中国西南地区汉族人群肿瘤坏死因子基因多态性与鼻咽癌遗传易感性

目的:分析肿瘤坏死因子基因多态性分布与中国西南地区汉族人群鼻咽癌易感性的关系。方法:选择2000-10/2005-09在华西医科大学第一附属医院就诊的100例鼻咽癌患者为鼻咽癌组,均经过病理科活检确诊,其中包括未治疗44例,放疗后37例,放疗加化疗后19例,选择100名同期入院健康体检者为对照组。所有受试对象为中国西南地区汉族人,均对检测项目知情同意。采用聚合酶链反应-限制性片段长度多态性的方法检测100例中国西南地区汉族鼻咽癌患者和100名健康对照者肿瘤坏死因子α基因启动子区-308位点及肿瘤坏死因子β基因第一内含子252位点的等位基因以及基因型频率,分析两位点多态性与鼻咽癌遗传易感性的关系。结果:鼻咽癌组患者肿瘤坏死因子β( 252)位点G/A杂合子基因型频率显著高于对照组(57%,29%,P<0.01),野生型(G/G基因型)频率低于健康对照组(23%,51%,P<0.01),等位基因A的频率高于健康对照组(48.5%,13%,P<0.01);肿瘤坏死因子α(-308)位点基因型以及等位基因频率与对照组相比较无统计学差异。结论:本实验人群中未发现肿瘤坏死因子α(-308)位点多态性与鼻咽癌易感性无关;肿瘤坏死因子β( 252)位点基因多态性与鼻咽癌具有相关性,A等位基因可能是鼻咽癌的遗传易感基因,G/A杂合子基因型个体较易患鼻咽癌。     

In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins

It has been shown recently in China that arsenic trioxide (As2O3) is a very effective treatment for acute promyelocytic leukemia (APL). APL patients resistant to all-trans retinoic acid (ATRA) and conventional chemotherapy can still respond to AS2O3. In this study, we addressed the possible cellular and molecular mechanisms of this treatment by using NB4 cells as a model. The results show that: (1) As2O3 triggers relatively specific NB4 cell apoptosis at micromolar concentration, as proved by morphology, histogramic related nuclear DNA contents, and DNA gel eletrophoresis. (2) As2O3 does not influence bax, bcl-x, c-myc, and p53 gene expression, but downregulates bcl-2 gene expression at both mRNA and protein levels. (3) As2O3 induces a significant modulation of the PML staining pattern in NB4 cells and HL-60 cells. The micropunctates characteristic of PML-RAR alpha in NB4 cells dissappear after treatment with As2O3, whereas a diffuse PML staining occurs in the perinuclear cytoplasmic region. In addition, a low percentage of untreated NB4 cells exhibits an accumulation of PML positive particles in a compartment of cytoplasm. The percentage of these cells can be significantly increased after As2O3 treatment. A similar PML staining pattern is observed in apoptotic cells. (4) ATRA pretreatment does not influence As2O3-induced apoptosis. These results suggest that induction of cell apoptosis can be one of the mechanisms of the therapeutic effect of As2O3. Moreover, this apoptosis induction occurs independently of the retinoid pathway and may be mediated, at least partly, through the modulation of bcl-2, as well as PML-RAR alpha and/ or PML proteins.     

喹诺酮类C-2位构效关系的分子力学和量子化学研究

利用CNDO/2(全略微分重叠半经验分子轨道法)和MMPI(适于含π体系计算的分子力学法)对喹诺酮类化合物C-2位构效关系进行了研究。结果表明:羧基与酮基的共平面性对生物活性有重要影响;羧基与酮基上氧和N1位氮上的电荷密度与生物活性有一致性关系。     

莶脂溶性成分的研究

从莶（ＳｉｅｇｅｓｂｅｃｋｉａｏｒｉｅｎｔａｌｉｓＬ）的地上部分，分离出八个化合物，其中Ｉ和Ｉ根据理化性质和光谱数据确定其结构为ｅｎｔ１７ａｃｅｔｏｘｙ１８ｉｓｏｂｕｔｙｒｙｌｏｘｙ１６（α）ｋａｕｒａｎ１９ｏｉｃａｃｉｄ（Ｉ）和ｅｎｔ１７ｅｔｈｏｘｙ１６（α）ｋａｕｒａｎ１９ｏｉｃａｃｉｄ（ＩＩ），均为新化合物，分别被命名为莶酯酸（ｓｉｅｇｅｓｅｓｔｅｒｉｃａｃｉｄ，Ｉ）和莶醚酸（ｓｉｅｇｅｓｅｔｈｅｒｉｃａｃｉｄ，Ｉ）。其余化合物分别鉴定为腺梗莶萜醇酸（ｅｎｔ１６β，１７ｄｉｈｙｄｒｏｘｙｋａｕｒａｎ１９ｏｉｃａｃｉｄ，ＩＩ），奇任醇（ｋｉｒｅｎｏｌ，ＩＶ，β谷甾醇葡萄糖甙（βｓｉｔｏｓｔｅｒｏｌｇｌｕｃｏｓｉｄｅ，Ｖ），二十一醇（ｈｅｎｅｉｃｏｓａｎｏｌ，ＶＩ），花生酸甲酯（ｍｅｔｈｙｌａｒａｃｈｉｄａｔｅ，ＶＩＩ）和β谷甾醇（βｓｉｔｏｓｔｅｒｏｌ，ＶＩＩ）。除奇任醇和β谷甾醇外，均为首次从该植物中分得。     

