7—氯—6—氟—4—乙氧基喹啉—3—羧酸乙酯的转化

报道了7-氯-6-氟-4-乙氧基喹啉-3-羧酸乙酯(1)在 DMF 和 DMSO 中的转化反应。在DMSO中加热或用碘化四丁铵催化,转化率100%,转化产物经证明为2和8的混合物。并用~1HNMR 测定了转化产物中2的相对含量。同时考察了3乙基化时不同溶剂对1和2生成比例的影响。     

倍半萜类2—甲基—6—苯基—2—庚烯—4—酮及其衍生物的合成

本文叙述了三个倍半萜类衍生物—2-甲基-6-苯基-2-庚烯-4-酮(Ⅱ),2-甲基-6-苯基-4-乙烯基-2-庚烯-4-醇(Ⅳ)及2-甲基-6-苯基-4-乙烯基-2,4-庚=烯(Ⅴ)的合成。初步药理筛选结果表明,(Ⅲ)有一定的抗生育活性。化合物(Ⅲ)、(Ⅳ)、(Ⅴ)均未见文献报道,测定了它们的结构并得到了证实。     

7，8，9—三—O—乙酰—N—乙酰—2—脱氧—2，3—二脱氢—4β—羟基—D—神经氨酸甲酯的合成

7,8,9-三-O-乙酰-N-乙酰-2-脱氧-2,3-二脱氢-4β羟基-D-神经氨酸甲酯是合成抗流感药物扎那米韦的关键中间体,本文对其合成方法进行了研究和改进。以N-乙酰神经氨酸为起始原料,经酯化、氯化、脱氯化氢同时环合成e唑环及水解开环等六个反应、三步操作即可制目的物。该路线反应步骤少,操作简单,收率高,重复性较好。     

2—（2—氨基—1,3—噻唑—4）—2—羟基亚氨基丁酸衍生物的合成

近年来,出现了一大类对革蓝氏阳性及阴性细菌具有高活性的抗生素。如头孢噻肟、C(?)ftazidime、Aztreonam等。在上述化合物的合成中,2-(2-氨基-1,3-噻唑-4-2-羟基亚氨基乙酸衍生物(Ⅰ)是其关键原料。     

2—羟基—3—氨基—4—苯丁酸的合成

2-羟基 - 3-氨基 - 4-苯丁酸 (1 )是制备二肽免疫增强剂类抗癌新药乌苯美司的关键中间体 ,有多种合成方法 ,如 α-氨基苯乙酮法 [1]、α-氨基苯丙醛法 [2 ]、α-氨基苯丁腈法[3] 、苯丁烯酸甲酯法 [4 ] 、苯丙氨酸法 [5]和苹果酸二乙酯法 [6]等。以上各法均存在不同缺点 ,如α-氨基苯乙酮法 ,总收率不到 1 0 % ;α-氨基苯丙醛法和α-氨基苯丁腈法 ,均用剧毒氰化钾(钠 ) ;苯丁烯酸甲酯法用爆炸性的过氧化物 ;苯丙氨酸法合成步骤长 ,且用氢化铝锂和氰化钠等试剂 ;苹果酸二乙酯法中的烃化反应需在 - 78℃的低温下进行。上述各法均不适合工业化…     

雄甾—1,4—二烯—3,17—二酮产生菌的诱变

用N′-甲基-N′-亚硝基-N~3-硝基胍(NTG)、溴化3,8-二氨基-5-乙基-6-苯基菲啶鎓(EB)和紫外线照射(UV)等分别对诺卡氏菌36野生型菌株进行诱变,发现NTG和UV的诱变效果比EB好,在NTG1000～2000μg/ml、UV2～3min条件下,经多次诱变处理,得到了一菌株诺卡氏菌22~#,它转化胆甾醇为雄甾-1,4-二烯-3,17-二酮的能力为原来36~#菌的4倍以上(底物浓度1％)。     

抗生素L—892—3,L—892—4的分离和鉴别

在寻找大环内酯类抗生素的过程中,运用萃取、硅胶薄层层析和重结晶等分离纯化技术,从吸水链霉菌L-892发酵液中分离得到两个小组份L-892-3和L-892-4.应用~1H、~(1s)C-NMR、MS、IR、UV等光谱法测定了它们的化学结构。分别鉴定抗生素L-892-3、L-892-4为methymycin和cyclizidine。     

2，4—二氯—5—氟—6—甲基苯甲酸的新合成法

以2，4-二氯氟苯为原料，经硝化、还原、硫醚化得5，后者脱甲硫基得6，再经重氮化和氰基取代生成7，最后水解即得2，4-二氯-5-氟-6-甲基苯甲酸（1）。中间体5、6、7和8及1均为未见报道的新化合物，其结构经MS和^1HNMR确证。     

