高迁移率蛋白1、核因子-κB与人颈动脉粥样硬化斑块稳定性关系的研究

目的探讨高迁移率蛋白1(HMGB1)、核因子-κB(NF-κB)与人颈动脉粥样硬化斑块的稳定性关系。方法收集54例人颈动脉粥样硬化斑块标本作为颈动脉斑块组,其依据术前螺旋CTA检查将颈动脉粥样硬化斑块分为软斑组(A1组,n=21)、混合斑组(A2组,n=15)、硬斑组(A3组,n=18)。收集25例人肠系膜动脉标本及其血清作为对照组(B组,n=25)。分别采用反转录-聚合酶链反应(RT-PCR)及Western Blotting检测HMGB1mRNA及蛋白表达水平,用酶联免疫法(ELISA)法检测颈动脉斑块组和对照组血清中NF-κB含量。结果颈动脉粥样硬化斑块的HMGB1 mRNA及蛋白表达与对照组相比显著上调,差异有统计学意义(P<0.05);而且软斑组HMGB1 mRNA及蛋白表达水平明显高于硬斑组,差异有统计学意义(P<0.05);混合斑组与软斑组和硬斑组分别比较无统计学差异(P>0.05)。颈动脉斑块组患者血清中NF-κB含量明显高于对照组(P<0.05);其中软斑组患者血清中NF-κB含量明显高于混合斑及硬斑组(P<0.05);混合斑组与软斑组和硬斑组分别比较无统计学差异(P>0.05);颈动脉斑块组中NF-κB含量与HMGB1蛋白表达水平呈明显正相关表达(r=0.721,P<0.05)。结论 HMGB1和NF-κB与人颈动脉粥样硬化斑块稳定性密切相关,其可能成为预测人颈动脉斑块病变情况及稳定性的指标。     

激活蛋白-1、巨噬细胞游走抑制因子与人颈动脉粥样硬化斑块的关系研究

目的探讨激活蛋白-1(activator protein-1,AP-1)、巨噬细胞游走抑制因子(macrophage migration inhibitory factor,MIF)在人颈动脉粥样硬化斑块中的表达变化及作用机制。方法收集60例人颈动脉粥样硬化斑块标本(试验组,A组)和30例正常人肠系膜动脉标本(对照组,B组)。根据颈动脉超声检查结果将颈动脉粥样硬化斑块标本分为软斑组(A1,n=20)、混合斑块组(A2,n=20)、硬斑组(A3,n=20)。分别采用反转录-聚合酶链反应(RT-PCR)和Western blot法测定标本中AP-1亚单位c-Jun mRNA及蛋白表达水平,反映AP-1的表达水平。用酶联免疫法(ELISA)测定斑块组和对照组血清中MIF水平。结果 (1)人颈动脉粥样硬化斑块中c-Jun mRNA及蛋白较对照组表达上调(P0.05),A1组较A3组表达显著升高(P0.05),A2组与A1组和A3组分别比较无明显差异(P0.05)。(2)斑块组比健康对照组血清中MIF的含量显著增高(P0.05);A1组较A3组含量显著增高(P0.05),A2组与A1组和A3组分别比较无明显差异(P0.05)。(3)在人颈动脉粥样硬化斑块中,MIF浓度与c-Jun表达水平明显呈正相关(r=0.759,P0.01)。结论 AP-1和MIF与人颈动脉粥样硬化斑块的形成及稳定性显著相关,其可能作为预测颈动脉粥样硬化斑块病变情况及斑块稳定性的一个指标。AP-1表达量与MIF浓度越高,斑块不稳定性越高。     

