以225名健康儿童建立呼出气一氧化氮正常值

目的探讨6-14岁儿童呼出气一氧化氮（FeNO）正常值范围及其影响因素。方法选取苏州市6-14岁在校儿童进行问卷调查及FeNO、肺功能、外周血嗜酸粒细胞（EOS）计数的检测,筛选出健康儿童建立FeNO正常值。FeNO的测定采用电化学法,根据美国胸科学会/欧洲呼吸学会指南进行操作。分析性别、年龄、身高、体重、外周血EOS计数、肺功能和FeNO的相关性。结果参与调查的450名儿童中符合纳入标准者225名（男生107名,女生118名）进入分析。FeNO值呈偏态分布,经自然对数转换后呈正态分布。FeNO平均值为11ppb（95%CI：5-28ppb）,最小值〈5ppb,最大值为83ppb。男生FeNO平均值为11ppb（95%CI：5-31ppb）,女生FeNO平均值为11ppb（95%CI：5-25ppb）。FeNO与外周血EOS计数相关性最为显著（r=0.291,P〈0.001）,与身高（r=0.148,P=0.027）和FEV1（r=0.138,P=0.038）显著相关;〉9岁儿童FeNO显著高于≤9岁儿童（P=0.002）;FeNO与性别、体重、BMI、FEV1/FVC无显著相关性。结论苏州地区6-14岁儿童FeNO正常参考值为5-28ppb;FeNO水平与外周血EOS计数、身高、FEV1显著相关。     

成人哮喘患者Treg/Th17细胞失衡与呼出气一氧化氮的相关性研究

目的:探讨成人哮喘患者Treg/Th17细胞失衡与呼出气一氧化氮(FeNO)的相关关系。方法:募集成人哮喘患者17例,慢性咳嗽非哮喘患者16例。所有患者均检测FeNO值,并用ELISA法检测血浆IL-17的表达水平,流式细胞术检测外周血中Treg、Th17细胞占CD4~+T淋巴细胞比例。比较两组患者FeNO水平的差异及其与Treg/Th17的相关关系。结果:与慢性咳嗽组相比,哮喘组血浆IL-17浓度升高(P<0.05)、外周血Th17/CD4~+T细胞比值升高(P<0.001)、FeNO水平升高(P<0.001)、Treg/Th17细胞的比值降低(P<0.001),而Treg/CD4~+细胞比值无明显变化(P>0.05)。哮喘组FeNO值与外周血Treg/CD4~+T细胞比值无明显相关性,而与Th17细胞占CD4~+T淋巴细胞比例呈正相关(r=0.663,P=0.01),与Treg/Th17细胞比值呈负相关(r=-0.757,P=0.002)。结论:哮喘患者FeNO水平升高与Treg/Th17失衡有关,主要与Th17细胞表达升高有关。     

初诊哮喘患者的呼出气一氧化氮与大小气道功能的 相关性及临床价值分析

目的 探讨初诊支气管哮喘患者的呼出气一氧化氮水平与大小气道功能的相关性,以及在哮喘规范化治疗中的变化趋势及临床意义。方法 选择2016年3月~2016年5月就诊于新乡医学院第一附属医院呼吸科的初诊成人支气管哮喘患者80例,为哮喘组;选择同期健康体检志愿者40名,为对照组。哮喘组在治疗前及治疗后3、6、9、12月分别行FeNO和肺功能检查包括FEV1%、FEF75%、FEF50%、MMEF%以及哮喘控制测试（ACT）;健康志愿者仅行一次肺功能及FeNO检查。结果 初诊哮喘的FeNO与FEV1%无相关性（P＞0.05）,与FEF75%、FEF50%、MMEF%存在负相关（P＜0.05）。经治疗大气道功能的恢复时间6个月早于小气道功能的恢复时间12个月,FeNO的恢复时间约3月。小气道功能异常的哮喘患者比小气道功能正常者具有更高的FeNO,且在1年的治疗过程中具有更高的急性发作次数和吸入糖皮质激素（ICS）用量,差异有统计学意义（P＜0.05）。结论 相比于大气道,小气道功能异常与气道炎症FeNO的关系更密切。大气道功能不能完全反映哮喘的临床控制情况,需联合检测FeNO与小气道功能。     

