原始生殖细胞发生的机制

生殖细胞的发生是发育和遗传的基础。在几乎所有哺乳动物中,原始生殖细胞（primordial germ cell,PGC）均由近端上胚层体细胞在周边细胞特定的信号诱导下特化而成。目前的研究已经发现一些与生殖细胞特化有关的信号分子和关键转录调控元件,以及特化后生殖细胞获得的与体细胞不同的生物特性。生殖细胞的特化是一个结合了体细胞发育程序的抑制、细胞多能性程序的启动和全基因组表观遗传重编程三个方面的动态的复杂过程。多能性干细胞（胚胎干细胞或诱导型多能干细胞）具有发育全能性,能分化为机体任何一种细胞类型,包括生殖细胞。利用多能性干细胞体外分化形成生殖细胞有助于深入系统地研究配子发生的调控机制,为干细胞在不育症治疗方面的应用带来新希望。     

细胞移植治疗脑瘫的研究现状

小儿脑性瘫痪（简称脑瘫）是目前小儿时期最主要的神经运动功能伤残疾病,且终生存在。尽管有支持性医护。但是目前并没有效治疗的方法。近几年,许多实验室开展了利用干细胞移植治疗脑瘫动物模型的研究,并且报道说人脐血干细胞和间充质干细胞对于脑瘫是有治疗作用的。而神经干细胞也被用于移植治疗脑瘫动物模型,并被证明这些移植的神经干细胞能迁移至受损脑部并分化为神经元。本文就至今已发表的一些细胞移植治疗脑瘫的研究中所用到的细胞种类做一综述。     

人诱导多能干细胞与人胚胎干细胞分化过程中Oct4/Nanog 基因 表达的比较

目的:比较通过慢病毒方法获得的人诱导多能性干细胞(iPSCs)与人胚胎干细胞(hESCs)分化过程中全能性基因Oct4、Nanog的表达变化。方法:收集分化不同时间点的拟胚体(EBs),检测三胚层分化基因以及全能性基因Oct4/Nanog的表达,并通过畸胎瘤组织切片的荧光染色分析Oct4的表达。结果:iPSCs获得的EB中内外三胚层分化基因表达的出现明显晚于hESCs来源的EB。不同于hESCs,iPSCs悬浮培养获得的EBs在体外培养18天未见内源性Oct4、Nanog基因表达的下调。未分化的iPSCs注射严重联合免疫缺陷(SCID)小鼠培养10周后获得的畸胎瘤中仍存在Oct4阳性的细胞,但iPS-#2中明显少于iPS-#5。结论:通过慢病毒方法获得的iPSCs虽然具有向三胚层分化的能力,但在分化过程中仍维持较高水平的全能性基因Oct4、Nanog的表达。     

CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies

Previous studies of families with multiple cases of breast cancer have indicated that a frameshift alteration in the CHEK2 gene, 1100delC, is associated with an elevated frequency of breast cancer in such families, but the risk associated with the variant in other situations is uncertain. To evaluate the breast cancer risk associated with this variant, 10,860 breast cancer cases and 9,065 controls from 10 case-control studies in five countries were genotyped. CHEK2*1100delC was found in 201 cases (1.9%) and 64 controls (0.7%) (estimated odds ratio 2.34; 95% CI 1.72–3.20; P=.0000001). There was some evidence of a higher prevalence of CHEK2*1100delC among cases with a first-degree relative affected with breast cancer (odds ratio 1.44; 95% CI 0.93–2.23; P=.10) and of a trend for a higher breast cancer odds ratio at younger ages at diagnosis (P=.002). These results confirm that CHEK2*1100delC confers an increased risk of breast cancer and that this risk is apparent in women unselected for family history. The results are consistent with the hypothesis that CHEK2*1100delC multiplies the risks associated with susceptibility alleles in other genes to increase the risk of breast cancer.     

生态系统供给服务评估及经济价值测算

针对目前生态系统产品供给服务评估中缺乏空间表达、未考虑产品可获得性等不足,基于ArcGIS9.2,综合考虑生态系统产品的供、需两方面因素,构建了生态系统供给服务物质量和价值量的空间表达技术方法和评估模型,并对2000年丽江老君山地区的木材产品提供进行了分析.结果表明:2000年,老君山地区实际木材产品年供给服务总量为11.12×104m3.a-1,仅为年总蓄积增加量的3.2%;木材产品供给服务总价值为6669.27万元,其中以针叶林为主(90.41%).由于研究区东部人口及道路较密集,部分区域位于保护区外,且森林植被分布零散,供给服务物质量的空间分布呈"东高西低"格局.     

