基于气相色谱-质谱联用技术的痛风病人血清代谢特征分析

痛风是一组仅见于人类的异质性疾病,随着时间的推移,将导致慢性关节炎并逐渐致残。该研究将基于气相色谱-质谱联用技术(GC-MS)的代谢组学方法应用于痛风病人的血清代谢特征分析。首先利用GCMS获得痛风病人和健康人的血清代谢指纹图谱,采用多变量统计分析对所得数据进行分析。主成分分析(PCA)得分图显示,痛风病人与健康人的血清代谢谱有差异。通过偏最小二乘-判别分析(PLS-DA)对样品进行进一步分型,根据模型的变量重要性因子(VIP值)及非参数检验结果筛选差异代谢物。共筛选出43种可能与痛风相关的代谢物,并对其中22个变量进行结构鉴定,主要包括丙二醇、2,3-二羟基丁酸、2,4-二羟基丁酸、赤藓糖醇、苏糖醇、苏糖酸、阿拉伯糖醇、D-葡萄糖酸、肌醇、次黄嘌呤、尿酸、尿苷、3-羟基-3-甲基丁酸、鸟氨酸、吲哚-3-乳酸、单乙醇胺、甘油、甘油酸、月桂酸及亚油酸等代谢物。与健康人相比,痛风病人的糖代谢、核苷酸代谢、氨基酸代谢及脂类代谢均发生了明显的紊乱。这些结果将为痛风临床诊断及治疗提供重要依据。     

基于UPLC-Q/TOF MS技术的痛风患者血清代谢组学研究

采用超高效液相色谱-飞行时间质谱联用技术（UPLC-Q/TOF MS）对恩施土家族苗族自治州60例健康志愿者（对照组）和65例痛风患者（痛风组）的血清样本建立代谢图谱,基于主成分分析及正交偏最小二乘判别分析对所得数据进行模式识别,并结合变量权重投影分析及火山图筛选出痛风患者的血清代谢标志物。通过数据分析和数据库检索,共筛选出63种差异代谢物,其中27种代谢物显著上调（P <0.05）,36种代谢物显著下调（P <0.05）,主要包括甘油磷脂类、氨基酸类及胆碱等成分。首先,对以上差异代谢物进行受试者工作特征曲线（ROC）分析,其中曲线下面积（AUC）大于0.8的14种代谢物是诊断效能较好的代谢物;然后对筛选的63种差异代谢物进行代谢通路富集分析,以Impact> 0.1且P <0.05为标准,得到影响最大的代谢通路主要有甘油磷脂代谢、醚性脂质代谢、亚油酸代谢、半胱氨酸和蛋氨酸代谢、花生四烯酸代谢及戊糖和葡萄醛酸的互相转化等。综上,痛风患者和健康对照人群的血清代谢水平有明显差异,差异代谢物的鉴定为痛风的发病机制和早期筛查提供了实验依据。     

分析痛风性关节炎诊断中双源CT和MRI的应用价值

选取2017年5月~2019年5月于我院就诊的痛风性关节炎患者100例,均行双源CT及MRI检查。通过比较双源CT及MRI对痛风性关节炎的阳性诊断率、诊断灵敏度,以及不同影像学表现的差异(包括痛风结节、关节骨质破坏、关节软骨侵蚀、关节积液、周围间隙水肿、滑膜破坏和尿酸盐结晶等),探讨双源CT和MRI在痛风性关节炎诊断中的应用价值。结果显示,双源CT检出患病关节的阳性率及诊断敏感度均高于MRI,且差异具有统计学意义;双源CT对于痛风结节以及骨质破坏的检出率高于MRI,且差异具有统计学意义;在检测尿酸盐结晶方面,双源CT具有特异性;MRI对于关节积液、关节周围间隙水肿、软骨侵蚀、滑膜侵蚀的检出率高于双源CT,且差异具有统计学意义。上述结果表明双源CT具有尿酸盐结晶诊断特异性,其在痛风性关节炎诊断中的应用价值高于MRI。     

模块式护理计划对痛风患者疼痛及生活质量的影响分析

目的研究分析痛风患者采取模块式护理计划后对其生活质量、疼痛的影响。方法将佛山市第一人民医院风湿免疫内科2015年12月至2016年11月经临床诊断为痛风的住院患者156例随机分为常规组和实验组各78例,常规组采取常规护理措施,实验组采取模块式护理计划,比较两组患者的疼痛评分、疼痛缓解时间、生活质量评分。结果实验组、常规组疼痛缓解时间分别为(4.6±1.8)d、(7.3±2.7)d,(P0.05),护理2周后疼痛评分分别为(1.9±1.1)分、(4.1±2.5)分,(P0.05),生活质量评分分别为(8.2±2.6)分、(4.9±1.5)分,(P0.05)。结论模块式护理计划应用于痛风患者的护理中,能够显著降低患者的疼痛程度,提升其生活质量,缩短疼痛缓解时间,提高护理质量及效率,建议推广使用。     

