原发性骨髓增生异常综合征患者NPM1基因突变的研究

目的 探讨原发性骨髓增生异常综合征(MDS)患者NPM1基因突变情况及其与MDS患者临床特征的关系.方法 对232例原发性MDS患者采用基因组DNA聚合酶链反应(PCR)扩增NPM1基因第12外显子,直接测序检测突变状态,克隆后测序鉴定突变类型.比较NPM1突变患者与野生型患者的临床及实验室特征.结果 232例患者中NPM1突变9例(3.9%),均为A型突变.NPM1突变患者中性粒细胞绝对值(ANC)较低[突变型和野生型患者分别为0.60(0.12～2.91)×109/L和1.02(0～10.23)×109/L,P=0.046],骨髓原始细胞比例较高[突变型和野生型患者分别为0.050(0～0.090)和0.025(0～0.190),P=0.035],干/祖细胞培养后红系爆式集落(BFU-E)数量减低[突变型和野生型患者105个骨髓单个核细胞中集落数分别为0(0～0)和6(0～40),P=0.038],血清维生素(Vit)B12水平较高[突变型和野生型患者分别为936.40(373.80～2400.00)pmol/L和557.85(17.00～3032.10)pmol/L,P=0.045].NPM1突变患者以正常核型为主.结论 NPM1基因突变的MDS患者具有一些独特的临床和实验室特征,此为进一步研究NPM1基因突变与原发性MDS发生及转变为白血病的关系提供了重要线索.     

Pediatric and adult H3 K27M-mutant diffuse midline glioma treated with the selective DRD2 antagonist ONC201

Journal of Neuro-Oncology - Smoking is agreed to be a major health risk factor, but it is debated whether it has an influence on perioperative adverse events (AEs) in elective cranial tumor...     

Mechanisms by which fibroblast growth factor 20 improves motor performance in a mouse model of Parkinson's disease

Genome-wide studies have reported that Parkinson's disease is associated with abnormal expression of various growth factors. In this study, male C57 BL/6 mice aged 10 weeks were used to establish Parkinson's disease models using an intraperitoneal injection of 60 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 28 days later, 10 or 100 ng fibroblast growth factor 20 was injected intracerebroventricularly. The electrophysiological changes in the mouse hippocampus were recorded using a full-cell patch clamp. Expression of Kv4.2 in the substantia nigra was analyzed using a western blot assay. Serum malondialdehyde levels were analyzed by enzyme-linked immunosorbent assay. The motor coordination of mice was evaluated using the rotarod test. The results showed that fibroblast growth factor 20 decreased A-type potassium current in neurons of the substantia nigra, increased long-term potentiation amplitude in the hippocampus, and downregulated Kv4.2 expression. A high dose of fibroblast growth factor 20 reduced serum malondialdehyde levels and enhanced the motor coordination of mice. These findings confirm that fibroblast growth factor 20 has a therapeutic effect on the toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and its mechanism of action is associated with the inhibition of A-type K+ currents and Kv4.2 expression. All animal procedures were approved by the Animal Care and Use Committee of Qilu Hospital of Shandong University, China in 2017(approval No. KYLL-2017-0012).     

NAXE基因突变相关渐进性早发性脑病的临床及遗传学特点

渐进性早发性脑病是由于NAXE基因变异导致的致死性脑病。本研究报道1例渐进性早发性脑病的临床和遗传性特征。患儿,男,4岁,因行走不稳,肢体无力2年就诊。患儿及其兄（已去世）均在2岁左右起病,均表现为斜视、共济失调、肌张力降低、发育落后,且感染后多次出现呼吸衰竭。患儿NAXE基因存在新发复合杂合突变：c.255（外显子2） A > T来自患儿母亲,c.361（外显子3） G > A来自患儿父亲。NAXE基因编码NADHX和NADPHX细胞代谢产物修复所必需的差向异构酶。本病存在线粒体NAD （P） HX修复系统的缺陷,进展快,极易在感染后迅速出现呼吸衰竭。     

New technologies reduce greenhouse gas emissions from nitrogenous fertilizer in China

