Studies on NMR-based Metabolomics and Its Applications on Metabolic Syndrome

代谢组学方法是上世纪90年代中期发展起来的一门新学科，它借助高通量、高灵敏度与高精确度的现代分析技术，分析细胞、组织和生物体液中内源性代谢物的整体组成，并通过代谢物复杂的、动态的变化，辨识和解析被研究对象的生理病理状态。与其它化学分析技术相比，NMR技术具有预处理过程简单、测试手段丰富、无损伤性、无偏向性等优点，因此被广泛地应用于代谢组学研究。 本文将NMR代谢组学方法应用于2型糖尿病动物模型的研究，还综合考察了饮食因素对糖尿病发生发展过程的影响，分析了长期素食者以及高脂饲料喂养的肥胖大鼠模型的体液样品。本论文主要内容归纳如下： 一、简要介绍了系统生物学和代谢组学的基本概念，引出了基于NM...The quantitative measurement of the dynamic multi-parametric metabolic response of a living system to pathophysiological stimuli or genetic modification is termed “metabolomics”. The 1H NMR spectroscopy has been shown to be one of the most important analytical techniques used in metabolomics, as it can detect many endogenous metabolites rapidly and reproducibly without tendentiousness or separatio...学位：理学博士院系专业：物理与机电工程学院物理学系_无线电物理学号：1982007015391

Research on Chaotic Modulation-Based Cooperative Communication System

混沌调制技术DCSK（DifferentialChaosShiftKeying，差分混沌键控）作为一种集调制与扩频于一身的通信技术，在多径衰落信道下表现出良好的鲁棒性和优异的BEP（BitErrorprobability，比特错误概率）性能，实现结构简单。协作分集技术作为一种虚拟的MIMO（Multiple-Input-Multiple-Output）系统，合作伙伴共享彼此的天线，可以使单天线的终端实现空域分集来提高系统性能，能有效的对抗信道衰落，适合低成本，低功耗传输系统，获得了广泛的关注和研究。 本文在DCSK调制抗多径性能优越的基础上引入了协作分集的思想，提出了基于DCSK调制的协作系...Chaotic modulation technique Differential Chaos Shift Keying (DCSK) is a scheme joining chaotic modulation with spread-spectrum property, which is robust in multipath fading channels and is simple in implementation. Cooperative diversity, a virtual Multiple-Input-Multiple-Output (MIMO) technique, users sharing each other’s single antenna, so that the spatial diversity can be realized in single-ant...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332008115330

Metabolic Response of Basal Ganglia in Copper-laden Rat to Gandouling Based on ~1H NMR Spectroscopy

采用核磁共振氢谱(1H NMR)技术与多元统计分析相结合的方法,对肝豆灵对大鼠基底节铜损伤的调节机制进行研究。24只雄性Wistar大鼠随机分为正常组、模型组和肝豆灵组,每组8只,以铜负荷法造模。从造模第7周开始,肝豆灵组大鼠以肝豆灵灌胃。数据分析显示:与正常组比较,模型组的基底节细胞凋亡指数显著增高(p<0.01);基底节组织中的谷氨酰胺、尿苷、苏氨酸含量升高(p<0.05),甘露醇、腺苷、N-乙酰天冬氨酸、谷氨酸、N-乙酰谷氨酸(NAG)、天冬酰胺、乙酸、天冬氨酸、肌醇、三磷酸腺苷(ATP)含量降低(p<0.05);与模型组相比,肝豆灵组的基底节细胞凋亡指数显著降低(p<0.01);基底节组织中的谷氨酰胺、尿苷、乙酸、天冬氨酸含量降低(p<0.05),甘露醇、腺苷、苏氨酸、N-乙酰天冬氨酸、谷氨酸、N-乙酰谷氨酸、天冬酰胺、肌醇、ATP含量升高(p<0.05)。研究结果表明,肝豆灵可影响铜负荷大鼠基底节的代谢,对铜损伤具有一定的修复作用,其机制可能是通过调节氨的解毒和兴奋性氨基酸类神经递质的代谢,干预能量代谢,恢复神经元和神经胶质细胞功能。1H NMR spectroscopy combined with multivariate statistical method was introduced in this paper to explore the regulation effect of Gandouling on basal ganglia injury in copper-laden rats. 24 male Wistar rats were randomly divided into control group,model group and Gandouling group,with8 rats in each group. The rat model was established by copper-laden method. From the 7th week of modeling,Gandouling group was given Gandouling formula via gavage. Compared with the control group,the index of apoptosis cells in basal ganglia of model group increased significantly( p < 0. 01),and glutamine,uridine and threonine in basal ganglia were increased( p < 0. 05) while mannitol,adenosine,N-acetylaspartate, glutamate, N-acetylglutamine asparagine, acetate, aspartate, myoinositol and ATP were decreased( p < 0. 05). Compared with the model group,the index of apoptosis cells in basal ganglia of Gandouling group was significantly decreased( p < 0. 01),and glutamine,uridine,acetate and aspartate were reduced( p < 0. 05) while mannitol, adenosine, threonine,N-acetylaspartate,glutamate,N-acetylglutamine,asparagine,myo-inositol and ATP were elevated( p < 0. 05). The results showed that Gandouling could influence the metabolism of basal ganglia in copper-laden rats,which has a certain therapeutic effect on damage caused by copper. The mechanism may be restoration of the functions of neurons and glial cells,through adjusting the detoxification of ammonia and metabolism of excitatory amino acid neurotransmitter and interfering the energy metab-olism.国家自然科学基金(81202691,81201143,81371639);; 福建省自然科学基金(2015Y0032

