美国临床遗传学进展

第四讲 不孕症及高风险妊娠 临床遗传学医生的另一项重要职责是通过以下多种措施提供优生优育的建议和指导：①不孕症的病因诊断；②试管婴儿的产前及孕前咨询；③产前筛查及普查；④携带者的检出及产前咨询；⑤超声波的应用及所带来的困惑；⑥产前诊断及手段。     

Pretreatment with Tongxinluo protects porcine myocardium from ischaemia/reperfusion injury through a nitric oxide related mechanism

Background The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo. Methods Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor Nω-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively.Results Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA. Conclusions Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.     

Autologous peripheral blood stem cell transplantation in the patients with hematologic malignancies and solid tumors

Objective To evaluate the long-term therapeutic effects of autologous peripheral blood st em cell transplantation (auto-PBSCT) on the treatment of hematological and soli d tumors. Methods Fifty-one patients were recruited in this auto-PBSCT study, in which several p otentially important parameters were studied including the optimal time for stem cell co llection, the dose of stem cell reinfusion, the time of hematopoietic reconsti tution, the disease free survival (DFS) and overall survival (OS), complication s related to transplantation, and maintenance chemotherapy after auto-PBSCT. Results After APBSCT, 3-year and 5-year survival rates of NHL were 83.3%; those of AM L were 74.7%; those of MM were 37.9% and 19%; those of ALL were 40% and 0% res pectively. Hematopoietic reconstitution was greatly promoted by granulocyte col ony stimulating factor (G-CSF). The mean time for patients’ neutrophil to reco ver up to >0.5×10(9) /L after APBSCT was 11.14 days in the group of the patien ts receiving G-CSF in contrast to 17.6 days in the group receiving no G-CSF. The most common complications of transplantation were fever, liver dysfunction and hypokalaemia, which were curable. No death was due to transplantation related complications.Conclusion Comparing with conventional chemotherapy, our study suggests that auto-PBSCT i s a very important therapeutic option that can significantly improve the prognos is in the patients with hematological and solid tumors, especially in the patien ts with AML and NHL.     

Interleukin-6 in bronchoalveolar lavage fluid from patients with COPD

目的　本研究通过检测支气管肺灌洗液 (BALF)中及肺泡巨噬细胞 (AM)产生的IL 6 ,揭示IL 6与慢性支气管炎(COPD)肺气肿发生的关系 ,为IL 6提供新的研究领域。方法　检测 6名正常无吸烟人及 2 1名COPD患者BALF中及AM释放的IL 6 ,根据正常人组BALF中IL 6的 95 %正常值可信区限 ,将COPD患者分为二组 ,在正常值可信区限内为第一组 ,在正常值可信区限外为第二组。结果　表明 2组中AM产生的IL 6第二组明显高于第一组 ,且 2组患者肺功能 (Dlco ,FEV1,FEV1/FVC和RV/TLC)有明显差异结论　AM产生的IL 6可能与COPD患者肺功能变化有关 ,在COPD患者肺气肿发生发展过程中发挥重要作用     

Effect of ipratropium bromide on airway and pulmonary muscarinic receptors in a rat model of chronic obstructive pulmonary disease

Objective　To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). Methods　This model was developed by exposure of rats to 250 ppm SO2 gas, 5?h/d, 5d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Muscarinic receptors in airway and lung tissues of normal rats, ipratropium bromide-treated COPD rats and the recovering COPD rats were measured by the radio-ligand binding assay. Results　Airway/lung pathology and pulmonary function tests showed that chronic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038±0.011, pmol/mg protein) and affinity (Kd, 23±11 pmol/L) of muscarinic receptors in airway and lung tissues of COPD rats were not changed compared with those of normal control rats (0.030±0.008 and 29±19, respectively, P>0.05). Densities of the muscarinic receptors were not changed after inhalation of ipratropium bromide for 5 days, but increased significantly after inhalation for 30 days, as compared with those of the untreated COPD rats. The muscarinic receptors returned the normal levels at day 6 after cessation of ipratropium bromide treatment. There were no differences among different groups of rats in equilibrium dissociation constants (Kd). Conclusion　A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no significant change in the number and function of muscarinic receptors in airway and lung tissues of the COPD rats, but upregulation of the muscarinic receptors was observed after long-term inhalation of ipratropium bromide.     

内皮素与脑梗死

目的 :检测脑梗死病人的内皮素 - 1(ET - 1)水平 ,研究ET - 1与脑梗死的关系。方法 :检测脑梗死病人ET - 1的水平 ,并与正常对照组比较。结果 :脑梗死病人的ET - 1明显高于正常对照组水平 (U =13.45 ,P<0 0 1) ,还发现ET - 1与高血压、糖尿病、高血脂症有一定的关系。结论 :ET - 1的增高是脑梗死发病的内源性危险因素之一 ,ET - 1的增高不但与脑梗死的发病有关而且与脑梗死的发展有关     

槲皮素对NB4细胞株p53及蛋白的影响

目的研究治疗白血病的有效药物。方法将槲皮素作用于培养的NB4细胞株,应用RT-PCR及Westem bolt方法,研究不同浓度槲皮素(30、60、90μmol/L)诱导细胞24、48、72、96、120h后,急性早幼粒细胞白血病NB4细胞株中突变型p53基因及蛋白表达的情况。结果证实其在30～90μmol/L浓度时对突变型p53基因无影响,而对突变型p53蛋白的表达有抑制作用。结论本研究为槲皮素应用于急性早幼粒细胞白血病的研究提供了有效手段。     

中药肛滴在治疗消化道恶性肿瘤中的应用

探讨中药肛滴在治疗消化道恶性肿瘤中的应用。通过对６例典型病例的回顾分析,观察中药肛滴在缓解癌性粘连性肠梗阻、缓解消化道恶性肿瘤患者症状、提高晚期消化道恶性肿瘤患者生存质量的作用。应用中医理论“通则不痛”之说,对消化道恶性肿瘤患者进行中药肛滴治疗．认为有较好的临床效果。     

工程化纳米囊泡结合化疗用于增强肿瘤免疫治疗

目的：结合免疫治疗与化疗,以改善肿瘤的治疗效果,为安全有效的肿瘤免疫治疗策略的发展提供更多见解。方法：使用工程化纳米囊泡,囊泡膜上表达PD-1受体,可以靶向肿瘤细胞表面的PD-L1,通过破坏PD-1/PD-L1免疫抑制通路增强抗肿瘤反应。同时,囊泡包裹的化疗药物阿霉素可以进入肿瘤细胞核,抑制DNA与RNA的合成,诱导肿瘤细胞死亡。结果：实验证实,制备的PD1-阿霉素材料具备良好的稳定性、安全性,能准确靶向肿瘤部位,阿霉素在细胞核部位起作用,能有效地进行肿瘤杀伤。结论：本研究首次将PD-1免疫检查点抑制与化疗药物阿霉素相结合,利用PD-1囊泡安全性高、长循环的特点作为包裹化疗药物阿霉素的载体,这种方法可以进行肿瘤细胞的有效靶向与治疗,实现肿瘤的有效清除。