ACI患者治疗前后血浆ET-1和血清Hcy、11,-6检测的临床意义

目的：探讨急性脑梗死（ACI）患者治疗前后血浆ET-1和血清Hcy、IL-6水平的变化及意义。方法：应用放射免疫分析和酶联法对33例ACI患者进行了治疗前后血浆ET-1和血清Hcy、IL-6检测,并与35例正常健康人作比较。结果：ACI患者治疗前血浆ET．1和血清Hey、IL-6水平非常显著地高于正常人组（P〈0．01）,经治疗2周后与正常人组比较无显著性差异（P〉0．05）。结论：检测ACI患者治疗前后血浆ET．1和血清Hcy、IL-6水平的变化有助于对治疗效果和预后的监察。     

桑银降糖胶囊对实验性糖尿病大鼠微血管的影响

目的观察桑银降糖胶囊对实验性糖尿病大鼠治疗后心脑微血管病的变化,探讨桑银降糖胶囊对实验性糖尿病大鼠血管调节因子的影响。方法用微量血糖测试仪检测各组糖尿病大鼠血糖和糖耐量,用化学比色法测定血清中NO的含量,应用放免法测定血浆内皮素（ET-1）含量。电镜观察心脑超微结构。结果与模型组比较,桑银降糖胶囊对STZ大鼠均有显著的降血糖作用（P〈0．01）;2h血糖曲线下面积为38．88±8．59（P〈0．01）。大剂量组ET-1为（149．60±16．83）pg／ml（P〈0．01）,NO为（61．20±11．36）μmol／L（P〈0．01）。结论桑银降糖胶囊可提高糖尿病大鼠血清NO含量,下调血浆ET水平,有效抑制由于高血糖等因素引起血管内皮细胞损伤。对糖尿病内皮细胞损伤及微血管病变具有一定的保护作用。     

葛根素注射液对早期糖尿病肾病患者血液流变学和可溶性粘附分子-1的影响

目的观察葛根素注射液对早期糖尿病肾病患者血液流变学和血清可溶性细胞粘附分子-1（SICAM-1）的影响。方法将76例早期糖尿病肾病患者随机分为治疗组（42例）和对照组（34例）。两组均采用饮食控制和糖尿病常规治疗，治疗组加用葛根素注射液治疗，疗程3周。结果治疗组血液流变学各项指标较治疗前显著下降（P〈0．05）；尿白蛋白排泄率、血可溶性粘附分子-I（sICAM-1）均明显下降（P〈0．01），且明显优于对照组（P〈0．05）。结论葛根索注射液能改善早期糖尿病肾病患者的血液流变性和微循环，减少尿白蛋白的排出，降低血清sICAM-1水平，减轻肾损害。     

金芪降糖片对2型糖尿病患者血清P-SLT、TNF-α、血糖及HbAlc的作用探讨

目的:探讨金芪降糖片中主要成分黄芪、黄连对2型糖尿病患者血清P-SLT、TNF-α、血糖及糖基化血红蛋白(HbAlc)的作用及临床应用价值.方法:随机将糖尿病患者分为西药治疗对照组和金芪降糖片加西药治疗组,患者于治疗前后检测空腹与餐后2h血糖、糖基化血红蛋白(HbAlc)、血清P-SLT和TNF-α水平.结果:金芪组和对照组治疗前空腹血糖、餐后2h血糖、HbAlc、P-SLT和TNF-α水平比较无显著性差异(P＞0.05),治疗后两组空腹血糖、餐后2h血糖均有明显下降;金芪组治疗后HbAlc、P-SLT、TNF-α水平明显降低,与治疗前及对照组比较均有差异(P＜0.05、P＜0.01、P＜0.01).结论:在常规西药治疗的基础上加用黄芪和黄连进行治疗,对于降低P-SLT、TNF-α及HbAlc水平,稳定血糖、预防或延缓微血管病变不失为一种较好的方法.     