The metabolic profilings study of serum and spinal cord from acute spinal cord injury rats ^1H NMR spectroscopy

目的：采用-1H NMR核磁共振代谢组学的方法研究急性脊髓损伤模型大鼠的代谢组学特征及生物标志物,探讨核磁共振代谢组学应用于脊髓损伤研究的可行性。方法：取8周龄清洁级雄性SD大鼠20只,体重（200±10）g,按照随机数字法分为假手术组和模型组,每组10只,模型组采用改良的Allens法制作急性脊髓不完全损伤模型,假手术组不损伤脊髓,术后第1、5、7天采用BBB运动功能评分法进行行为学观察,术后第7天收集脊髓组织作病理学观察,核磁共振代谢组学对两组大鼠血清和脊髓样本进行代谢组学分析。结果：BBB评分显示假手术组术后后肢运动无明显改变,各时间点差异无统计学意义,模型组大鼠术后双下肢呈迟缓性瘫痪,BBB运动评分较低,各时间点差异存在统计学意义,两组运动功能评分在各时间点的差异均有统计学意义;病理切片显示假手术脊髓结构正常,神经分布均匀,模型组脊髓组织结构紊乱,神经元数目减少,存在炎性细胞浸润和空腔坏死组织。代谢组学分析表明,血清中极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）、谷氨酰胺（glutamine）、柠檬酸（citrate）、二甲基甘氨酸（DMG）等物质和脊髓中谷胱甘肽（glutathione）、3-羟基丁酸（3-OH-butyrate）、N-乙酰天冬氨酸（NAA）、磷酸胆碱（GPC）、谷氨酸（glutamate）、抗坏血酸（ascorbate）等物质浓度有明显变化（P〈0.05）。结论 ：通过对假手术组和模型组大鼠血清和脊髓样本进行代谢组学检测和分析得到了两组样本的差异性代谢物质,有助于解释急性脊髓损伤后血清和脊髓组织中的特异性小分子物质的变化规律,为后期针对性地研究这些代谢标记物在急性脊髓损伤中的作用提供研究基础。Objective： To establish the rat model of acute spinal cord injury,followed by aprimary study on this model with 1H NMR based on metabonomics and to explore the metabonomics and biomarkers of spinal cord injury rat.Methods： Twenty eight-week-old adult male SD rats of clean grade,with body weight of （200±10） g,were divided into sham operation group and model group in accordance with the law of random numbers,and every group had 10 rats. The rats of sham operation group were operated without damaging the spinal cord,and rats of model group were made an animal model of spinal cord incomplete injury according to the modified Allen＇s method. According to BBB score to observate the motor function of rats on the 1th,5th,and 7th days after surgery. Postoperative spinal cord tissue was collected in order to pathologic observation at the 7th day,and the metabolic profilings of serum and spinal cord from spinal cord injury rats were studied by 1H NMR spectroscopy.Results： The hindlimb motion of rats did not obviously change in sham operation group,there was no significant difference at each time point;and rats of model group occurred flaccid paralysis of both lower extremities,there was a significant difference at each time; there was significant differences between two groups at each time. Pathological results showed the spinal cord structure was normal with uniform innervation in shame group,while in model group,the spinal cord structure was mussy,and the neurons were decreased,with inflammatory cells and necrotic tissue. Analysis of metabonomics showed that concentration of very low density fat protein （VLDL）,low density fat protein （LDL）,glutamine,citric acid,dimethylglycine （DMG） in the serum and glutathione,3-OH-butyrate,N-Acetyl-L-aspartic acid （NAA）,glycerophosphocholine （GPC）,glutamic acid,and ascorbate in spinal cord had significant changes（P〈0.05）.Conclusion： There are significant differences in metabolic profile from serum and spinal cord sample between model group and sha浙江省自然基金（编号：LY15H270003）;浙江省中医药科技计划项目（编号：2015ZZ017

