取代四氢异喹啉衍生物的合成及其生物活性

粉防己碱有钙拮抗作用,临床试用于治疗高血压,其裂解产物钙拮抗作用降低,但有α-肾上腺素能受体拮抗作用,本文以裂解物为先导化合物设计合成了两类取代的四氢异喹啉衍生物Ⅲ及Ⅳ。初步药理试验表明:大部分化合物有α-肾上腺素能受体拮抗作用,少数化合物钙拮抗活性有所增强,其中Ⅲ_15,19对正常麻醉大鼠有一定的降压作用、Ⅳ_17,19对实验性动物心律失常有明显的保护作用。部分化合物量化计算表明:化合物与α₁-受体作用方式可能是形成电荷转移复合物。     

O,O′-二烷基-O″-(5-取代-3-苯并噻吩乙腈肟)磷酸酯及硫代磷酸酯的合成

合成了18个O,O′-二烷基-O″-(5-取代-3-苯并噻吩乙腈肟)磷酸酯及硫代磷酸酯类化合物(Ⅰ_1～18)。初步杀螺试验结果表明,其中5个化合物,即Ⅰ_2,3,7,11,12有明显的杀螺增效作用。     

Comparative Study on the Immunogenicity between Recombinant MS-Sj26GST Vaccine and Recombinant BCG-Sj26GST Vaccine in Schistosoma japonicum

TuberculosisandSchistosomiasisarethemajorcontagiousdiseaseswhicharethemostdangeroustothepeople’shealth Inordertogetridofthem ,wemustlookforamoreusefulvaccine Bythetech niquesofmolecularbiology ,2 6 0 0 0DaGlutathionStransferase (GST) genewasclonedintotheE coli MycobacteriumtransferringandexpressionvectorpBCG 2 0 0 0totransformittoMycobacteriumsmeg matismc2 15 5 (MS)andBCGseparatelyinordertoconstructrMS Sj2 6GSTvaccineandrBCG Sj2 6GSTvaccine Inthisstudy ,theBALB/cmicewereimmu niz…     

双特异性抗体对LAK细胞增殖和细胞毒作用影响的体外研究

将抗ＣＤ３与抗ＨＢｓ的单克隆抗体经化学偶联得到双特异性抗体，观察该双特异性抗体对ＬＡＫ细胞增殖和增强细胞毒性的作用。结果显示双特异性抗体显著提高ＬＡＫ细胞与２．２．１５细胞结合率；促进淋巴细胞增殖。１２５Ｉ－ＵｄＲ释放试验检测发现双特异性抗体增强ＬＡＫ细胞对２．２．１５细胞的细胞毒性且与抗体浓度呈正相关。进一步对抗体的特异性研究表明，加入双特异性抗体后ＬＡＫ细胞对２．２．１５细胞毒性作用显著高于对照组。     

A novel mis-sense mutation (G1381A) in the G6PD gene identified in a Chinese man

Objective　To detect new mutations among 29 glucose-6-phosphate dehydrogenase (G6PD) deficient individuals from Yunnan province. Methods　The nitroblue tetrazolium (NBT) method was used to screen G6PD deficient individuals. Mutation was identified by single strand conformation polymorphism (SSCP), amplification created restriction site (ACRS), amplification refractory mutation system (ARMS) and DNA sequencing. Results　Among 29 cases, 18 cases of G1388A, 1 case of C1004A, and 1 case of G1381A were identified. Nine cases remained to be defined. The G1381A mutation is a novel mis-sense mutation, with a substitution of threonine for alanine (A461T). The resultant G6PD had reduced enzymatic activity. In addition, G1381A caused a restriction site of Stu I to disappear, providing a rapid method for the detection of this mutation. Conclusion　A novel mis-sense mutation G1381A was found. This mutation results in a substitution of threonine for alanine, producing enzyme with reduced activity. The loss of the Stu I restriction site offers a rapid method for the detection of this mutation.     

