低剂量辐射增强小鼠肿瘤基因-放射治疗效应的免疫学机制研究

目的 探讨低剂量辐射全身照射对小鼠Lewis肺癌移植肿瘤基因-放疗方案中的免疫增强作用机制。方法 小鼠右后肢皮下接种Lewis肺癌细胞建立荷瘤模型,基因-放疗组中小鼠肿瘤局部注射由多聚乙烯亚胺包裹的pEgr-IL18-B7.1重组质粒,分别接受由2 Gy 局部照射和0.075 Gy 全身照射组合的不同治疗方案,通过³H-TdR标记方法检测小鼠CTL和NK细胞毒活性,ELISA方法检测TNF-α和IFN-γ分泌活性,观察各治疗组对荷瘤小鼠抗肿瘤免疫的作用。结果 在pEgr-IL18-B7.1基因治疗方案中,单次大剂量辐射局部照射后加多次低剂量全身照射与常规多次大剂量辐射局部照射相比,小鼠CTL和NK细胞毒活性显著增强,TNF-α和IFN-γ分泌活性有不同程度的增高。 结论 低剂量辐射可以通过促进CTL和NK细胞毒效应,上调TNF-α和IFN-γ细胞因子表达,从而增强机体抗肿瘤免疫功能,提高肿瘤基因-放疗的抑瘤效果。     

P16INK4、PCNA在肺癌中表达的研究

目的 通过检测肺癌组织中p16、PCNA的表达，探讨其在肺癌发生发展中的作用及相互关系。方法 采用S—P免疫组化方法，检测83例肺癌标本及15例正常肺组织标本中P16^INK4和PCNA的表达。结果 P16^INK4和PCNA在正常肺组织和肺癌组织中表达的阳性率存在显著性差异。P16^INK4表达的阳性率在小细胞癌与非小细胞癌之间有显著性差异。PNTM分期高的肺癌标本P16^INK4及PCNA表达阳性率显著高于分期低的肺癌标本。不同分化程度的肺癌组织P16^INK4及PCNA表达阳性率有显著性差异。结论 肺癌的发生与P16^INK4的低表达和PCNA的高表达有关。而P16^INK4的表达与肺癌的组织学类型、分化程度、临床分期有关；PCNA的表达与肺癌的分化程度、临床分期有关。     

Lung function development in the first 2 yr of life is independent of allergic diseases by 2 yr

The aim of the study was to assess if lung function at birth predicts lung function at 2 yr and secondly, if lung function development was influenced by the common phenotypes of recurrent bronchial obstruction (rBO) or atopic eczema (AE) by 2 yr. Lung function was assessed at birth (n = 802) and at 2 yr within the prospective birth cohort study 'the Environment and Childhood Asthma Study' in Oslo. The 135 children with lung function measured at birth by tidal flow volume (TFV) loops and passive respiratory mechanics, who were included in a nested case-control study were reinvestigated at 2 yr with clinical examination, TFV loops (n = 90) (mean age 26.6 (3.7 s.d.) months), skin prick test and parental interview. Children were categorized into quartiles (lower, middle two, upper) according to time to peak tidal expiratory flow/total expiratory time (t(PTEF)/t(E)) at birth as well as clinical phenotype based on the presence of rBO and/or AE (ever) by 2 yr. The observed reduction in mean t(PTEF)/t(E) from birth to 2 yr within the quartiles, were not significantly different after controlling for 'regression to the mean'. t(PTEF)/t(E) at birth correlated significantly with t(PTEF)/t(E) at 2 yr, (r = 0.475, p < 0.001). Children with both rBO and AE by 2 yr had significantly lower t(PTEF)/t(E) at 2 yr (p = 0.002) and at birth (p = 0.027), compared with children with no rBO or AE. Clinical phenotype at 2 yr did not influence the change in t(PTEF)/t(E) from birth to 2 yr. This study demonstrates a clear tracking of lung function from birth, not influenced by rBO or AE by 2 yr.     