气体/高黏液体两相间歇流动时液相含率的变化特性研究

为了准确地了解两相流动过程中相含率的变化情况从而实现监测长距离管道混输中的流态转化、流量波动以及压力脉动等,本研究基于实验数据研究了垂直管、水平管、倾斜管中气体/高黏液体两相间歇流动时液相含率的变化特性。研究结果揭示了水平、垂直和倾斜管路中液相含率的影响因素(包括黏度、倾斜角度、混合雷诺数和弗汝德数等)和变化趋势。同时提出了液相含率预测模型。误差分析表明,模型预测结果与实验测试数据较为一致。该研究对油气混输中的安全监控和保障具有重要意义

Study on the central response mechanism in gastric ulcer rats treated by electroacupuncture using ~1H NMR metabolomics techniques

目的:采用核磁共振氢谱技术(~1H; NMR)研究电针胃经穴治疗应激性胃溃疡大鼠大脑皮质、下丘脑、延髓代谢物谱的表达。方法:40只Wistar大鼠随机分为正常组、模型组、胃经组和胆经; 组。利用束缚冷应激法制备应激性胃溃疡模型大鼠,造模成功后用电针分别刺激胃经组和胆经组相关穴位。收集大鼠大脑皮质、下丘脑、延髓,获取一维~1H; NMR谱,并利用模式识别方法分析各组间的代谢轮廓差异。结果:模型组与正常组、胃经组、胆经组大鼠大脑皮质、下丘脑和延髓代谢物谱均有明显区分,其中正; 常组与模型组分离最明显,胃经组最接近正常组,说明其代谢物谱趋向正常。与模型组比较,胃经组大鼠大脑皮质乳酸、萘乙酸、甘露醇等表达上升(P<0.05; ),而肌酸、腺苷、肌苷等表达下降(P<0.05),下丘脑乳酸、肌醇、谷氨酸酯等表达上升(P<0.05),gamma-氨基丁酸等表达下降(P<0.; 05),延髓乳酸、谷氨酸脂、肌醇、丙氨酸等表达上升(P<0.05),而萘乙酸、肌酸等表达下降(P<0.05)。结论:电针胃经穴可调节胃溃疡大鼠大; 脑皮质、下丘脑、延髓的代谢产物表达,大脑皮质、下丘脑和延髓是电针胃经穴治疗胃溃疡的中枢响应位点。Objective: To study the metabolic profiling of the cerebral cortex,; hypothalamus and medulla oblongata from irritable gastric ulcer rats; treated with electroacupuncture on acupoints of the stomach meridian; with 1H nuclear magnetic resonance (~1H NMR) spectroscopy. Methods:; Forty SD rats are randomly divided into the control group, the model; group, the stomach meridian group and the gallbladder meridian group.; The irritable gastric ulcer rat model was established by water-immersion; and restraint stress method. After modeling, the rats from the stomach; meridian group and the gallbladder meridian group were treated with; electroacupuncture on the stomach meridian and gallbladder meridian; respectively. ~1H NMR spectroscopy was applied to detect the metabolic; profiling of the cerebral cortex, hypothalamus and medulla oblongata,; then analyzed metabolic contour differences among the groups using; pattern recognition method. Results: Obvious distinctions were found; between the metabolites spectrum of the cerebral cortex, hypothalamus; and medulla oblongata from the model group, the normal group, the; stomach meridian group and the gallbladder meridian group. More; significant differences were found between the normal group and the; model group, while the metabolites spectrum of the stomach meridian; group was more distinctly close to that in the normal group, indicating; that metabolites spectrum of the stomach meridian group was likely to; normal. Compared with the model group, the concentration of lactic acid,; acetic acid, mannitol increased while creatine, adenosine and inosine; decreased in cerebral cortex of the stomach meridian group (P<0.05), the; concentration of lactic acid, glutamic acid, inositol and alanine; increased while gamma aminobutyric acid decreased in hypothalamus of the; stomach meridian group (P<0.05), the concentration of lactate,; glutamate, myo-lnositol, alanine increased (P<0.05) and naphthylacetic; acid and creatine decreased in medulla oblongata of the stomach meridian; group (P<0.05). Conclusion: Electroacupuncture on acupoints of the; stomach meridian could regulate specific metabolites in the cerebral; cortex, hypothalamus and medulla oblongata, indicating that the cerebral; cortex, hypothalamus and medulla oblongata as the central response site; in the treatment of gastric ulcer by electroacupuncture on acupoints of; the stomach meridian.国家自然科学基金项目; 广东省自然科学基金项目; 深圳市科技计划项

