持续胸痛4个月及进行性下肢无力2个月

患儿,男,5岁。因胸痛4个月,右下肢无力2个月,双下肢无力10 d入院,无排便、排尿障碍,无意识障碍,双下肢呈上运动神经元性瘫痪,无颅神经受累,无感觉障碍。脊髓MRI示颈6~胸2椎管内肿瘤,压迫脊髓。转入神经外科手术治疗,患儿手术切除肿瘤后逐渐康复,随访6年未复发。该患儿病理诊断为透明细胞型脑（脊）膜瘤（WHO Ⅱ级）。儿童胸痛伴运动障碍,应与脊膜瘤这种椎管内肿瘤鉴别。     

LHRHa靶向紫杉醇脂质体的制备及体外抗肿瘤作用

目的:制备促黄体激素释放激素类似物(Luteinizing hormone-releasing hormone analogues,LHRHa)靶向紫杉醇脂质体(Paclitaxel liposomes,PTX-Lipo),研究其在体外增强紫杉醇(Paclitaxel,PTX)对卵巢癌A2780/DDP细胞的抑制作用。方法:采用薄膜超声法制备PTX-Lipo与LHRHa靶向紫杉醇脂质体(LHRHa-Paclitaxel liposomes,LHRHa-PTX-Lipo),用透射电镜考察脂质体形态;高效液相色谱法测定2种PTX-Lipo的包封率;激光共聚焦法通过卵巢癌A2780/DDP细胞对4-氟-7-硝基-2,1,3-苯并氧杂恶二唑荧光素的摄取检测来反映细胞对NBD-Lipo与NBD-LHRHa-Lipo的摄取情况;MTT法及细胞克隆形成实验检测LHRHa-PTX-Lipo体外对卵巢癌细胞的生长抑制情况。结果:制备LHRHa-PTX-Lipo的平均粒径123.4 nm,包封率在90%以上;A2780/DDP细胞对NBD-LHRHa-Lipo组的荧光摄取明显高于NBD-Lipo组;LHRHa-PTX-Lipo对A2780/DDP细胞的生长及克隆形成抑制明显高于PTX组及PTX-Lipo组(P<0.05)。结论:采用薄膜超声法制备的LHRHa-PTX-Lipo可使药物在靶部位聚集,增强药物对卵巢癌细胞的抑制作用。     

四氢生物蝶呤反应性苯丙氨酸羟化酶缺乏症的临床与基因研究

目的 探讨四氢生物蝶呤（tetrahydrobiopterin,BH4）反应性苯丙氨酸羟化酶（phenylalanine hydroxylase,PAH）缺乏症临床表型和基因型的关系。方法 38例高苯丙氨酸血症（hyperphenylalaninemia,HPA）患儿均进行口服BH。负荷试验（20ms／kg）或Phe-BH。联合负荷试验,同时进行尿蝶呤谱分析、红细胞二氢蝶啶还原酶（dihyaropteridine reductase,DHPR）测定。对7例BH4反应性PAH缺乏症患儿采用聚合酶链反应（PCR）和单链构象多态性（single strand conformation polymorphism,SSCP）分析对PAH外显子进行突变筛检,并结合DNA直接测序方法进行突变分析。结果 确诊10例BH4反应性PAH缺乏症患儿,男6例,女4例;平均年龄7．8个月;生化代谢表型均为轻度或中度HPA。7例BH4反应性PAH缺乏症患儿PAH基因型分别为S70del／-、R241C／R243Q、S70del／A389G、Y166X／-、R11lX/-、EX6-96A〉G／R241C和IVS4-1G〉A／R241C。A389G是新发现的突变基因型。结论 BH4反应性PAH缺乏症多表现为轻、中度HPA生化代谢表型,R241C是BH4反应性相关突变基因型中较常见的一种类型。推测S70del可能是一种BH4反应性相关突变类型.     

白癜风伴矮小、耳聋、视力下降一例

报道1例白癜风伴矮小、耳聋、视力下降。患者,男,6岁,出生时即出现黄疸,1岁时发现发育延迟,4岁时出现听力减退,5岁时诊断为矮小,同年发生右上臂白斑。全外显子测序发现PTPRQ基因突变。皮肤科检查：右上臂屈侧多片色素减退斑。诊断：白癜风合并矮小、耳聋、视力下降。     

Ruthenium-catalyzed asymmetric hydrogenation of aromatic and heteroaromatic ketones using cinchona alkaloid-derived NNP ligands

A series of cinchona alkaloid-based NNP ligands, including a new one, have been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various aromatic and heteroaromatic ketones were smoothly reacted, yielding valuable chiral alcohols with extremely high 99.9% ee. Moreover, a proposed reaction mechanism was discussed and verified by NMR.

