临床病例讨论第310例——胸闷、双下肢疼痛、腰腹痛

患者男，48岁。因间断胸闷、双下肢疼痛、间歇性跛行2年，加重并伴腰腹痛2个月，于2003年10月29日入院。患者2001年5月16日晨起无诱因突发心前区压榨性疼痛，于当地医院诊为“冠心病、急性心肌梗死(AMI)(下壁)”，予尿激酶溶栓，低分子肝素抗凝，扩冠及抗血小板等治疗。5月20日突发双眼左侧偏盲，头颅CT示腔隙性脑梗死。5月30日患者冠状动脉造影示右冠状动脉100％闭塞，前降支中段     

705例血脂结果分析

<正> 脂代谢受年龄、性别、生活习惯等因素影响,为了解本区域脂代谢状况,对705例体检者血清胆固醇(TC)、甘油三脂(TG),高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)测定,现将结果分析报告如下:     

世界健康十大威胁

<正> 世界卫生组织(WHO)近日公布了人类健康十大危险因素(Lancet 2002,360:1347),它们是:①营养不良。在贫穷国家,每年有超过300万人死于饥饿和贫困所造成的营养不良。②不安全性行为。在非洲,超过99％的人由于不安全的性行为,感染上了艾滋病病毒,以撒哈拉沙漠和以南地区最为严重。③不洁水源或环境和个人卫生。每     

糖耐量减低患者胰岛素抵抗与颈动脉粥样斑块的相关性分析

目的　探讨胰岛素抵抗 (IR)在糖耐量减低 (IGT)大血管并发症中的作用。方法　测定 1 2 0名IGT患者和 96名糖耐量正常(NGT)对照者的空腹血糖 (FBG)、胆固醇 (TC)、甘油三酯 (TG)、胰岛素 (FINS)及餐后 2h血糖 (PBG) ,并测量身高、体重、腰围、臀围 ,计算相对胰岛素敏感指数 (RISI)、体重指数 (BMI)、腰臀比 (WHR) ,结合其颈动脉多普勒超声检测结果进行对比分析。结果　IGT组及NGT组颈动脉粥样斑块发生率有显著性差异 (P <0 .0 0 1 ) ,斑块面积与RISI呈负相关 (r =- 0 .45 ,P <0 .0 1 ) ,与餐后 2h血糖 (r =0 .39,P <0 .0 1 )、BMI(r=0 .48,P <0 .0 1 )及WHR(r=0 .41 ,P <0 .0 1 )正相关 ,而与TG、FBG、TC、FINS无相关性 (P >0 .0 5)。IGT组患者有斑块和无斑块者之间RISI、WHR、BMI、餐后 2h血糖、TG之间也存在显著性差异 (P <0 .0 1 )。结论　胰岛素抵抗与颈动脉粥样硬化的发生密切相关 ,是IGT患者发生大血管并发症的重要原因。     

Extracellular signal regulated kinases 1/2 signal pathway and responses of astrocytes after diffuse brain injury

BACKGROUND: The treatment of diffuse brain injury during an acute period is focused on relieving degrees of secondary brain injury. Generation and development of pathological changes of secondary brain injury depend on signal conduction, so down-regulating over response of astrocyte through interfering a key link of signal conduction pathway may bring a new thinking for the treatment of diffuse brain injury. OBJECTIVE: To observe the effect of over activity of extracellular signal regulated kinases 1/2 (ERK1/2) signal pathway on the response of astrocyte during an acute period of diffuse brain injury. DESIGN: Completely randomized grouping and controlled animal study. SETTINGS: Department of Neurosurgery, the Third Affiliated Hospital, Nanchang University; Department of Neurosurgery, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology. MATERIALS: A total of 158 healthy male SD rats, of 11 weeks old, weighing 320–370 g, were provided by Experimental Animal Faulty, Tongji Medical College, Huazhong University of Science and Technology. Rabbit-anti-phosphorylated ERK1/2 (pERK1/2) polyclonal antibody was provided by R&D Company; rabbit-anti-glial fibrillary acidic protein (GFAP) polyclonal antibody, SP immunohistochemical kit and horseradish peroxidase (HRP)-labeled goat-anti-rabbit IgG by Santa Cruz Company; specific inhibitor U0126 of ERK1/2 signal pathway by Alexis Company. METHODS: The experiment was carried out in the Laboratory of Neurosurgery, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from September 2004 to March 2006. ① Detection of pERK1/2 expression: A total of 110 rats were randomly divided into sham operation group (n =5), model group (n =35), high-dosage U0126 group (n =35) and low-dosage U0126 group (n =35). Rats in the sham operation group were only treated with incision of epicranium and fixation of backup plate, but not hit. Rats in the model group were used to establish diffuse brain injury models based on Marmarou free falling body without drug intervention. Rats in the high- and low-dosage U0126 groups were injected into caudal vein with 0.1 and 0.05 mg/kg U0126, respectively, and then, rats were hit to establish injured models. Every 5 rats were collected from model, high- and low-dosage U0126 groups at 5, 30 minutes, 3, 12, 24, 72 hours and 7 days after diffuse brain injury to detect pERK1/2 expression in cortex of parietal lobe based on Western blot technique. ② Distribution of pERK1/2 and positive GFAP cells in brain tissue: Another 48 rats were randomly divided into sham operation group (n =3), model group (n =15), high-dosage U0126 group (n =15) and low-dosage U0126 group (n =15). The intervention and administration were dealt as the same as those mentioned above. Every 3 rats were collected from model, high- and low-dosage U0126 groups at 30 minutes, 3, 12, 24 and 72 hours after model establishment to observe the distribution of pERK1/2 and postive GFAP cells in brain tissue which was cut from coronal section at Bregma –4.8 mm layer with immunohistochemical staining. MAIN OUTCOME MEASURES: pERK1/2 expression in cortex of parietal lobe and distribution of pERK1/2 and positive GFAP cells in brain tissues. RESULTS: ① pERK1/2 expression: After diffuse brain injury, pERK1/2 expression in cortex of parietal lobe was rapidly increased in the model group, reached at peak at 5 minutes and then decreased gradually. But the expression was still in a high level until the 72nd hour and fallen to the basic level on the 7th day. pERK1/2 level was lower in high- and low-dosage U0126 groups than that in model group at various time points (P < 0.01); meanwhile, pERK1/2 level was lower in high-dosage U0126 group than that in low-dosage U0126 group. The results showed that there was a certain dosage dependence on pERK1/2 expression. ② Distribution of pERK1/2 and positive GFAP cells in brain tissue: Positive expression of pERK1/2 lasted in brain tissue from 30 minutes to 72 hours after diffuse brain injury (P < 0.05). In addition, from 30 minutes to 3 hours, brown-yellow stained cells were mainly distributed in plasma, but rarely in nucleus. A lot of positive cells had tree-like apophysis, which was similar to neurons. With the time passing by, more and more nuclei manifested positive stains; moreover, nuclei mainly manifested positive staining until 24 hours after diffuse brain injury. Immune-positive pERK1/2 cells were widely distributed in brain tissue, especially mainly in binding site between deep cortex and cerebral white matter, and then in hippocampus. In addition, ependymal cell and vascular endothelial cells of choroids plexus also manifested strongly positive staining. As compared with model group, positive cells were decreased gradually in high- and low-dosage U0126 groups. However, number of positive cells was less in high-dosage U0126 group than that in low-dosage U0126 group. CONCLUSION: Diffuse brain injury strongly induces the activity of ERK1/2 signal pathway and response of astrocyte; in addition, U0126 can inhibit response of glial cells during an acute period, and the effect manifests dosage dependence.     

