海墨痔疮胶囊的药效学实验研究

目的观察海墨痔疮胶囊对兔直肠粘膜溃疡的治疗作用及急性毒性。方法通过醋酸法致兔直肠粘膜溃疡,海墨痔疮胶囊按高、中、低剂量(600、300、150mg.kg-1.d-1)灌胃给药,以4、7、10d溃疡面直径和完全愈合天数为观察指标,观察治疗溃疡疗效;小鼠一次性灌胃给药20g.kg-1,观察其急性毒性。结果海墨痔疮胶囊高、中两个剂量组和阳性对照组与阴性对照比较灌胃给药后7、10d的溃疡面直径减小、愈合天数缩短,均有统计学意义;急性毒性实验,未见小鼠明显异常。结论海墨痔疮胶囊对兔直肠粘膜溃疡具有较好的治疗作用,且毒性较小。     

低分子肝素钙、阿司匹林联合治疗急性脑梗死的临床研究

 目的观察低分子肝素钙、阿司匹林及其联合应用治疗急性脑梗死的疗效及其安全性。方法共选择240例急性脑梗死患者,随机分为低分子肝素钙治疗组、阿司匹林治疗组、低分子肝素钙与阿司匹林联合治疗组及对照组,每组各60例。治疗前后分别作神经功能缺损程度评分及临床疗效判定,并观察每组的不良反应。结果低分子肝素钙治疗组、阿司匹林治疗组、低分子肝素钙与阿司匹林联合治疗组神经功能恢复均明显优于对照组,低分子肝素钙与阿司匹林联合治疗组临床疗效明显优于低分子肝素钙治疗组与阿司匹林治疗组,各组出血发生率无显著差异性。结论脑梗死急性期给予低分子肝素钙联合阿司匹林治疗安全有效,且明显优于单药治疗。     

脊柱结核的影像学诊断及临床病理分析

研究脊柱结核的影像学诊断价值,并探讨各型脊柱结核的临床病理特点.对156例经临床及病理证实且影像学资料完整的脊柱结核进行回顾性分析,比较其X线(或CR)、CT及MRI的影像学特点及符合率.结果显示①X线(或CR)、CT及MRI对脊柱结核诊断符合率分别为90.5%、96.2%及99.5%.②X线(或CR)、CT及MRI对椎体骨质破坏、椎间隙狭窄的敏感性分别为74.5%、89.9%及96.87%.③对椎旁软组织肿块和腰大肌脓肿、附件破坏及骨性椎管受累的显示,CT优于X线(和CR)片;对早期病变的显示及脊髓受累情况,MRI优于X线(或CR)及CT,有显著差异性(P＜0.01).④对死骨及钙化的显示CT优于X线(或CR)及MRI.认为X线(或CR)检查为诊断脊柱结核的基本方法,但对早期病变的显示有限度;CT显示早期微小的骨质破坏、死骨、脓肿、钙化及脓肿对椎管脊髓压迫明显优于X线;MRI可清晰显示硬膜外脓肿及脊柱后突畸形对脊髓的压迫和脊髓变性情况,尤其是对早期病变的诊断,有较高的敏感性和特异性,但对死骨及钙化不敏感.     

环丙沙星大黄治疗急性重症胰腺炎与IL-6 IL-8相关性的实验研究

目的:探讨应用环丙沙星与大黄治疗急性重症胰腺炎(SAP)与IL-6、IL-8相关性.方法:将实验动物随机分成3组:A-对照组(急性重症胰腺炎但未应用抗生素及中药组);B-SAP应用环丙沙星组;C-SAP应用中药 环丙沙星组.ELISA法(酶联免疫吸附法)检测IL-6、IL-8.结果:环丙沙星与大黄配伍可以明显下调SAP时各个时段IL-6、IL-8、血AMY水平,IL-6、IL-8与血AMY、胰腺湿重呈正相关,环丙沙星 大黄与环丙沙星组IL-6、IL-8与血AMY、胰腺湿重低于对照组.结论:环丙沙星 大黄治疗作用与降低IL-6、IL-8有关.     

VEGF inhibition and cytotoxic effect of aplidin in leukemia cell lines and cells from acute myeloid leukemia.

BACKGROUND: Aplidine (APL) is a marine depsipeptide isolated from the Mediterranean tunicate Aplidium albicans that is under clinical phase II development. In contrast to the lack of bone marrow toxicity reported in phase I/II studies, it has been shown to induce cytotoxicity at very low concentration against lymphoblastic leukemia blast, as well as having an impact in the vascular endothelial growth factor (VEGF)/VEGF receptor 1 loop. PATIENTS AND METHODS: To confirm these findings we investigated APL-related VEGF inhibition and its cytotoxic effect on myeloid leukemic cells lines (K-562, HEL and HL60) and fresh leukemia blasts derived from 30 patients with acute myeloid leukemia (AML). The conventional active 4-demetoxi-daunorubicin (idarubicin; IDA) was included as a positive control. RESULTS: APL was found to be significantly (P<0.001) more active than IDA in obtaining 50% growth-inhibition in K-562, HEL and HL60 cell lines. Results obtained with AML blast cells were super imposible. ID(50) ranged from 0.024 to 0.610 microM for IDA (0.200+/-0.176) and from 0.001 to 0.108 microM for APL (0.020+/-0.031). Annexin V tests and cell cycle analysis performed on cell lines confirmed the stronger citotoxic capability of APL as apoptotic inducer and as a G(1) blocker. The inhibitory effects of APL on VEGF release and secretion have been confirmed by ELISA tests performed on HEL: the VEGF concentration in cell surnatant was reduced from 169 to 36 pg/ml after 24 h of exposure to a pharmacological concentration of APL. CONCLUSIONS: APL harbors a strong in vitro antileukemic activity at a concentration achievable in patients at non-myelotoxic doses. Our data also support the notion of an impact on VEGF secretion. Clinical studies with this new marine-derived compound in relapsed/resistant leukemia are underway.     