乌鲁木齐地区维汉哮喘儿童ADAM33基因多态性与IgE、维生素D的相关性研究

目的 探讨乌鲁木齐地区维汉支气管哮喘儿童ADAM33基因多态性、IgE及VitD水平及其相关性研究,期望从基因水平为指导喘患儿的防治提供理论依据.方法 选取同期3 ～15岁于乌鲁木齐地区生活的维汉哮喘息儿197例(其中汉族111例,维族86例),同时设立对照组120例(汉族64例,维族56例),首先采用PCR对ADAM 33基因S2位点SNP分型,用ELISA法检测IgE、VitD水平,进一步根据民族进行组内分层,进行S2位点SNP、IgE、VitD水平分析并进行相关性分析.结果 ①ADAM33 s2位点基因型频率分布在病例组和对照组间差异有统计学意义(x2 =24.949,P＜0.001),同时等位基因频率间差异也有统计学意义(x2 =25.640,P=0.000).②S2位点3种基因型频率分布在维、汉哮喘儿童中分布均存在统计学意义(x2=7.992,P=0.018;x2 =20.140,P＜0.001).③实验组IgE水平高于对照组、VitD水平低于对照组,差异有统计学意义(x2 =13.250,P＜0.001;x2=4.793,P＜0.001).④实验组组内维族哮喘儿童IgE水平高于、VitD水平低于汉族哮喘儿童,差异有统计学意义(x2=2.434,P=0.016;x2 =2.956,P=0.004);对照组组内维汉儿童IgE、VitD比较无统计学差异(x2=1.072,P=0.286;x2 =0.619,P=0.537).⑤ADAM 33基因s2位点与IgE、VitD均无明显相关(r=0.129,P=0.021;r=-0.181,P=0.001).结论 ①ADAM33基因S2位点突变与乌鲁木齐地区维汉哮喘儿童发病均相关,可能是维汉哮喘儿童共同易感基因.②维族哮喘儿童IgE水平高于、VitD水平低于汉族哮喘儿童.③ADAM33基因S2位点不影响IgE及VitD水平.     

哮喘儿童血清白细胞介素-25、嗜酸细胞趋化因子的动态变化和意义

目的:通过监测哮喘儿童血清白细胞介素(IL)-25、嗜酸细胞趋化因子(Eotaxin)表达水平, 探讨其水平变化及其在哮喘发病中的作用.方法:收集哮喘急性发作期、缓解期儿童及健康儿童的静脉血标本, 用双抗体夹心ELISA法测定血清IL-25、Eotaxin的水平.结果:哮喘儿童急性发作期组血清IL-25水平(56.75±11.68) ng/L显著高于缓解期组(47.09±10.96) ng/L及健康对照组(45.77±10.43) ng/L, 差异有统计学意义(P＜0.05), 缓解期组与健康对照组比较差异无统计学意义;哮喘急性发作期组儿童血清Eotaxin水平(120.95±23.97) ng/L显著高于缓解期组(105.47±22.01) ng/L及健康对照组(105.01±18.47) ng/L , 差异有统计学意义(P＜0.05), 缓解期组与健康对照组比较差异无统计学意义.哮喘儿童血清IL-25水平与Eotaxin之间存在明显正相关关系(r=0.642, P＜0.01).结论:哮喘儿童血清IL-25及Eotaxin 水平能反应哮喘气道炎症活动情况及疾病严重程度, 两者存在正相关关系.     

呼出气一氧化氮浓度检测在儿童咳嗽变异性哮喘中的应用

目的 探讨FeNO检测在儿童咳嗽变异性哮喘中的临床价值。方法 选择2016年3月~2017年3月在我院确诊为CVA的患儿80例及健康儿童40例作为研究对象,比较两组儿童FeNO水平,比较FeNO正常的CVA患儿与FeNO升高患儿的皮肤点刺结果、肺功能,分析CVA患儿FeNO水平与肺功能的相关性。结果 CVA患儿FeNO水平高于健康儿童,差异有统计学意义（P＜0.05）。同FeNO正常的CVA患儿相比,FeNO升高的CVA患儿拥有更高的体重指数,皮肤点刺阳性率更高,强度更强,差异有统计学意义（P＜0.05）,但两组患儿肺功能无统计学差异,CVA患儿FeNO水平与肺功能无相关性（P＞0.05）。结论 FeNO可以辅助诊断CVA,但不能作为评估病情严重程度的指标。     

血清SDC-1、HIF-1α、PGRN与AECOPD患者肺功能及预后恢复的相关性分析

目的 分析多配体蛋白聚糖(SDC-1)、缺氧诱导因子(HIF-1α)、颗粒蛋白前体(PGRN)与急性加重期慢性阻塞性肺疾病(AECOPD)患者肺功能及预后的相关性.方法 选取2019年1月至2021年1月本院收治的AECOPD患者114例作为观察组,另选取同期体检健康的志愿者48例作为对照组,收集两组临床资料及外周血2 mL,检测血清SDC-1、HIF-1α、PGRN水平,比较两组1秒用力呼气容积占预计值百分比(FEV1％pred)、1秒用力呼气容积/用力肺活量(FEV1/FVC);114例AECOPD患者依据30 d存活情况分为生存组和死亡组,对影响预后的因素进行相关性分析.结果 观察组血清SDC-1、HIF-1α、PGRN显著高于对照组(P<0.01),FEV1％pred、FEV1/FVC显著低于对照组(P<0.01);SDC-1与FEV1％pred、FEV1/FVC呈线性负相关(r=-0.635,r=-0.700,P=0.001);HIF-1α与FEV1％pred、FEV1/FVC呈线性负相关(r=-0.849,r=-0.816,P=0.001);PGRN与FEV1％pred、FEV1/FVC呈线性负相关(r=-0.643,r=-0.666,P=0.001);114例AECOPD患者存活72例,病死42例.Logistic分析结果显示,HIF-1α、PGRN是AECOPD预后不良的危险因素(P<0.05).结论 AECOPD患者血清SDC-1、HIF-1α、PGRN高于正常水平,三者与肺功能密切相关,高龄、住院时间延长、肺功能低下,血清HIF-1α、PGRN水平偏高是预后不良的危险因素.     