6—氟—2,3—二氢苯并吡喃—4—酮的合成

以对乙酰胺基苯酚为原料,通过醚化、环合、水解、重氮化和氟化合成6-氟-2,3-二氢苯并吡喃-4-酮(2)。曾试图以Michael反应合成化合物4,但丙烯腈被引入对乙酰胺基苯酚的氮原子,得到化合物8。化合物5～9均未见文献报道。     

2,2—二甲基—1,3—丙二胺的制备

2,2-二甲基-1,3-丙二胺(1)是合成药物的中间体,目前国内尚无销售,我们因需要而对其进行了合成,同时对氢化催化剂进行了比较。 1的合成主要有两种方法,一是由2,2-二甲基-1,3-丙二醇经溴化和氨解制得,该法步骤多,产率低。另法是由2,2-二甲基-1,3-二硝基丙烷(2)催化还原合成,此法原料易得,产率较高,操作简便,因此为我们选用。     

基于HMGR、SQS1、β-AS基因CNVs的甘草道地性机制研究

本文利用real-time PCR方法对不同产地甘草的3-羟基-3-甲基戊二酰CoA还原酶 (3-hydroxy-3-methylglutaryl-CoA reductase, HMGR)、鲨稀合成酶1 (squalene synthetase 1, SQS1)、β-香树脂醇合成酶 (β-amyrin synthase, β-AS) 基因的拷贝数进行了研究, 发现不同产地的HMGR基因存在1～3个拷贝数变异, SQS1基因存在1～2个拷贝数变异, 未发现β-AS基因拷贝数变异。甘草HMGR、SQS1、β-AS基因拷贝数存在5种自然组合类型: A型 (2+1+1)、B型 (1+1+1)、C型 (3+2+1)、D型 (2+2+1) 和E型 (3+1+1), 其中内蒙古杭锦旗甘草存在A、B两种类型, A与B的比例为1∶1.3; 内蒙古赤峰甘草也存在A、B两种类型, 但A与B比例为3∶1; 宁夏盐池甘草存在A、B、C、D 4种类型, A/B/C/D比例为1∶5.1∶1∶2, A/B比例为1∶5.1; 甘肃民勤甘草存在A、B、E 3种类型, A/B/E比例为4.1∶2.1∶1, A/B比例为2∶1。本研究证明中药功能基因基因组拷贝数变异 (copy number variations, CNVs) 与产地具有相关性, 可能是道地药材形成的机制之一。     

无痛可视人工流产术有效性安全性相关因素研究

目的：研究探索无痛可视人工流产术有效性与安全性之间的相关因素。方法：比较五组麻醉药（瑞芬太尼、瑞芬太尼＋丙泊酚、瑞芬太尼＋咪唑安定、丙泊酚、丙泊酚＋芬太尼）作用时间、止痛效果、副反应及对体温、呼吸、脉搏、血压及血氧饱和度的影响等,严格操作规范,完善各环节工作,总结有效性与安全性之间的相关因素。结果：五组麻醉药中对诱导、手术、苏醒时间和定向力恢复时间以瑞芬太尼＋丙泊酚组最佳,镇痛效果显著,差异具有统计学意义,P〈0．05：对生命指征的影响以瑞芬太尼＋丙泊酚组最小,安全系数最高,经统计学处理．P〈0．05。瑞芬太尼＋丙泊酚最佳用药量分别为0．9-1．4ug／kg、1．9—2．2mg／kg。无痛可视人工流产术有效性与安全性之间的相关因素有：手术适应证、全麻药组合及剂量的选择、施术环境及设备的配置、受术者知情同意、手术医生、护士和麻醉医师的责任心及技术水平、术后指导及随访等。结论：无痛可视人工流产术有效性安全性与手术适应证、全麻药组合及剂量的选择、施术环境及设备的配置、受术者知情同意、手术医生、护士和麻醉医师的责任心及技术水平、术后指导及随访等因素有关。     

Comparison of the gastrointestinal anatomy,physiology, and biochemistry of humans and commonly used laboratory animals

