目的 比较颈动脉粥样硬化斑块与正常颈动脉中的人巨细胞病毒核酸(HCMV DNA)、血凝素样氧化低密度脂蛋白受体-1(LOX-1)、基质金属蛋白酶(MMP)-2、MMP-9的表达情况,探讨人巨细胞病毒感染与颈动脉粥样硬化的关系.方法 收集31例行颈动脉内膜剥脱术后的颈动脉粥样硬化斑块标本作为动脉粥样硬化组,所有标本均于手术后12 h内取材.另选择性别、年龄与动脉粥样硬化组相匹配的28例正常颅内动脉标本作为对照组,均于死亡后12 h内行尸体解剖并取材.应用原位杂交技术检测2组标本中HCMV DNA表达情况,利用免疫组化法检测LOX-1、MMP-2、MMP-9表达情况;统计颈动脉粥样硬化组伴及不伴危险因素者HCMV DNA阳性细胞计数,HCMV DNA阳性与阴性表达者、血脂水平正常与异常者LOX-1、MMP-2、MMP-9阳性细胞计数.结果 动脉粥样硬化组HCMV DNA、LOX-1、MMP-2、MMP-9阳性表达率及LOX-1、MMP-2、MMP-9阳性染色面积中位数和OD值中位数均明显高于对照组(P均<0.05).颈动脉粥样硬化组中高TG血症、血清LDL水平>2.60 mmol/L和既往吸烟者HCMV DNA阳性细胞计数高于相应不伴危险因素者(P均<0.05).动脉粥样硬化组中HCMV阳性者LOX-1阳性细胞计数明显高于HCMV阴性者(P均<0.05),而HCMV阳性者与HCMV阴性者MMP-2、MMP-9阳性细胞计数比较差异均无统计学意义(P均>0.05).TG正常与升高者LOX-1、MMP-2和MMP-9阳性细胞数比较差异均无统计学意义(P均>0.05);LDL>2.6 mmol/L者LOX-1阳性细胞数明显高于LDL正常者(P<0.05).结论 HCMV感染是动脉粥样硬化危险因素之一,LOX-1、MMP-2及MMP-9参与颈动脉粥样硬化的病理过程,HCMV感染可能通过上调LOX-1基因表达从而促进动脉粥样硬化的发生、发展.

Human cytomegalovirus (HCMV) has been reported to be linked to vascular disease through the induction of neovessel formation. We have previously reported that microRNA (miR)-217 and miR-199a-5p enhance endothelial angiogenesis via inhibition of sirtuin 1 (SIRT1) in HCMV-infected human umbilical vein endothelial cells (HUVECs). Here, we found that miR-138 also suppressed the expression of the SIRT1 protein and stimulated phosphorylation of signal transducer and activator of transcription 3 (p-STAT3). Moreover, the regulation of p-STAT3 expression mediated by SIRT1 was found to promote HCMV-induced angiogenesis. These findings revealed that miR-138 might promote angiogenesis of HCMV-infected HUVECs by activating the SIRT1-mediated p-STAT3 pathway, and this could provide novel insights into HCMV-induced angiogenesis.

Aim To analyze the relationship of hippocampus serotonin with alternations of serum tryptophan and branched chain amino acids (BCAA) on the basis of improved Rats’ Chronic Exercise-induced Central Fatigue Model.Methods① Rats’ Chronic Exercise-induced Central Fatigue Model was established.② The method of HPLC-MC to measure the level of tryptophan and BCAA in rat’s serum was adopted and the relationship between them was analyzed.③ The method of HPLC-ECD to measure the content of 5-HT in rat hippocampus was used.Results It was easily found that there was a signiifcant decrease of serum tryptophan in rats with central fatigue after running (P<0.01), compared with the control group, while BCAA (serum leucine, isoleucine and valine), the rival competitor of tryptophan when entered into the central nervous system, were not signiifcantly changed. Ratios of leucine, isoleucine and valine to tryptophan were also signiifcantly increased (P<0.01), and the ratio of sum of BCAA to tryptophan as well. Conclusion Rats’ level of 5-HT had a sharp increase with both chronic central fatigue after exercise and after one-time exhaustive exercise. But there was some difference in regulation mechanism between them. The fall of serum tryptophan and the rise of the ratio of BCAA/TRP were favorable for BCAA to enter the central nerve. And at the same time, the measurement of tryptophan in serum was likely to become the biochemical indicators of the extreme fatigue of organism.

