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Single-nucleotide polymorphisms and haplotypes of non-coding area in the CP gene are correlated with Parkinson's disease

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Neuroscience Bulletin 2015年第2期31卷 245-256页

作者： Na Zhao Jianqiu Xiao Zhiyong Zheng guoqiang fei Feng Zhang Lirong Jin Chunjiu Zhong Department of Neurology Zhongshan Hospital and Shanghai Medical College State Key Laboratory of Medical Neurobiology Institute of Brain Science Fudan University School of Life Sciences Fudan University Xinxiang College of Medicine

Our previous studies have demonstrated that ceruloplasmin （CP） dysmetabolism is correlated with Parkinson＇s disease （PD）. However, the causes of decreased serum CP levels in PD patients remain to be clarified. This study aimed to explore the potential association between genetic variants of the CP gene and PD. Clinical features, serum CP levels, and the CP gene （both promoter and coding regions） were analyzed in 60 PD patients and 50 controls. A luciferase reporter system was used to investigate the function of promoter single-nucleotide polymorphisms （SNPs）. High-density comparative genomic hybridization microarrays were also used to detect large-scale copy-number variations in CP and an additional 47 genes involved in PD and/or copper/ iron metabolism. The frequencies of eight SNPs （one intronic SNP and seven promoter SNPs of the CP gene） and their haplotypes were significantly different between PD patients, especially those with lowered serum CP levels, and controls. However, the luciferase reporter system revealed no significant effect of the risk haplotype on promoter activity of the CP gene. Neither these SNPs nor their haplotypes were correlated with the Hoehn and Yahr staging of PD. The results of this study suggest that common genetic variants of CP are associated with PD and further investigation is needed to explore their functions in PD.

关键词： Parkinson's disease ceruloplasmin single-nucleotide polymorphism haplotype copy-number variation

Long-Term Cognitive Improvement After Benfotiamine Administration in Patients with Alzheimer＇s Disease

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Neuroscience Bulletin 2016年第6期32卷 591-596页

作者： Xiaoli Pan Zhichun Chen guoqiang fei Shumei Pan Weiqi Bao Shuhua Ren Yihui Guan Chunjiu Zhong Department of Neurology Zhongshan Hospital State Key Laboratory of Medical Neurobiology Institutes of Brain Science and Collaborative Innovation Center for Brain Science Fudan University Shanghai 200032 China PET Center Huashan Hospital Fudan UniversityShanghai 200443 China

Abstract To date, we still lack disease-modifying thera- pies for Alzheimer＇s disease （AD）. Here, we report that long-term administration of benfotiamine improved the cognitive ability of patients with AD. Five patients with mild to moderate AD received oral benfotiamine （300 mg daily） over 18 months. All patients were examined by positron emission tomography with Pittsburgh compound B （PiB-PET） and exhibited positive imaging with β- amyloid deposition, and three received PiB-PET imaging at follow-up. The five patients exhibited cognitive improve- ment as assayed by the Mini-Mental Status Examination （MMSE） with an average increase of 3.2 points at month 18 of benfotiamine administration. The three patients who received follow-up PiB-PET had a 36.7% increase in the average standardized uptake value ratio in the brain com- pared with that in the first scan. Importantly, the MMSE scores of these three had an average increase of 3 points during the same period. Benfotiamine significantly improved the cognitive abilities of mild to moderate AD patients independently of brain amyloid accumulation. Ourstudy provides new insight to the development of disease- modifying therapy.

关键词： Alzheimer's disease. Therapy. Benfotiamine PiB-PET Amyloid deposition

Correlat ion of thiamine metabolite levels with cognitive function in the non-demented elderly

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Neuroscience Bulletin 2015年第6期31卷 676-684页

作者： Jingwen Lu Xiaoli Pan guoqiang fei Changpeng Wang Lei Zhao Shaoming Sang Huimin Liu Meng Liu Hui Wang Zhiliang Wang Chunjiu Zhong Department of Neurology Zhongshan Hospital and Shanghai Medical CollegeFudan University State Key Laboratory of Medical Neurobiology and Institutes of Brain Science Fudan University Regional Health Service Center of Xujiahui

