Y型聚乙二醇干扰素琢-2b注射液治疗HCV基因2/3型慢性丙型肝炎患者疗效和安全性的多中心随机对照试验研究

目的以标准剂量的聚乙二醇干扰素(Peg IFN)α-2a联合利巴韦林作为阳性对照,评价新型试验药物Y型Peg IFNα-2b注射液联合利巴韦林治疗2型/3型慢性丙型肝炎(CHC)患者的疗效和安全性。方法采用多中心、随机开放、阳性药对照的Ⅲ期临床试验,筛选符合要求的2型/3型CHC患者,按照2:1的比例随机分配到Y型Peg IFNα-2b组和Peg IFNα-2a组,同时口服利巴韦林,疗程24 w,停药随访24 w。采用Abbott Real Time HCV Genotype II检测HCV基因型,采用Cobas Taq Man实时定量PCR法检测血清HCV RNA水平。详细记录不良事件。主要疗效指标为持续病毒学应答(SVR),并进行非劣效检验。结果本试验实际入组2型/3型CHC患者255例,实际治疗241例。全分析集(FAS)数据显示,158例试验组和83例对照组患者SVR分别为85.4%(95%CI 79.94%~90.94%)和79.5%(95%CI 70.84%~88.20%,P=0.2402);对符合方案分析集(PPS)人群分析显示,试验组和对照组患者SVR分别为87.9%(95%CI 82.45%~93.27%)和85.9%(95%CI 77.82%~94.01%,P=0.7060),率差的95%可置信区间均符合非劣效标准;对PPS人群分析显示,85.8%受试者获得了早期病毒学应答(RVR),RVR的阳性预测值为90.1%;试验组和对照组不良事件发生率相似,分别为95.6%和95.2%,严重不良事件发生率分别为3.8%和3.6%。结论应用Peg IFNα联合利巴韦林治疗2型/3型CHC患者,新型试验药物Y型Peg IFNα-2b具有与对照药物Peg IFNα-2a相似的疗效和安全性。国家科技部“十二五”重大专项(编号:2012ZX10002-003)；“重大新药创制”十二五科技重大专项(编号:2012ZX09303019)

南海中深层动力格局与演变机制研究进展

南海是连接印度洋-太平洋的最大边缘海,在季风、海峡水交换以及复杂地形影响下,南海环流呈现出独特的三层结构以及远强于大洋的混合特征.理论与观测表明,南海内潮、内孤立波以及强风等过程是强混合的动力来源.在南海强混合作用下,南海发育了活跃的中深层动力系统,一方面促进了南海与大洋之间的水体交换,另一方面调控上层风生环流,使得南海环流显著区别于其他热带与副热带海盆.南海活跃的中深层环流所具有的物质搬运能力又显著影响着南海的地质沉积、生物地球化学循环等过程.中国对深海研究持续投入,在南海中深层环流动力学研究方面取得了显著的成果,文章就该方面进行总结,并对南海深海环流未来研究设想进行初步探讨