Synthetic nitrogen (N) fertilizer has played a key role in enhancing food production and keeping half of the world’s population adequately fed. However, decades of N fertilizer overuse in many parts of the world have contributed to soil, water, and air pollution; reducing excessive N losses and emissions is a central environmental challenge in the 21st century. China’s participation is essential to global efforts in reducing N-related greenhouse gas (GHG) emissions because China is the largest producer and consumer of fertilizer N. To evaluate the impact of China’s use of N fertilizer, we quantify the carbon footprint of China’s N fertilizer production and consumption chain using life cycle analysis. For every ton of N fertilizer manufactured and used, 13.5 tons of CO₂-equivalent (eq) (t CO₂-eq) is emitted, compared with 9.7 t CO₂-eq in Europe. Emissions in China tripled from 1980 [131 terrogram (Tg) of CO₂-eq (Tg CO₂-eq)] to 2010 (452 Tg CO₂-eq). N fertilizer-related emissions constitute about 7% of GHG emissions from the entire Chinese economy and exceed soil carbon gain resulting from N fertilizer use by several-fold. We identified potential emission reductions by comparing prevailing technologies and management practices in China with more advanced options worldwide. Mitigation opportunities include improving methane recovery during coal mining, enhancing energy efficiency in fertilizer manufacture, and minimizing N overuse in field-level crop production. We find that use of advanced technologies could cut N fertilizer-related emissions by 20–63%, amounting to 102–357 Tg CO₂-eq annually. Such reduction would decrease China’s total GHG emissions by 2–6%, which is significant on a global scale.     

IKKi在肝硬化相关肝细胞癌中的表达

目的:研究核因子κB(nuclear factorκB,NF-κB)信号通路中IKKi蛋白在肝硬化相关肝细胞癌(hepatocellular carcinoma,HCC)中的表达水平及其临床病理意义.方法:采用免疫组织化学方法检测66例肝硬化相关HCC IKKi蛋白表达,同一病例癌旁肝硬化组织作为对照,收集患者临床病理资料,分析HCC IKKi蛋白表达水平以及与临床病理参数的关系.结果:(1)IKKi在HCC与癌旁肝硬化组织表达水平有明显差异性(P=0.016),IKKi在癌周肝硬化组织表达强度明显强于HCC;(2)IKKi在HCC中的表达水平与肿瘤分化程度呈正相关,即IKKi表达水平越低,HCC分化程度越低(P=0.019,r=0.278);与肿瘤直径呈负相关,即IKKi表达水平越低,肿瘤体积越大(P=0.011,r=-0.311);(3)IKKi在HCC中的表达水平与年龄(P=0.034,r=0.261)、Child-Pugh分级(P=0.046,r=0.246)、乙型肝炎家族史(P=0.017,r=0.292)呈正相关.结论:IKKi在HCC表达下调提示IKKi在乙型肝炎病毒感染-病毒性肝炎-肝硬化-HCC的发生中可能起抑制肿瘤形成的作用.     

化脓性角膜炎病原学分析

目的分析化脓性角膜炎病原学的变迁特征。方法回顾性分析1989年至2006年间在北京同仁医院眼科拟诊为真菌性、细菌性及棘阿米巴性角膜炎患者11302例微生物实验室检查资料。结果培养鉴定出病原微生物2896份,其中真菌1602份、细菌1161份、棘阿米巴原虫133份,总阳性率为25.62%.真菌培养阳性率为33.83%,夏秋季为高发季节,常见的致病真菌为镰刀菌属(62.23%)和曲霉菌素(14.61%);对2000年至2006年间培养的895株真菌进行体外药敏实验,结果显示那他霉素、特比萘酚、伊曲康唑和氟康唑的药物敏感性分别为88.83%、55·75%、28·60%和11·84%;镰刀菌属对那他霉素最敏感,曲霉菌素对特比萘酚敏感性高。常见细菌培养阳性率为18.78%(1126/5995),以G 球菌和G-杆菌为主,占检出细菌的85·52%;主要致病菌属为铜绿假单胞菌,其所占比例近年来有所下降,而金黄色葡萄球菌、凝固酶阴性葡萄球菌和微球菌属所占比例有明显增高;对2000年至2006年间培养的430株细菌行体外药敏实验,结果显示左氧氟沙星、氧氟沙星、妥布霉素和环丙沙星药物敏感性分别为82.09%、75.81%、66.98%和62.33%;假单胞菌属对4种抗菌药物敏感性无显著性差异。棘阿米巴检查(培养 刮片)阳性率为23.25%(133/572),其检出例数逐年升高。放线菌、非结核分枝杆菌和厌氧菌为少见病原体,非结核分枝杆菌多分离自屈光手术后的角膜感染。结论真菌和细菌为化脓性角膜炎的主要病原体,棘阿米巴角膜炎病例数逐年升高,放线菌及非结核分枝杆菌引起的角膜感染应引起重视。     

