肾移植术后检测可溶性白介素2受体和肿瘤坏死因子的临床意义

本文用ＥＬＩＳＡ和放射免疫分析检测了５７例肾移植患者血清中可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）和肿瘤坏死因子（ＴＮＦ）水平。患者术前ｓＩＬ－２Ｒ和ＴＮＦ明显高于正常对照组，术后两者都逐渐下降，排斥反应时升高，排斥组无排斥组差异显著。ＣｓＡ中毒组与无排斥组无明显差异，因此ｓＩＬ－２Ｒ和ＴＮＦ水平监测也可区别ＣｓＡ中毒和排斥反应。动态检测ｓＩＬ－２Ｒ和ＴＮＦ水平可作为肾移植后判断疗效和预后的重要观察     

NK细胞在小鼠异基因骨髓移植中的作用

目的:研究自然杀伤(NK)细胞在异基因骨髓移植中对移植物抗宿主病(GVHD)、移植排斥、骨髓植入及造血重建的影响。方法:以近交系小鼠C57/6j(H-2^b)为供鼠、BALB/c(H-2^d)为受鼠,在移植物中增加供者的外周T细胞和/或NK细胞进行异基因骨髓移植,用流式细胞仪检测受鼠的CD₃₄^＋细胞计数和H-2K^b＋细胞表达水平,血细胞自动分析仪检测外周血白细胞计数,并结合临床表现和病理检查,比较不同移植组的存活率、GVHD、植入水平及造血重建等。结果:增加NK细胞组的小鼠存活率显著大于不增加NK细胞组,小鼠出现GVHD的数量少、程度轻,外周血白细胞及骨髓CD₃₄^＋细胞恢复快、H-2K^b＋细胞表达水平高。结论:NK细胞抑制小鼠异基因骨髓移植中的GVHD和移植排斥,促进骨髓植入及造血重建。     

AT_1受体在脑胆碱能刺激引起的孤束核TH-IR变化中的作用

本工作选用清醒SD雄性大鼠,利用免疫组织化学方法,观察大鼠侧脑室注射胆碱能激动剂氨甲酰胆碱后孤束核内儿茶酚胺能神经元活性的变化以及阻断脑AT1受体对上述变化的影响。免疫组织化学结果显示:侧脑室注射氨甲酰胆碱(.5μg)后40 min,孤束核内酪氨酸羟化酶(TH)免疫反应阳性神经元数目明显增多(P<0.05),免疫染色强度明显增强(P<0.05)。losartan(20μg)预处理后孤束核内TH免疫反应活性明显下降(P<0.05)。上述结果提示,侧脑室注射胆碱能激动剂氨甲酰胆碱对孤束核内儿茶酚胺能神经元具有兴奋作用,阻断脑血管紧张素能AT1受体可部分抑制氨甲酰胆碱在孤束核诱导的上述变化。     

Understanding the recent evolution of the human genome: insights from human-chimpanzee genome comparisons

The sequencing of the chimpanzee genome and the comparison with its human counterpart have begun to reveal the spectrum of genetic changes that has accompanied human evolution. In addition to gross karyotypic rearrangements such as the fusion that formed human chromosome 2 and the human-specific pericentric inversions of chromosomes 1 and 18, there is considerable submicroscopic structural variation involving deletions, duplications, and inversions. Lineage-specific segmental duplications, detected by array comparative genomic hybridization and direct sequence comparison, have made a very significant contribution to this structural divergence, which is at least three-fold greater than that due to nucleotide substitutions. Since structural genomic changes may have given rise to irreversible functional differences between the diverging species, their detailed analysis could help to identify the biological processes that have accompanied speciation. To this end, interspecies comparisons have revealed numerous human-specific gains and losses of genes as well as changes in gene expression. The very considerable structural diversity (polymorphism) evident within both lineages has, however, hampered the analysis of the structural divergence between the human and chimpanzee genomes. The concomitant evaluation of genetic divergence and diversity at the nucleotide level has nevertheless served to identify many genes that have evolved under positive selection and may thus have been involved in the development of human lineage-specific traits. Genes that display signs of weak negative selection have also been identified and could represent candidate loci for complex genomic disorders. Here, we review recent progress in comparing the human and chimpanzee genomes and discuss how the differences detected have improved our understanding of the evolution of the human genome.     