质子型离子液体功能调控及NH3分离研究

离子液体由于极低的蒸汽压、良好的热稳定性、结构可设计及较高的气体溶解度等优点在气体分离净化领域备受关注。目前已有少量关于离子液体吸收NH3基础研究的报道，但存在物理吸收NH3的离子液体低分压下吸收能力差、化学吸收NH3的金属离子液体再生困难、功能化离子液体合成工艺较复杂且难以实现规模化制备等问题，因此设计低粘度、高NH3吸收量、可再生的新型离子液体是离子液体NH3分离领域的研究难点。基于以上背景，本论文开展了质子型离子液体和双活性位点离子液体的设计合成、离子液体结构与NH3吸收性能、质子型离子液体吸收NH3机理及NH3吸收过程物性变化的系统研究；基于复合质子型离子液体吸收剂，课题组开发了一套低分压NH3尾气净化回收工艺，为NH3尾气净化回收新技术的开发提供重要支撑。本论文的主要研究内容及成果如下：（1）新型咪唑类质子型离子液体设计合成及吸收NH3构效关系研究。合成了一系列咪唑类质子型离子液体，系统研究了阳离子侧链长度、2-H、阴离子种类以及温度压力对NH3吸收性能的影响，考察了质子型离子液体的再生性能。研究发现质子型离子液体的NH3吸收性能高于文献报道的其它非金属离子液体，在40℃，101.8 kPa下，[Bim][NTf2]的NH3摩尔吸收量和质量吸收量分别达到2.703 mol NH3/mol IL和0.113 g NH3/g IL，是常规离子液体NH3吸收量的近10倍，且可以完全再生，而粘度仅为47.138 mPa?s。质子型离子液体阳离子碳链长短对NH3吸收性能几乎无影响，2-H可以提高离子液体的NH3吸收量；阴离子对应酸的酸性越强，离子液体NH3吸收性能越高；低温、高压有利于提高离子液体的NH3吸收性能。（2）质子型离子液体吸收NH3过程物性变化及机理研究。与常规离子液体[Bmim][NTf2]和羧基功能化离子液体[HOOC(CH2)3mim][NTf2]相比，酸性比前者强、比后者弱的质子型离子液体[Bim][NTf2]表现出最高的NH3吸收量，说明离子液体酸性不是决定NH3吸收量的唯一因素。通过氘代实验中质子氘被NH3置换成质子氢、红外谱图N-H红移及咪唑环振动形式的变化，说明质子型离子液体与NH3形成较强的氢键作用，根据不同NH3浓度的离子液体核磁氢谱位移变化以及阳离子与NH3相互作用的量化计算结果，提出质子型离子液体的NH3吸收机理为质子氢可以先后与两个NH3分子形成氢键。NH3吸收过程中，[Bim][NTf2]-NH3体系密度线性下降，粘度先小幅升高后持续下降，原因是NH3分子破坏离子液体原有结构，进入到阴、阳离子之间，使离子液体阴、阳离子间距增大，因而密度降低，同时NH3分别与阴、阳离子形成的新的氢键作用提高了二者的相互作用能，使得NH3吸收初期离子液体粘度增大，随着其它位点及阴、阳离子间的NH3增多，粘度开始下降。（3）新型双质子型离子液体设计合成及高效NH3吸收研究。基于质子型离子液体质子氢可以与两分子NH3形成氢键作用，进一步设计合成了阳离子结构对称的咪唑类双质子型离子液体[2-Mim][NTf2]和[Im][NTf2]，相同条件下，其NH3摩尔吸收量分别达到3.037 mol NH3/mol IL和3.461 mol NH3/mol IL，且可以完全再生，二者的NH3吸收量较单质子型离子液体[Bim][NTf2]分别高12%和28%，但是并未实现NH3吸收量翻倍增加的效果。通过红外、核磁谱图表征及量化计算的方式考察了双质子型离子液体与单质子型离子液体NH3吸收机理的异同，结果表明，双质子型离子液体的两个质子氢分别与一分子NH3形成氢键作用后，由于NH3推电子作用的影响，只能另有一个NH3分子可以继续与离子液体形成氢键，因此咪唑类双质子型离子液体的预期NH3吸收量为3 mol NH3/mol IL。（4）双酸性离子液体和非咪唑类质子型离子液体设计合成及NH3吸收研究。基于分子量较小的碱金属离子与NH3的络合作用，开发了兼具Br?nsted和Lewis酸性的碱金属质子型离子液体，其中[2-Mim][Li(NTf2)2]的NH3吸收量在40℃，常压下可以达到7.012 mol NH3/mol IL，是双质子型离子液体的2倍以上，且可以完全再生，是一种极具潜力的NH3吸收剂；基于咪唑类质子型离子液体与NH3分子间的氢键作用，设计合成了系列吡啶类和哌啶类质子型离子液体，结果表明，相同条件下NH3吸收性能顺序为：吡啶类 &gt; 咪唑类 &gt; 哌啶类质子型离子液体，吡啶类质子型离子液体[2-mPy][NTf2]最高NH3吸收量为3.015 mol NH3/mol IL，但是由于吡啶阳离子与NH3分子间过强的氢键作用，可能导致质子氢剥离，导致NH3吸收量随时间增长而缓慢降低，其稳定性较咪唑类质子型离子液体差。（5）离子液体法NH3尾气分离连续评价实验。针对低分压NH3尾气，设计了一种氢键强化的复合质子型离子液体吸收剂，测定了该吸收剂的物性、NH3吸收及再生性能，通过热重、模拟NH3尾气吸收-解吸连续实验等方式，考察吸收剂稳定性，目前该吸收剂已在NH3吸收-解吸装置运行超过1000 h，NH3回收率99%以上，吸收剂性能保持稳定。本课题组开发的低分压NH3尾气净化回收工艺，既能满足NH3尾气&ldquo;净化&rdquo;的要求，又能实现NH3&ldquo;回收&rdquo;利用的目标。;Ionic liquids (ILs) are regarded as a series of new solvents in gas separation field owing to their negligible vapor pressure, high thermal stability, adjustable structures and high selectivity for different gases. Some reports have been published on the fundamental NH3 solubility data in ILs. However, there are still problems causing barriers for the applications of NH3 capture with ILs, such as the poor NH3 solubility in ILs with physical absorption ability at low NH3 partial pressure, the difficulty for NH3 desorption from metal-containing ILs and the the high cost of the systhesis of the hydroxyl-functionalized ILs. Therefore, it is of great significance to design low-cost ILs with high and reproducible NH3 absorption ability and low viscosities for NH3 separation. In this work, the designing of a series of protic ionic liquids (PILs), the NH3 solubility in these PILs, the NH3 absorption mechanism and the variations of physical properties were systematically studied. Based on the PILs absorbents, a set of process was established for the treatment of tail gas with low NH3 concentration. The main innovative work and results are as follows:(1) Study on the relationship between the structures of imdazolium-based PILs and the NH3 absorption ability. A series of imdazolium-based PILs were designed and synthesized and the effects of side chain length of the cation, 2-H, anions, temperatures and pressures on the NH3 absorption performances were systematically studied as well as the recyclability of PILs. The NH3 solubility in PILs was found to be higher than that reported in other nonmetallic ionic liquids. At 40℃ and 101.8 kPa, the NH3 molar and mass fraction in [Bim][NTf2] reach 2.703 mol NH3/mol IL and 0.113 g NH3/g IL, respectively and [Bim][NTf2] can be completely regenerated, while the viscosity is only 47.138 mPa?s. This solubility was about 10 times the conventional ILs. The length of the cationic side chain of the PILs has little effect on the NH3 absorption performance but 2-H would increase the NH3 solubility of the both protic and conventional ILs. As for the anions&rsquo; influence, the stronger the acidity of the acids corresponding to the anions, the higher the NH3 absorption ability of the PILs. (2) Study on the physical properties variations and mechanism of PILs absorbing NH3. Taking [Bim][NTf2] as an example, the NH3 absorption mechanism in PILs was investigated. Compared with conventional IL [Bmim][NTf2] and carboxyl-functionalized IL [HOOC(CH2)3mim][NTf2], the PIL [Bim][NTf2] with moderate acidity shows the highest NH3 capacity. Through deuteration experiments, IR and NMR spectra and quantitative calculations, it was found that the protic hydrogen of the [Bim][NTf2] can form hydrogen bonds with two NH3 successively. After NH3 absorption, the densities of [Bim][NTf2]-NH3 decreased linearly as the NH3 concentrations increased and the viscosities first increased slightly and then decreased continuously. The reason may be that NH3 &ldquo;squeezed&rdquo; into the anion and cation of the [Bim][NTf2], resulting in an increase in the volume of the PIL and then a decrease in the density of the [Bim][NTf2]-NH3. The new hydrogen bonding between the NH3 and anion and cation ions tied the interactions of the cations and anions, which increased the viscosities at the low NH3 concentrations. As the NH3 absorbed on the other active sites increased, the viscosities began to decrease.(3) Study on the NH3 absorption performance and mechanism of diprotic ILs. Based on the PILs, two kinds of diprotic ILs [2-Mim][NTf2] and [Im][NTf2] were designed and synthesized. The NH3 capacities of the two ILs researched 3.037 mol NH3/mol IL and 3.461 mol NH3/mol IL and were about 12% and 28% higher than that of [Bim][NTf2], which was lower than the expectation of the doubling of the NH3 capacity. Also the mechanism of NH3 absorption in diprotic ILs was investigated through IR, NMR spectra and quantification calculations and found that once one proton formed hydrogen bond with two NH3, it became difficult for more than one NH3 to connect on the other proton side and the expected NH3 capacities of diprotic ILs was 3 mol NH3/mol IL.(4) Study on the absorption performances of dual acidic ILs and pyridinium and piperidinium-based PILs. Based on the complexation of NH3 with lithium ion, kinds of Br?nsted and Lewis acidic ILs were developed and NH3 capacity of [2-Mim][Li(NTf2)2] was up to 7.012 mol NH3/mol IL, which was two times that of diprotic ILs and could be totally regenerated. According to the hydrogen bonds between protic hydrogen and NH3, pyridinium and piperidinium-based PILs were also designed to compare the NH3 absorption performances. The results showed that NH3 solubility order was pyridinium &gt; imidazolium &gt; pyridinium based PILs. However, owing to the strong interactions between NH3 and protic hydrogen of pyridinium based PILs, the protic hydrogen might drop down from the cation the NH3 capacities of pyridinium based PILs decreased after long time NH3 absorption.(5) Establishment of process for the treatment of tail gas with low NH3 concentration based on protic ILs. A kind of protic absorbent BN composed of two ILs was designed and the physical properties, NH3 absorption and regeneration performances of the absorbent were studied as well as the physical and chemical thermal stabilities. The BN absorbent has been used in an absorption-desorption continuous apparatus for more than 1000 h and kept stable NH3 removal rate over 99%.&nbsp;</p