In vitro Anti-viral Activity of the Total Alkaloids from Tripterygium hypoglaucum against Herpes Simplex Virus Type 1

Herpes simplex virus type 1 (HSV-1) is a commonly occurring human pathogen worldwide. There is an urgent need to discover and develop new alternative agents for the management of HSV-1 infection. Tripterygium hypoglaucum (level) Hutch (Celastraceae) is a traditional Chinese medicine plant with many pharmacological activities such as anti-inflammation, anti-tumor and antifertility. The usual medicinal part is the roots which contain about a 1% yield of alkaloids. A crude total alkaloids extract was prepared ...     

Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine

The multiple transmembrane protein Niemann-Pick C1 like1 (NPC1L1) is essential for intestinal cholesterol absorption. Ezetimibe binds to NPC1L1 and is a clinically used cholesterol absorption inhibitor. Recent studies in cultured cells have shown that NPC1L1 mediates cholesterol uptake through vesicular endocytosis that can be blocked by ezetimibe. However, how NPC1L1 and ezetimibe work in the small intestine is unknown. In this study, we found that NPC1L1 distributed in enterocytes of villi and transit-amplifying cells of crypts. Acyl-CoA cholesterol acyltransferase 2 (ACAT2), another important protein for cholesterol absorption by providing cholesteryl esters to chylomicrons, was mainly presented in the apical cytoplasm of enterocytes. NPC1L1 and ACAT2 were highly expressed in jejunum and ileum. ACAT1 presented in the Paneth cells of crypts and mesenchymal cells of villi. In the absence of cholesterol, NPC1L1 was localized on the brush border of enterocytes. Dietary cholesterol induced the internalization of NPC1L1 to the subapical layer beneath the brush border and became partially colocalized with the endosome marker Rab11. Ezetimibe blocked the internalization of NPC1L1 and cholesterol and caused their retention in the plasma membrane. This study demonstrates that NPC1L1 mediates cholesterol entering enterocytes through vesicular endocytosis and that ezetimibe blocks this step in vivo.     

Association of N-Terminal Pro-Brain Natriuretic Peptide with Cognitive Function and Depression in Elderly People with Type 2 Diabetes

Background

Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS).

Methodology and Principal Findings

Cross-sectional analysis of 1066 men and women aged 60–75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, ‘g’. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower ‘g’ and higher depression scores (ß −0.09, 95% CI −0.13 to −0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of ‘g’) and ‘possible’ depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β −0.02, 95% CI −0.07 to 0.03, p>0.05 for ‘g’; β 0.03, 95% CI −0.02 to 0.07, p>0.05 for depression scores).

Conclusion

Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.     

两性霉素B脂质体、氟胞嘧啶和伊曲康唑联合治疗隐球菌性脑膜炎的临床回顾性研究

目的 观察两性霉素B脂质体、氟胞嘧啶和伊曲康唑联合治疗非AIDS、非器官移植隐球菌性脑膜炎患者的疗效和安全性,探讨非AIDS、非器官移植隐球菌性脑膜炎患者诱导治疗的新方案.方法 采用回顾性病例对照研究,18例非AIDS、非器官移植隐球菌性脑膜炎患者诱导期分别接受两性霉素B脂质体、氟胞嘧啶和伊曲康唑联合(研究组n=7)与两性霉素B、氟胞嘧啶和氟康唑联合治疗(对照组n=11).比较两组治疗方案在临床症状、体征变化、病死率、病原学转阴率、脑脊液改变等方面的差异及血常规、肝肾功能损害等不良反应发生情况.结果 治疗前研究组和对照组脑脊液新型隐球菌培养阳性分别为5例和8例(P =0.676),治疗1周后分别为5例和8例(P =0.676),治疗2周后分别为2例和4例(P =0.572),治疗3周后分别为0例和1例(P=0.611),治疗4周后,无死亡病例,两组脑脊液新型隐球菌培养均为阴性,脑脊液生化两组之间差异无统计学意义,对照组较研究组丙氨酸氨基转移酶(156.82±41.30 vs 97.00±22.02,P=0.003)、尿素氮(8.45±3.18 vs 5.54±1.28,P=0.020)升高更明显.结论 两性霉素B脂质体、氟胞嘧啶及伊曲康唑联合治疗非AIDS、非器官移植隐球菌性脑膜炎患者疗效确切,安全性较好,可以作为诱导期治疗的选择.     

气囊漏气实验预测严重上气道狭窄的临床意义

目的:观察气囊漏气实验预测拔管后发生严重上气道梗阻的临床价值.方法:共有156例气管插管患者入组,根据气囊漏气实验的情况分为两组,阴性组和阳性组,拔除气管插管后观察两组喘鸣发生与二次气管插管情况.结果:156例患者中气囊漏气实验阴性组125例,阳性组31例,拔除气管插管后,有13例患者需再次插管,其中1例患者无法插管,予经皮气管切开.结论:气囊漏气实验是一项简单方便筛查拔管后可能上气道梗阻的方法,如为阴性其因严重上气道梗阻再插管可能性很小,如为阳性则要注意可能发生拔管后上气道梗阻.