白细胞介素-10 基因启动子多态性与慢性阻塞性肺疾病易感性的关系

目的　探讨中国汉族人白细胞介素 - 10基因启动子单核苷酸多态性及其与慢性阻塞性肺疾病易感性之间的关系。　方法　应用聚合酶链反应 -限制性片段长度多态性分析方法 ,检测 94名健康吸烟者和 88例吸烟慢性阻塞性肺疾病 (chronic obstructive pulmonary disease,COPD)患者白细胞介素 - 10(interleukin- 10 ,IL- 10 )基因启动子 - 10 82 G/ A、- 819C/ T、- 5 92 C/ A单核苷酸多态性位点基因型。　结果共发现 11种启动子基因型 ,以 AA·TT·AA、AA·TC· AC、AA· TC· AA基因型多见 ;通过对 11种启动子基因型进行分析 ,新发现 ATC、ACA两种单倍型 ;健康吸烟者和吸烟 COPD患者 IL- 10基因启动子- 10 82 G/ A、- 5 92 C/ A位点基因型分布频率差异无显著性 ,- 819C/ T多态性位点与中国汉族人 COPD易感性有关 ;中国汉族人 IL- 10基因启动子等位基因频率与日本人相似 ,与白种人之间差异存在显著性。　结论　中国汉族人 COPD易感性与 IL- 10基因启动子 - 819C/ T位点多态性有关 ;中国汉族人 IL- 10基因启动子至少存在 ATA、ACC、GCC、ATC、ACA5种单倍型。     

白细胞介素6与钙感应性受体基因多态性对青春期女童骨量增长的交互作用

目的 探讨白细胞介素6(interleukin-6,IL-6)与钙感应性受体(calcium sensing receptor,CASR)基因多态性对青春期女童骨量增长的交互作用.方法 选择228名9-11岁半未月经初潮的健康女童进行两年追踪,采用双能X线骨密度仪检测对象追踪前后全身、左侧近端股骨(包括股骨颈、大转子、粗隆间和华氏三角区)和L1-L4腰椎骨矿含量(bone mineral content,BMC)和骨密度(bone mineral density,BMD),采用聚合酶链反应-限制性片段长度多态性技术检测IL-6-634C/G位点多态性,等位基因特异性突变分离扩增-PCR技术检测CASR A986S位点多态性.结果 176名女童完成整个研究.IL-6基因-634C/G和CASR基因A986S位点多态性与青春期女童骨量增长有关联,IL-6基因-634C/G位点CG+GG基因型女童全身和股骨大转子BMD较CC基因型分别低25.7%和20.6%,CASR基因A986S位点AS+SS基因型女童L1.L4腰椎BMC和华氏三角区BMD增长率较AA基因型分别低14.9%和51.3%,差异有统计学意义(P＜0.05).交互作用分析发现,同时具有IL-6基因-634C/G位点G等位基因和CASR基因A986S位点S等位基因的女童,其股骨颈和L1-L4腰椎BMC增长率最低.结论 同时具有IL-6基因-634C/G位点G等位基因和CASR基因A986S位点S等位基因的女童,可能是低骨量增长的危险人群.     

瘦素受体基因Gln223Arg位点多态性与哮喘和代谢综合征之间关系的研究北大核心CSCD

目的:探讨瘦素受体基因Gln223Arg位点多态性与哮喘和代谢综合征之间的关系。方法:选择120例哮喘病人(A)、92例代谢综合征病人(M)、54例哮喘合并代谢综合征病人(A+M)和81例健康对照者(NC),其中哮喘组根据肺功能进一步分为轻-中度哮喘组和重度哮喘组。应用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)方法测定所有受试者瘦素受体基因Gln223Arg位点基因型,ELISA法检测血清瘦素浓度,同时测定所有受试者BMI、血压、肺功能及空腹血糖。结果:(1)代谢综合征组和哮喘合并代谢综合征组AA+AG基因型和A等位基因频率较健康对照组显著性增高(P<0.05);(2)哮喘组中重度持续组AA+AG基因型和A等位基因频率较健康对照组显著增高(P<0.05);(3)AA+AG基因型的血浆瘦素浓度、MBI、收缩压与GG基因型比均显著升高,FEV1%、FEV1/FVC明显下降(P<0.05)。结论:瘦素受体Gln223Arg位点基因多态性与哮喘和代谢综合征具有相关性,其中A等位基因可能通过瘦素抵抗诱导哮喘和代谢综合征的发生,是哮喘和代谢综合征的共同遗传易感因子。     