A series of cinchona alkaloid-based NNP ligands including a new one has been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various ketones were smoothly reacted with up to 99.9% ee.

Since the well-known failure of using racemic thalidomide, attention has been paid to the manufacture of optically pure compounds as effective components in pharmaceuticals and agrochemicals. Asymmetric hydrogenation of ketones, especially heteroaromatic ketones, has emerged as a popular facile route to approach enantiopure secondary alcohols as essential intermediates for the construction of biologically active molecules.^1–4 Knowles et al.⁵ pioneered the production of enantioenriched chiral compounds in 1968, and Noyori and co-workers^6–8 laid the cornerstone of asymmetric hydrogenation in 1990s. Subsequently, numerous catalytic systems have been developed. Ru-BICP-chiral diamine-KOH was developed and proved to be effective for asymmetric hydrogenation of aromatic ketones by Xumu Zhang.⁹ Cheng-yi Chen reported asymmetric hydrogenation of ketone using trans-RuCl₂[(R)-xylbinap][(R)-daipen] and afforded secondary alcohol in 92–99% ee.¹⁰ Mark J. Burk and Antonio Zanotti-Gerosa disclosed Phanephos-ruthenium-diamine complexes catalyzing the asymmetric hydrogenation of aromatic and heteroaromatic ketones with high activity and excellent enantioselectivity.¹¹ Qi-Lin Zhou et al. designed and synthesized chiral spiro diphosphines as a new chiral scaffold applied in the asymmetric hydrogenation of simple ketones with extremely high activity and up to 99.5% ee.^12–15 Similarly, Kitamura and co-workers have developed a set of tridentate binan-Py-PPh₂ ligands for the asymmetric hydrogenation of ketones affording excellent results.¹⁶ Recently, chiral diphosphines and tridentate ligands based on ferrocene have been developed for the asymmetric hydrogenation of carbonyl compound with a remarkable degree of success.^17–21 Despite many ligands for asymmetric hydrogenation of ketones have been reported, expensive reagent and multistep complicated reactions were employed to synthesize most of them.^22–24 In light of increasing industrial demand, easily obtained, cheap and practical chiral ligands are still highly desirable. In addition to chiral ligands, the selection of metals was essential for asymmetric hydrogenation.^25–27 Although Mn,^28–30 Fe,^31–34 Co,^35–37 Ni^38,39 and Cu^40,41 metals were proved to be effective for asymmetric hydrogenation in recent years, Rh,^42–44 Ir^45,46 and especially Ru remained the most preferred metals. Ruthenium^47–51 was chosen owing to its superior performances in terms of low price, selectivity and activity. Takeshi Ohkuma,⁵² Hanmin Huang^53,54 and Johannes G. de Vries⁵⁵ all successfully used ruthenium catalysts for asymmetric hydrogenation of ketones. Admittedly, there is a continuing interest in the development of cheaper, simpler and more efficient catalysts for the asymmetric hydrogenation of ketones under mild conditions to access corresponding secondary alcohols. Recently, we developed new NNP chiral ligands derived from cinchona alkaloid for the asymmetric hydrogenation of various ketones in extremely excellent results using a iridium catalytic system.⁵⁶ Prompted by these encouraging results, we were interested in exploring a ruthenium-catalyzed asymmetric hydrogenation of ketones with NNP chiral ligands derived from cinchona alkaloid. Here, we showed that changing from iridium to ruthenium, with the same simple synthetic ligands, delivered a catalyst catalyzed asymmetric hydrogenation of ketones to give the industrially important chiral alcohols with up to 99.9% ee. Although the catalytic activity of ruthenium catalyst was not as high as that of the iridium catalyst, the enantioselectivity could be maintained, and even showed higher enantioselectivity in the hydrogenation of some substrates.Chiral tridentate ligand NNP (L1–L10) were synthesized and characterized as reported in our previous publication. With tridentate ligands in hand, we began to evaluate the catalytic performance in benzylidene-bis(tricyclohexylphosphine) dichlororuthenium-catalyzed asymmetric hydrogenation of acetophenone employed as a standard substrate (Fig. 2). MeOH was found to be a better one as the conversion and enantioselectivity were 99.9% and 98.2%, respectively. Bases screening showed that Ba(OH)₂ was superior to the others, giving >99.9% conversion and 98.8% ee in the present catalytic system (Fig. 1). Ligand screening revealed that the configuration of chiral centers of cinchona alkaloids of the ligand markedly affected the catalytic performance. NNP ligands derived from cinchonine and quinidine appeared to benefit both the reaction rate and enantioselectivity, while those derived from cinchonidine and quinine had the opposite effect. Further, different NNP ligands that bearing different substituents on the phenyl rings were evaluated. Similar to our previous research, ligands with electron-withdonating substituents showed better catalytic performance than those with electron-withdrawing substituents. However, it was noted that the more electron-withdonating substituents furnished lower activity but same enantioselectivity. The optimal ligand L5 derived from quinidine with one methoxy group on benzene ring provided the corresponding chiral alcohol with 99.9% conversion and 98.8% ee. Considering that L3 derived from cinchonine had similar catalytic performance to L4 derived from quinidine, new ligand L10 similar to L5 with one methoxy group on benzene ring was synthesized and applied to the asymmetric hydrogenation of template substrate. 99.6% conversion and 97.6% ee was obtained. Hence, L5 was employed as better ligand in subsequent experiments.Open in a separate windowFig. 1The effect of different bases for the asymmetric hydrogenation of acetophenone (substrate/Ru/L5 = 500/1/2, ketones: 0.429 mol L⁻¹, base: 0.15 mol L⁻¹, MeOH: 2 mL, 30 °C, 6 MPa, 2 h.).Open in a separate windowFig. 2The effect of different solvents for the asymmetric hydrogenation of acetophenone. (substrate/Ru/L5 = 1000/1/2, ketones: 0.858 mol L⁻¹, Ba(OH)₂: 0.15 mol L⁻¹, solvent: 2 mL, 30 °C, 6 MPa, 2 h.).The effect of different ligand for the asymmetric hydrogenation of acetophenone^a