>早期准确识别具有高卒中风险的短暂性脑缺血发作(TIA)患者, 对于卒中的预防、预后的改善极为重要[1]。Rothwell等[2]基于临床资料提出ABCD评分用于筛查具有高卒中风险的TIA患者, 根据评分高低对TIA患者进行分层管理, 最初的ABCD评分包括4项指标, 即TIA患者的年龄(age)、血压(blood)、临床特征(clinical features)和持续时间(duration);此后

Objective The paper aims to study the regulatory changes of monoamines transmitters in the central nerve system of rats under the state of chronic exercise - induced fatigue. Methods The rat model of chronic exercise - induced central fatigue was used in this study. The frontal cortex of the rats was removed. The contents of 5 - HT,epinephrine,norepinephrine and dopamine in frontal cortex were quantitatively ana-lyzed by high performance liquid chromatography(HPLC). Results It was found that compared with control group,there was a significant in-crease of frontal cortex 5 - HT in rats with exercise - induced central fatigue after constant training and there was,at the same time,a significant decrease of dopamine( P < 0. 01). However,there was no significant change of the levels of epinephrine and norepinephrine which both belong to monoamine neurotransmitter. Conclusion With central fatigue,the levels of 5 - HT and dopamine,the two important neurotransmitters in cen-tral nerve system,have significant changes simultaneously. And both of the changes have a direct inhibitory trend,which explains that the rats are under the state of central fatigue and this state causes the change of regulatory mechanism of the transmitter in the brain.

Objective We detected the enterovirus in the CSF of patients with sporadic aseptic meningitis and viral encephalitis in to investigate the enterovirus infection in this area,and two methods were used in this study.Methods CSF samples of 36 patients with sporadic aseptic meningitis and viral encephalitis were collected during 2009-2013.All the samples were frozen and stored at-80℃ immediately before RNA extraction.Total viral RNA extraction was taken within 3 month after the sample was stored by using an RNA extraction kit according to the method described by the instruction of the kit.Then RNA was reversed into cDNA immediately after the extraction of RNA.cDNA was stored at-80℃.Finaly,we used a rapid and sensitive method for the detection of all members of the enterovirus genus by using real-time PCR.We also detected the IgM of 7enterovirus including Echo virus and Coxsackie virus 1-6 serotype by Enzyme-Linked Immunosorbent Assay(ELISA) method.Results Of all the 36 CSF samples,9 (25％) were positive for enterovirus by PCR method.For patients with aseptic meningitis,viral encephalitis and meningoencephalitis,the proportion were 42.86％,12.50％ and 11.11％.Only 2 samples were positive for Coxsackie virus by ELISA method,and both of them had aseptic meningitis.Conclusion Enterovirus infection is a common cause of sporadic CNS virus infection among patients with viral encephalitis,aseptic meningitis and aseptic meningoencephalitis in Beijing,especially for the patients with aseptic meningitis.Real-time PCR was more sensitive than ELISA,while the better way is to use both of them to detect the serotype of the enterovirus.

As a new subdiscipline, neurovirology derives from medical virology and neurology. Its research field includes both clinical practice of viral infectious diseases of the nervous system and fundamental research of medical virology. With rapidly advancing of molecular biology and development of new technique, virology is developed into molecular level from antibody and cellular levels. Technology of monoclonal antibody, nucleic acid hybridization and viral genetic engineering not only promote theoretical study of molecular virology, but also possess application value on both rapid diagnosis of viral infectious diseases and preparation of vaccine. doi: 10.3969/j.issn.1672⁃6731.2014.07.002

OAE Publishing Inc. is an international scholarly publisher specializing in peer-reviewed academic journals. To promote academic exchange and knowledge sharing, OAE provides an outstanding academic platform for biomedical experts and scholars all over the world.

doi: 10.3969/j.issn.1672-6731.2014.07.001

Objective The aim of this paper is to analyze mechanisms of motion regulation of tryptophan and branched-chain in chronic exercise central fatigue,through the analysis of tryptophan and leucine in serum in rat's model of chronic exercise central fatigue. Methods To set up the rat's model of chronic exercise central fatigue. To test the tryptophan and leucine in Rats' serum with HPLC-MS. Results Compared with the control rats,the level of tryptophan in exercise central fatigue rats reduces sharply and there is a significant difference( P 0. 05). There is no statistical difference in the level of leucine. Leu /Trp rises sharply with significant difference( P 0. 05). Conclusion There is a clear trend of declining in the level of tryptophan in the blood of rats under training with chronic exercise central fatigue. Because of the rising level of the ratio between leucine and tryptophan in branched-chain amino acids. It refines tryptophan to entering the central nerves system,regulating the occurring and development of the central fatigue. This alternation is possibly a self-regulation reaction in order to adapt to chronic exercise central fatigue.