In addition to metabolic differences, the anatomical, physiological, and biochemical differences in the gastrointestinal (G.I.) tract of the human and common laboratory animals can cause significant variation in drug absorption from the oral route. Among the physiological factors, pH, bile, pancreatic juice, and mucus and fluid volume and content can modify dissolution rates, solubility, transit times, and membrane transport of drug molecules. The microbial content of the G.I. tract can significantly affect the reductive metabolism and enterohepatic circulation of drugs and colonic delivery of formulations. The transit time of dosage forms can be significantly different between species due to different dimensions and propulsive activities of the G.I. tract. The lipid/protein composition of the enterocyte membrane along the G.I. tract can alter binding and passive, active, and carrier-mediated transport of drugs. The location and number of Peyer's patches can also be important in the absorption of large molecules and particulate matter. While small animals, rats, mice, guinea pigs, and rabbits, are most suitable for determining the mechanism of drug absorption and bioavailability values from powder or solution formulations, larger animals, dogs, pigs, and monkeys, are used to assess absorption from formulations. The understanding of physiological, anatomical, and biochemical differences between the G.I. tracts of different animal species can lead to the selection of the correct animal model to mimic the bioavailability of compounds in the human. This article reviews the anatomical, physiological, and biochemical differences between the G.I. tracts of humans and commonly used laboratory animals.     

Molecular pathology of drug-disease interactions in chronic autoimmune inflammatory diseases

The aetiology of autoimmune, chronic inflammatory disease is reviewed, together with the contributing roles of oxygen radicals, the cytochromes P450, the eicosanoids, the interleukins, and the corticosteroids and estrogens. The importance of drug metabolism in the formation of reactive intermediates of drugs and environmental chemicals, and hence in the production of neoantigens, autoantibodies and autoimmune disease is considered, together with the possible involvement of genetic variations in sulphoxidation, sulphotransferase and acetyltransferase activities in predisposing patients to rheumatoid arthritis, lupus and other autoimmune diseases. The toxicity of anti-inflammatory drugs, and the molecular mechanisms involved, are reviewed, including the formation of neoantigens and autoantibodies by the acylation of proteins by ester glucuronide metabolites of non-steroidal anti-inflammatory drugs, by the formation of disulphide protein conjugates of penicillamine, by theN-oxygenation of sulphonamides, and the oxygenation of hydralazine, procainamide and other drugs by leukocyte NADPH-oxidase and myeloperoxidase. The limitations of the existing procedures for the safety evaluation of new drugs, and their inability to identify potential immunotoxicity in man, are considered, and the advantages of the molecular structure procedure of COMPACT (Computer Optimised Molecular Parametric Analysis for Chemical Toxicity), and the enzyme induction procedure of ENACT (Enzyme Induction Analysis for Chemical Toxicity), for identifying potential carcinogenic and immunotoxic chemicals, are briefly discussed.     

Toxic response of HIPCO single-walled carbon nanotubes in mice and RAW264.7 macrophage cells

In this study, we identified the toxic response of pristine single-walled carbon nanotubes (P-SWCNTs) synthesized by HIPCO method in mice and RAW264.7 cells, a murine peritoneal macrophage cell line. P-SWCNT contained a large amount of Fe ion (36 wt%). In the lungs of mice 24 h after intratracheal administration, P-SWCNTs increased the secretion of IL-6 and MCP-1, and the number of total cells, the portion of neutrophils, lymphocytes, and eosinophils, also significantly increased at a 100 μg/mL of concentration. In RAW264.7 cells, cell viability and ATP production decreased in a dose-dependent manner at 24 h after exposure, whereas the generations of ROS and NO were enhanced at all concentrations together with the activation of the MAP kinase pathway. Moreover, the levels of both apoptosis- and autophagy-related proteins and ER stress-related proteins clearly increased, and the concentrations of Fe, Cu, and Zn ions, but not of Mn ions, increased in a dose-dependent manner. TEM images also revealed that P-SWCNTs induced the formation of autophagosome-like vacuoles, the dilatation of the ER, the generation of mitochondrial flocculent densities, and the separation of organelle by disappearance of the cell membrane. Taken together, we suggest that P-SWCNTs cause acute inflammatory response in the lungs of mice, and induce autophagy accompanied with apoptosis through mitochondrial dysfunction and ER stress in RAW264.7 cells. Furthermore, further study is required to elucidate how the physicochemical properties of SWCNTs determine the cell death pathway and an immune response.     

检验检测机构化学试剂QC实验室的关键要素分析

目的：验证实验试剂的质量,为检验工作选择符合要求的化学试剂提供数据依据。方法：对QC实验室成立以来已完成的2批常用化学试剂的检测情况进行总结,并对样品、人员、仪器设备、实验材料、方法标准、环境等6个控制要素进行分析。结果与结论：检验检测机构所使用的实验材料品质,是影响其工作结果的重要因素,建立质量控制实验室（QC实验室）并进行化学试剂质量控制具有重要意义,便于筛选合格供应商,指导并规范实验用试剂及耗材的采购,从而进一步满足食品药品各项检验检测工作的需要,确保检验检测数据与结论的公正性、有效性。     

Trends and prospects in graphene and its derivatives toxicity research: A bibliometric analysis