锦州市雾霾的特征及影响因子研究

改革开放以来,我国经济高速发展,能源消耗量攀升,污染物排放增加,区域能见度不断恶化,近年区域性霾污染问题愈加突出。霾是悬浮在大气中的大量微小尘粒、烟粒或盐粒的集合体,使空气浑浊,水平能见度降低的天气现象。霾的核心物质是空气中悬浮的灰尘,气象学上称之为气溶胶颗粒。霾发生时,细粒子浓度升高,由气溶胶和气体污染物造成城市和空气区域性污染,大量极细微的干性尘粒、烟粒、盐粒等均匀的悬浮在空气中,严重危害人体健康。本文利用气象观测站2003年-2013年观测资料,常规micaps资料,雷达产品等对锦州市霾的特征及影响因子进行研究。结果表明,形成霾主要有三方面的因子：一是水平方向静风的增多,二是垂直方向的逆温现象,三是悬浮颗粒物的增加。</jats:p

氨气吸附材料的研究进展

氨是一种典型的有毒有害气态碱性污染物,也是PM2.5二次颗粒物的主要成因之一,大量含氨尾气排放不仅严重影响人类健康和生活环境,还会造成氨资源浪费。本工作综述了近年来多孔材料用于氨气吸附分离的研究现状和进展,重点论述了沸石、硅胶、活性炭、氧化石墨烯、多孔有机聚合物、共价有机骨架和金属-有机骨架材料改性前后对氨气的吸附性能,总结了吸附材料的改性方法,分析了该领域发展面临的主要问题,对未来的研究方向提出了建议