Objective To investigate the relationship between matrix metalloproteinase‐9 (MMP‐9) , interleukin‐6 (IL‐6 ) , interleukin‐10 (IL‐10 ) and the stability of cerebral atherosclerotic plaque and cerebral infarction .Methods Serum of 56 patients with acute cerebral vascular diseases (including 16 repeated transient ischemic attack (TIA) and 40 acute cerebral infarction (ACI)) ,were collected within 3 days of onset ,all the patients were given examinations such as computed tomography angiography (CTA) or Doppler ultrasonography or magnetic resonance angiography (MRA ) to investigate if there was unstable plaque . The control group includes 21 healthy volunteers .The levels of serum MMP‐9 ,IL‐6 and IL‐10 were detected using enzyme‐linked immunosorbent assay (ELISA) in all the subjects .Results Patients with ACI and TIA had higher serum levels of MMP‐9 [(137.10 ± 69.38) ng/mL and (119.79 ± 65.54) ng/mL vs. (65.42 ± 36.81) ng/mL , P<0.05] and IL‐10 [ (39.16 ± 32.82) pg/mL and (33.00 ± 21.36) pg/mL vs. (19.83 ± 12.16) pg/mL , P< 0.05] than controls ,there were also significant difference between the group ACI and TIA (P<0.05) .But there was no significant difference between groups in IL‐6 level (P>0.05) .Conclusions MMP‐9 and IL‐10 levels rise in the acute period of ACI and TIA ,suggesting that it may be related with the rupture of unstable plaque .

Human cytomegalovirus (HCMV) infection has been shown to contribute to vascular disease through the induction of angiogenesis. However, the role of microRNA in angiogenesis induced by HCMV infection remains unclear. The present study was thus designed to explore the potential effect of miR-199a-5p on angiogenesis and to investigate the underlying mechanism in endothelial cells. We found that HCMV infection of endothelial cells (ECs) enhanced expression of miR-199a-5p and reduced the SIRT1 protein level at 24 h postinfection (hpi). Transfection with miR-199a-5p mimics significantly suppressed SIRT1 protein expression and promoted cellular migration and tube formation induced by HCMV infection, which could be reversed by transfection with an miR-199a-5p inhibitor. Furthermore, pretreatment with resveratrol depressed motility and tube formation of HCMV-infected ECs, which could be reversed by SIRT1 siRNA. Finally, overexpression of miR-199a-5p decreased the level of eNOS modulated by SIRT1, an effect repressed by transfection with an miR-199a-5p inhibitor. In summary, HCMV infection of endothelial cells upregulates miR-199a-5p expression and enhances cell migration and tube formation through downregulation of SIRT1/eNOS by miR-199a-5p.

Background Human cytomegalovirus (HCMV) is closely related to diseases including atherosclerosis, transplanted vascular sclerosis and arterial restenosis. It has been proved that angiogenesis induced by HCMV infection could result in vascular diseases. This article aims to investigate the mechanism of angiogenesis induced by HCMV infection in endothelial cells. Methods Endothelial cells (EA.hy926 cells) were divided into HCMV infected group and mock infected group. The cells were collected at 2, 6, 12 and 24 h after infection. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to analyze SIRT1 mRNA and protein levels. Endothelial cells were incubated respectively by Resveratrol and SIRT1 small interference RNA (siRNA) for 2 h before infection. Twenty⁃four hours after infection, the proliferation, migration and tubule formation of cells were assessed by CCK-8, migration assay and tubule formation assay to detect the angiogenic response of endothelial cells. Results Compared to mock infected group, the expression of SIRT1 mRNA in HCMV infected group remained unchanged (F = 1.395, P = 0.304), but the expression of SIRT1 protein decreased gradually (F = 23.927, P = 0.000). Under the treatment of Resveratrol and SIRT1 siRNA, migration (P = 0.008, 0.003) and tubule formation (P = 0.012, 0.008) of endothelial cells increased or reduced. The proliferation, however, remained unchanged (P = 0.969, 0.948). Conclusion HCMV infection promotes proliferation, migration and tubule formation of endothelial cells, and its mechanism may be related to the supression of SIRT1.

