 评估烟酰胺磷酸核糖转移酶(NAMPT)基因启动子区甲基化水平与脑梗死患者及相关临床指标的相关性.方法 使用病例对照的方法,选取152例(男112例,女40例)确诊脑梗死患者为病例组,152例(男112例,女40例)健康人为对照组,提取基因组DNA,经亚硫酸转化后使用荧光定量甲基化特异性PCR(qMSP)测定受试者的NAMPT基因启动子区DNA甲基化水平.结果 用卡方检验对两组进行分析,病例组NAMPT甲基化率为24.59％,对照组为19.69％;按性别分亚组后,男性中两组甲基化率分别为30.23％、23.08％,女性中两组甲基化率均为11.11％,差异无统计学意义.然而,根据是否甲基化分组后分析,NAMPT甲基化组受试者的平均年龄水平显著高于非甲基化组[(60.92±13.97)比(52.75±11.98),t=4.443,P<0.05),NAMPT甲基化组的C反应蛋白(CRP)水平显著高于非甲基化组[(11.12±7.16)比(4.87±2.71),t=3.429,P=0.001].结论 外周血NAMPT启动子区高甲基化水平不能作为脑梗死的1个标志物,NAMPT基因甲基化水平与炎性指标和年龄、衰老有着显著的关联性,值得进一步研究.

BACKGROUND:Telomere length is closely related to the onset and prognosis of ischemic stroke. This study was to investigate the relationship between telomere length and the incidence of ischemic stroke in Han population of northern China. METHODS:In the present study, 152 patients with ischemic stroke were selected as the case group, and 152 healthy persons were used as the control group. Detection of telomere length was done by real-time polymerase chain reaction after extraction of genomic DNA from peripheral venous blood. RESULTS:Our results showed that the telomere length of the patients in the case group was significantly lower than that of the control group (Z = -11.843, P < .0001). Further analysis found that the telomere length of the control group was inversely correlated with age (r = -0.234, P = .004), and the telomere length and homocysteine (HCY) were inversely correlated in the case group (r = -0.176, P = .03), especially in women (r = -0.357, P = .024). Multivariate regression analysis showed that telomere length was a protective factor for ischemic stroke (odds ratio [OR] 95% confidence interval [95% CI] = 0.748 [0.681-0.823], β = -0.29, P < .0001). The receiver operating characteristic curve showed that telomere length was a good diagnostic biomarker of ischemic stroke (area under the curve: 0.894, sensitivity: 84.7%, specificity: 93.4%). CONCLUSION:Our results indicate that shorter telomere length has some connection with the risk of ischemic stroke in the northern Chinese Han population. Telomere length might serve as a potential candidate biomarker for ischemic stroke. This requires a large sample to be further verified.

Alzheimer's disease (AD) is a great threat for the health and life of elderly people. MicroRNA-128 (miR-128) has been reported to be abnormally expressed in the brain of AD patients and associated with the pathogenesis of AD. Our study aimed to have a deep insight into the roles and molecular basis of miR-128 in the development and progression of AD. The cognitive ability and exploratory behaviors were assessed by morris water maze and open-field tests, respectively. The concentrations of amyloid-β (Aβ) 40, Aβ 42, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 and activity of β-secretase and α-secretase were determined by corresponding ELISA commercial kits. RT-qPCR assay was performed to detect miR-128 level and the mRNA expression of peroxisome proliferator-activated receptor gamma (PPARγ), ionized calcium-binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP). Western blot assay was conducted to determine protein expression of PPARγ, amyloid precursor protein (APP), β-APP cleaving enzyme (BACE1), sAPPα and sAPPβ. The effect of miR-128 and PPARγ on amyloid plaque formation was assessed by immunohistochemistry assay. PPARγ mean optical density was determined by immunofluorescence assay. The interaction between miR-128 and PPARγ were validated by bioinformatics analysis and luciferase reporter assay. We found AD mice showed AD-like performance and an increased cerebral cortex Aβ production. MiR-128 expression was upregulated and PPARγ expression was downregulated in cerebral cortex of AD mice. Moreover, PPARγ was a target of miR-128. Additionally, miR-128 knockout or PPARγ upregulation inhibited AD-like performances, amyloid plaque formation, Aβ generation, APP amyloidogenic processing and inflammatory responses in AD mice, while these effects of miR-128 knockout were abrogated by PPARγ inhibitor. The results indicated MiR-128 knockout weakened AD-like performances, and reduced Aβ production and inflammatory responses by targeting PPARγ in AD mice.

目的 评价Hcy代谢相关基因S-腺苷高半胱氨酸水解酶基因(AHCY)、胱硫醚β合成酶基因(CBS)甲基化与脑梗死之间有无相关关系.方法 应用荧光定量甲基化特异性PCR(qMSP)检测研究对象外周血中AHCY、CBS基因甲基化水平,并分析其与脑梗死的相关关系.结果 (1)病例组AHCY甲基化水平为0.16％(0.07％,0.32％),对照组为0.25％(0.02％,0.67％),差异无统计学意义(P=0.115,Z=-1.577).(2)病例组CBS甲基化水平70.20％(49.19％,94.87％),对照组为104.10％(74.65％,132.30％),差异有统计学意义(P=3.71E-10,Z=-6.266).按性别、年龄进行亚组分析,CBS基因甲基化水平均低于对照组,且差异具有统计学意义(P<0.05).结论 AHCY基因甲基化与脑梗死发病不相关,而CBS基因低甲基化与脑梗死的发病相关.