EVI1基因在白血病中的研究进展

EVI1基因主要控制胚胎的发育,3q重排、MLL易位、7号染色单体或者与其他基因的相互作用都可使其异常表达或户生融合基因.新近研究发现,EVI1基因在部分急性淋巴细胞性白血病、急性髓细胞性白血病和慢性粒细胞性白血病中都有异常表达,并且与不良预后相关,其致白血病机制有表观遗传学的修饰、调控转录、调节信号通路、提高白血病细胞黏附、增殖、集落形成和抗凋亡能力.基因治疗药物有表观遗传学制剂、mTOR抑制剂、抗人ITGA6/ITGB4复合物抗体、抗CD52单克隆抗体.     

有机阴离子转运体1B1基因与新生儿黄疸关系的研究进展

有机阴离子转运体2(OATP2)是一种肝细胞膜上转运胆红素等物质的转运体,影响胆红素的代谢.OATP2 由有机阴离子转运体1B1(SLCO1B1)基因编码,该基因突变可抑制OATP2 的转运功能,致胆红素清除减慢,引起高胆红素血症.近年的研究显示,SLCO1B1 基因多态性可能与新生儿黄疸发生相关.该文综述了SLCO1B1 基因结构、功能及SLCO1B1 基因突变与新生儿黄疸的关系.     

1型糖尿病自身抗原研究进展

自身免疫是1型糖尿病发病的重要机制.1型糖尿病自身抗原的发现为疾病的发病机制及临床诊治开拓了视野.胰岛素、谷氨酸脱羧酶65、胰岛细胞瘤相关抗原2等是已发现的1型糖尿病主要的自身抗原.近年来,1型糖尿病自身抗原如嗜铬粒蛋白A、胰岛淀粉样多肽、锌转运体8、胰-十二指肠同源盒因子1备受重视.该文就1型糖尿病自身抗原的研究进展进行综述.     

SCN1A基因相关癫痫研究进展

SCN1A基因编码电压门控钠离子通道α1亚基,其致病性变异可通过影响钠通道的功能导致癫痫发作.SCN 1 A基因致病性变异相关的癫痫患者具有高度的临床异质性,可表现出从良性表型到严重表型的一系列癫痫表型谱.基因变异的位置及类型、嵌合体变异以及修饰基因的作用等都是影响癫痫表型的因素.早期识别SCN 1 A基因相关癫痫的临...     

CHFR基因和PARP-1基因对裸鼠Raji淋巴瘤细胞增殖和凋亡调控的研究

目的 CHFR基因是一种抑癌基因,低表达或表达缺失可能促淋巴瘤细胞增殖,PARP-1基因参与其对淋巴瘤细胞增殖的调控,本研究旨在通过过表达CHFR基因及分别沉默CHFR、PARP-1基因,观察其对裸鼠移植瘤Raji细胞的影响,探讨CHFR基因和PARP-1基因调控裸鼠Raji淋巴瘤细胞的增殖和凋亡机制。方法 在非霍奇金B细胞裸鼠Burkitt淋巴瘤移植瘤Raji细胞中,用5-氮杂-2′-脱氧胞苷(5-Aza-dC)过表达CHFR基因,及用慢病毒介导的shRNA分别沉默CHFR、PARP-1基因,测定各组裸鼠移植瘤的肿瘤的大小及重量;采用实时荧光定量PCR技术测定各组CHFR及PARP-1基因mRNA含量;应用MSP方法检测各组CHFR的甲基化状态;分别通过TUNEL试剂盒和免疫组化监测凋亡指数(AI)和微血管密度(MVD)。结果 5-Aza-dC组的裸鼠在非霍奇金B细胞Burkitt淋巴瘤移植瘤Raji细胞能增强CHFR基因mRNA的表达,降低PARP-1基因mRNA的表达;在体内环境中,5-Aza-dC能够促进移植瘤Raji细胞的凋亡,抑制移植瘤的生长(P<0.05),这些结果...     

Forkhead Box f1基因与新生儿肺出血的研究进展

新生儿肺出血仍然是新生儿期主要的危重疾病及死亡原因。最新的研究提示，一种新的转录因子Forkhead Box f1（Foxf1）的表达参与新生大鼠肺出血的发病机制，Foxf1表达缺陷将导致Notch信号系统异常，并引起致死性肺出血。     

甲型H1N1流感的研究进展

甲型H1N1流感病毒是人流感病毒基因、禽流感病毒基因和猪流感病毒基因混合的重配株,其造成的疫情来势凶猛,引起世界各国的广泛关注.为了早发现、早诊断、早治疗及有效地预防甲型H1N1流感,本文综述了甲型H1N1流感病毒的特点、流行病学、致人发病的机制、甲型H1N1流感患者的临床表现、实验室检查及有效的治疗和预防措施.     

