Early onset of liver steatosis in a Japanese girl with maturity-onset diabetes of the young type 3 (MODY3)

Maturity-onset diabetes of the young type 3 (MODY3) is caused by heterozygous mutation in the HNF1A gene. Liver adenomatosis has been reported in MODY3 patients. The patient reported in this paper is a Japanese girl who first developed hepatomegaly, fatty liver, and hepatic dysfunction at age 5 years. Liver biopsy demonstrated steatosis and degeneration of hepatocytes. At that time, blood glucose and HbA1c levels were within normal ranges. Elevated HbA1c was noticed 4 years later, but islet cell and glutamic acid decarboxylase antibodies were not detected in the serum. Therefore, MODY3 was suspected and subsequent analysis of the HNF1A gene identified a heterozygous germline splice donor-site mutation in intron 9. MODY3 patients should be screened by non-invasive liver imaging, and careful follow-up of liver disease should be performed.     

Coalition of DNA polymorphisms of ApoB and ApoAI genes is related with coronary artery disease in Kazaks

Objective To explore the relationship between polymorphisms of XbaI and MspI loci of apolipoprotein B (ApoB) gene and -75 bp, +83 bp loci of apolipoprotein AI (ApoAI) gene and coronary heart disease (CHD) in Kazaks of Xinjiang Uyghur Autonomous Region, China. Methods These loci were analyzed by PCR-restriction fragment length polymorphism (PCR-PFLP). Two hundred and five patients with CHD and two hundred and thirty six controls were involved. Results There were significant distinctions among low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and the ApoAI/ApoB ratio between the two groups, but no significant distinction among the polymorphism frequencies of the four sites between the two groups. The polymorphism coalition frequency of X--/Ms++/M1+-/M2++ (named Coalition 11) was significantly higher in CHD compared to the control group (14.6% vs. 7.2%, P < 0.05). The level of total cholesterol (TC) in Coalition 11 was significantly higher and the level of the ApoAI/ApoB ratio in Coalition 11 was significantly lower than Coalition 1~10 in CHD patients. The level of the ApoAI/ApoB ratio of Coalition 11 was significantly lower than the Coalition 1~10 in control group. The levels of ApoAI/ApoB ratio of Coalition 3 were significantly higher compared to Coalition 11 in the two groups, respectively. The level of LDL-C of Coalition 3 was significantly lower than in the Coalition 11 in control group. The level of TC of Coalition 5 was significantly higher than Coalition 3 in the CHD group. The level of the ApoAI/ApoB ratio of Coalition 5 was significantly lower than in Coalition 3 or Coalition 1~10 of the two groups, respectively. The level of LDL-C of Coalition 5 was significantly higher than in Coalition 3 in control group. The ratio of ApoAI/ApoB was negatively related to TC, LDL-C and was positively related to HDL-C, both in CHD and control groups. Conclusion Coalition 11 of the 4 loci polymorphisms of the ApoB and ApoAI genes was correlated with CHD in Kazaks, and perhaps the ratio of ApoAI/ApoB was the most diagnostic parameter related with CHD among all lipid parameters. CHD may also be associated with Coalition 5, and, perhaps, Coalition 3 may have been confirmed as a protection factor against CHD, if more samples were enrolled.     

北京地区妇女宫颈人乳头瘤病毒感染及亚型分布情况分析

目的探讨北京地区妇女宫颈人乳头瘤病毒(HPV)感染及其亚型分布情况。方法采用聚合酶链反应(PCR)体外扩增和脱氧核糖核酸(DNA)反向点杂交相结合的DNA芯片技术,对920例宫颈脱落细胞标本进行HPV基因分型检测。结果 920例标本共检出HPV感染508例,总感染率为55.22%。23种亚型共检出21种,高危亚型MM4及低危亚型44未检测出;感染率居前五位的基因亚型是HPV-16 238例(24.74%),HPV-11 100例(10.4%),HPV-6 95例(9.88%),HPV-58 84例(8.73%)和HPV-33 75例(7.8%)。单一基因型感染285例,占总感染数的56.1%;多重感染223例,占总感染数的43.9%。<20、20～29、30～39、40～49和≥50岁五个不同年龄组阳性感染构成比分别为1.97%、25.78%、37.60%、23.43%和11.22%。结论北京地区妇女宫颈HPV感染率较高,HPV感染高发年龄段为20～49岁性活跃阶段女性,HPV基因分型检测技术对宫颈癌预防有积极作用。     