妊高征肾病患者血浆ET-1和血清TGF-β1、IL-10检测及其临床意义

目的：探讨妊高征肾病患者治疗前后血浆ET-1和血清TGF-β1、IL-10水平的变化及临床意义。方法：应用放射免疫分析和酶联法对32例妊高征肾病患者进行了治疗前后血浆ET-1和血清TGF-β1、IL-10检测,并与35名正常人作比较。结果：妊高征肾病患者在治疗前血浆ET-1和血清TGF-β1、IL-10均非常显著地高于正常人组（P〈0.01）,经治疗2周后则与正常人组比较无显著性差异（P〉0.05）,血浆ET-1和血清TGF-β1、IL-10水平呈正相关（r=0.4812、0.5784,P〈0.01）结论：检测妊高征肾病患者血浆ET-1和血清TGF-β1、IL-10水平的变化,对患者的病情判断、疗效观察具有重要的临床价值。     

肾病综合征患儿输注悬浮红细胞前后血浆ET-1和血清MMP-2、MMP-9水平的变化及临床价值

目的：探讨肾病综合征患儿输注悬浮红细胞前后血浆ET-1和血清MMP-2、MMP-9水平的变化及临床意义。方法：采用放射免疫分析和酶联法对32例肾病综合征患儿进行了输注红细胞前后血浆ET-1和血清MMP-2、MMP-9测定,并与35名正常健康儿作比较。结果：肾病综合征患儿输注悬浮红细胞前血浆ET-1和血清MMP-2水平非常显著地高于正常儿组（P〈0．01）,而血清MMP-9水平又显著地低于正常儿组（P〈0．01）,经输注悬浮红细胞2周后与正常儿组比较仍有显著性差异（P〈0．05）,且血清MMP-9水平与血浆ET-1和血清MMP-2水平呈现显著负相关（r=-0．4982、-0．014,P〈0．01）。结论：检测肾病综合征患儿输注悬浮红细胞前后血浆ET-1和血清MMP-2、MMP-9水平的变化对其病情发展及预后判定均有重要的临床价值。     

急性脑梗死患者治疗前后血浆Hcy、CGRP和ET-1检测的临床意义

目的：探讨了急性脑梗死患者治疗前后血浆Hcy、CGRP和ET-1水平的变化及意义。方法：应用放免法和ELISA对33例急性脑梗死患者进行了治疗前后血浆Hcy、CGRP和ET-1的检测,并与35名正常健康人作比较。结果：在治疗前,急性脑梗死患者血浆Hcy、ET-1水平非常显著地高于正常人组（P〈0.01）,而CGRP水平则显著地低于正常人组（P〈0.01）;治疗后,则与正常人组比较无显著性差异（P〉0.05）。结论：检测急性脑梗死患者血浆Hcy、CGRP和ET-1水平的变化对了解病情、观察预后均有重要的临床价值。     

无创通气对老年重度心力衰竭患者血浆脑钠素、内皮素-1和血管紧张素II水平的影响

探讨老年重度心力衰竭时血浆脑钠素（brain natriuretic peptide,BNP）、内皮素-1（endothelin—1,ET-1）和血管紧张素II（angiotensin II,AngII）水平的变化及无创通气（non—invasive ventilation,NIV）对其影响。老年重度心力衰竭患者42例,随机分为无创通气（NIV）治疗组（21例）和常规治疗组（21例）。常规治疗组为强心、利尿剂、血管扩张剂等药物并加用鼻导管给氧治疗;NIV治疗组为在常规治疗同时加用NIV治疗,分别观察治疗3～5天后两组患者临床症状、体征、心率（HR）、呼吸频率（RR）、血压、血气分析和左室射血分数（left vertricular ejection fraction,LVEF）,以及血浆BNP、ET-1和AngII的变化。结果显示,与常规治疗组比较,NIV组治疗3～5天后,患者临床症状与体征改善明显,其SaO2、PaO2和LVEF显著升高（P〈0．05）,HR、RR显著下降（P〈0．05）。NIV治疗后血浆BNP、ET-1和AngII水平随心衰的纠正而显著降低（P〈0．01）,与LVEF呈显著负相关（P〈0．01）。结论：NIV在改善老年重度心力衰竭患者心功能同时,也降低患者血浆BNP、ET-1和AngII水平,NIV对老年重度心力衰竭患者神经内分泌的影响可能在治疗过程中发挥一定作用。     