管道式油气水高效分离技术

目前我国原油开采面临陆上油田采出液含水率高,以及海上平台空间局促、指标严苛等实际问题,因此对传统油气水分离技术提出了巨大挑战。中国科学院力学研究所研发的新型管道式油气水高效分离技术,主要包括T型管分离技术、柱型旋流管分离技术、以及导流片型分离技术等,不仅取得了创新性的研究成果,还进一步推动了技术成果转化,在工业现场取得了良好的应用效果,符合我国未来科学技术的发展方向

高含气井下气液混合输送技术研究

为了确保油田开采过程中电潜泵在高含气油井的正常运行,结合气液分离技术和引射技术,该文运用CFD模拟软件FLUENT研究了一种高含气井下气液混合输送技术.该技术通过建立气体及液体分采通道,利用引射原理将增压后的高压动力液携带富气流举升至地面,以实现利用生产井自身流体实现自我举升.研究表明:经过对比分析发现,对于不同入口气体含量的工况,由于射流泵引射装置的引射比影响,入口气体体积含量40%是一拐点,当入口气体含量超过40%时,引管内的气相含量以及流速基本达到一定值;对于不同入口流量,随着流量的增加,气液分离效果亦逐渐变佳,取气管内的气相含量基本稳定在一定的范围,而取气管内的流速则随着流量的增加而增大.该研究结果对提高电潜泵在油田开采高含气油井中的应用范围具有重要意义

Metabolomics Data Filtering Method Based on PCA

代谢组学数据不可避免地受到各种刺激因素的作用,如何降低干扰因素的影响是代谢组学数据预处理的一个重要任务。详细分析了代谢组学数据方差的构成及其在特征空间中的分布特点,并在此基础上提出一种滤除未知干扰因素的新方法,提高感兴趣因素的显著性。文中采用真实的代谢组学数据验证新滤波算法的有效性,并与正交信号校正(OrTHOgOnAl SIgnAlCOrrECTIOn,OSC)方法进行比较。实验结果表明,新滤波方法可以在抑制未知干扰因素影响的同时,较好地保留感兴趣因素信息以及生物体内在的个体差异信息,降低模型发生过拟合的危险,使后续的统计分析结果更可靠。The metabolomics dataset is disturbed by various stimuli inevitably.The main task for metabolo mics data preprocessing is to reduce the impacts of the disturbing factors.In present work,the formation of data variance and their distribution in feature space are analyzed.Furthermore,a new method to filtrate unknown disturb ing factors is proposed and the significance of interesting factors is improved.The efficiency of the new filtering al gorithm is estimated by real metabolomics dataset.Comparing with orthogonal signal correction(OSC) method,the experiment shows that the new method is superior in reducing unknown disturbing factors and retaining useful in formation and intrinsic individual differences in organisms.In addition,it can also prevent the overfitting of model and make the subsequent statistical analysis more reliable.国家自然科学基金(81171331;11175149);中央高校基本科研业务费专项资金(2011121046

井下气液混合输送技术研究

为了确保油田开采过程中电潜泵在高含气油井的正常运行,结合气液分离技术和引射技术,运用CFD模拟软件FLUENT研究了一种高含气井下气液混合输送技术。该技术通过建立气体及液体分采通道,利用引射原理将增压后的高压动力液携带富气流举升至地面,以实现利用生产井自身流体实现自我举升。研究表明:经过对比分析发现,对于不同入口气体含量的工况,由于射流泵引射器的引射比影响,入口气体体积含量40%是一拐点,当入口气体含量超过40%时,引管内的气相含量以及流速基本达到一定值;对于不同入口流量,随着流量的增加,气液分离效果亦逐渐变佳,取管内的气相含量基本稳定在一定的范围,而取气管内的流速则随着流量的增加而增大。该研究结果对提高电潜泵在油田开采高含气油井中的应用范围具有重要意义