瘦素基因-2548A/G和瘦素受体基因Gln223Arg位点多态性与哮喘和代谢综合征的关系

目的:研究瘦素基因-2548A/G和瘦素受体基因Gln223Arg位点多态性与哮喘和代谢综合征的关系。方法:选取82例哮喘合并代谢综合征病人(A+M)、114例哮喘病人(AS)、100例代谢综合征病人(MS)以及96例健康对照者(NC)。根据肺功能将AS组分为轻度AS和中重度AS,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法分析所有受试者瘦素基因-2548A/G和瘦素受体基因Gln223Arg位点单核苷酸多态性及基因型,并比较不同组之间这两个基因位点和多态性之间的差异。结果:1不同组间生化指标有差异(P均<0.05);2瘦素基因-2548A/G位点多态性:MS、A+M和中重度AS组与NC相比AA基因型及A等位基因频率显著升高(P均<0.05);3瘦素受体基因Gln223Arg位点多态性:MS与NC和AS相比AG+AA基因型及A等位基因频率显著升高(P均<0.05),A+M与AS相比A等位基因频率显著升高(P<0.05),AS组、轻度AS组和中重度AS组与NC组相比均没有差异(P均>0.05)。结论:瘦素基因-2548A/G多态性与哮喘和代谢综合征都有一定的相关性,其A等位基因可能是代谢综合征的致病基因,而且与哮喘严重程度相关;瘦素受体基因Gln223Arg A等位基因可能是代谢综合征的致病基因,却与哮喘无关。     

IL-10通路基因多态性与哮喘及OPN、TGF-β1水平相关性探讨

目的探讨IL-10通路基因多态性与哮喘以及OPN、TGF-β1水平的关系。方法选择我院63例哮喘患儿为研究组,50例健康儿童为对照组,均采集外周血标本,采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术检测IL-10通路基因多态性,酶联免疫吸附试验(ELISA)检测外周血白介素-10(IL-10)、骨桥蛋白(OPN)及转化生长因子β1(TGF-β1)水平,分析IL-10通路基因多态性与哮喘、IL-10、OPN、TGF-β1的相关性。结果哮喘组患儿IL-10通路基因分型以AG+AA型比例最高(76.19%),A等位基因频率39.68%,G等位基因频率60.32%,对照组GG型36.00%,AG+AA型64.00%,A等位基因频率51.00%,G等位基因频率49.00%,2组等位基因频率之间差异具有统计学意义(P0.05)。研究组患儿血清IL-10、OPN、TGF-β1水平均高于对照组[(95.37±26.88)pg/ml vs(81.05±17.73)pg/ml、(19.52±5.37)ng/ml vs(14.19±3.95)ng/ml、(70.35±12.54)pg/ml vs(46.38±8.15)pg/ml,P0.05]。研究组患儿AA+AG基因分型患者血清IL-10水平高于GG型(P0.05),OPN、TGF-β1在研究组患儿和对照组儿童不同基因分型中差异均无统计学意义(P0.05)。IL-10通路AG+GG基因型、G等位基因与哮喘正相关(r=0.521、0.392,P0.05),与IL-10呈正相关(r=0.435、0.507,P0.05),与OPN、TGF-β1水平无关(P0.05)。结论哮喘患者IL-10、OPN、TGF-β1水平明显升高,IL-10通路单核苷酸多态性与哮喘发生有关,AG+AA基因型、G等位基因可能增加哮喘发生的风险。     

IL-2基因多态性与中国汉族人群特发性扩张型心肌病的相关性研究

目的 研究中国西南地区汉族特发性扩张型心肌病(idiopathic dilated cardiomyopathy,IDCM)患者白细胞介素-2(interleukin-2,IL-2)基因启动子区-384T/G、-475A/T、-631G/A多态性与IDCM的相关性.方法 采用聚合酶链反应-限制性片段长度多态性技术分析中国西南地区无血缘关系的109例汉族IDCM患者和210名正常对照者IL-2基因启动子区-384、-475、-631位点的单核苷酸多态性.结果 IL-2基因启动子区-384位点TT+TG基因型频率和T等位基因频率在IDCM患者中升高,与正常对照组相比差异有统计学意义(分别为95.41%vs.87.62%,P=0.042和72.94%vs.64.52%,P=0.039);而IL-2基因-631位点与-475位点基因型和等位基因频率在IDCM组与正常对照组之间无差异.结论 IL-2基因启动子区单核苷酸多态性与人类IDCM相关,IL-2基因启动子区-384位点T等位基因可能会增加发生IDCM的危险性.     