RP/HPLC法测定痛风颗粒中白藜芦醇甙的含量

痛风颗粒是由茵陈、虎杖、当归、羌活、独活等多味药材组成,用于治疗急性痛风.白藜芦醇甙是虎杖中主要有效成分之一,具有强心扩血管、抑制血小板聚集、降血酯、镇咳平喘、抗菌、抗病毒等多种作用[1].关于白藜芦醇甙的含量测定方法,文献报道有薄层扫描法,高效液相色谱法等.本文以RP/HPLC法测定其主要有效成分白藜芦醇甙在成药中的含量,建立了质量标准,本法操作简单,精密度高,分离良好,对痛风颗粒的生产和使用中的质量检验和控制都有较大的意义.     

体内过量钼有无害处

有关钼的中毒报告很少。钼盐的毒性较低 ,机体对它的排泄又很快。不过 ,也不能掉以轻心。苏联就有一则研究说一地区居民患“痛风症” ,原因是该地区的土壤和环境中钼的含量过高 ,人体的钼也就高于正常的需要量 ,因此 ,黄嘌呤氧化酶的活性增强 ,造成尿酸形成过多沉积在软骨组织中而引起的。另外 ,体内钼缺少 ,易引起肾结石 ,那是黄嘌呤得不到分解 ,在体内积聚过多的缘故。但是 ,体内钼过多 ,也会引起肾结石 ,这是因为黄嘌呤分解产生尿酸太快太多 ,排泄速度赶不上 ,从而形成尿酸和尿酸盐结晶 ,造成肾结石的。体内过量钼有无害处…     

托匹司他的合成研究进展

托匹司他是一种黄嘌呤氧化还原酶(ROX)抑制剂,对痛风有显著的治疗作用,其耐受性好,不良反应小,是目前治疗痛风最有效的药物之一。托匹司他由三唑环片段和两个吡啶环片段拼合而成,其合成关键步骤在于吡啶2-位氰基的引入(Ⅰ)、两个吡啶环的拼接(Ⅱ)和三唑环的构建(Ⅲ)。该文根据各关键步骤的顺序不同,将托匹司他的合成策略分为"Ⅰ+Ⅱ+Ⅲ"、"Ⅱ+Ⅲ+Ⅰ"和"Ⅱ+Ⅰ+Ⅲ"三种策略,并以这3种策略为主线综述了托匹司他自2002年发现至今的合成研究进展。     

双波长吸光度比值K系数法同时测定三组分体系的研究与应用

本文用双波长吸光度比值Ｋ系数法同时测定撒痛风注射液中水杨酸钠，咖啡因和安替比林三组分的含量，其平均回收率及变异系数分别为１０１．５％，０．４０％；９９．９９％，０．３７％；１００．０％，０．３０％。既改善了选择性，又提高了灵敏度，弥补了常规Ｋ系数法的不足。     

论中药化学技术在中医风湿免疫的临床表现探究--评《中药化学技术》

风湿免疫科是医院内科学领域中的新兴的一种学科,主要研究和治疗风湿免疫类疾病。风湿疾病是一大类疾病,它主要指影响骨关节及周围软组织的一组疾病,风湿疾病的范畴,有弥漫性结缔组织病,如类风湿关节炎、系统性红斑狼疮、多肌炎、血管炎;还有脊柱关节病,如强直性脊柱炎、反应性关节炎、银屑病关节炎;还有退行性变,比如骨关节炎;还有代谢性疾病,比如痛风;还有非关节性风湿病,比如椎间盘突出等。     

原位核磁共振技术考察L-缬氨酸导引下合成花状纳米结构聚苯胺形成机理的研究

利用~1H-NMR原位追踪在L-缬氨酸存在下合成花状纳米聚苯胺的形成过程中发现此结构的形成经历3个阶段:首先在苯胺与缬氨酸构成的类胶束结构内聚合成吩嗪类寡聚物;其次通过p-p重叠作用及胶束融合过程成为片状聚集体;最终通过与缬氨酸形成氢键组装成花瓣状纳米聚苯胺.通过改变反应条件,对比形成过程中核磁共振图谱及产物形貌的变化发现花状纳米聚苯胺的形成有如下特征:反应初期L-缬氨酸作为缓冲试剂可以避免苯胺的骤然质子化,有利于生成具有吩嗪结构的寡聚物;反应前苯胺单体与缬氨酸形成稳定的反应环境保证寡聚物始终在其内聚集生长,有效避免了外部环境的影响.     