丝裂原活化蛋白激酶信号转导系统对Vp-16诱导分化作用的影响

目的:探讨丝裂原活化蛋白激酶(mitogen-acti-vated protein kinases,MAPKs)信号转导系统对依托泊苷(Vp-16)诱导K562细胞分化作用的影响。方法:采用四甲基偶氮唑盐(MTT)法测定细胞增殖活性;流式细胞仪解析细胞周期;硝基四氮唑蓝(NBT)还原实验检测细胞向单核/巨噬系统分化。结果:0·1~0·8μg/mL的Vp-16抑制K562细胞增殖,引起细胞G2/M期阻滞,诱导细胞向单核/巨噬系统分化;细胞外信号调节激酶(extracellular signal-regulated kinases,ERK)抑制剂PD98059降低Vp-16的诱导分化作用,P<0·05;p38丝裂原活化蛋白激酶(p38mitogen-activated protein kina-ses,p38MAPK)抑制剂SB203580增强Vp-16的作用,P<0·05;而C-JUN氨基末端激酶(c-jun N-terminal ki-nases,JNK)抑制剂SP600125对Vp-16的诱导分化作用无明显影响,P>0·05。结论:在Vp-16诱导K562细胞向单核/巨噬系统分化过程中,ERK正向,p38MAPK负向调节Vp-16的诱导分化作用。     

DC联合小剂量IL-2大量扩增白血病特异性CTL的实验研究

目的： 建立和优化体外大量扩增白血病特异性CTL的方法。 方法： 用1×107FBL3细胞冻融产物（FBL3LY）冲击的DC每10天1次对C57BL/6小鼠反复接种，在第3次接种5 d后处死小鼠制备脾T细胞，每周用FBL3LY冲击的DC刺激，体外培养10 d后加入小剂量的IL2。 结果： 共培养至21 d， T细胞可扩增100倍以上，其中CD8+细胞比率明显增高。乳酸脱氢酶释放试验证实扩增所得CTL对FBL3细胞具有高效的杀伤作用（81.84±8.68%），而对K562细胞无特异性杀伤作用。 结论： FBL3LY冲击的DC联合小剂量IL2可大量扩增FBL3白血病特异性CTL，该方法的建立对提高白血病特异性CTL免疫治疗的临床疗效具有重要意义。     

No evidence of association of methylenetetrahydrofolate reductase polymorphism with occurrence of second neoplasms after treatment of childhood leukemia

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been associated not only with the risk for acute lymphoblastic leukemia (ALL) in adults and children, but also with increased methotrexate toxicity. The present study aimed to investigate whether MTHFR polymorphisms modify the risk for development of secondary malignancies in children treated for ALL with protocols that included high-dose methotrexate. MTHFR genotypes were determined in DNA samples isolated from archived bone marrow smears of 15 patients with a second malignancy and a matched control group of 30 patients who did not developed a second malignancy after the treatment for ALL. The frequencies of MTHFR C677T and A1298C genotypes in all patients were: C677T: CC 40%, CT 46.7% and TT 13.3% and A1298C: AA 46.7%, AC 44.4% and CC 8.9%. The relative risk for second malignancy was not significantly increased in ALL patients having at least one polymorphic C667T [odds ratio (OR) 1.51; 95% confidence interval (CI) 0.43 - 5.31] or one polymorphic A1298C allele (OR 1; 95% CI 0.29 - 3.46). Our study suggests that MTHFR polymorphisms are not associated with increased risk of second cancer in children treated with high-dose methotrexate.     

CIK细胞对慢性粒细胞白血病G0期CD34+白血病细胞的杀伤作用

目的研究细胞因子诱导杀伤细胞(cytokine induced killer,CIK)对慢性粒细胞白血病(chronic myeloid leukemia,CML)中G0期原始干细胞(CD34+)的杀伤作用。方法5例CML慢性期患者外周血标本在体外诱导培养CIK细胞,流式细胞仪(FCM)检测其表型。G带法检测CIK细胞核型。应用免疫磁珠技术分选CD34+CML白血病细胞,AO染色后利用FCM检测CIK细胞对G0期CD34+CML白血病细胞的杀伤作用。半固体培养法检测CIK细胞对正常骨髓CFU-GM、BFU-E集落的影响。结果CIK细胞在培养第3周时,CD3+细胞数量达(97.29±3.55)%,CD3+CD56+细胞绝对数量增加了356倍,染色体分析证实,CIK细胞为正常核型,流式细胞仪检测CIK细胞对G0期CD34+CML白血病细胞平均杀伤率为66.73%。对照组与加入CIK细胞组的CFU-GM集落数分别为150±16和145±20,差异无统计学意义,P=0.38;两组的BFU-E集落数分别为68±5和65±8,差异无统计学意义,P=0.23。集落类型、大小两组相似,差异无统计学意义,P=0.46。结论CIK细胞可从CML患者外周血中大量扩增,来源于正常淋巴细胞,对G0期CD34+CML白血病细胞有明显抑制作用,对正常造血前体细胞无抑制作用,可作为过继细胞免疫治疗的效应细胞治疗CML。