三磷酸腺苷结合盒运转体A1与颈动脉粥样硬化斑块的关系

目的 探讨三磷酸腺苷结合盒运转体A1(ATP binding cassette transporter A1,ABCA1)在人颈动脉粥样硬化斑块中的表达变化及作用机制.方法 收集24例人颈动脉粥样硬化斑块标本和10例肠系膜动脉标本(对照组),采用RT-PCR测定ABCA1 mRNA和视黄酸X受体α(RXRα)mRNA表达水平,并采用Western Blot检测ABCA1及RXRα的蛋白表达水平.24例人颈动脉粥样硬化斑块标本按病理分级,比较病理组织为Ⅲ级和Ⅰ级动脉粥样硬化组织间ABCA1 mRNA、RXRαmRNA表达水平及蛋白表达水平.结果 颈动脉粥样硬化斑块组的ABCA1 mRNA(0.79±0.04)和RXRα mRNA(0.73±0.04)表达与对照组相比上调,差异有统计学意义(P＜0.05);ABCA1 mRNA与RXRα mRNA增加水平相关(P＜0.05);颈动脉粥样硬化斑块的ABCA1蛋白表达(0.22±0.03)下调水平与对照组(0.53±0.03)相比差异有统计学意义(P＜0.05);Ⅲ级和Ⅰ级动脉硬化斑块ABCA1mRNA、RXRα mRNA及蛋白表达水平差异有统计学意义(P＜0.05).结论 ABCA1及RXRα蛋白表达水平下调可能是进展性动脉粥样硬化损害的关键因素.     

颈动脉粥样硬化与急性脑梗死的关系探讨

目的通过对急性脑梗死患者进行颈动脉超声检测,探讨颈动脉粥样硬化与急性脑梗死之间的关系。方法选取2015-07—2016-07我院收治的急性脑梗死患者41例,同时选取同期健康体检者50例为对照组,所有患者均进行颈动脉超声检查,测量颈动脉后壁内中膜厚度(IMT)、血管内径、粥样硬化斑块形成、斑块数量、斑块回声强度、斑块部位及形态、管腔是否狭窄及狭窄程度。结果颈动脉斑块发生部位以颈总动脉分叉处发生率最高,其次为颈内动脉。实验组在颈内动脉分叉处、颈内动脉起始段发生率高于对照组(P0.01),实验组颈内动脉内膜增厚发生率高于对照组(P0.01)。颈动脉粥样硬化斑块类型以混合斑发生率最多,实验组其次为软斑、硬斑,对照组其次为硬斑、软斑。实验组软斑及混合斑发生率高于对照组(P0.05),2组硬斑发生率无显著差异(P0.05)。颈内动脉狭窄程度以轻度狭窄为主,2组轻度狭窄发生率无显著差异(P0.05),实验组中度狭窄及重度狭窄发生率明显高于对照组(P0.05)。结论颈动脉粥样硬化是引起缺血性脑梗死的重要原因,需对脑梗死及脑血管疾病患者行超声检测颈动脉,早期发现颈动脉的狭窄及斑块,给予早期干预,以降低脑血管疾病的发生。     

脂蛋白相关磷脂酶A2、颈动脉斑块内新生血管与颈动脉粥样硬化及缺血性脑卒中的相关性研究

目的探究脂蛋白相关磷脂酶A2(Lipoprotein Associated Phospholipase A2,Lp-PLA2)、颈动脉斑块内新生血管与颈动脉粥样硬化及缺血性脑卒中的相关性。方法收集2016年12月～2017年12月于河北医科大学第二医院神经内科就诊的存在颈动脉粥样硬化斑块患者60例为病例组,健康体检者60例为对照组,应用增强免疫比浊法测定Lp-PLA2含量,病例组应用超声造影(Contrast-enhanced Ultrasonography,CEUS)检测颈动脉斑块内新生血管水平,根据影像学分为脑梗死与非脑梗死组。结果病例组和对照组Lp-PLA2水平差异有统计学意义(P 0. 05),Lp-PLA2是颈动脉粥样硬化斑块形成的危险因素(OR=1. 007,95%CI 1. 004～1. 011),但校正血脂等因素后相关性降低(OR=1. 004,95%CI 0. 999～1. 010)。脑梗死组与非脑梗死组颈动脉斑块内新生血管等级差异有统计学意义(P 0. 05),且新生血管III级与颈动脉粥样硬化患者发生脑梗死密切相关(OR=24,95%CI 1. 952～295. 061)。Lp-PLA2水平与缺血性脑卒中及颈动脉斑块内新生血管等级之间差异无统计学意义(P 0. 05)。结论血清中Lp-PLA2水平是颈动脉粥样硬化斑块形成的危险因素,一定程度上受血脂等因素的影响。应用CEUS技术可以检测动脉粥样硬化斑块内的新生血管水平,新生血管等级与缺血性脑卒中存在相关性。其中新生血管III级是发生缺血性脑卒中的独立危险因素。尚未发现Lp-PLA2水平与缺血性脑卒中及颈动脉斑块内新生血管之间的相关性。     