Thiamine metabolism is critical for glucose metabolism and also vital for brain function, which is susceptible to decline in the elderly. This study aimed to investigate whether thiamine metabolites correlate with cognitive function in the non-demented elderly and their impact factors. Volunteers 〉60 years old were recruited and their blood thiamine metabolites and Mini-Mental State Examination （MMSE） scores were measured. The apolipoprotein E （APOE） genotype, routine blood parameters, liver and kidney function, and levels of fasting blood glucose and triglycerides were also measured. The results showed that the thiamine diphosphate （TDP） level weakly correlated with MMSE score in the non-demented elderly. Participants with high TDP levels performed better in Recall and Attention and Calculation than those with low TDP. TDP levels were associated with the APOE E2 allele, body mass index, hemoglobin level, fasting blood glucose, and triglycerides. Our results suggest that TDP, which is easily affected by many factors, impacts cognitive function in the elderly.

关键词： thiamine diphosphate cognitive function non-demented elderly

Brain iron deposition in Parkinson’s disease: Mechanism, consequence, and implication for clinical diagnostic and therapeutic strategies

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Brain iron deposition in Parkinson’s disease: Mechanism, co...

中国神经科学学会第十二届全国学术会议

作者： Lirong Jin Wenbin Wan Na Zhao guoqiang fei Chunjiu Zhong Department of Neurology Zhongshan Hospital Fudan University

Nigral iron deposition plays an important role in Parkinson’s disease（PD）. Phase values of magnetic susceptibility-weighted phase imaging（SWI） are reversely correlated with iron content and can be utilized to evaluate iron levels in different brain regions, such as substantia nigra, globus pallidus, and so forth. Phase values of different brain regions in 45 PD patients and 45 age-and gender-matched control subjects were measured using a 3 T magnetic resonance system. The results showed that average phase values in bilateral substantia nigra but not in other brain regions of PD patients were significantly lower than that in control subjects and correlated with serum ceruloplasmin level. PD patients with low serum ceruloplasmin levels exhibited decreased nigral phase values, suggesting increased nigral iron content, as compared to control subjects and patients with normal serum ceruloplasmin levels. The levels of serum mi R-133 b expression were significantly decreased in PD patients with low serum ceruloplasmin levels as compared with that in control subjects and PD patients with normal ceruloplasmin levels. Mi R-133 b expression was correlated with ceruloplasmin levels in PD patients. Iron loading significantly increased α-synuclein and reactive oxygen species（ROS） levels in primary dopaminergic neurons and SH-SY5 Y cells cultured in vitro but did not affect intracellular α-synuclein m RNA levels. Further, iron loading significantly downregulated Beclin-1 levels and decreased the ratio of microtubule-associated protein 1 light chain 3 isoforms（LC3 II/LC3 I）. Autophagy-related gene 5（Atg5） expression had not significant change after iron treatment. Rapamycin significantly reversed the enhancement of α-synuclein level due to iron loading and alleviated ROS generation. Vitamin E treatment significantly eliminated iron-induced ROS production but did not significantly affect the increase in α-synuclein levels. These results indicate that the inhibition of autophagy is c

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薄板焊接壳体成形后的校形技术

机械制造 2001年第3期39卷 35-37页

作者：费国强马连英西北核技术研究所西安710024

　　我单位承担的某重要生产线设备安装工程中有大量大型不锈钢箱壳，为3mm薄板焊接件，图1为其中的一个(1500mm×1500mm×1500mm)箱壳体。　　如何对薄板焊接壳体进行校型是壳体加工中的主要技术难题，也是国内机械、焊接行业的技术难... 详细信息

　　我单位承担的某重要生产线设备安装工程中有大量大型不锈钢箱壳，为3mm薄板焊接件，图1为其中的一个(1500mm×1500mm×1500mm)箱壳体。　　如何对薄板焊接壳体进行校型是壳体加工中的主要技术难题，也是国内机械、焊接行业的技术难题之一。　　为了保证工程的顺利进行，我们从以下几个方面对壳体的焊接变形问题进行了研究及实验，提出了解决方案，取得了满意的效果。[1]壳体变形的应力分析　　经过我们多次实验分析，认为变形主要是由焊接、圆弧折弯及热切割几个方面的加工所引起的应力变化及应力相互叠加而引起的应力集中及应力分布不均，从而引起壳体变形。以下是影响变形的几个方面的应力分析：　　(1)双面焊接双面成形技术为了保证焊接质量，焊接时采用双面焊接双面成形的氩弧气体保护的焊接先进技术。这种焊接方法熔化好，成形后可以满足焊接技术要求。焊接示意如图2。A所指的为焊接形成的三个热影响区。