CTLA4基因与Ⅰ型糖尿病易感性的关联研究

目的探讨细胞毒性T淋巴细胞相关抗原4(CTLA4)基因单核苷酸多态性位点rs231775(G/A)与Ⅰ型糖尿病(TIDM)易感性的关系。方法采用病例对照研究,收集TIDM患者及正常儿童外周血,提取基因组DNA,应用PCR扩增产物直接测序法对多态性位点rs231775进行分析。结果 T1DM组GG基因型频率高于对照组频率(48.1%对31.9%,OR值2.615,95%CI 1.061~6.447,P0.05),且T1DM组G等位基因频率也高于对照组频率(69.8%对58.6%,OR值1.63,95%CI1.11~2.41,P0.05)。结论 CTLA4+49A/G基因多态性与天津地区TIDM相关,GG基因型与G等位基因显著增加TIDM的发病风险。     

Allo-HSCT 受者细胞因子基因多态性与急性移植物抗宿主病的关系

目的:探讨在异基因造血干细胞移植(allo-HSCT)中肿瘤坏死因子琢(TNF )、白细胞介素6(IL-6)、白细胞介素10(IL-10)、转化生长因子茁1(TGF-1)、干扰素酌(IFN )等多种疾病相关细胞因子基因多态性与急性移植物抗宿主病(aGVHD)的相互关系。方法:选取2014 年1 月至2015 年12 月进行allo-HSCT 的受者32 例及正常人群36 例作为研究对象,采用聚合酶链式反应(PCR)联合基因测序对目的基因特殊SNP 位点基因分型进行检测,观察受者术后出现aGVHD 的不同情况,分析细胞因子基因多态性对allo-HSCT 预后的影响,探讨疾病相关细胞因子特殊SNP 点突变与aGVHD 发病严重程度的潜在相关性。结果:在全部allo-HSCT 受者中,TNF-308(G/ A)、IL-6-174(G/ C)、IL-10-1082(A/ G)、TGF-1+915(G/ C)、IFN +874(T/ A)等细胞因子的基因多态性分布与重度aGVHD 的发生率未见有显著性的差异(P>0.05)。在TGF-1+869SNP 位点上,C/ T 型allo-HSCT 患者中重度aGVHD 发病率显著高于C/ C、T/ T 两个基因型患者组(P<0.01)。结论:在allo-HSCT 患者中TGF-1+869(C/ T)基因多态性与aGVHD 发病的严重程度具有密切联系。C/ T 型allo-HSCT 患者更容易发生重度aGVHD,是诱发严重aGVHD 出现的潜在危险因素。因此,在allo-HSCT 患者中针对TGF-1+869(C/ T)进行基因多态性检测,制定合理的aGVHD 预防方案,可能有助于减少减轻aGVHD 的发生。     