1-deoxypaclitaxel and abeo-taxoids from the seeds of Taxus mairei

A new paclitaxel derivative and two new 2(3-->20)-abeo-taxoids were isolated from a methanol extract of the seeds of Taxus mairei, and their structures were established as 1-deoxypaclitaxel (1), 7beta,10beta-diacetoxy-2alpha,5alpha,13alpha-trihydroxy-2(3-->20)-abeo-taxa-4(20),11-dien-9-one (2), and 2alpha,13alpha-diacetoxy-10beta-hydroxy-2(3-->20)-abeo-taxa-4(20),6,11-triene-5,9-dione (3) on the basis of spectroscopic data analysis. Taxane 1 is the first example of a paclitaxel analogue with a C-1beta hydrogen substituent. Taxane 3 is an 2(3-->20)-abeo-taxane with a rare C-5 ketone and C-6 double bond.     

Isolation and characterization of cancer stem like cells in human glioblastoma cell lines

To identify and compare the features of stem like cells in human glioblastoma cell lines U251, U87MG, A172 with primary cultured glioblastoma stem cells, the ratio of CD133⁺ cells, the ability of tumor sphere formation, and self-renewing capacity of U251, U87MG, A172 cells in serum free medium plus EGF, bFGF and B27 supplement were detected. The results suggested that there might be more cancer stem like cells in U251 cells compared with others. CD133⁺ cells enriched in SP cells and in U251 cells cultured with the serum free medium. They expressed the neural stem cell markers CD133 and Nestin, but lacked of neuronal and astrocyte marker MAP2, β-III tubulin and GFAP. They could apparently generate both neurons and glial cells after serum retrieved in vitro. Gli1, Bmi1, Notch2 and PTEN were also found expressed highly in them. Moreover, CD133⁺ cells were more resistant to hypoxia, irradiations and some chemotherapeutics than CD133⁻cells. So we suggested that glioblastoma stem like cells were existed in CD133⁺ cells in U251 cell line with characteristics of self-renew and generation of an unlimited progeny of non-tumorigenic cells. Molecular and functional characterization of such a tumorigenic population may be exploited in the development of novel cancer therapeutic drugs.     

臭氧对高脂喂养诱导新西兰兔非酒精性脂肪性肝炎的防治作用

目的:研究臭氧对非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)炎症水平的防治作用及安全性评估.方法:24只♂新西兰兔分为3组:模型组10只,臭氧组4只,普拉固加阿司匹林组10只.实验时间12wk,每周称量1次体质量.超声检测第2周、第5周、第8周及第12周的颈总动脉和腹主动脉内膜-中层厚度(intimal-medial thickness,IMT).病理观察颈总动脉、主动脉、肝、心及肾脏病理变化.检测血清生化、血脂、肌酐和尿酸水平.ELISA测定血清8-OHdG、TRX、4-HNE、8-iso-PGF2a、LEP、ADPN、FFA、ET、IL-6、TNF-α、MDA、MCP-1、hs-CRP、NOS、NO、GSH、reduced glutathione、GSH-Px的含量.结果:实验动物超声检测内膜增厚,提示模型成功,臭氧组体质量明显轻于其他组.各组主动脉内膜下脂质沉积斑块大小有统计学意义(P=0.037,P<0.05),而脂质沉积厚度各组无统计学意义.臭氧组肝脏气球样变性程度明显轻于模型组和普拉固加阿司匹林组(P=0.04,P<0.05),但肝脂肪变性程度3组间无统计学意义.病理心脏脂质沉积及肾脏肾小管上皮细胞空泡变性程度均无统计学意义.各组血清生化指标均无统计学差异(P>0.05).氧化应激、脂质过氧化、炎症水平相关等18个血清细胞因子检测,与模型组相比,臭氧组除了ET、8-OHdG、GSH、GSH-Px及FFA无统计学意义,其余13个因子均有统计学意义(P<0.05),其中LEP、ADPN、IL-6、TNF-α、MCP-1、hs-CRP、NOS、TRX、MDA、4-HNE、8-iso-PGF2a水平增高,NO、reduced glutathione水平降低,但普拉固组加阿司匹林组上述所有因子与模型组间均无统计学意义.结论:臭氧减轻非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)炎症的同时可改善颈总动脉、腹主动脉粥样硬化斑块面积的趋势,未发现臭氧作为抗氧剂对肝脏、肾脏和心脏造成的病理可见损伤.臭氧全面提高了血清中众多涉及氧化应激、脂质过氧化、炎症细胞因子水平,其作用机制值得进一步探讨.关键词:非酒精性脂肪性肝病;非酒精性脂肪性肝炎;动脉粥样硬化;臭氧