2011年笔者有幸获得北京市李桓英医学基金资助,到美国Baylor医学院神经内科和全美最大的私立医院Methodist医院的神经内科参观学习。期间主要在神经内科病房和运动障碍门诊学习,因此,有机会了解两院神经内科住院医师的培训情况,并对中美两国住院医师培训进行了一点比较和思考。现从以下几个方面

Miller Fisher’s syndrome (MFS) commonly presents in the fourth and fifth decades and are rare in people over 70 years. An 85-year-old female with no significant medical history presented with upper extremity anesthesia, ptosis, and unsteady gait. The patient had a history of hypertension and diabetes mellitus. Physical examination showed bilateral total external ophthalmoplegia, areflexia, and cerebellar ataxia. Radiological and laboratory studies were unremarkable. Lumbar puncture showed albuminocytological dissociation. The combined history, physical examination, and lumbar puncture results established a presumptive diagnosis of MFS. Intravenous immunoglobulin was given for 5 days. The patient gradually improved 10 days after the onset of symptoms. Ophthalmoplegia had fully recovered after 6 months. To the best of our knowledge, this case represented the oldest patient with MFS.

<正>一、Sirtuin基因家族Sirtuin家族目前已发现七种同源体(SIRT1～SIRT7),其中SIRT1是目前研究最多,且结构最接近酵母菌Sir2的同源体[1]。七种同源体都具有高度保守的NAD+依赖性催化基团[1],但是在细胞内位置各不相同。其中SIRT1、SIRT6和SIRT7定位于胞核,但也有研究表明SIRT1并不仅局限于胞核,在核外也发挥作

Human cytomegalovirus(HCMV) infection has been shown to contribute to vascular disease through the induction of angiogenesis. However, the role of microRNA in angiogenesis induced by HCMV infection remains unclear. The present study was thus designed to explore the potential effect of miR-1217 on angiogenesis and to disclose the underlying mechanism in endothelial cells. We found that HCMV infection of endothelial cells(ECs) enhanced expression of miR-217 and reduced SIRT1 and FOXO3A protein level in 24 hours post infection(hpi). Transfection of miR-217 inhibitor not only depressed cellular migration and tube formation induced by HCMV infection, but also enhanced SIRT1 and FOXO3A protein expression. Additionally, luciferase assay confirmed that miR-217 directly targeted FOXO3A mRNA 3`UTR. Furthermore, pretreatment with resveratrol depressed motility and tube formation of HCMV-infected ECs, which could be reversed by SIRT1 siRNA. Similarly, delivery of FOXO3A overexpression lentivirus suppressed proliferative rate, migration and tube formation of HCMV-infected ECs, which reversed by transfection of FOXO3A siRNA. In summary, HCMV infection of endothelial cells induces angiogenesis by both of miR-217/SIRT1 and miR-217/FOXO3A axis.

特殊抗原/抗体介导的脑病为一组与副肿瘤综合征和非副肿瘤综合征相关的脑病,具有亚急性起病、存在病理性抗体和或广泛性炎性反应的特点,其病程进展迅速,免疫调节剂或肿瘤相关治疗对其有效。该组脑病通常累及边缘叶和皮质结构,皮质下结构亦可受累,常伴有认知障碍。本文对其临床特点、诊断和治疗做一全面综述。

Encephalitis is one of the common emergencies of neurology.The early diagnosis and the appropriate treatment are very important.Autoimmune encephalitis(AE) refers to a major category of diseases resulting from a reaction of the immune system against antigens of central nervous system and has been gradually considered as an important non-specific factor to cause reversible encephalitis.According to the differences in etiology and therapy,AE may be divided into specific antigen(or antibody) associated AE and non-specific antigen(antibody) associated AE.Knowing more about AE is of major significance in finding new diseases and deepening the understanding of immune pathological mechanism of central nerve system.