Ventilation imaging of the lung: Comparison of hyperpolarized helium-3 MR imaging with Xe-133 scintigraphy

RATIONALE AND OBJECTIVES: To compare hyperpolarized helium-3 (HHe) magnetic resonance imaging (MRI) of the lung with standard Xe-133 lung ventilation scintigraphy. MATERIALS AND METHODS: We performed a retrospective review of 15 subjects who underwent HHe MRI and Xe-133 lung ventilation imaging. Coronal MRI sections were acquired after a single inhalation of HHe gas, and standard posterior planar lung ventilation scintigraphy was performed during continuous breathing of Xe-133 gas. The first breath scintigram of each patient was compared with a composite MR image composed of the sum of the individual MR images and with the individual helium-3 MR images. Ventilation defects on the two imaging modalities were compared for size, conspicuity, and concordance in presence and location. Assessment was done separately for each of four lung quadrants. RESULTS: Comparing the composite HHe MR images with Xe-133 scintigraphy, ventilation defect size, conspicuity and concordance were the same in 67% (40/60), 63% (38/60), and 62% (37/60) quadrants, respectively. Comparing the individual HHe MR image sections with the Xe-133 ventilation scan, there was concordance between the ventilation defects in 27% (16/60) of quadrants. More defects were identified on the individual HHe MR images in 62% (37/60) of quadrants. CONCLUSION: There was good agreement between composite HHe MR image and first breath Xe-133 scintigraphic images, supporting the widely held assumption that HHe MRI likely depicts first breath lung ventilation.     

survivin、P53蛋白在非小细胞肺癌的表达及其相关性研究

目的 :研究survivin、P5 3蛋白在非小细胞肺癌 (NSCLC)组织的表达及其生物学意义 ,并探讨其相关性。　方法 :用免疫组化 (S P法 )染色技术对 95例NSCLC组织石蜡标本进行survivin、P5 3蛋白表达的检测和分析。　结果 :survivin、P5 3在肺癌细胞中阳性表达率 (6 2 .1 %、5 5 .8% )明显高于癌旁的正常肺组织 (1 4 %、7% ) (P <0 .0 1 )。survivin的表达与肿瘤病理分级、组织学分型、淋巴结转移、TNM分期无明显相关 (P >0 .0 5 ) ;P5 3表达与淋巴结转移相关 (P <0 .0 5 ) ,而与肿瘤病理分级、组织学分型、TNM分期无明显相关 (P >0 .0 5 ) ;此外 ,survivin与P5 3蛋白的表达呈显著正相关 (r =0 .5 72 ,P <0 .0 1 )。　结论 :凋亡抑制蛋白survivin与突变型P5 3蛋白在NSCLC的发生发展中可能起协同作用 ,也提示抑癌基因p5 3(野生型 )可能对survivin的表达起负反馈调节作用。survivin和P5 3蛋白可作为靶点用于NSCLC靶向治疗的研究     

双光气致急性损伤对兔肺泡Ⅱ型细胞形态学的影响

目的：通过对日本大耳兔双光气肺损伤后肺泡Ⅱ型细胞内磷脂和形态学变化的观察，探讨双光气对肺Ⅱ型细胞的损伤及其机制．方法：将纯种日本大耳白兔35只随机分为对照组(n＝10)、染毒即刻组(n＝5)、染毒2h组(n＝5)染毒4h组(n＝5)、染毒8h组(n＝5)、染毒12h组(n＝5)；采用浓度一时间法动态式染毒，染毒后按不同时间点对实验动物进行颈总动脉插管放血处死，取肺并用肺灌洗液对支气管肺泡进行灌洗，然后取肺组织作冰冻切片，进行电镜观察，并测定细胞内磷脂含量．结果：肺Ⅱ型细胞内磷脂含量在染毒即刻开始时较正常组含量下降(P＜0．01)；在染毒2h时降到最低，之后上升(P＜0．05)，而在4h后又下降(P＜0．05)．染毒终止后，损伤逐渐加重，染毒后2h磷脂因消耗而降低．染毒后4h，由于代偿功能启动，磷脂短暂升高，出现致伤性代偿期．从染毒2h后开始，细胞损伤加重，磷脂合成进入失代偿期，合成逐渐减少．到染毒后8h，肺泡Ⅱ型细胞内细胞处于致伤性和致死性细胞改变的临界点，细胞出现致死性改变，磷脂合成、分泌停止，细胞出现死亡．结论：兔在双光气染毒12h内，肺泡表面活性物质磷脂的改变有差异，随细胞损伤程度发生改变，出现明显中毒分期：即致伤性改变期、致伤性代偿期、致伤性失代偿期、致死性改变期．     