5-Aza-7-deazaguanine–Isoguanine and Guanine–Isoguanine Base Pairs in Watson–Crick DNA: The Impact of Purine Tracts,Clickable Dendritic Side Chains,and Pyrene Adducts

The Watson–Crick coding system depends on the molecular recognition of complementary purine and pyrimidine bases. Now, the construction of hybrid DNAs with Watson–Crick and purine–purine base pairs decorated with dendritic side chains was performed. Oligonucleotides with single and multiple incorporations of 5-aza-7-deaza-2′-deoxyguanosine, its tripropargylamine derivative, and 2′-deoxyisoguanosine were synthesized. Duplex stability decreased if single modified purine–purine base pairs were inserted, but increased if pyrene residues were introduced by click chemistry. A growing number of consecutive 5-aza-7-deazaguanine–isoguanine base pairs led to strong stepwise duplex stabilization, a phenomenon not observed for the guanine–isoguanine base pair. Spacious residues are well accommodated in the large groove of purine–purine DNA tracts. Changes to the global helical structure monitored by circular dichroism spectroscopy show the impact of functionalization to the global double-helix structure. This study explores new areas of molecular recognition realized by purine base pairs that are complementary in hydrogen bonding, but not in size, relative to canonical pairs.     

Retention Behavior of Nucleic Acid Bases and Purine Derivatives on Titania

The retention of nucleic acid bases and purine derivatives on titania was studied using a 0.4 mM acetic acid–sodium acetate buffer (pH 6.0) and 70% aqueous methanol as mobile phases. We observed that the retention strength of tested analytes on titania was dependent on the structural differences between pyrimidine and purine skeletons and the variety and number of substituents. The retention order was purine derivatives with methyl groups, pyrimidine bases and purine derivatives with hydrophilic functional groups, which were retained most strongly on titania. We concluded that the retention of each analyte was caused by the analyte’s hydrophobicity in the case of purine derivatives with methyl groups and pyrimidine bases. In the case of purine and its derivatives with hydrophilic functional groups, it was considered that the retention was dependent on the analyte’s ability to form chelates, and the variety and number of functional groups on C6 and C2.     

A liquid chromatography-tandem mass spectrometry method for comprehensive determination of metabolites in the purine pathway of rat plasma and its application in anti-gout effects of Lycium ruthenicum Murr.

It has been proved that purine metabolites are implicated in various biological syndromes and disorders. Therefore, the realization of panoramic detection of purine metabolites will be of great significance to the pathogenesis of purine metabolic disorders. In the present study, an ultra-high performance liquid chromatography with tandem mass spectrometry method was developed for the comprehensive quantification of purine metabolites in rat plasma. The 17 purine metabolites were separated and quantified in the short running time of 15 min. The proposed method was strictly validated by applying SeraSub solution as a matrix and proved to be linear (R² ≥ 0.9944), accurate (the recoveries of all analytes ranged from 85.3% to 103.0%, with relative standard deviation values ≤ 9.3%), and precise (the intra- and inter-day precisions were less than 10.8% and 12.4%, respectively). The method was then successfully applied to the qualification of the endogenous purine metabolites in acute gouty arthritis rats, as well as colchicine and anthocyanin-intervened rats. Results showed that uric acid, xanthine, hypoxanthine, and xanthine were considered the key factors of acute gouty arthritis. The established method and measurement of purines in rat plasma might help the investigation of the action mechanisms between purine disorders and related diseases.     

New nucleoside analogs from 2-amino-9-(beta-D-ribofuranosyl)purine

Four novel derivatives of 2-amino-9-(beta-D-ribofuranosyl)purine (1) were synthesised and fully characterised. When 1 was reacted with chloroacetaldehyde (a), 2-chloropropanal (b), bromomalonaldehyde (c) and a mixture of chloroacetaldehyde + malonaldehyde (d), 3-(beta-D-ribofuranosyl)-imidazo-[1,2a]purine (2), 3-(beta-D-ribofuranosyl)-5-methylimidazo-[1,2a]purine (3), 3-(beta-D-ribofuranosyl)-5-formylimidazo-[1,2a]purine (4) and 9-(beta-D-ribofuranosyl)-2-(3,5-diformyl-4-methyl-1,4-dihydro-1-pyridyl)purine (5) were formed, respectively. The products were isolated, purified by chromatography and characterised by MS, complete NMR assignment as well as fluorescence and UV spectroscopy. The yields of these reactions were moderate (14-20%). The fluorescence properties differed from those of the starting compound and the quantum yields were considerably lower.     