脑出血患者血TNF-α、ET、NSE水平变化

此研究旨在通过观察脑出血（intracerabral hemorrhage．ICH）患者血TNF-α（tumor necrosis factor alpha。TNF-α）、ET（endothelin．ET）及神经元特异性烯醇化酶（neuron-specific．NSE）水平的动态变化并探讨其临床意义。     

结直肠癌发病机理的新位点——PPARδ

目的探讨PPARδ在结直肠癌发病机理中的作用。方法回顾有关PPARδ研究及结直肠癌发病机理的文献。结果PPARδ是Wnt信号通路的下游分子，在结直肠癌组织中表达上调，并能抑制结直肠癌细胞凋亡。结论PPARδ与结直肠癌的发生密切相关。     

不同月龄自发性高血压大鼠杏仁中央核nNOS免疫阳性神经元的变化

OBJECTIVE: To observe the changes of neuronal nitric oxide synthase (nNOS)-immunopositive neurons in the central amygdaloid nucleus of spontaneously hypertensive rats (SHRs). METHODS: Thirty SHRs and 30 Wistar-Koyto rats (WKYs) were sacrificed at the ages of 90, 180, and 360 days respectively to observe the changes of nNOS-immunopositive neurons with ABC immunocytochemical assay. RESULTS: No significant changes were observed in the blood pressure of WKY rats at the specified time points, when SHRs maintained significantly higher blood pressures from 20.8+/-1.1 and 26.3+/-1.0 kPa (P<0.05), gradually increasing during the development of hypertension. The nNOS-immunopositive neurons in the central amygdaloid nucleus were of moderate sizes with long intersected nerve fibers. No significant changes were found in WKY rats. The number of the positive neurons decreased with age in SHRs, especially obvious at 360 days (P<0.05), which was significantly different from that in the WKYs (P<0.05). CONCLUSION: The reduction of nNOS-immunopositive neurons in the central amygdaloid nucleus of SHRs might accelerate the development of hypertension by modulating the cardiovascular function and sensory transmission.     

诱生型一氧化氮合酶特异性抑制肽的制备

目的：通过噬菌体展示技术筛选iNOS特异性抑制肽。方法：将iNOSFAD结合区及其附近序列的基因片段装入pET-28A( )，在大肠杆菌BL21中表达，His.bind^TM亲和层析柱纯化目的蛋白，使用纯化蛋白筛选Ph.D.-12^TM噬菌体库，筛选iNOS活性抑制作用较高的噬菌体克隆，测序并合成其中具有一致序列的短肽。结果：得到具有较高表达量的目的蛋白，经His.Bind^TM柱亲和层析纯化后纯度大于95％，以纯化蛋白筛选Ph.D.-12^TM噬菌体库，经4轮筛选获得10株iNOS活性抑制作用较高的噬菌体克隆，测序发现其中5株序列完全相同，合成该12肽，初步研究表明其对iNOS表现为高浓度抑制，低浓度兴奋的作用，而对nNOS及eNOS则没有影响。结论：以iNOSFAD片段蛋白为靶蛋白筛选得到的克隆对iNOS活性具有特异性影响，可根据这些特征设计合成小分子前导药物，创造新的活性药物。