颈动脉粥样硬化斑块与脑梗死的相关性研究

目的探讨脑梗死与颈动脉粥样斑块硬化之间的关系。方法对脑梗死患者和非脑梗死患者进行颈动脉彩色多普勒超声检查,分析脑梗死与颈动脉粥样硬化斑块之间的关系。结果脑梗死组颈动脉粥样硬化斑块检出率、颈动脉软斑及混合斑检出率均明显高于对照组(P0.05);重型脑梗死的颈动脉软斑及混合斑检出率显著高于轻型脑梗死(P0.05)。结论脑梗死发病与颈动脉粥样硬化斑块相关。脑梗死病情的轻、重在一定程度上与硬化斑块的性质有关。     

老年脑梗死与颈动脉粥样硬化斑块的相关性及预后分析

目的：分析老年脑梗死与颈动脉粥样硬化斑块的相关性及预后的关系。方法选取100例老年脑梗死患者作为观察组和100例同期非脑梗死患者作为对照组,观察和比较2组颈动脉粥样硬化斑块情况、治疗前和治疗3个月、6个月后神经功能缺损评分（NIHSS评分）和日常生活活动能力评分（Barthel指数评分）。结果2组颈动脉粥样硬化斑块检出率分别为86％和17％,观察组显著高于对照组（ P＜0.05）,观察组软斑和混合斑的比例显著高于对照组（ P＜0.05）,无斑块比例显著低于对照组（P＜0.05）;重型患者中有软斑和混合斑的比例显著高于中型患者（P＜0.05）,中型患者显著高于轻型患者（P＜0.05）;轻型患者中无斑块和有硬斑患者比例显著高于中型和重型患者（ P＜0.05）;有软斑和混合斑患者治疗前和治疗后3个月、6个月的NIHSS评分显著高于有硬斑患者（P＜0.05）,有硬斑患者治疗前和治疗后3个月、6个月的NIHSS评分显著高于无斑块患者（P＜0.05）,有硬斑和无斑块患者在治疗3个月、6个月的Barthel指数评分显著高于有软斑和混合斑的患者（P＜0.05）。结论颈动脉粥样硬化斑块的形成是与老年脑梗死发病具有相关性的危险因素,颈动脉粥样硬化斑块的类型与患者的病情具有相关性,有软斑和混合斑患者的神经功能损害和生活能力缺失症状更加严重、预后情况更差,有硬班和无斑块患者的神经功能损害症状较轻,预后情况较好。     

血清ox-LDL、Lp-PLA2水平与缺血性脑卒中患者动脉粥样硬化及神经功能缺损的相关性研究

目的 探讨缺血性脑卒中患者血清中氧化低密度脂蛋白(ox-LDL)和脂蛋白相关磷脂酶A2(Lp-PLA2)水平与颈动脉粥样硬化及神经功能缺损的相关性。方法 选取2015年7月～2016年7月本院神经内科收治的急性脑梗死患者135例(ACI组)和同期本院体检中心健康人群150例(对照组),均对所有入选者血清中的ox-LDL、Lp-PLA2水平进行检测,比较ACI组和对照组的血清ox-LDL、Lp-PLA2及其他血脂指标水平; 行颈动脉超声检查,对无斑块组、稳定斑块组和不稳定斑块组患者的ox-LDL、Lp-PLA2水平进行比较; 按美国国立卫生研究院卒中量表(NIHSS)评分,对轻型、中型、重型患者的ox-LDL、Lp-PLA2水平进行比较。结果 ACI组的血清ox-LDL、Lp-PLA2水平均高于对照组(P<0.01); 稳定斑块组、不稳定斑块组血清ox-LDL、Lp-PLA2水平显著高于无斑块组(P<0.05); 不稳定斑块组血清ox-LDL、Lp-PLA2 水平显著高于稳定斑块组(P<0.05); NIHSS评分中型组、重型组血清ox-LDL、Lp-PLA2水平均显著高于轻型组(P<0.05),重型组血清ox-LDL、Lp-PLA2水平显著高于中型组(P<0.05)。结论 缺血性脑卒中患者血清ox-LDL、Lp-PLA2水平较正常者显著上升,其在一定程度上反映患者颈动脉粥样硬化的程度及神经功能缺损的程度,ox-LDL、Lp-PLA2 可作为急性缺血性脑血管病的血清标记物,在评估急性缺血性脑血管病的病情及预后方面有一定的临床意义。     