我国细粒棘球蚴新疆分离株AgB亚基基因克隆及序列分析

目的 对我国细粒棘球蚴新疆分离株AgB亚基基因进行克隆、测序,对序列进行遗传变异性分析.方法 根据参考文献设计特异性引物,从新疆源细粒棘球蚴(Echinococcus granulosus,Eg)原头节中提取总RNA,通过RT-PCR扩增目的基因片段并克隆入TA载体中测序.用Bioedit分析软件和Blastn和clusterW2等在线分析系统对序列进行分析.结果 从细粒棘球蚴中克隆获得AgB抗原的3个亚单位基因,经测序确定为正确的目的序列;序列比对分析表明,3个亚单位基因的核苷酸序列一致性为43％ ～ 60％,氨基酸序列一致性为30％ ～ 42％.结论 EgAgB的亚单位基因变异性较大.     

Keap1-Nrf2-ARE通路与脑缺血

Keap1 -Nrf2-ARE通路在抗肿瘤、抗应激、抗凋亡、抗炎症等方面具有广泛的细胞保护功能.其在神经系统疾病中的神经保护作用已成为目前的研究热点之一.文章综述了Keap1-Nrf2-ARE通路在脑缺血中的神经保护作用.     

非小细胞肺癌患者中肿瘤坏死因子相关凋亡诱导配体基因多态性及单倍型研究

目的 探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)基因多态性及单倍型与非小细胞肺癌(NSCLC)的关系.方法 收集NSCLC患者592例,健康对照者636例,聚合酶链反应(PCR)扩增TRAIL目的基因后,直接测序检测TRAIL基因3’非编码区(G1525A/G1588A/C1595T)3种单核苷酸多态性,并做TRAIL单倍型分析.结果 与对照组比较,TRAIL G1525A突变等位基因(A)和基因型(GA+ AA)的频率在NSCLC组中明显降低(P＜0.01);NSCLC组TRAIL GI588A和C1595T两位点突变等位基因(A)和(T)的频率亦明显低于对照组(P＜0.01).进一步分层分析显示,Ⅰ期+Ⅱ期NSCLC患者中TRAIL C1595T突变等位基因(T)和(CT+ TT)基因型频率分别为47.89％和62.01％,Ⅲ期+Ⅳ期NSCLC患者中分别为58.80％和74.65％,两组差异均有统计学意义[优势比(OR)值分别=1.553和1.804,95％可信区间(CI):1.234 ～1.955和1.268～2.567,P＜0.01].Ⅲ期+Ⅳ期NSCLC患者中TRAIL G1525A突变等位基因(A)的频率为47.54％,较Ⅰ期+Ⅱ期NSCLC患者明显增加(40.75％,OR=1.318,95％ CI:1.658 ～1.047,P＜0.05).单倍型分析TRAIL基因(G1525A/G1588A/C1595T)3个位点紧密连锁,NSCLC组中AAT单倍型频率显著低于对照组(42.45％比58.23％,95％CI:1.525～2.824,P＜0.01);GAT单倍型频率在NSCLC组中明显增高(9.98％比0.21％,95％ CI:0.015～0.059,P＜0.01).结论 TRAIL(G1525A/G1588A/C1595T)基因多态性及单倍型与NSCLC的易感性密切相关.     

eIF5A-2在非小细胞肺癌上皮间质化过程中的作用机制

目的 探讨真核细胞翻译起始因子5A-2(eIF5A-2)的表达在非小细胞肺癌(NSCLC)上皮间质化(EMT)过程中的作用及其机制.方法 通过Westrn-blotting和免疫荧光检测细胞表型变化,利用siRNA转染下调eIF5A-2表达后再以Western-blotting和免疫荧光检测细胞表型的改变.用TGF-β1刺激诱导NSCLC细胞系NCI-H358和HCC827发生EMT后并利用Western-blotting检测eIF5A-2的表达.结果 NCI-H358和HCC827细胞系低表达eIF5A-2,为上皮表型,而NCI-H1299细胞高表达eIF5A-2,为间质表型.eIF5A-2 siRNA干扰后可以改变NCI-H1299细胞的间质表型.NCI-H358和HCC827细胞经TGF-β1诱导后可发生EMT变化,而eIF5A-2 siRNA干扰后则可防止这种变化的发生.结论 在不同的NSCLC细胞系中,间质表型细胞较上皮表型者高表达eIF5A-2.TGF-β1可诱导上皮表型细胞发生EMT,而干扰eIF5A-2则可阻止EMT的发生.     