糖尿病及糖尿病肾病患者血浆尾加压素Ⅱ的变化

目的研究2型糖尿病及糖尿病肾病患者血浆尾加压素Ⅱ（UⅡ）的变化，探讨UⅡ在糖尿病及糖尿病肾病中的作用及其临床意义。方法2型糖尿病患者按尿白蛋白排泄率（UAER）分为三组：Ⅰ组：UAER〈20μg/min，Ⅱ组：UAER：20μg/min～200μg/min，Ⅲ组：UAER〉200μg/min。采用放射免疫分析法检测52例2型糖尿病及20例对照者血浆UⅡ含量。结果2型糖尿病各组患者血浆UⅡ水平均明显高于健康人血浆UⅡ水平（P〈0．01），并且Ⅲ组患者血浆UⅡ水平均高于Ⅰ组及Ⅱ组患者血浆UⅡ水平（P〈0．01），而且Ⅱ组患者血浆UⅡ水平高于Ⅰ组患者血浆UⅡ水平（P〈0．05）。血浆UⅡ水平与空腹血糖（FBS）、糖化血红蛋白（HbA1c）均无相关。结论UⅡ水平与糖尿病肾病的发生和发展可能有关。联合测定糖尿病患者血UⅡ及UAER水平，不仅可作为诊断糖尿病肾病早期损害较灵敏的预警指标，还将有助于监测、判断糖尿病肾病的病程进展。     

非糖尿病冠心病患者的HbA1C分析

目的：研究非糖尿病人群糖化血红蛋白（HbA1C）水平与冠心病（CHD）发病及病变程度的关系。方法：非糖尿病CHD组121例，其中单支病变组56例，二支病变组40例，三支病变组25例，正常对照组115例。测定受试者HbA1C、空腹血清胰岛素（FINS）、空腹血糖（FIG）及OGTT 2h血糖（2hPC）水平。结果：CHD组HbA1C、FINS、FPG及2hPG均明显高于正常对照组（P〈0．001～0．05），三支病变组HbA1C及FPG水平明显高于单支病变组和二支病变组（P〈0．001）。结论：在非糖尿病人群中，HbA1C是CHD发病的独立危险因素，并与CHD病变程度呈正相关。     

HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 genes in Japanese multiple sclerosis patients

Japanese MS patients and controls were examined for the distribution of HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 alleles using in vitro amplification of genomic DNA and probing with sequence-specific oligonucleotides. No significant difference in frequency of the examined alleles was observed among the two groups. This is in contrast to Norwegian MS patients, where an association to a combination of certain DQA1 and DQB1 alleles has previously been demonstrated.     

NDE1 and NDEL1: Multimerisation,alternate splicing and DISC1 interaction

Nuclear Distribution Factor E Homolog 1 (NDE1) and NDE-Like 1 (NDEL1) are highly homologous mammalian proteins. However, whereas NDEL1 is well studied, there is remarkably little known about NDE1. We demonstrate the presence of multiple isoforms of both NDE1 and NDEL1 in the brain, showing that NDE1 binds directly to multiple isoforms of Disrupted in Schizophrenia 1 (DISC1), and to itself. We also show that NDE1 can complex with NDEL1. Together these results predict a high degree of complexity of DISC1-mediated regulation of neuronal activity.     