The purpose of this paper is to explore the current research status, hot topics, and future prospects in the field of graphene and its derivatives toxicity. In the article, the Web of Science Core Collection database was used as the data source, and the CiteSpace and VOSviewer were used to conduct a visual analysis of the last 10 years of research on graphene and its derivatives toxicity. A total of 8573 articles were included, and we analyzed the literature characteristics of the research results in the field of graphene and its derivatives toxicity, as well as the distribution of authors and co-cited authors; the distribution of countries and institutions; the situation of co-cited references; and the distribution of journals and categories. The most prolific countries, institutions, journals, and authors are China, the Chinese Academy of Sciences, RSC Advances, and Wang, Dayong, respectively. The co-cited author with the most citations was Akhavan, Omid. The five research hotspot keywords in the field of graphene and its derivatives toxicity were “nanomaterials,” “exposure,” “biocompatibility,” “adsorption,” and “detection.” Frontier topics were “facile synthesis,” “antibacterial activity,” and “carbon dots.” Our study provides perspectives for the study of graphene and its derivatives toxicity and yields valuable information and suggestions for the development of graphene and its derivatives toxicity research in the future.     

miR-15b基因干扰在脑缺血再灌注损伤中的作用及机制研究

目的 探讨微小核糖核酸-15b(miR-15b)基因干扰对脑缺血再灌注损伤的影响及其作用机制。方法 取新生24 h内Wistar乳鼠的大脑皮层星形胶质细胞传代培养并鉴定,氧糖剥夺/再恢复法处理模拟体内脑缺血再灌注损伤（模型组）;无特殊处理的大脑皮层星形胶质细胞为对照组。构建miR-15b干扰腺病毒载体及阴性对照载体,分别转染上述模型组细胞,记为过表达组、沉默组、过表达对照组、沉默对照组,另设置空白组。24 h后,倒置相差显微镜观察各组细胞形态学改变;氮兰四唑盐（MTS）法检测细胞存活率,乳酸脱氢酶（LDH）漏出率实验检测细胞活力;流式细胞术检测细胞凋亡率;实时荧光定量聚合酶链反应检测各组细胞miR-15b以及B淋巴细胞瘤-2(Bcl-2)、胱天蛋白酶-3(Caspase-3)、Caspase-9 mRNA表达;Western blot检测各组细胞Bcl-2、Caspase-3、Caspase-9蛋白表达;荧光素酶报告基因实验验证miR-15b是否靶向调控Bcl-2。结果 与对照组比,空白组、过表达对照组和沉默对照组贴壁细胞减少,细胞缩小变圆,分布松散,细胞存活率和Bcl-2 mRNA及...     

金属改性玉米秸秆生物质炭吸附恩诺沙星的机理研究

目的 提高传统玉米秸秆生物质炭对抗生素的吸附能力,研究生物质炭对恩诺沙星的吸附机理。方法 利用FeCl3和ZnCl2对玉米秸秆生物质炭进行铁改性和锌改性,运用SEM、FTIR、XRD等分析方法研究改性前后生物质炭的性质和结构,并进行吸附试验。结果 铁改性和锌化生物质炭表面含氧官能团数量增加,微孔所占体积增大,比表面积分别增大了9.7和8.1倍;XRD图谱显示改性后生物质炭结晶性降低,稳定性下降。铁改性和锌化后的生物质炭,对恩诺沙星的最大吸附量分别提高了21.30%和10.81%,准二级动力学方程跟Langmuir方程能很好的描述3种炭的吸附过程,吸附热力学分析显示3种炭对恩诺沙星的吸附是一个自发、吸热、无序的过程。结论 经过铁改性和锌改性后,能够增大生物质炭的比表面积及孔隙结构,使得生物质炭能够提供更多的吸附位点,从而增强其对恩诺沙星的吸附能力。     

金属改性玉米秸秆生物质炭吸附恩诺沙星的机理研究

目的 提高传统玉米秸秆生物质炭对抗生素的吸附能力，研究生物质炭对恩诺沙星的吸附机理。方法 利用FeCl3和ZnCl2对玉米秸秆生物质炭进行铁改性和锌改性，运用SEM、FTIR、XRD等分析方法研究改性前后生物质炭的性质和结构，并进行吸附试验。结果 铁改性和锌化生物质炭表面含氧官能团数量增加，微孔所占体积增大，比表面积分别增大了9.7和8.1倍；XRD图谱显示改性后生物质炭结晶性降低，稳定性下降。铁改性和锌化后的生物质炭，对恩诺沙星的最大吸附量分别提高了21.30%和10.81%，准二级动力学方程跟Langmuir方程能很好的描述3种炭的吸附过程，吸附热力学分析显示3种炭对恩诺沙星的吸附是一个自发、吸热、无序的过程。结论