宫内发育迟缓大鼠肾脏Wilms瘤1基因DNA甲基化与蛋白尿关系

目的:观察宫内环境对肾脏Wilms瘤1（WT1）基因甲基化状态的影响及其与肾脏功能的关系,探讨宫内环境引发肾脏疾病的可能分子机制。方法:采用孕期全程低蛋白饮食法建立宫内发育迟缓（IUGR）大鼠模型,至自然分娩。对照组以孕期常规饲料饲养至自然分娩。12周龄时,比色法测定24 h尿蛋白定量,光镜下计数肾小球数目,实时PCR方法检测肾脏WT1基因mRNA水平及甲基转移酶DNMT1、DNMT3a和DNMT3b mRNA水平,MassARRAY定量分析检测WT1基因启动子区DNA甲基化状态。结果:①IUGR组新生鼠出生体重显著低于对照组（P<0.000 1）,直至12周龄时体重仍低于对照组（P=0.043）。②与对照组相比,12周龄时IUGR组大鼠24 h尿蛋白定量显著升高（P=0.016）;血清胱抑素C水平显著升高（P =0.036）,肾小球数目显著下降（P=0.001）。③与对照组相比,12周龄时IUGR组大鼠肾组织WT1基因mRNA的表达显著增高（P=0.047）,WT1基因启动子区甲基化水平显著降低（P=0.029）,并且其M1段甲基化水平与WT1基因mRNA的表达呈负相关（r=-0.939,P=0.000 1）,DNMT1和DNMT3b mRNA表达水平也显著下降（P值分别为0.003和0.010）。结论:不良的宫内环境可以影响大鼠肾脏WT1基因的甲基化状态,继而导致其异常表达,可能参与了IUGR大鼠成年期蛋白尿的发生。     

儿童1型糖尿病血糖波动的意义

糖化血红蛋白被公认为是预示糖尿病并发症发生的重要因子,而近年来,血糖波动可能成为影响血管并发症发生的另一血糖控制指标.血糖波动是1型糖尿病胰岛素治疗后的常见现象,因此明确1型糖尿病血糖波动与血管并发症的相关性,将对指导儿科内分泌临床医师选择治疗方案具有重要意义.而氧化应激是血管并发症发生机制的核心环节,因此研究焦点集中在血糖波动与氧化应激相关性方面.     

KCNMA1基因相关神经系统疾病表型谱及治疗研究进展

近年来，癫痫与运动障碍共患逐渐受到神经科医生的关注。其中离子通道病是其重要病因。KCNMA1基因为钾离子通道编码基因，KCNMA1变异相关神经系统疾病表型谱包括阵发性非运动诱发性运动障碍和（或）癫痫。文章旨在针对KCNMA1基因变异相关神经系统疾病表型谱及治疗进行系统总结，以指导临床工作。     

Antioxidant enzyme activities and DNA damage in children with type 1 diabetes mellitus after 12 weeks of exercise

Objective: The objectives of this study are to assess the effects of a low‐intensity exercise training which is not risky for children with type 1 diabetes mellitus (T1DM) on the antioxidant enzyme activities and oxidative stresses compared with healthy controls. Patients and methods: We studied 10 boys with T1DM (11.21 ± 0.97 age) and 10 age‐matched healthy controls (11.90 ± 1.85 age) during the 12 weeks of moderate intensity aerobic exercise. Measurements included peak oxygen uptake, body composition, blood lipid profiles, glycated haemoglobin (HbA1c), oxidized low density lipoprotein (ox‐LDL), 8‐hydroxy‐2′‐deoxyguanosine, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Results: In T1DM patients, the baseline diastolic blood pressure and HbA1c were higher than that in controls (p < 0.05), while the GPx level was lower. The training‐induced DNA damage peak was higher in T1DM patients than in controls (p < 0.05), and exercise improved both SOD and GPx levels. Conclusion: Although our exercise programme increase antioxidant enzyme activities, the results of the study demonstrate that low‐intensity aerobic exercise training programme performed over 12 weeks may accelerate adverse effects of antioxidant defence capacity in children with T1DM. Therefore, the future studies should be performed to clarify much more the relationship to exercise and antioxidant capacity in children with T1DM.     