颈动脉粥样硬化斑块患者血清血管内皮生长因子研究

目的探讨颈动脉粥样硬化斑块患者血清血管内皮生长因子(vascular endothelial growth factor,VEGF)的变化。方法纳入经颈部血管彩超确诊的颈动脉粥样硬化软斑和(或)混合斑患者60例(实验组),健康体检者60例(对照组),分别测定2组受试者血清VEGF的含量。将粥样硬化斑块患者分为单发组和多发组;钙化性斑块组和不稳定斑块组;分别测定VEGF含量并进行比较。结果血清VEGF含量颈动脉粥样硬化斑块患者为(295±60)pg/mL,健康体检者为(137±37)pg/mL,2组相比差异有统计学意义(P<0.05)。不稳定斑块组较钙化性斑块组、多发性斑块组较单发性斑块组VEGF含量均明显升高,差异有统计学意义(P<0.05)。结论颈动脉粥样硬化斑块患者血清VEGF明显升高,这可能和斑块的不稳定有关。     

血浆脂蛋白相关磷脂酶A2水平与急性颈动脉硬化性脑梗死防治效果及硬化斑块稳定性的相关性研究

目的 探讨血浆脂蛋白相关磷脂酶A2水平与急性颈动脉硬化性脑梗死防治效果及硬化斑块稳定性的关系。方法 收集2015年1月-2016年12月来中信惠州医院就诊的急性颈动脉硬化性脑梗死患者80例,为患病组; 同期收集来本院进行体检的正常志愿者40例,为健康对照组; 患病组脑梗死各时间点(入院后第1 d、第2、4、8周)对患者的Lp-PLA2水平进行检测,健康对照组人群在体检时进行相同检测,对比2组间的差异。采用颈动脉超声检测患者的颈动脉硬化斑块稳定性,计算颈动脉粥样硬化斑块Crouse积分,分析Crouse积分与Lp-PLA2水平的相关性。治疗后应用NIHSS和改良Rankin量表(mRS)对治疗效果进行评估,分析其与LP-PLA2水平的关系。结果 各时间点患病组患者的血浆Lp-PLA2水平均高于健康对照组(P<0.05),患病组患者从发病到缓解血浆Lp-PLA2水平逐渐改善(P<0.05); 患者的Crouse积分比较,患病组中不稳定斑块组>混合斑块组>稳定斑块组>无斑块组(P<0.05); 患病组中患者Lp-PLA2水平比较,不稳定斑块组>混合斑块组>稳定斑块组>无斑块组(P<0.05); Lp-PLA2水平与斑块稳定存在相关性,并与稳定斑块呈负相关(OR=-2.586,P<0.05); 治疗后各时间点神经功能缺损轻型患者的Lp-PLA2水平低于中型与重型患者(P<0.05),预后良好患者的Lp-PLA2水平低于预后不良的患者(P<0.05)。结论 Lp-PLA2可能是颈动脉硬化性脑梗死发生的重要危险因素之一,其水平可能与动脉粥样硬化斑块的稳定性有关。     

CIP2A and PP2A in human leptomeninges,arachnoid granulations and meningiomas

Previously we have found that mitogens stimulate proliferation of meningioma cells of all grades, in part, by activation of the PI3K-PKB/Akt-PRAS40-mTOR pathway regulated to some degree by the tumor suppressor phosphatase PP2A. PP2A activity is inhibited by the oncoprotein cancerous inhibitor of PP2A (CIP2A), which has not been studied in meningiomas to our knowledge. Six fetal and one adult human leptomeningeal samples and 38 meningiomas were evaluated by western blot. Fifteen adult arachnoid granulations and 58 formalin-fixed meningiomas (36 World Health Organization grade I, 15 grade II and seven grade III) were evaluated by immunohistochemistry. The effects of the mitogens platelet derived growth factor-BB (PDGF-BB) and cerebrospinal fluid on CIP2A were also studied. By western blot, CIP2A and PP2A were found in the five fetal and one adult leptomeninges and all meningiomas. By immunohistochemistry, CIP2A was detected in the arachnoid granulations and all meningiomas. CIP2A tended to be higher in grade III tumors. Three fetal leptomeningeal (two grade I and one grade II) and meningioma cells treated with PDGF-BB and/or human cerebrospinal fluid resulted in a slight increase in CIP2A in the leptomeningeal cells but not meningioma cells. Considered the mechanism of action and seen in other neoplasms, these findings raise the possibility that CIP2A may participate in the biology of meningiomas.     