韩国人CYP450 1A1、CYP450 2E1和GSTM1、GSTT1、GSTP1基因座遗传多态性分析

目的 调查代谢相关的CYP4501A1、CYP4502E1和GSTM1、GSIT1、GSTP1基因座在韩国人群中的遗传多态性分布状况。方法 采用多重聚合酶链式反应、聚合酶链式反应-限制性片段长度多态性技术，分析300名韩国健康大学生的CYP1A1基因3′端限制性内切酶Msp Ⅰ位点、CYP2E1基因5′端转录调节区Pst Ⅰ位点和GSTM1、GSTT1缺失与存在、GSTP1基因第5外显子BsmA Ⅰ位点的基因型，计算基因型和基因频率。结果 CYP1A1基因型频率为ml／ml型39．7％、ml／m2型49．7％、m2／m2型10．7％，基因频率为ml 0．645、m2 0．355。CYP2E1基因型频率为cl／cl型66．7％、cl／c2型30％、c2／c2型3．3％，基因频率为C1 0．818、C2 0．182。GSTM1基因缺失型频率为53．3％。GSTT1基因缺失型频率为54．7％。GSTP1基因型频率为Ile／Ile型62％、Ile／Val型34．3％、VaL／Val型3．7％，基因频率为Ile 0．792、Val 0．208。基因分布符合Hardy-Weirtberg平衡定律。结论 韩国人CYP1A1、CYP2E1、GSTM1、GSTT1基因分布与我国人群较为相近，半数以上人缺乏GSTM1和GSTT1基因，纯合缺失型频率超过印度人的3倍。     

Rb1cc1 is critical for myoblast differentiation through Rb1 regulation

Rb1-inducible coiled-coil 1 (Rb1cc1) expressed at high levels is associated with the maturation of human embryonic musculoskeletal cells. To clarify the molecular role of Rb1cc1 in muscular differentiation, we investigated the expression of Rb1cc1 and other genes that regulate differentiation in murine embryonic tissues and in C2C12 myoblasts. We also evaluated the effects of RNA interference (RNAi)-mediated Rb1cc1 knockdown on C2C12 myoblast differentiation. After Rb1cc1, Rb1 and myosin heavy chain (Myhc) were expressed in mouse embryonic muscles. The synchronous expression of Rb1cc1 and Rb1 predicted Myhc expression during C2C12 myoblast differentiation. RNAi-mediated knockdown of Rb1cc1 led to Rb1 suppression, and C2C12 myoblasts failed to differentiate. These results indicated that Rb1cc1 is a potent regulator of the Rb1 pathway and a novel mediator that plays a crucial role in muscular differentiation. Rb1cc1 expression is, thus, a prerequisite for myogenic differentiation.     

Maternal genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 and the risk of hypospadias

Hypospadias is one of the most common congenital anomalies. Increased exposure to environmental factors (endocrine-disrupting chemicals and smoking) or maternal endogenous estrogen may cause hypospadias because male sexual differentiation is dependent on normal androgen homeostasis. Moreover, interactions between genetic factors and cigarette smoking and other chemicals have been suggested. It has been demonstrated that the CYP1A1 metabolizes not only environmental chemicals but also estrogens, and glutathione-S-transferases (GSTs) are detoxification enzymes that protect cells from toxicants by conjugation with glutathione. In this study, to investigate the association of CYP1A1 (MspI), GSTM1 and GSTT1 polymorphisms with hypospadias, a case-control study of 31 case mothers who had boys with hypospadias and 64 control mothers was performed in Japan. These polymorphisms were investigated by PCR-based methods using DNA from peripheral lymphocytes. We found that the heterozygous CYP1A1 and heterozygous and homozygous CYP1A1 were less frequent in the case mothers than in the control mothers [adjusted odds ratio (OR)=0.17, 95% confidence interval (CI)=0.04-0.74, OR = 0.28, 95% CI = 0.08-0.97, respectively]. We found no effect of maternal smoking on the hypospadias risks among the gene polymorphisms. The results suggest that mothers with the CYP1A1 MspI variant allele may have a decreased risk for hypospadias.     

Circulatinglong non-coding RNA FEZF1-AS1 and AFAP1-AS1 serve as potential diagnostic biomarkers for gastric cancer