胰岛素样生长因子-1对新生大鼠神经细胞氧化损伤保护作用的研究

目的 探讨氧化应激状态下,胰岛素样生长因子-1（IGF-1）对新生大鼠神经细胞氧化损伤的保护作用。方法 原代培养新生大鼠大脑皮层神经元、少突胶质细胞及星形胶质细胞,不同浓度H2O2（0~60 μM）诱导氧化应激细胞模型,LDH 法检测各种神经细胞损伤程度,MTT 法检测各种神经细胞活力;不同浓度H2O2（0~80 μM）诱导氧化应激神经元细胞模型,Western blot 检测IGF-1（25 ng/mL）施加前后神经元细胞内Akt 的磷酸化水平。结果 与未经H2O2 处理组相比,不同浓度H2O2 处理细胞24 h 后,大脑皮层神经元、少突胶质细胞及星形胶质细胞损伤程度均有升高、细胞活力均有降低;但神经元变化更为显著,与少突胶质细胞和星形胶质细胞相比,差异有统计学意义（均P2O2 处理大脑皮层神经元5 min 后,相比于未经H2O2 处理组,可见Akt 磷酸化水平呈H2O2 浓度依赖性降低（均P2O2 导致的神经元细胞Akt 磷酸化,与未经H2O2 处理组比较,差异无统计学意义（P>0.05）,但是对高浓度H2O2 导致的Akt 磷酸化作用无明显效果,其磷酸化水平均低于未经H2O2 处理组（均P2O2 处理1 h 后,再加入25 ng/mL 的IGF-1,IGF-1 处理前后Akt 磷酸化水平均已恢复至未经H2O2 处理时的水平（均P>0.05）。结论 大脑皮层神经元对H2O2 诱导的氧化应激损伤较其他神经细胞敏感;IGF-1 对皮层神经元氧化应激损伤具有保护作用。     

Role of DNA methylation at the placental RTL1 gene locus in type 1 diabetes

Genome‐wide association studies (GWAS) have identified more than 40 T1D loci associated with type 1 diabetes (T1D). How these polymorphisms interact with environmental factors to trigger T1D is unknown, but recent evidence suggests that epigenetic mechanisms could play a role. To begin to explore the contribution of epigenetics to T1D, we have examined DNA methylation in a pilot study of whole blood cells DNA from 10 young T1D patients and 10 young controls. Through the study of >900 000 CG loci across a diverse set of functionally relevant genomic regions using a custom DNA methylation array, we identified 250 T1D‐differentially methylated region (DMR) at p < 0.05 and 1 DMR using next a permutation‐based multiple testing correction method. This DMR is located in an imprinted region previously associated with T1D on the chromosome 14 that encompasses RTL1 gene and 2 miRNAs (miR136 and miR432). Using pyrosequencing‐based bisulfite PCR, we replicated this association in a different and larger set of T1D patients and controls. DNA methylation at this DMR was inversely correlated with RTL1 gene expression and positively correlated with miR136 expression in human placentas. The DMR identified in this study presents suggestive evidence for altered methylation site in T1D and provide a promising new candidate gene. RTL1 is essential for placental permeability function in the mid‐to‐late fetal stages. We suggest that hypo‐methylation could increase the fetal exposure to environmental factors in T1D susceptibility.     

Variabilidad glucémica y estrés oxidativo en niños con diabetes tipo 1 asistentes a un campamento

ObjectiveTo assess glycemic variability, oxidative stress and their relationship in children and adolescents with type 1 diabetes (T1DM) attending a summer camp.Patients and methodCross-sectional study that included 54 children and adolescents with T1DM aged 7-16, attending a 7 day summer camp. Sociodemographic information, clinical data, and blood glucose values measured using an Accu-Chek Nano® glucose meter were recorded. Glucose variability markers (standard deviation [SD], low blood glucose index [LBGI], high blood glucose index [HBGI], mean amplitude of glycemic excursions [MAGE] and mean of daily differences [MODD]) were calculated. Oxidative stress was assessed by the measurement of 8-iso-prostaglandin F2 alpha (PGF2α) in a 24-hour urine sample collected at the end of the camp in 14 children.ResultsThe Median SD, MAGE and MODD indexes were in the high range (61, 131 and 58 mg/dl, respectively), LBGI in the moderate range (3.3), and HBGI in the low range (4.5). The mean HbA1c was 7.6% and the median urinary excretion rate of 8-iso-PGF2α was 864.39 pg/mg creatinine. The Spearman correlation coefficients between markers of glycemic variability (SD, HBGI, MAGE, MODD) were significant. Non-significant correlations were found between markers of glycemic variability and urinary 8-iso-PGF2α.ConclusionsHigh glycemic variability was observed in children and adolescents attending a summer camp. However, no correlations were found between markers of glycemic variability and oxidative stress measured by urinary 8-iso-PGF2α. Further studies are needed to address the relationship between oxidative stress and glycemic variability in children with T1DM.     