锌指蛋白A20 RNAi载体的构建及筛选

目的我们前期的实验结果显示A20 mRNA和蛋白在人脑胶质瘤组织及细胞系（U251、U87、BT325）中高表达，本研究拟构建A20RNAi载体，并检测其对U251细胞A20表达的抑制作用。方法构建三种针对人A20基因的真核干涉表达载体，以脂质体法将其分别转染人脑胶质瘤细胞系U251，以RT-PCR、蛋白印迹法检测各干涉载体对U251细胞中A20mRNA和蛋白表达的抑制作用。结果成功构建三种针对A20基因的RNAi载体，经RT-PCR、蛋白印迹检测筛选出对A20基因干涉效果最佳的载体，命名为pSilencer3．1-A20R1。结论成功构建A20基因干涉载体，为进一步探讨A20与脑胶质瘤恶性增殖、血管形成以及抗凋亡的关系奠定实验基础。     

Oestradiol-dependent and -independent modulation of tyrosine hydroxylase mRNA levels in subpopulations of A1 and A2 neurones with oestrogen receptor (ER)alpha and ER beta gene expression

Oestradiol (E2) induces luteinizing hormone-releasing hormone (LHRH) hypersecretion, thereby triggering LH surge release in ovariectomized (OVX) rats. Neural signals responsible for the surge are marked by a morning increase in LHRH gene expression and an afternoon increase in LHRH release. Evidence suggests that subpopulations of noradrenergic neurones may be responsible for one or both of these signals. To further investigate this issue, we examined effects of E2 on the activity of A1 and A2 noradrenergic neurones, as reflected in changes in tyrosine hydroxylase (TH) mRNA expression, on the day of LH surge release. We then used dual-label in situ hybridization to determine whether E2-induced changes occurred primarily in A1 and A2 subdivisions wherein most noradrenergic neurones expressed oestrogen receptor (ER)alpha and/or ER beta mRNA. We found that in all subdivisions, levels of TH mRNA were higher in E2- than oil-treated rats at 12.00 h. These differences resulted from a decline in TH mRNA expression in oil-treated rats, as well as a rise in levels in E2-treated rats between 10.00 h and 12.00 h. During the afternoon, TH mRNA expression in most A1 and A2 subdivisions peaked at 14.00 h when LH surge release began. However, in all but the middle and caudal A2 subdivisons, levels were similar in E2-treated and control rats at this time. This was attributable to a widespread increase in TH mRNA expression between 12.00 h and 14.00 h in OVX rats. There was no evidence that E2 induced changes in TH mRNA expression preferentially in regions wherein most neurones contained ER alpha or ER beta mRNA. Our findings suggest that E2 activation of middle and caudal A2 neurones, in conjunction with the widespread E2-independent activation of noradrenergic neurones in other subdivisions, may play a role in the induction of LH surge release.     

Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system

Adenosine receptors (ADORs) in the enteric nervous system may be of importance in the control of motor and secretomotor functions. Gene expression and distribution of neural adenosine A1, A2a, A2b, or A3 receptors (Rs) in the human intestine was investigated using immunochemical, Western blotting, RT-PCR, and short-circuit current (I(sc)) studies. Adenosine A1R, A2aR, A2bR, or A3R mRNAs were differentially expressed in neural and nonneural layers of the jejunum, ileum, colon, and cecum and in HT-29, T-84, T98G, and Bon cell lines. A1R, A2aR, A2bR, and A3R immunoreactivities (IRs) were differentially expressed in PGP 9.5-immunoreactive neurons. A2bR IR occurs exclusively in 50% of submucosal vasoactive intestinal peptide (VIP) neurons (interneurons, secretomotor or motor neurons) in jejunum, but not colon; A2aR is also found in other neurons. A3R IR occurs in 57% of substance P-positive jejunal submucosal neurons (putative intrinsic primary afferent neurons) and less than 10% of VIP neurons. Western blots revealed bands for A3R at 44 kDa, 52 kDa, and 66 kDa. A2aR and A2bR are coexpressed in enteric neurons and epithelial cells. 5'-N-methylcarboxamidoadenosine or carbachol evoked an increase in I(sc). A2bR IR is more prominent than A2aR IR in myenteric neurons, nerve fibers, or glia. A1R is expressed in jejunal myenteric neurons and colonic submucosal neurons. Regional differences also exist in smooth muscle expression of ADOR IR(s). It is concluded that neural and nonneural A1, A2a, A2b, and A3Rs may participate in the regulation of neural reflexes in the human gut. Clear cell and regional differences exist in ADOR gene expression, distribution, localization, and coexpression.     