2006年国外皮肤病治疗回顾

本文回顾2006年部分国外皮肤性病期刊关于皮肤病治疗的报道,其中大部分为个案报道,对幼年透明纤维瘤病、硬化性黏液水肿、Rothmann-Makai综合征等18种皮肤病的治疗情况进行了介绍.     

HPLC法测定红花微乳中羟基红花黄色素A的含量

目的:建立HPLC法测定红花微乳中羟基红花黄色素A的含量。方法:采用色谱柱:Diamonsil C18(2)5μm,250mm×4.6mm;流动相:甲醇-0.4%的磷酸水溶液(三乙胺调至pH=3.3)为30∶70;检测波长:402nm;柱温:室温。结果:羟基红花黄色素A在0.3128～3.128μg的范围内呈良好的线性关系(r=0.9990)。结论:本测定方法快捷,简便,准确,重现性好。     

和血祛风冲剂对类风湿关节炎大鼠细胞因子的影响

目的：通过对大鼠福氏完全佐剂性关节炎动物模型进行观察,探讨和血祛风冲剂对该动物模型细胞因子的影响。方法：观察和血祛风冲剂不同剂量组与寒湿痹冲剂对大鼠福氏完全佐剂性关节炎动物模型白介素1（IL－1）、肿瘤坏死因子α（TNF－α）、类风湿因子（RF)、免疫球蛋白G、A、M（IgG,IgA,IgM)进行观察。结果;和血祛风冲剂各剂量组及寒湿痹冲剂均有消肿作用,均楫IL-1、TNF－α、RF、IgG水平,对IgG抑制作用前者优于后者。结论：和血祛风冲剂治疗类风湿关节炎的机理 可能是抑制炎性细胞因子及免疫球蛋白的水平。     

植物源抗菌活性成分的研究进展

介绍近年来国内外研究发现的多种已知结构类型及新结构类型的植物源抗菌活性成分。简要归纳了其抗菌活性及其相应的MIC值。同时对构效关系进行了分析。并对其中抗菌活性较强。具有进一步研究开发价值的化合物及结构类型进行了概括。