关键词：薄板焊接壳体校形壳体加工焊接变形

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大型高精度锥体部件加工工艺

现代制造工程 2016年第2期 123-125,77页

作者：费国强马连英西北核技术研究所西安710024

基于某光学实验系统,从锥体部件提出的物理需求出发,根据锥体部件的结构特点和技术要求,重点分析了去应力热处理工艺、焊接工艺和重要切削参数(刀具进给量、切削速度等)对锥体加工质量的影响,最终确定了锥体部件合理的热处理方式和机械... 详细信息

基于某光学实验系统,从锥体部件提出的物理需求出发,根据锥体部件的结构特点和技术要求,重点分析了去应力热处理工艺、焊接工艺和重要切削参数(刀具进给量、切削速度等)对锥体加工质量的影响,最终确定了锥体部件合理的热处理方式和机械加工工艺方案。实际应用证明,该方案完全保证了锥体部件的加工精度和几何形位稳定性,满足光学实验的要求。

关键词：加工工艺锥体激光

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冷凝器薄壁小径冷凝管的成形技术研究

新技术新工艺 2000年第11期 24-25页

作者：费国强马连英西北核技术研究所 710024

根据冷凝器的技术要求和技术特性要求。

关键词：焊接加工工艺冷凝器反应堆成形技术

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自走式甘蓝收获机的设计与试验

农业工程学报 2015年第14期31卷 16-23页

作者：杜冬冬费国强王俊黄江军游鑫荣浙江大学生物系统工程与食品科学学院杭州310058 湖州思达机械制造有限公司湖州313023

针对中国甘蓝收获机械化水平低、缺乏相应甘蓝收获装备的现状,在统计分析主要甘蓝品种物理参数的基础上,设计了一种适合南方田间作业的自走式甘蓝联合收获机。该机型采用单行一次性收获方式,配置有专用动力底盘,收获台架主体包括引拔装... 详细信息

针对中国甘蓝收获机械化水平低、缺乏相应甘蓝收获装备的现状,在统计分析主要甘蓝品种物理参数的基础上,设计了一种适合南方田间作业的自走式甘蓝联合收获机。该机型采用单行一次性收获方式,配置有专用动力底盘,收获台架主体包括引拔装置、输送提升装置、切根装置、剥叶装置、收集装置等,动力由液压系统驱动,可一次完成甘蓝的拔取、输送、切根、剥叶、装箱等作业。田间试验表明,该收获机各工作部件工作稳定,表现出了良好的收获效果,收获速度为0.3 m/s时,拔取成功率为86.7%,输送成功率达93.3%,切根合格率为75.0%,剥叶合格率为81.7%,基本满足甘蓝的机械化收获要求。该研究为中国解决甘蓝的机械化收获提供了参考。

关键词：机械化农业生产设计甘蓝收获机

Recombinant vaccine containing an RBD-Fc fusion induced protection against SARS-CoV-2 in nonhuman primates and mice

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Cellular & Molecular Immunology 2021年第4期18卷 1070-1073页

作者： Shihui Sun Lei He Zhongpeng Zhao Hongjing Gu Xin Fang Tiecheng Wang Xiaolan Yang Shaolong Chen Yongqiang Deng Jiangfan Li Jian Zhao Liang Li Xinwang Li Peng He Ge Li Hao Li Yuee Zhao Chunrun Gao Xiaoling Lang Xin Wang guoqiang fei Yan Li Shusheng Geng Yuwei Gao Wenjin Wei Zhongyu Hu Gencheng Han Yansong Sun State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijingChina National Institutes for Food and Drug Control BeijingChina Institute of Military Veterinary Academic of Military Medical SciencesChangchunChina JOINN Biologies BeijingChina ZHONGYIANKE Biotech Co. LTDTianjinChina Beijing Institute of Basic Medical Sciences BeijingChina

The novel coronavirus SARS-CoV-2 has infected more than 104 million individuals and resulted in more than 2.2 million deaths worldwide as of February 7,2021(https://***).The COVID-19 pandemic highlights the need for s... 详细信息

关键词： vaccine infected vaccines