金属蛋白酶抑制剂对外源Rac1表达介导的细胞侵袭胶原屏障的影响

目的 体外研究金属蛋白酶(MMPs)抑制剂对外源Rac1基因表达介导的HT1080纤维肉瘤细胞侵袭胶原屏障的影响.方法 分别转染显性负调控突变体Rac1V12N17(HN)、持续活化型Rac1V12(HV)或空载体(HW)于纤维肉瘤HT1080细胞,G418筛选.蛋白印迹分析检测外源性Rac1基因表达,并在含胶原蛋白凝胶的3D基质中培养,用得克萨斯红结合的鬼笔环肽染色显示细胞肌动蛋白骨架构型.在含胶原蛋白凝胶覆盖滤膜的Transwell小室进行细胞侵袭胶原屏障实验,并观察MMPs抑制剂和抑肽酶对上述细胞侵袭实验的影响.结果 HV细胞伸出明显的突起,HN细胞形态紧凑,HV细胞侵袭胶原屏障的能力大于HW细胞,而后者又强于HN细胞,这种差别在应用广谱MMPs抑制剂后消失,而抑肽酶则无影响.结论 外源活化型Rac1基因在纤维肉瘤HT1080细胞内稳定表达可诱发肌动蛋白纤维聚集,并可增加HT1080纤维肉瘤细胞侵袭胶原屏障的能力,但这种细胞侵袭胶原蛋白能力的增强可被MMPs抑制剂阻断.     

黏膜耐受治疗变应性疾病的研究进展

变态反应性疾病的治疗研究来进展很快,特别是通过黏膜耐受途径进行治疗引起人们广泛的关注。黏膜耐受是指通过口服、鼻腔或舌下等黏膜途径接触变应原,以降低外周淋巴组织中成熟淋巴细胞对变应原的敏感程度,进而达到治疗的目的。本文对黏膜耐受的机制及其在过敏性哮喘、变应性鼻炎、变应性喉炎等变态反应性疾病中的治疗研究进展予以综述。     

抑郁症认知功能损害特点的初步研究

目的:研究抑郁症认知损害的特点,尤其是难治性抑郁症认知损害的特点。方法:纳入符合入选及排除标准的抑郁症及难治性抑郁症患者,于基线时进行HAMD-17、HAMA-14量表评分,及认知功能测验,包括汉诺塔(TOH)、连线测验、WAIS-RC、语言流畅性、WCST。完成检查后,接受TCA、SSRI、SNRI三类抗抑郁药物中的一种药物治疗。治疗第1周末、第2周末、第4周末、第6周末用HAMD量表、HAMA量表、CGI量表评定疗效、用TESS量表观察不良反应。治疗第6周末复查认知功能测验。结果:病例组认知功能测验成绩显著低于对照组;治疗前后言语流畅性测验、WCST的总测验次数、持续错误数及随机错误数的比较均有统计学差异;治疗后患者的WCST的总测验次数、随机错误数的成绩较治疗前有改善但仍低于对照组。结论:抑郁症患者存在认知功能的缺损,随着临床症状的改善,认知功能可得到部分改善,但均不能在短时间内达到正常水平。     

脂联素基因276位点多态性与2型糖尿病肾病的关系

目的 研究山西地区汉族人脂联素基因276位点单核苷酸多态性(SNP)与2型糖尿病肾病之间的关系. 方法 选取262名山西地区汉族人,包括正常对照76例,2型糖尿病无肾病患者108例,2型糖尿病肾病患者78例.观测所选人群的临床指标,并针对脂联素基因276位点用聚合酶链反应-限制性内切酶长度多态性(PCR-RFLP)技术进行基因分型. 结果 ①SNP276基因型及等位基因频率在正常对照组和2型糖尿病组之间分布差异有统计学意义(P<0.05),2型糖尿病组G等位基因频率显著高于正常对照组(P<0.01).SNP276基因型及等位基因频率在2型糖尿病无肾病组与2型糖尿病肾病组之间分布差异无统计学意义(P>0.05).②正常对照组GG或GT型体重指数、收缩压、空腹胰岛素、胰岛素抵抗指数、空腹血糖均显著高于TT型.2型糖尿病无肾病组GG或GT型收缩压、空腹胰岛素、胰岛素抵抗指数、空腹血糖均显著高于TT型.2型糖尿病肾病组GG或GT型收缩压、胰岛素抵抗指数显著高于TT型. 结论 在中国山西汉族人群中,与TT型相比,携带GG GT型者患2型糖尿病的危险因素增加.G等位基因是胰岛素抵抗、2型糖尿病的危险因素;脂联素SNP276G/T与2型糖尿病相关,与糖尿病.肾病无关.     