IL-18 水平表达及IL-18 基因多态性与哮喘病的相关性研究

目的:探讨IL-18基因多态性位点(IL-18/-607C/A,IL-18/-137G/C)多态性及血清IL-18水平与哮喘发生的关系。方法:选取我院301例哮喘患者作为哮喘组,并选取288例健康成人作为健康组。提取研究对象全血DNA,采用等位基因特异性引物PCR检测两组IL-18基因多态性位点(IL-18/-607C/A,IL-18/-137G/C),并对其PCR反应产物进行测序验证;观察IL-18基因多态性位点(IL-18/-607C/A,IL-18/-137G/C)等位基因频率分布,同时通过酶联免疫吸附法检测IL-18在不同组别血清浓度,分析影响哮喘发生的危险因素。结果:与对照组相比IL-18基因(-607C/A)、3种基因型、等位基因等差异较大(χ2=10. 24,P0. 001;χ2=50. 26,P0. 001),差异具有显著统计学意义。哮喘组基因位点-137G/C的CC与GG基因型差异有显著统计学意义(χ2=4. 717,P0. 05),其等位基因频率差异无显著性(χ2=3. 711,P0. 05);哮喘组患者血清IL-18水平显著低于健康组(t=85. 34,P0. 001),其中基因多态性位点(-607C/A) CC基因型的哮喘患者血清IL-18的水平为(18. 02±3. 92) pg/ml,携带AA基因型患者IL-18的水平为(41. 68±8. 08) pg/ml,两者比较差异具有统计学意义(t=22. 26,P0. 001);基因多态性位点(-137G/C) 3种基因型哮喘患者血清IL-18的水平差异无统计学意义(F=0. 281,P0. 05)。结论:哮喘患者血清IL-18水平降低,提示哮喘的发生可能与血清IL-18水平低下有关。IL-18多态性位点(IL-18/-607C/A,IL-18/-137G/C)的基因分型中携带(-607C/A) AA基因型的人群患哮喘风险更大。     

白介素13＋2044G〉A基因多态性与尘螨变应性鼻炎的关系探讨

目的对尘螨诱导引起变应性鼻炎的患者行白介素13＋2044G〉A基因分型,探讨白介素13＋2044G〉A基因与尘螨变应性鼻炎遗传易感性的相关性。方法用PCR-RFLP法为97名无亲缘关系的尘螨变应性鼻炎患者和119名无血缘关系的健康汉族人行白介素13＋2044G〉A基因分型。结果尘螨变应性鼻炎组与对照组相比,白介素13＋2044G〉A基因型频率差异均无统计学意义（P〉0.05）。结论白介素13＋2044G〉A基因多态性与尘螨变应性鼻炎不存在相关性,大样本和单倍体研究将可能有助于阐明关系。     

P63 in pulmonary epithelium,pulmonary squamous neoplasms,and other pulmonary tumors

p63 is a p53-homologous nuclear protein that appears to play a crucial role in regulation of stem cell commitment in squamous and other epithelia. In this study, p63 expression was examined in benign lung and in neoplasms of pulmonary origin. Eighty sections from routinely fixed and processed archival bronchoscopic biopsy or lobectomy specimens were pretreated with citric acid (pH 6.0) for antigen retrieval, then incubated overnight with anti-p63 monoclonal antibody 4A4. Slides were stained using a streptavidin-biotin kit and diaminobenzidine as chromagen, and were counterstained with hematoxylin. In normal lung, p63 intensely stained nuclei of bronchial reserve cells but did not stain ciliated cells, alveolar epithelial cells, or nonepithelial cells. The lower strata of squamous metaplastic bronchial epithelium stained positively. All squamous-cell carcinomas stained positively (n = 30). In some well-differentiated carcinomas, staining was found at the periphery of tumor nests but was negative in central zones showing squamous maturation. Poorly differentiated carcinomas showed very high proportions (80% to 100%) of p63-positive nuclei. All small-cell carcinomas were p63 negative (n = 9). Staining of bronchioloalveolar carcinomas (n = 7) and adenocarcinomas (n = 23) was variable: some tumors showed no detectable staining, others showed heterogeneously positive staining. Adenosquamous carcinomas (n = 5) displayed a unique basalar staining pattern. Carcinoid tumors were almost entirely negative (n = 5). We conclude that p63 is expressed in benign bronchial stem cells, in neoplastic cells with either squamous differentiation or squamous differentiating potential, and in a subpopulation of adenocarcinomas. p63 immunostaining may also aid in some histopathologic distinctions, such as in small biopsies where the differential diagnosis is poorly differentiated squamous carcinoma versus small-cell carcinoma. A stem cell biology-based classification system for squamous carcinomas is proposed.     