B cell elimination in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution, potentially life-threatening with considerable morbidity. The elimination of pathogenic B cells has emerged as a rational therapeutic option. Many open label studies have reported encouraging results in which clinical and serological remission have invariably been described, often enabling the reduction of steroid and immunosuppressive treatment. However, the results from randomized controlled studies have been disappointing and several questions remain to be answered. In this review we will focus on results of B cell direct depletion in the treatment of patients with systemic lupus erythematosus.     

EL9611红白血病小鼠急性GVHD动物模型的建立

目的: 建立EL9611红白血病小鼠急性移植物抗宿主病(GVHD)的动物模型。方法: 同种异基因骨髓移植(allo-BMT)以C57BL/6(H-2^b)鼠为供鼠,BALB/c(H-2^d)为受鼠。设白血病组(n=10)、照射对照组(白血病鼠照射后不进行allo-BMT,n=4)、GVHD组(白血病鼠照射+allo-BMT,n=10)及正常对照组(n=4)。白血病组采用每只BALB/c鼠尾静脉输注2×10⁶个EL9611红白血病细胞建立红白血病动物模型;GVHD组于接种白血病细胞7 d后行总剂量为8.0 Gy的1次性 γ射线全身照射(TBI),照射后5 h内每只小鼠尾静脉输注C57BL/6鼠骨髓细胞2×10⁶个＋脾细胞1×10⁷个,建立EL9611红白血病小鼠的急性GVHD动物模型。观察小鼠体位、皮毛、大便等临床表现,病理检查肝脾、皮肤、小肠、外周血和骨髓,计算生存率。结果: 白血病组生存时间(14.5±2.1) d ,生存时间与GVHD组相比P<0.01,死亡率100％,无自发缓解,死亡时肝脾肿大(肝重2.40 g±0.48 g,脾重0.84 g±0.20 g,与正常对照组比P<0.01),外周血WBC升高 ,病理检查示组织正常结构破坏,白血病细胞浸润。照射对照组生存时间为(9.0±0.7) d,生存时间与GVHD组和正常对照组相比差异显著(P<0.01),死亡率100％,病理检查显示造血衰竭。GVHD组生存时间为(32.0±3.2)d,生存时间与其它各组相比P<0.01,死亡率100％,allo-BMT后第10-13 d出现症状,临床表现和病理检查符合Ⅰ到Ⅱ度GVHD的改变。结论: 采用EL9611红白血病细胞(2×10⁶/鼠)静脉输注的方式可成功建立EL9611红白血病动物模型;接种EL9611红白血病细胞第7 d行TBI +allo-BMT可成功建立EL9611红白血病小鼠的急性GVHD动物模型。     

2-正丁基-4-氯-5-甲酰基咪唑的合成新路线

目的：合成抗高血压药氯沙坦的关键中间体2-正丁基-4-氯-5-甲酰基咪唑。方法：戊腈与甲醇在甲醇钠的作用下加成得到1-甲氧基-1-亚胺戊烷（2）,经取代、环合得到目标化合物2-正丁基-4-氯-5-甲酰基咪唑（1）。结论：本工艺具有试剂易得,反应条件温和,收率高（59.02%）的特点,适合工业化生产。     

高脂环境下ET-1在系膜细胞与内皮细胞相互关系中的作用及氯沙坦的干预作用

目的探讨高脂条件下内皮素-1（ET-1）在系膜细胞与内皮细胞相互关系中的作用及氯沙坦的干预作用。方法建立人肾小球系膜细胞与内皮细胞的共培养模型，待细胞生长至80％融合时加入无血清DMEM同步化12h，实验分为对照组、高脂组、干预组及氯沙坦组，分别加入D-葡萄糖、溶血卵磷脂（LPC）、LPC拮抗剂BQ-123及氯沙坦，培养24h后采用ELISA法测定细胞上清液Ⅳ型胶原（Col Ⅳ）、纤维连接蛋白（Fn）含量，放免法测定上清液ET-1水平。结果高脂组共培养和单培养细胞上清液中Fn、Col Ⅳ和ET-1水平显著高于对照组（P均〈0．05），尤以共培养时为著；干预组Col Ⅳ、Fn、ET-1水平及氯沙坦组Col Ⅳ、Fn水平显著低于高脂组（P均〈0．05）。结论高脂环境下，系膜细胞与内皮细胞存在异常的相互作用，这种作用能促进Fn、Col Ⅳ、ET-1产生；高脂刺激的Fn、Col Ⅳ分泌增加可能与ET-1有关；氯沙坦通过干预系膜细胞与内皮细胞的相互关系而产生肾脏保护作用。     