SLC22A18基因启动子甲基化与胶质瘤SLC22A18表达的关系

目的 探讨胶质瘤中SLC2218基因肩动子甲基化与其表达的关系.方法 选取上海交通大学医学院附属第三人民医院神经外科自2006年9月至2009年6月、武汉大学中南医院神经外科自2002年9月至2005年6月间手术切除的胶质瘤标本30例,另选10例行内减压术颅脑损伤患者的正常脑组织作为对照.采用甲基化特异性聚合酶链反应(MSP)检测标本中SLC22A18基因启动子甲基化的状态,RT-PCR和Westem blotting分别检测SLC22A18 mRNA和蛋白的表达.体外培养胶质瘤U251细胞于含2 μmol/L去甲基化药物5-aza-2-deoxycytidine的培养液(实验组1中,同时设普通培养液作对照,培养3、5、7 d后进行细胞计数并应用Western blotting检测SLC22A18蛋白的表达.结果 MSP检测结果显示15例胶质瘤组织出现甲基化,对照脑组织均表现出非甲基化;15例甲基化胶质瘤组织中SLC22A18 mRNA、蛋白的表达明显低于对照脑组织.培养5、7 d实验组U251细胞计数少于对照组,差异有统计学意义(P＜0.05).培养7 d Western blotting检测结果发现实验组细胞SLC22A18蛋白的表达明显高于对照组.结论 SLC22A18基因启动子甲基化导致其表达下调;去甲基化药物能恢复U251细胞SLC22A18的表达,并抑制U251细胞增殖.

Abstract：

Objective To investigate the relationship between aberrant methylation of SLC22A18 gene promoter and SLC22A18 expression in human glioma. Methods Thirty patients with glioma and 10 patients with craniocerebral injury performed decompression were chosen in our study;their tissue samples were prepared. Methylation-specific PCR (MSP) was used to detect the methylation status of SLC22A18 gene promoter;and Western blotting and RT-PCR were employed to measure the protein and mRAN expressions of SLC22A18 in these tissue samples. U251 cells were cultured in vitro with demethylating agent 5-aza-2-deoxycytidine (experimental group, 2μmol/L) and common medium (control group), resepectively;the re-expression of SLC22A18 in U251 cells was measured by Western blotting and cell growth suppression induced by 5-aza-2-deoxycytidine was also observed 3, 5 and 7 d after the culture. Results The methlylation of SLC22A18 gene promoter existed in glioma tissues of 15 patients (50%) but that did not exist in the tissues of patients with craniocerebral injury. The protein and mRAN expressions of SLC22A18 in the tissue samples of these 15 patients were significantly decreased as compared with those in patients with craniocerebral injury (P<0.05);cell counting of U251 cells in the experimental group on the 5th and 7th d of culture was significantly decreased as compared with that of those in the control group (P<0.05). On the 7ht d of culture, Western blotting indicated that the protein b expression level of SLC22A18 in the experimental group was obviously higher than that in the control group. Conclusion The aberrant methylation of SLC22A18 gene promoter plays a key role in down-regulating SLC22A18 expression, and demethylation agents can restore the SLC22A18 expression and suppress the growth of U251 cells.     