Peroxisome proliferator-activated receptor α agonist attenuates oxidized-low density lipoprotein induced immune maturation of human monocyte-derived dendritic cells

Accumulating evidence suggests that the Thl immune .response induced by various antigens such as oxidized low density lipoprotein （ox-LDL） and heat shock proteins （HSPs） play a key role in the process of atherosclerosis.1Dendritic cells （DCs） are the most potent antigen-presenting cells （APCs） in the body with the unique ability to initiate a primary immune response to certain antigens by the activation of ＂naive＂ T cells.2 The maturation of DC with the upregulation of costimulatory molecules such as CD83, CD40, CD86, and major histocompatibility complex （MHC） class molecules such as human leukocyte antigen （HLA）-DR, is required for DC to activate T cells. Pathologic studies have shown that immature DCs are present in normal arterial while abundant mature DCs clustered with T cells could be visualized in atherogenic vessels suggesting that DC 3 maturation is linked to the progression of atherosclerosls. Peroxisome proliferator-activated receptors （PPARs） a, one member of the family of PPARs, was found to have favorable effects on slowing the progression of atherosclerosis and reducing the risk of coronary heart disease in high-risk patients independent from their metabolism effects.4＇5 Furthermore, PPAR-α is also expressed on monocytes and monocyte-derived DCs.6 The effects of PPAR-α on DCs maturation and immune function remain unknown now, we therefore observed the effects of fenofibrate, a PPAR-α agonist, on the maturation and immune function of oxidized LDL-treated DCs in this study.     

Combining TGF-beta inhibition and angiotensin II blockade results in enhanced antifibrotic effect

BACKGROUND: Although angiotensin II (Ang II) blockade is rapidly becoming standard antifibrotic therapy in renal diseases, current data suggest that Ang II blockade alone cannot stop fibrotic disease. New therapies, such as antibodies to transforming growth factor-beta (TGF-beta), or drug combinations will be required to further slow or halt disease progression. Here, using the anti-Thy1 model of glomerulonephritis, the maximally therapeutic dose of the TGF-beta neutralizing mouse monoclonal antibody (1D11) was determined and compared with the maximally effective dose of enalapril. Then, the effect of combining both treatments at maximal doses was determined. METHODS: After disease induction with the anti-Thy1 antibody, OX-7, increasing doses of 1D11 were given intraperitoneally (IP) on days 1, 3, and 5. Enalapril was administered in drinking water from day 1. The fibrotic response was assessed at day 6. RESULTS: 1D11 dose-dependently reduced fibrosis, with the 0.5 and 5 mg/kg doses showing maximal therapeutic effects, reducing period-acid Schiff (PAS) staining by 56% and 45%, respectively. Fibronectin and collagen I staining was reduced by 32% to 36%, respectively. Glomerular mRNA and production of fibronectin, plasminogen activator inhibitor-1 (PAI-1), TGF-beta1, and p-Smad2 protein were also reduced. The maximal therapeutic effects of 1D11 and enalapril alone were very similar. However, combination therapy led to further reduction in disease. Notably, matrix deposition was reduced by 80%. CONCLUSION: While 1D11 or enalapril at maximal doses reduce fibrosis equally, simultaneous blockade of Ang II and TGF-beta reduces fibrotic disease considerably more, offering hope that such drug combinations may confer a therapeutic advantage over angiotensin blockade alone.     

咽痛灵合剂的薄层色谱鉴别方法研究

目的鉴别咽痛灵合剂中的一枝黄花、土牛膝。方法采用薄层色谱法。结果建立简便、灵敏、可靠的薄层色谱(TLC)法。结论可用于该品质量控制。     

退热贴凝胶剂制备工艺的研究

目的优选退热贴凝胶剂最佳成型工艺。方法以正交法设计实验,对比凝胶剂的均匀性、可涂展性、残留性、剥离强度、皮肤粘贴性、搅拌时间、搅拌速度、黏度与pH的关系、基质各组分的添加顺序进行实验研究。同时对最佳含水量进行单因素考察。结果优选出制备工艺的最佳条件,搅拌时间420 min,搅拌速度600 r.min-1;增稠剂组分先与胶粘剂组分混合,最后再加入黏度调节剂组分;膏体含水量为45%~53%时粘贴性能好,pH5.0~7.0时粘贴性能最佳。结论应用该法制备的退热贴凝胶剂配方合理,粘性有显著改善,产品符合《中国药典》2005年版的规定。     

"三联疗法"治疗乳腺增生症68例

近几年来，笔者在中医辨证施治的基础上．配合巾药局部外敷及食疗，简称“三联疗法”，治疗乳腺增生症68例，获得满意疗效，现报道如下：     

淋巴-浆细胞恶性血液病患者p73基因表达及与预后的关系

目的：探讨p73基因在急性淋巴细胞白血病（ALL）和多发性骨髓瘤（MM）发生发展中的机制。方法：应用RT-PCR技术检测58例ALL患者和40例多发性骨髓瘤的p73基因mRNA表达情况,并结合患者的临床资料进行分析。结果：58例ALL患者中,p73mRNA阴性表达率为32.8%（19/58）,40例MM患者p73mRNA均阳性表达。p73mRNA阴性表达与ALL患者首次化疗既获完全缓解及平均缓解时间的降低有明显关系。结论：p73mRNA检测对判断ALL患者预后有一定的意义。p73基因异常可能不是MM发病的重要分子事件。