XIAP修饰的脂肪间充质干细胞在心肌梗死治疗中的作用

目的 探讨XIAP修饰的脂肪间充质干细胞(ADMSCs)是否具有更强的活力,能否更好地恢复心功能,及基因修饰干细胞治疗模式的可行性.方法 10周的雄性SD大鼠,体质量200 ～ 300 g,取其腹股沟处脂肪组织,提取脂肪间充质干细胞行体外培养扩增.应用电转染的方法将XIAP表达质粒导入脂肪干细胞内,进行基因修饰.另取61只SD大鼠,年龄和体质量同前,顺序编号,按照随机数字表法完全随机分为对照组(18只)、ADMSCs组(18只)、XIAP修饰ADMSCs组(18只)和未处理组(7只).结扎大鼠冠状动脉左前降支,选取梗死中央及边缘区共5个注射点,按分组每点注射生理盐水、ADMSCs悬液或经XIAP修饰的ADMSCs悬液或不做任何处理.结果 注射4周后,同对照组相比,ADMSCs组的左心室射血分数明显改善[(0.57 ±0.05)对(0.53±0.03),P＜0.05],心肌梗死面积百分比显著减小[(5.17±2.03)对(10.62±3.50),P＜0.05];与ADMSCs组相比,XIAP修饰的ADMSCs对心肌梗死的治疗作用更为明显,射血分数0.64±0.03,心肌梗死面积百分比3.26±0.95,P＜0.05.结论 ADMSCs能有效恢复梗死后心功能;XIAP修饰的ADMSCs在移植区的生存效率更高,能更好的恢复心功能.     

微小RNA-494过表达与RNA干扰抑制Survivin基因对前列腺癌移植瘤生长的比较

目的 比较过表达微小RNA (microRNA)-494与采用RNA干扰抑制前列腺癌PC-3细胞中Survivin基因的表达,对前列腺癌移植瘤生长的影响.方法 将过表达microRNA-494的腺病毒载体Ad-494及负载Survivin短发卡RNA (shRNA)腺病毒载体Ad-sur分别或联合感染PC-3细胞后,将相应PC-3细胞接种于裸鼠右前肢皮下,建立前列腺癌移植瘤模型.并以磷酸盐缓冲液(PBS)组及空载体组(Ad-GFP)作为对照.动态测量肿瘤体积.55 d后处死各组裸鼠,瘤体称重计算抑瘤率.Western blot检测肿瘤组织中Survivin表达变化.免疫组织化学测定Survivin、B淋巴细胞/白血病-2(bcl-2)、bcl-2相关X蛋白(bax)及半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3表达变化.结果 Ad-sur组、Ad-494组、Ad-sur+ Ad-494组裸鼠前列腺癌移植瘤的生长明显被抑制.第35天时即表现差异.其中Ad-sur+ Ad-494组瘤体积最小,为(40.69±0.69) mm3,Ad-sur、Ad-494组瘤体体积分别为(102.11±5.32) mm3、(99.03±3.50) mm3,3组肿瘤体积均明显小于PBS组(572.72±10.46) mm3、Ad-GFP组(544.85 ±10.28) mm3(P＜0.05).但Ad-sur组与Ad-494组间瘤体大小差异无统计学意义(P＞0.05).55 d后,Ad-sur、Ad-494、Ad-sur+ Ad-494组对移植瘤抑制率分别64.62％、65.98％、86.67％,Ad-sur+ Ad-494组具有抑瘤增效的相加作用(Q=0.99).同对照组比较,实验各组的Survivin基因均表达下降,差异有统计学意义(P＜0.05).其中,Ad-494组与Ad-sur组间差异无统计学意义(P＞0.05),Ad-sur+ Ad-494组较Ad-494、Ad-sur组更为显著;实验各组中的bax、Caspase-3表达上调,bcl-2表达下调,且Ad-sur+ Ad-494组效果优于Ad-sur、Ad-494组.结论 过表达microRNA-494与RNA干扰方法均可抑制前列腺癌裸鼠移植瘤Survivin基因表达,从而抑制移植瘤的生长,且两者联合效果更加显著.