动脉粥样硬化性脑梗死患者血同型半胱氨酸的变化

目的:探讨同型半胱氨酸(Hcy)与动脉粥样硬化性脑梗死的关系. 方法:采用高效液相色谱法检测98例动脉粥样硬化性脑梗死患者血浆Hcy水平,并与50例对照组进行比较分析. 结果:病例组空腹血浆Hcy含量(21.4±2.3) μmol/L显著高于对照组(10.2±1.5) μmol/L(P﹤0.01). 血浆Hcy升高率,病例组(48.0%)高于对照组(6.0%),两者存在极显著差异. 结论:高Hcy血症作为一种新的独立危险因素参与了动脉粥样硬化性脑梗死的发生、发展过程.     

辛夷水溶性成分研究

从辛夷(Magnolia biondii pamp.)水溶性部位分离得到三个化合物,木兰碱(Ⅰ),E-对羟基桂皮酸乙酯(Ⅱ)及一个新化合物(Ⅲ),利用光谱法确定其结构为山萘素-7-O-β-(6″-对羟基桂皮酰)-D-葡萄糖甙。命名望春花黄酮醇甙Ⅰ(biondnoidⅠ,Ⅲ)。     

Histopathological changes of Macaca mulatta infected with Plasmodium knowlesi

目的　探讨诺氏疟原虫 (Plasmodiumknowlesi)感染恒河猴 (Macacamulatta)引起有关脏器的病理组织学变化。方法　病解 3例感染疟原虫未经治疗病死的猴 ;2例感染疟原虫经青蒿琥酯 (artesunate)栓剂治疗后又复发的猴 ;1例感染疟原虫经磷酸哌喹 (piperaquinephosphate)治愈后死于上肢坏死感染的猴。对有关脏器均进行切片检查。结果　 3例 (1号、7号和 12号 )未经治疗而病死的猴和 1例 (72号 )虽经青蒿琥酯栓剂治疗但很快被排出体外的猴的心、肝、脾、肺、肾、大小脑、胰腺、甲状旁腺、脑垂体和淋巴结等均有严重病变 ,含原虫的红细胞和疟色素聚集于这些脏器的毛细血管内。 1例 (131号 )经用哌喹治愈而死于上肢坏死的猴 ,除见多个脏器内有色素沉积或被巨噬细胞吞噬外 ,可见胰岛细胞、甲状旁腺和垂体细胞萎缩和消失等病变。 1例 (33号 )用青蒿琥酯栓剂治疗后短期原虫转阴 ,但又复燃的猴被灌药致死 ,多个脏器所见与感染后未经治疗者明显不同 ,仅见肝脏Kupffer细胞和大脑基质细胞内含原虫和疟色素 ,多个脏器均呈修复。结论　本文报导了诺氏疟原虫感染恒河猴后各有关脏器的病理组织学变化 ,特别是观察到胰岛细胞、甲状旁腺和垂体细胞的萎缩和消失与心肌细胞的溶解是国内外文献所未记载过的。     