离子液体中电化学还原CO_2研究评述与展望

近百年来,伴随着矿石燃料的大量消耗,CO_2的排放量剧增,引发了全球性的生态环境和社会问题。CO_2同时也是廉价且可再生的碳资源,可作为生产醇、醚、酸、酯等重要化工品的原料。在众多吸引力十足的CO_2利用路线中,作为清洁、可控的反应过程,电化学还原固定CO_2技术在温和条件下生产化学品方面具有独特的优势。离子液体以其特有的性质被广泛用于电化学还原CO_2过程,本文对目前国内外离子液体介质中电化学还原CO_2的研究现状进行了综述,介绍了离子液体介质中电化学还原CO_2的主要反应及基本原理;针对离子液体对CO_2高效活化和转化等关键科学问题进行深入探讨,提出新型功能化离子液体的应用将成为CO_2电化学还原领域的发展方向和热点。</p

氨气吸附材料的研究进展

氨是一种典型的有毒有害气态碱性污染物,也是PM2.5二次颗粒物的主要成因之一,大量含氨尾气排放不仅严重影响人类健康和生活环境,还会造成氨资源浪费。本工作综述了近年来多孔材料用于氨气吸附分离的研究现状和进展,重点论述了沸石、硅胶、活性炭、氧化石墨烯、多孔有机聚合物、共价有机骨架和金属-有机骨架材料改性前后对氨气的吸附性能,总结了吸附材料的改性方法,分析了该领域发展面临的主要问题,对未来的研究方向提出了建议。</p

[Bmim][PF_6]高效吸收二氯甲烷及流程模拟

采用智能重量吸附仪测量了不同温度、压力下二氯甲烷(CH_2Cl_2)在离子液体1-丁基-3-甲基咪唑六氟磷酸盐([Bmim][PF_6])中的溶解度,用NRTL方程建立了离子液体-二氯甲烷体系的气液平衡模型,拟合得到二元交互作用参数,计算所得的二氯甲烷溶解度与实验数据吻合良好,平均相对误差为3.16%.构建了离子液体处理含二氯甲烷尾气及资源回收利用的常压吸收-减压闪蒸解吸工艺和模型,模型适用范围为温度278.15~308.15 K,压力0~0.1 MPa.对吸收塔进行了模拟和灵敏度分析,获得了常温常压吸收条件下的最佳操作工艺参数.</p

bmimpf6高效吸收二氯甲烷及流程模拟

采用智能重量吸附仪测量了不同温度、压力下二氯甲烷(CH_2Cl_2)在离子液体1-丁基-3-甲基咪唑六氟磷酸盐(BmimPF_6)中的溶解度,用NRTL方程建立了离子液体-二氯甲烷体系的气液平衡模型,拟合得到二元交互作用参数,计算所得的二氯甲烷溶解度与实验数据吻合良好,平均相对误差为3.16%.构建了离子液体处理含二氯甲烷尾气及资源回收利用的常压吸收-减压闪蒸解吸工艺和模型,模型适用范围为温度278.15~308.15 K,压力0~0.1 MPa.对吸收塔进行了模拟和灵敏度分析,获得了常温常压吸收条件下的最佳操作工艺参数

离子液体在氨气分离回收中的应用及展望

氨(NH3)是典型有毒有害工业气态污染物,也是形成PM2.5中二次颗粒物的根本原因之一,大量含氨气体的排放严重威胁人类的生活环境和健康。采用传统的酸法或水法,通常存在腐蚀性强、污染重、能耗高等问题,且难以回收利用氨资源。离子液体因其极低的挥发性、较好的化学/热稳定性、酸碱可调及高的氨溶解度等特点,为高效低能耗NH3分离提供了新途径。综述了近年来国内外离子液体在NH3分离中的研究进展,重点总结了常规离子液体、功能离子液体及离子液体溶剂/材料对NH3的吸收/吸附性能,阐明了阴阳离子、功能基团对NH3吸收性能的影响规律及其吸收机理,并探讨了该方向的研究和发展趋势