白藜芦醇对高氧诱导早产儿外周血单个核细胞氧化应激损伤的影响及其机制研究

目的 探讨沉默接合型信息调节因子2 同源蛋白1(SIRT1)激动剂白藜芦醇(Res)对高氧诱导早产儿外周血单个核细胞(PBMC)中SIRT1 表达和活性氧簇(ROS)产生的影响。方法 采集胎龄<32 周且未吸氧的早产儿外周血分离PBMC,随机分为对照组、空气+Res 组、高氧组和高氧+Res 组,在体外建模及培养48 h 后,采用激光共聚焦显微镜检测PBMC 内ROS 水平,全光谱分光光度仪检测培养液中丙二醛(MDA)含量,细胞免疫荧光检测SIRT1 定位,Western blot 检测PBMC 内SIRT1 蛋白表达水平。结果 与对照组相比,空气+Res 组中SIRT1 表达水平明显增加(P<0.05);高氧组中ROS、MDA 水平及SIRT1 转位率明显增加(P<0.05),SRIT1 蛋白表达水平明显降低(P<0.05)。与高氧组相比,高氧+Res 组中ROS、MDA 水平及SIRT1 转位率明显降低(P<0.05),SIRT1 蛋白表达水平明显增加(P<0.05)。结论 在高氧诱导下,Res 可以通过提高早产儿PBMC 的SIRT1 表达并抑制SIRT1 核-浆穿梭从而增加早产儿抗氧化应激的能力,进而减少早产儿氧化应激损伤。     

Heme oxygenase-1 expression in premature and mature neonates during the first week of life

Newborns are exposed to mechanical and oxidative stress during labor and to relative hyperoxia thereafter during the course of adaptation to the extrauterine conditions. Part of the adaptation mechanism is the rapid degradation of fetal hemoglobin and the oxidation of its heme moiety by heme oxygenases (HOs). Heme oxygenase-1 enzyme (HO-1) is the inducible isoform, which is induced by and protective against oxidative stress. We hypothesized that HO-1 may play a role in the physiological adaptation of newborns. We therefore measured the HO-1 mRNA expression with cRT-PCR during the first week after birth in healthy mature and premature newborns. We found that HO-1 was induced until day 2 or 3 after birth, but its level had dropped below the birth HO-1 mRNA level by the end of the first week. HO-1 levels and inducibility were similar in mature newborns and premature newborns. The fact that HO-1 was inducible even in gestation week 26 suggests that HO-1 plays an important role in the early adaptation processes.     

急性淋巴细胞白血病患儿WAVE1和p22phox的表达及WAVE1与氧化应激的关系

目的：研究儿童急性淋巴细胞白血病（ALL）患者外周血单个核细胞(PBMCs)中WASP家族富含脯氨酸同源蛋白1（WAVE1）及NADPH氧化酶亚基p22phox的表达并探讨WAVE1表达与白血病病程及氧化应激的关系。方法：实时定量PCR法测定41例ALL儿童及10例正常对照儿童PBMCs中WAVE1和p22phox的表达水平。黄嘌呤氧化酶法（羟胺法）和二硫代二硝基苯甲酸法（DTNB法）分别测定外周血血浆总超氧化物歧化酶（SOD）活性和谷胱甘肽过氧化物酶（GSH-Px）活性。结果：①儿童ALL活动期组（初治+复发）PBMCs中WAVE1,p22phox的表达水平与正常对照组和完全缓解组相比均显著增高(P< 0.01); ALL完全缓解组中,WAVE1,p22phox表达高于正常对照组(P<0.05);②正常对照组、活动期组和缓解组血浆SOD活力分别为166.35±27.93, 22.62±7.39, 107.11±28.57 U/mL; GSH-Px活力分别为490.94±39.38,91.73±28.88,267.56±82.64 μmol/L。ALL活动期组外周血血浆总SOD,GSH-Px活性较完全缓解和正常儿童明显降低（P<0.01）;③ 随着WAVE1和p22phox的高表达,血浆中SOD, GSH-Px活性呈现下降趋势。WAVE1的表达水平与p22phox表达水平呈正相关（r=0.34,P< 0.05）,与血浆SOD,GSH-Px活性呈负相关（r分别为-0.336和-0.408,P<0.05）。结论：与正常对照组相比,WAVE1和p22phox在儿童ALL PBMCs中表达增高,而且其变化与ALL病程相关。ALL患儿氧化应激可能参与了WAVE1表达的调控。［中国当代儿科杂志,2009,11（2）：88-92］     

A newly identified exonic mutation of the WT1 gene in a patient with Denys-Drash syndrome

An 11 month old boy with hypospadias and bilateral undescended testes developed renal failure. Denys-Drash syndrome was suspected and molecular analysis of the WT1 gene was performed, although no Wilms' tumor was identified. Direct sequencing analysis of genomic DNA from this patient revealed a G to A transition resulting in ³⁶⁶Arg to Leu substitution in exon 8 which has hitherto not been described. This newly identified mutation will help in the understanding of functional domains and in making a diagnosis of Denys-Drash syndrome.