丹参素和丹酚酸对胎鼠脑神经干细胞迁移的诱导

目的:以丹参水溶性成分丹参素、丹酚酸为干预药物,观察其对胎鼠脑神经干细胞迁移的诱导作用。方法:实验于2006-03/08在广州暨南大学医学院完成。①丹参素(粉剂,纯度大于90%,昆明长春花科技公司生产,批号1108552200203);丹酚酸(粉剂,纯度大于90%,昆明长春花科技公司生产,批号CCH601012);MBC96型趋化小室(NeuroProbe公司)。②取妊娠13.5d昆明种小鼠2只,处死后取出胎鼠,分离其胎脑神经干细胞进行传代培养。取培养至对数生长期的细胞,采用Boyden小室法观察细胞迁移情况。取单细胞悬液50μL,分别加入Boyden小室的12个上室;取分别含有5,10,20,40,80,100mg/L丹参素和5,10,20,40,80,100mg/L丹酚酸的DMEM培养基各450μL,加入Boyden小室的12个下室;另2孔以不含丹参素和丹酚酸的DMEM培养基作为空白对照。上下两室以预先包被Ⅰ型胶原的聚碳酸酯微孔滤膜相隔。将Boyden小室置于37℃、体积分数为0.05的CO2培养箱中培养24h,取出微孔滤膜,用甲醇将迁移至微孔滤膜下层的细胞固定,Nissl染色,显微镜下随机选择3个不同视野,计数膜上不同层次的细胞数。③选取昆明种小鼠18只,随机数字表法分为生理盐水对照组、丹参素组、丹酚酸组,6只/组。丹参素组于侧脑室内连续注射80mg/L丹参素5μL,丹酚酸组注射40mg/L丹酚酸5μL,生理盐水对照组注射等量生理盐水,共3d,术后14d处死,取脑,制备切片,行ABC免疫细胞化学染色,观察丹参素和丹酚酸干预后nestin阳性神经元的分布变化。结果:18只小鼠全部进入结果分析。①不同质量浓度的丹参素对神经干细胞迁移的诱导:与空白对照比较,5,10mg/L的丹参素促神经干细胞迁移的作用并不明显(t=1.037,1.374,P>0.05);20,40mg/L的丹参素可明显促进神经干细胞的迁移(t=2.894,3.468,P<0.01);当丹参素质量浓度为80mg/L时促迁移作用最为强烈(t=4.031,P<0.01),之后有所减弱。②不同浓度的丹酚酸对神经干细胞迁移的诱导:与空白对照比较,5mg/L的丹酚酸促神经干细胞迁移的作用并不明显(t=1.365,P>0.05);10,20mg/L的丹酚酸可明显促进神经干细胞的迁移(t=3.021,3.947,P<0.01);当丹酚酸质量浓度为40mg/L时促迁移作用最为强烈(t=4.342,P<0.01),之后有所减弱。③丹参素和丹酚酸对小鼠室管膜下nestin阳性神经元迁移的影响:丹参素组侧脑室内侧和外侧的nestin阳性细胞的数量多于生理盐水对照组,而且并不局限于侧脑室周围区,在脑皮质和尾壳核可见少量的阳性细胞,细胞的突起明显,伸向皮质方向,侧脑室内侧的阳性细胞有相似的特征。丹酚酸组侧脑室周围的阳性细胞数量多,而且在皮质和尾壳核检测到大量的阳性细胞。结论:丹参素和丹酚酸均具有诱导胎鼠脑神经干细胞迁移的作用,且丹酚酸的作用优于丹参素。     

Study on enhancement of fibronectin-mediated bacillus Calmette-Guerin attachment to urinary bladder wall in rabbits

To clarify whether intravesical usage of fibrin clot stabilizer epsilon-aminocaproic acid （EACA） or p-aminomethyl benzoic acid （PAMBA） and different injuries enhance fibronectin （FN）-mediated bacillus Calmette-Guerin （BCG） attachment to bladder wall. Thirty New Zealand male white rabbits were randomly divided into five groups and the bladder wall of each rabbit was injured by electrocautery, cryocautery or knife cutting on left lateral wall, right lateral wall and posterior wall in different groups, respectively. Different drug was instilled into the bladder： Group A： pure PBS; B： PBS and radiolabeled BCG （3H-BCG） ; C： EACA and 3H-BCG; D： PAMBA and 3H-BCG; E： heparin and 3 H-BCG. After instillation, each injured and non-injured bladder wall were surgically harvested and digested. The quan- tity of BCG attachment was detected by liquid scintillation counter （scintillation times per min, STPM）. Quantity of BCG attachment to injured bladder wall was significantly （P 〈 0.01 ） greater than that of non-injured one, no matter which injury was performed. The BCG attachment to bladder wall in Group C or Group D was significantly （ P 〈 0.05） greater than that of Group B. The quantity of BCG attachment to bladder of Group E was significantly （P 〈 0.05） less than that of Group B, C and D, respectively. Intravesical instillation of fi- brin clot stabilizer （PAMBA, EACA） enhances FN-mediated BCG attachment to bladder wall while heparin inhibits this process. Injuries; e.g. , cutting, cryocautery or electrocautery of bladder wall can significantly increase BCG attachment to the bladder wall.     

中西医结合治疗男性免疫性不育症1806例

0 引言近年来的免疫学研究发现,不明原因的不育患者体内存在着抗精子抗体(Anti-sperm antibody, ASAb)并对不育产生影响[1,2]. 我院近年来对抗体阳性者进行了中西医结合治疗,有效消除了抗体,取得了较好的临床效果,现报道如下.