12种嘌呤类化合物的滤纸基质室温燐光法研究

较为详细地研究了１２种嘌呤类化合物以滤纸为基质的室温燐光（ＲＴＰ）光谱特性与分子结构的关系，以及重原子效应和酸度效应对ＲＴＰ的影响。     

Synthesis, characterisation and theoretical calculations of 2,6-diaminopurine etheno derivatives

Four derivatives of 2,6-diaminopurine (1) were synthesised and characterised. When 1 was reacted with chloroacetaldehyde, 5-aminoimidazo[2,1-i]purine (2), 9-aminoimidazo[2,1-b]purine (3), 9-aminoimidazo[1,2-a]purine (4) and diimidazo[2,1-b:2',1'-i]purine (5) were formed. The purified products (3-5) were fully characterised by MS, complete NMR assignments as well as fluorescence and UV spectroscopy. The purified, isolated yields of these products (3-5) varied from 2.5 to 30%. The relative stability of different tautomers was investigated by theoretical calculations. Fluorescence characteristics are also discussed and compared to the starting material 1 and a reference molecule 2-aminopurine.     

嘌呤磺胺衍生物的合成及抗肿瘤活性

合成了一系列结构全新的嘌呤磺胺类衍生物, 并应用溴化噻唑蓝四氮唑(MTT)法进行了初步体外抗肿瘤细胞增殖活性研究. 结果表明, 嘌呤环C2位、 N6位和N9位的取代对活性均有较大影响, C2位引入苯磺酰基哌嗪片段后有利于提高抗肿瘤活性. 化合物17d对3株肿瘤细胞PC-3, HCT116和K562 的增殖均有明显抑制作用, 且强度与阳性对照药Roscovitine相近.     

Structure and synthesis of 6-(substituted-imidazol-1-yl)purines: versatile substrates for regiospecific alkylation and glycosylation at N9

X-ray crystal structures of several 6-(azolyl)purine base and nucleoside derivatives show essentially coplanar conformations of the purine and appended 6-(azolyl) rings. However, the planes of the purine and imidazole rings are twisted approximately 57 degrees in a 2-chloro-6-(4,5-diphenylimidazol-1-yl)purine nucleoside, and a twist angle of approximately 61 degrees was measured between the planes of the purine and pyrrole rings in the structure of a 6-(2,5-dimethylpyrrol-1-yl)purine nucleoside derivative. Shielding "above" N7 of the purine ring by a proximal C-H on the 6-azolyl moiety is apparent with the coplanar compounds, but this effect is diminished in those without coplanarity. Syntheses of 6-(azolyl)purines from both base and nucleoside starting materials are described. Treatment of 2,6-dichloropurine with imidazole gave 2-chloro-6-(imidazol-1-yl)purine. Modified Appel reactions at C6 of trityl-protected hypoxanthine and guanine derivatives followed by detritylation gave 6-(imidazol-1-yl)- and 2-amino-6-(imidazol-1-yl)purines. Imidazole was introduced at C6 of 2',3',5'-tri-O-acetylinosine by a modified Appel reaction, and solvolysis of the glycosyl linkage gave 6-(imidazol-1-yl)purine. Guanosine triacetate was transformed into the protected 2,6-dichloropurine nucleoside, which was subjected to S(N)Ar displacement with imidazoles at C6 followed by glycosyl solvolysis to provide 2-chloro-6-(substituted-imidazol-1-yl)purines. Potential applications of these purine derivatives are outlined.     

Promiscuous enzyme-catalyzed regioselective Michael addition of purine derivatives to α,β-unsaturated carbonyl compounds in organic solvent

Regioselective Michael addition of purine derivatives to α,β-unsaturated carbonyl compounds could be catalyzed by d-aminoacylase amano (DA) in DMSO. The influence of reaction conditions on the Michael addition, including solvent, temperature, and enzyme concentration was systematically investigated. Then we extended this methodology to six structurally diverse purine derivatives and a variety of α,β-unsaturated carbonyl compounds. 21 Michael adducts were selectively synthesized in moderate to high yields. It is the first report on enzyme-catalyzed Michael addition for the preparation of purine derivatives.     

Synthesis of C8-alkyl-substituted purine analogues by direct alkylation of 8-H purines with tetrahydrofuran catalyzed by CoCl_2·6H_2O

C8-Alkyl-substituted purine analogues were synthesized through direct alkylation of 8-H purine with tetrahydrofuran in the presence of Co catalyst in one step. The reactions gave a series of novel C8-oxygen heterocyclic alkyl purine compounds in good yields under mild reaction conditions by the readily available alkylating reagents, providing a complementary route to the classical coupling reactions for the synthesis of C8-alkyl-substituted purine analogues.