Sonography of the median nerve in CMT1A,CMT2A,CMTX, and HNPP

Introduction: In this study we compare the ultrasound features in the median nerve in patients with different types of Charcot–Marie–Tooth (CMT) disease and hereditary neuropathies with liability to pressure palsies (HNPP) as a typical entrapment neuropathy. Methods: Median nerve ultrasound and conduction studies were performed in patients with CMT1A (n = 12), MFN2‐associated CMT2A (n = 7), CMTX (n = 5), and HNPP (n = 5), and in controls (n = 28). Results: Median nerve cross‐sectional area (CSA) was significantly increased in CMT1A, whereas, in axonal CMT2A, fascicle diameter (FD) was enlarged. CSA correlated with nerve conduction slowing in CMT1A and with axonal loss, as shown by motor and sensory nerve amplitudes in both CMT1A and CMT2A. A relatively low wrist‐to‐forearm‐ratio (WFR <0.8) or a relatively high WFR (>1.8) appeared to be unlikely in MFN2 and Cx32 mutations of CMT2A and CMTX, respectively. Conclusion: Differences in CSA, FD, and WFR of the median nerve can be helpful in defining subtypes of hereditary neuropathies. Muscle Nerve 47:385‐395, 2013     

Adenosine A2A receptor gene disruption provokes marked changes in melanocortin content and pro-opiomelanocortin gene expression

A2A receptor knockout (A2AR-/-) mice are more anxious and aggressive, and exhibit reduced exploratory activity than their wild-type littermates (A2AR+/+). Because alpha-melanocyte-stimulating hormone (alpha-MSH) influences anxiety, aggressiveness and motor activity, we investigated the effect of A2AR gene disruption on alpha-MSH content in discrete brain regions and pro-opiomelanocortin (POMC) expression in the hypothalamus and pituitary. No modification in alpha-MSH content was observed in the hypothalamus and medulla oblongata where POMC-expressing perikarya are located. In the arcuate nucleus of the hypothalamus, POMC mRNA levels were not affected by A2AR disruption. Conversely, in A2AR-/- mice, a significant increase in alpha-MSH content was observed in the amygdala and cerebral cortex, two regions that are innervated by POMC terminals. In the pars intermedia of the pituitary, A2AR disruption provoked a significant reduction of POMC mRNA expression associated with a decrease in alpha-MSH content. By contrast, in the anterior lobe of the pituitary, a substantial increase in POMC mRNA and adrenocorticotropin hormone concentrations was observed, and plasma corticosterone concentration was significantly higher in A2AR-/- mice, revealing hyperactivity of their pituitary-adrenocortical axis. Together, these results suggest that adenosine, acting through A2A receptors, may modulate the release of alpha-MSH in the cerebral cortex and amygdala. The data also indicate that A2A receptors are involved in the control of POMC gene expression and biosynthesis of POMC-derived peptides in pituitary melanotrophs and corticotrophs.     

小儿结核性脑膜炎外周血补体因子 H、载脂蛋白A1和淀粉样蛋白A表达水平变化及其临床意义

目的 探讨小儿结核性脑膜炎（Tuberculous meningitis，TBM）外周血补体因子 H（Complement factor H，CFH）、载脂蛋白A1（Apolipoprotein AI，ApoAI）和淀粉样蛋白A（Serum amyloid A，SAA）表达水平变化，分析其与TBM病情和预后的关系。 方法 选择2017年3月-2021年1月本院收治的112例TBM患儿，根据英国医学研究理事会（Medical research council，MRC）分期标准分为Ⅰ期组（37例）、Ⅱ期组（46例）、Ⅲ期组（29例），根据改良Rankin量表（Modified Rankin Scale，mRS）评分将患儿分为预后良好组（0～2分，62例），预后不良组（≥3分，50例）。另选择71例健康儿童为对照组；检测血清CFH，ApoAI，SAA水平，分析其与TBM病情以及预后的关系。 结果 TBM 组血清CFH，SAA水平均高于对照组（P＜0.05），ApoAI水平低于对照组（P＜0.05）；重度组血清CFH，SAA水平高于中度组和轻度组（P＜0.05），ApoAI水平低于中度组和轻度组（P＜0.05）。MRC分期Ⅲ期、高水平CFH、高水平SAA是TBM患者预后不良的危险因素（P＜0.05），高水平ApoAI是TBM患者预后不良的保护因素（P＜0.05）。CFH，ApoAI，SAA水平预测TBM患者预后不良的曲线下面积为0.613、0.610、0.592，联合CFH，ApoAI，SAA水平曲线下面积为0.855，高于单独CFH，ApoAI，SAA（z=6.275、5.936、6.569，P＜0.05）。 结论 TBM患儿血清CFH，SAA水平升高，ApoAI水平降低，且与TBM患儿病情加重以及不良预后有关。