PULMONARY BLOOD DISTRIBUTION AFTER TOTAL CAVOPULMONARY CONNECTION OF DIFFERENT TYPES

Objective. To assess the feature of pulmonary blood flow distribution after total cavopulmonary connection (TCPC) of different types, and to provide the selection of the best type .Methods. Thirty-two consecutive survival patients after TCPC underwent radionuclide lung perfusion imaging. According to the radionuclide counts in the left and right lungs, analyses of the distribution of blood flow from superior venous cava (SVC) and inferior venous cava (IVC) and the whole pulmonary blood flow in both lungs were made. All patients were divided into 4 groups by the the anastomosis between IVC and pulmonary artery.Results. Group Ⅰ: The flow ratio of the IVC to left lung was greater than that to the right lung , P≤0. 01; the flow ratio of the SVC to right lung was greater than that to the left lung, P≤0. 01; and the whole pulmonary blood flow went dominantly to the left lung, P≤0. 05, which is not in line with physiological distribution. Group Ⅱ: the flows from the SVC and IVC were mixed in the middle of     

连续性静脉-静脉血液滤过联合机械通气治疗ARDS的临床观察

目的　观察连续性静脉 -静脉血液滤过 (CVVH)联合机械通气治疗ARDS患者的临床疗效。方法　选择入住ICU符合ARDS诊断标准的患者 4 0例 ,随机分为 2组 :A组 2 1例 ,采用常规治疗 +机械通气 ;B组 1 9例 ,采用常规治疗 +机械通气 +CVVH。分别观察 2组患者在使用呼吸机时间、氧合指数、吸入氧浓度、动脉血氧分压、PEEP水平、心率、血压及病死率等方面的差别。结果　A、B两组患者在病因、年龄、性别、APACHEⅡ评分及平均脏器功能障碍数等方面相似 ,B组患者加用CVVH后 ,各项指标经统计学处理显示 :病死率 ,B组与A组比较 ,差异有显著性意义 (P <0 0 5 ) :其他指标与A组比较 ,差异均有高度显著性意义 (P <0 0 1 )。结论　CVVH疗法可有效清除ARDS患者血管外肺水和各种应激激素、致炎介质 ,明显改善了ARDS患者肺部氧合功能及血流动力学指标 ,提高了抢救成功率     

Lung Transplant Metalloproteinase Levels Are Elevated Prior to Bronchiolitis Obliterans Syndrome

Parenchymal disease in the allograft lung is associated with interstitial remodeling believed to be mediated by matrix metalloproteinases (MMPs). Recent studies suggest high levels of MMP-9 are associated with bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Since BOS occurs late in the posttransplant period and may be preceded by episodes of acute rejection or infection, which are associated with interstitial remodeling, we examined MMP profiles in allograft bronchoalveolar lavage (BAL) fluid in the early posttransplant period (preceding BOS). Gelatin zymography, protein array analysis and specific ELISA on BAL fluids from transplanted lungs indicated that MMP-8, MMP-9 and TIMP-1 were strongly expressed in allograft BAL fluid from stable patients, or those with infection or rejection compared to BAL fluid from normal volunteers. Elevated expression of MMP-8, MMP-9 and TIMP-1 occurred early, and was sustained for the 3.2 years covered in this study. Elevations of MMP-8, MMP-9 and TIMP-1 in the first 2 years posttransplant appear to be associated with lung transplantation itself, and not infection or rejection. These data suggest that ongoing and clinically silent MMP activity could perpetuate progressive disease in the allograft lung.     

盲肠结扎穿刺致豚鼠急性肺损伤动物模型建立

目的 研究败血性急性肺损伤的动物模型，并探讨其在急性肺损伤研究中的意义。方法 用盲肠结扎穿刺(CLP)法的豚鼠急性肺损伤模型，结合动脉血气分析、外周血白细胞计数、肺湿重／干重比值(W／D)及肺组织病理观察。结果 CLP模型中动物的症状和表现缓慢出现，逐渐恶化．最后导致败血性休克，于2d左右出现大量死亡。结论 用盲肠结扎穿刺的方法制作豚鼠急性肺损伤动物模型较大鼠内毒素性休克，表现更类似于人类的肠源性肺损伤，且症状缓慢发生，逐渐恶化，有利于观察和进行各种干预。