肺部超声对重症肺部感染患者肺通气的评估价值

目的:探讨肺部超声评价重症肺部感染患者通气情况的应用价值。方法:选取88例重症肺部感染患者,采用半定量方法对肺部超声征象进行评分,以CT检查结果为金标准,分析肺部超声评分与患者肺通气的关系;同时分析存活和死亡患者临床资料、肺部超声评分的差异,以及肺部超声评分预测患者死亡的价值。结果:88例患者全肺超声评分平均为（18.50±2.12）分,全肺CT值平均为（-620.50±88.13） HU,不通气/低通气肺组织比例平均为（10.41±3.35）%,正常通气肺组织比例平均为（71.54±6.69）%,过度通气肺组织比例平均为（17.65±4.11）%;患者肺部超声评分与全肺CT值、不通气/低通气肺组织比例呈正相关（r=0.775、0.648, P<0.05）,与正常通气肺组织比例、过度通气肺组织比例无明显相关性（r=-0.170、0.046, P>0.05）;死亡组患者年龄、糖尿病比例、APACHEⅡ评分、肺泡-动脉氧分压差、机械通气治疗和肺部超声评分分别为（59.28±8.12）岁、44.83%、（22.19±2.40）分、（344.40±82.29） mmHg、72.41%和（20.20±1.72）分,明显高于存活组（P<0.05）,而氧合指数为（104.42±21.18）,明显低于存活组（P<0.05）;Logistic回归分析结果显示:年龄、APACHEⅡ、肺部超声评分是重症肺部感染患者死亡的影响因素（OR=1.758、2.841、2.440, P<0.05）;肺部超声评分预测重症肺部感染患者死亡的ROC曲线下面积为0.901（95%CI:0.836~0.966）,截断值为20分,灵敏性和特异性分别为82.80%和84.70%。结论:肺部超声可以作为重症肺部感染患者肺通气的评估指标,同时其在预测患者预后方面有一定应用价值。     

The pulmonary matrix, glycosaminoglycans and pulmonary emphysema

This paper reviews recent evidence of the effect of intratracheal hyaluronan (HA) to limit the induction of experimental emphysema in hamsters. Experimental emphysema was induced by both neutrophil and pancreatic elastase instilled intratracheally. Emphysema was quantified anatomically by measurement of alveolar mean linear intercept. Hyaluronidase, instilled intratracheally, enhanced the induction of experimental emphysema. Air-space size measured one week after intratracheal instillation of elastase showed that administration of 1 mg HA immediately following elastase administration resulted in a marked reduction in air-space enlargement (82 microM vs 122 microM, p < 0.01). Similarly, animals given either 1 or 2 mg HA 2 h before elastase or 2mg HA 1 h after elastase showed a significant decrease in air-space enlargement compared to controls (96 microM, 88 microM vs 120 microM and 66 microM vs 104 microM, respectively; p < 0.05. Experimental emphysema induced by neutrophil elastase was also limited by the administration of 1 or 4 mg of HA, administered 2 h prior to elastase (57 and 59 microM, respectively vs 64 for controls, p < 0.05). Characterization of administered HA showed a mean molecular weight of 104,800 Da, less than 5% protein and a uronic acid/hexosamine ratio of 1, which is characteristic of HA. Studies using fluorescein-labeled hyaluronan (HA) showed fluorescence associated with interstitial, pleural and vascular elastic fibers. The mechanism of attachment of the administered HA to elastin remains unknown. Fluorescein labeling of elastin was visible for at least 4 h post-instillation. These studies indicate a protective effect of hyaluronan against elastase degradation of pulmonary elastin in vivo by both pancreatic and neutrophil elastases. The anatomical studies further suggest a mechanism of protective coating of hyaluronan which may limit access to pulmonary elastin from neutrophils and alveolar macrophages. Results also suggest that a reduction in pulmonary hyaluronan content increases the susceptibility of elastin to degradation by elastases. These studies provide evidence for an antielastase effect of hyaluronan which is not dependent upon enzyme inhibition but on anatomical protection of pulmonary elastin by other mechanisms.     

Changes in pulmonary hemodynamics in acute pulmonary edema

Summary Experiments were made on dogs to study the hemodynamic changes following intravenous injections of chloramine and adrenaline. Chloramine injections were followed by the development of a severe pulmonary edema in an of the dogs. In most of them, however, the capillary pressure in the pulmonary circulation increased, but insignificantly. The great increase in the pulmonary capillary pressure following adrenaline injection did not culminate in the development of edema or caused very slight edema. The conclusion is drawn that increase of filtration pressure is not an indispensable decisive factor for the development of pulmonary edema, even if it is concurrent with considerable disturbances in the pulmonary circulation.(Presented by Academician V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 60, No. 8, pp. 25–29, August, 1965     

T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-β)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.