The construction ofSchistosoma Japonicum vaccine BCG-Sj26GST and its identification

Summary The expression of foreign gene,Schistosoma Japonicum 26 ku antigen (Sj26GST),in Bacillus Calmette-Guerin (BCG),Mycobacterium CM. smegmatis) andEscherichia coli (E. coli) were studied. The cDNA fragment encoding Sj26GST was amplified by PCR using plasmid pGEX, which could express Sj26GST inE. coli as template. The Sj26GST cDNA was cloned into the downstream of humanM. tuberculosis heat shock protein (hsp) 70 promoter with correct reading frame, and then the DNA fragment containing hsp70 promoter and Sj26GST gene were subcloned together intoE. coli-Mycobacteria shuttle plasmid pBCG-2000 to construct the expression shuttle plasmid pBCG-Sj26. The recombinant BCG andM. smegmatis mc²155, which were electroplated with pBCG-Sj26, could express Sj26GST and the recombinantSchistosoma Japonicum vaccine BCG-Sj26GST was made. The recombinant Sj26GST (rSj26GST) were soluble and could be observed on SDS-PAGE at molecular weight of 26 ku. The content of rSj26GST accounted for 15% and 10% of total bacterial protein in BCG andM. smegmatis respectively. The results of Western blot showed the combination of rSj26GST with antibody of GST. This project was supported by Primary Foundation of China (No. 94-Y-19), Chinese National Nature Science Foundation (No. 339480022) and Chinese Health Foundation (No. 94-1-131).     

肝癌患者中医辨证分型与肝癌细胞体外化疗药物敏感性的关系

目的:观察不同中医辨证分型肝癌患者肝癌细胞体外化疗药物敏感性.方法:选取60例肝癌切除标本,利用MTT法测定不同证型肝癌患者对6种常用化疗药物的体外敏感性.结果:脾气虚组、肝气郁结组、瘀血阻络组之间各药敏感性有逐步下降趋势,但无统计学意义;各药在肝瘀脾虚阻络组敏感性明显下降.结论:不同中医辨证分型肝癌患者对化疗药物的敏感性存在一定差异,中西医结合个体化治疗肝癌,就是要根据具体患者药敏实验结果结合辨证论治设计治疗方案.     

腓骨长肌腱前半部作为自体移植材料的临床研究

 目的 探讨腓骨长肌腱前半部（anterior half of the peroneus longus tendon,AHPLT）作为自体肌腱移植材料重建膝关节韧带的可行性及疗效。方法 2007年7月至2008年1月采用AHPLT作为自体肌腱移植材料的膝关节韧带损伤患者100例,男33例,女67例;年龄16~62岁,平均32.3岁。关节镜下内侧髌股韧带重建49例、多条韧带重建19例、后十字韧带双束重建18例和前十字韧带双束重建14例。切取AHPLT作为全部（49例）或部分（51例）重建材料,采用单切口或双切口技术,重建韧带用螺钉挤压固定。术后评估膝关节Kujala评分、Lysholm评分、Marx评分、国际膝关节文献委员会（International Knee Documentation Committee,IKDC）膝关节主观评估表和客观等级评定、踝关节足踝功能障碍指数（Foot and Ankle Disability Index,FADI）及美国足踝外科学会（American Orthopedic Foot and Ankle Society,AOFAS）评分。结果 92例获得2年以上随访。术后2年,不同韧带重建组患者膝关节IKDC主观评分、Kujala评分、Lysholm评分及Marx评分均高于重建术前。多条韧带重建、后十字韧带双束重建和前十字韧带双束重建术后IKDC客观等级评定结果达到正常及接近正常者分别为17例、15例和12例,优良率分别为89.5%（17/19）、93.7%（15/16）和100%（12/12）。全部患者手术前后AOFAS评分分别为（97.4±2.0）分和（97.2±1.6）分,FADI评分分别为（96.8±2.2）分和（96.9±2.5）分,差异均无统计学意义。患者均未出现腓神经损伤、腓骨长肌腱断裂等并发症。结论 AHPLT作为自体肌腱移植材料重建膝关节韧带具有操作可行性,近期临床疗效好,切取肌腱后对踝关节功能影响小。     

Novel Oxazolidinone Antibacterial Analogues with a Substituted Ligustrazine C‐ring Unit

A series of novel oxazolidinone compounds with a substituted ligustrazine C‐ring unit and different substituted groups at the C‐5 side chain were designed and synthesized using linezolid as a lead and based on a scaffold hopping strategy. Their antibacterial and anti‐inflammatory activities were evaluated. The results of in vitro antibacterial assays showed that all fourteen target compounds displayed potent activity against Gram‐positive pathogens, particularly 8b , 13b , 14a , 14b , 15a, and 15b . Moreover, 14a and 14b exhibited significant inhibitory activities on the production of inflammatory mediators, including nitric oxide, interleukin‐6, and tumor necrosis factor‐alpha. Thus, these derivatives could serve as valuable candidates to develop anti‐infective agents for the treatment of chronic wounds.