BackgroundGrowing evidence indicates that two long non-coding RNAs (lncRNAs), FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) and Actin filament associated protein 1 antisenseRNA1 (AFAP1-AS1), are highly expressed in different cancers, including gastric cancer (GC). However, the expression pattern and clinical utility of these two lncRNAs are still unknown.MethodsSerum expression levels of FEZF1-AS1 andAFAP1-AS1 were measured by quantitative real-time polymerase chain reaction (qRT-PCR). CEA and CA19-9 were detected by ARCHITET I2000 SR. Analyses were all performed using SPSS software version 20.0 (SPSS Inc., Chicago, USA). P < 0.05 was considered statistically significant.ResultsDetection of serum FEZF1-AS1 and AFAP1-AS1 showed both of them were up-regulated in GC patients compared with the normal controls (p < 0.0001), and high serum expression levels were correlated with tumor size, tumor-node-metastasis (TNM) stage and lymph node metastasis. Besides, the area under the ROC curve (AUC) demonstrated the two lncRNAs had higher diagnostic utility than CEA and CA19-9. Furthermore, when combined the two lncRNAs as a model, it yielded an AUC of 0.866, and the combination of the model, CEA and CA19-9 could observably improve diagnostic sensitivity to 95.5 %. What’s more, circulating FEZF1-AS1 and AFAP1-AS1 were significantly decreased after the GC patients underwent the operation (both p < 0.001).ConclusionOur study indicated that serum FEZF1-AS1 and AFAP1-AS1 had better sensitivity and efficiency for the diagnosis of GC and the combination of the two lncRNAs might be used as a potential prognostic indicator in GC.     

HIV-1 Nef stabilizes AP-1 on membranes without inducing ARF1-independent de novo attachment

HIV-1 Nef affects the trafficking of numerous cellular proteins to optimize viral replication and evade host defenses. The adaptor protein (AP) complexes, which form part of the cytoplasmic coat of endosomal vesicles, are key cellular co-factors for Nef. Nef binds these complexes and alters their physiologic cycle of attachment and release from membranes. Specifically, while AP-1 normally becomes cytosolic when attachment events are blocked by inhibition of the GTPase cycle of ADP-ribosylation factor-1 (ARF1), the complex remains membrane-associated in Nef-expressing cells. To investigate the mechanism of this effect, we used a permeabilized cell system to detect the de novo attachment of exogenous AP-1 to endosomal membranes. Nef did not mediate de novo attachment independently of ARF1, despite its ability to maintain the association of AP-1 with endosomal membranes when the activity of ARF1 was blocked. We conclude that Nef stabilizes AP complexes on endosomal membranes after ARF1-dependent attachment. This stabilization may facilitate coat formation and stimulate the trafficking of multiple cellular proteins.     

神经系统RNA结合蛋白Musashi1 RRM1的初步结晶

目的 对Musashi1发挥功能的 RRM1结构域进行结晶,得到可用来衍射的蛋白晶体,为之后的结构解析打基础。方法 通过构建Musashi1RRM1的原核表达载体,并在BL21中表达、纯化高纯度的蛋白质,通过筛选结晶体条件得到蛋白晶体。结果 通过系统筛选和优化晶体生长条件得到了蛋白晶体。结论 Musashi1 RRM1的蛋白晶体质量较好,满足蛋白晶体衍射和数据收集的要求。     

IL—1受体相关激酶—1和—2协同调控IL—1诱导的AP—1的活化

目的研究白介素 - 1受体相关激酶 - 1(IRAK- 1)和 IRAK- 2在白介素 - 1(IL - 1)诱导 AP- 1活化中的作用。方法L ipofectin介导反义 IRAK- 1寡核苷酸和反义 IRAK- 2寡核苷酸转染 Hep G2细胞。用逆转录 PCR法检测 IRAK - 1和 IRAK- 2m RNA表达水平 ;Western blot分析 IRAK- 1和 IRAK - 2蛋白表达水平。以 Sandwich EL ISA法检测 AP- 1的活化。结果反义IRAK- 1寡核苷酸和反义 IRAK- 2寡核苷酸通过抑制各自靶基因 m RNA和蛋白表达抑制 IL- 1诱导的 AP- 1活化 ;反义 IRAK-1寡核苷酸与反义 IRAK- 2寡核苷酸共转染 Hep G2细胞对 AP- 1的抑制作用较两者单独转染明显增强。结论 IRAK- 1和 I-RAK- 2在调控白介素 - 1诱导的 AP- 1活化时协同作用。     

Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not involved in the risk of recurrent pregnancy loss

The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40-1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68-2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.