Catheter ablation vs. amiodarone plus losartan for prevention of atrial fibrillation recurrence in patients with paroxysmal atrial fibrillation

Background  Although amiodarone plus angiotensin II receptor blockers (ARBs) and catheter ablation may improve sinus rhythm maintenance of paroxysmal atrial fibrillation (AF), their clinical efficacies have not been compared. This prospective cohort study was designed to compare clinical efficacy of catheter ablation and amiodarone plus losartan on sinus rhythm maintenance in patients with paroxysmal AF.
Materials and methods  A total of 240 patients with paroxysmal AF were assigned to four groups. CPVA group ( n =  60) was treated with circumferential pulmonary vein ablation (CPVA), SPVI group ( n  = 60) with segmental pulmonary vein isolation, AMIO group ( n  = 60) with amiodarone and AMIO + LO group ( n  = 60) with amiodarone plus losartan. The endpoint was documented recurrence of AF > 30 s by Holter or conventional 12-lead ECG in the 1-year follow-up period.
Results  During 12 months of follow-up, the primary end point was reached in 28 patients in CPVA group, 14 patients in SPVI group, 25 patients in AMIO group and 13 patients in AMIO + LO group, respectively. The sinus rhythm in SPVI and AMIO + LO group were significant higher than that in CPVA and AMIO group ( P  < 0·01 and 0·025), and no difference between CPVA and AMIO group. The maintenance rate of sinus rhythm in SPVI group was similar to that in AMIO + LO group.
Conclusions  This study demonstrates that segmental pulmonary vein isolation in preventing AF recurrence is similar to amiodarone plus losartan, but it is superior to CPVA and amiodarone alone in patients with paroxysmal AF. Larger multicentre studies are needed to confirm its long-term outcomes.     

膀胱充盈状态对前列腺癌三维适形放疗靶区和重要器官的影响

目的在前列腺癌三维适形放疗中,研究对比膀胱充盈和排空状态下靶区和周边重要器官体积改变以及照射剂量变化。方法临床穿刺细胞学证实的前列腺癌早期(T1～T2NOMO期)病例10例,无严重合并症,行对称6个野三维适形放疗。CT定位前1.0、0.5 h口服稀释造影剂各400 ml。定位时留置导尿,排空膀胱后仰卧位CT全盆腔定位扫描,然后注入稀释造影剂250～300 ml充盈膀胱,再次CT定位扫描。CT影像上勾画前列腺靶区和周围重要器官轮廓,三维计划设计。分别评估CTV、PTV、直肠、膀胱、股骨头和盆腔小肠体积,CTV、PTV、直肠、膀胱、股骨头、盆腔小肠平均照射剂量,以及50 Gy膀胱、直肠,30 Gy股骨头受照体积和盆腔小肠最大照射剂量,对比不同膀胱充盈状态下各器官结构体积变化以及照射剂量差别。结果与膀胱排空相比膀胱充盈使体积增加了499%,分别为(67±9)、(336±48)ml(P=0.000),CTV、PTV、直肠、股骨头、盆腔小肠的变化无统计学意义(P=0.153、0.501、0.929、0.771、0.081)。充盈时膀胱受照剂量仅为排空时的35%,分别为(1501±201)、(4267±216)cGy(P=0.000);盆腔小肠受照剂量下降了75%,分别为(257±223)、(60±25)cGy(P=0.012);CTV、PTV、直肠、股骨头的变化无统计学意义(P=0.423、0.540、0.123、0.704)。照射50 Gy的膀胱体积因膀胱充盈减少了14%(P=0.001),直肠、股骨头的变化无统计学意义(P=0.675、1.000),盆腔小肠最大照射剂量仅为排空状态下的10%(P=0.004)。结论前列腺癌三维适形放疗中膀胱充盈状态对膀胱体积有影响,与膀胱排空相比膀胱充盈能减少膀胱、盆腔小肠照射剂量,对膀胱、盆腔小肠起一定保护作用。