血清肥大细胞羧肽酶与支气管哮喘的相关性研究

目的：检测支气管哮喘患者外周血中肥大细胞羧肽酶的含量,研究其与哮喘患者FEV 1(%)、IgE的关系,探讨其在支气管哮喘发病机制中的作用。方法：35例临床确诊为中重度持续性支气管哮喘患者作为病例组,均行肺功能及IgE水平检测,依据血清IgE水平将支气管哮喘患者分为IgE升高组（n=20）和IgE正常（n=15）。另外,选取22名健康者作为对照组,采用ELISA法检测受试者血清肥大细胞羧肽酶水平。比较支气管哮喘患者与健康者血清中肥大细胞羧肽酶水平;分析血清肥大细胞羧肽酶水平与IgE及肺功能的相关性。结果：IgE升高组患者血清肥大细胞羧肽酶水平明显高于IgE正常组（P＜0.05）;支气管哮喘急性发作期患者血清肥大细胞羧肽酶水平明显高于健康对照组（P＜0.05）;另外,哮喘急性发作期患者血清肥大细胞羧肽酶水平与患者FEV(%)呈明显的负相关;缓解期血清肥大细胞羧肽酶水平与FEV-1(%)无相关性（r=-0.421, P=0.012;r=-0.284,P=0.099）。结论：血清肥大细胞羧肽酶可能参与了支气管哮喘急性发作的气道炎症反应。     

支气管哮喘患者FeNO的表达及临床意义

目的:探讨不同呼出气一氧化氮(Fractional exhaled nitric oxide,FeNO)水平下支气管哮喘患者痰液、血液、肺功能检测等多个观察指标的表达特点,并分析在气道高反应性中的预测价值。方法:选取2017年1月至2019年5月于我院就诊的120例疑似支气管哮喘患者作为研究对象进行前瞻性分析,根据FeNO水平不同,将FeNO>49 ppb的42例患者列为高水平组,FeNO为26~49 ppb的33例患者为低水平组,FeNO≤25 ppb的45例患者为正常组。比较三组患者的基本临床资料、痰嗜酸性粒细胞、痰中性粒细胞、血嗜酸性粒细胞阳离子蛋白(Eosinophilic cationic protein,ECP)和免疫球蛋白E(Immunoglobulin E,IgE)以及第1s用力呼气容积(Forced expiratory volume at 1s,FEV1)、FEV1占预测值百分比(FEV1%Pred)、用力肺活量(Forced vital capacity,FVC)以及FEV1与FVC比值(FEV1/FVC)等肺功能检测结果进行统计分析。结果:经Spearman相关性分析显示,血IgE、ECP水平与FeNO水平呈正相关(r=0.615/0.629,P>0.01),FEV1%pred、FEV1/FVC与FeNO水平呈负相关(r=-0.494/0.789,P>0.01)。其中血IgE、ECP、FEV1%pred、FEV1/FVC对于预测支气管哮喘有一定的价值,而联合上述指标对于预测支气管哮喘的准确性最佳(AUC=0.920,P>0.01)。结论:不同FeNO水平支气管哮喘患者在临床表现中具有显著差异,在血IgE、ECP和肺功能FEV1%pred、FEV1/FVC指标检测的基础上增加FeNO可大大增加预测支气管哮喘的准确性。     

2型糖尿病患者血清瘦素、NSF-1与血脂的关系研究

目的 研究2型糖尿病患者血清瘦素、NSF-1、载脂蛋白及血脂水平的相关性.方法 选择2016年6月至2017年1月我院收治的2型糖尿病患者64例作为观察组,于同期选择在我院健康体检的健康人群58例为对照组,抽取两组晨起空腹静脉血,比较两组血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、载脂蛋白A1、载脂蛋白E、瘦素、摄食抑制因子-1水平,并采用Pearson相关分析以上指标的相关性.结果 观察组与对照组血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、载脂蛋白E、瘦素、摄食抑制因子-1水平差异具有统计意义(P＜0.05),载脂蛋白A1比较无统计学差异.血清总胆固醇与甘油三酯、低密度脂蛋白胆固醇、载脂蛋白E呈正相关(r =0.341,P＜0.001;r=0.836,P＜0.001;r =0.337,P＜0.001),与摄食抑制因子-1呈负相关(r=-0.303,P＜0.001).甘油三酯与载脂蛋白E呈显著正相关(r =0.678,P＜0.001),低密度脂蛋白胆固醇与瘦素呈明显负相关(r=-0.266,P＜0.001),高密度脂蛋白胆固醇与载脂蛋白A1呈明显正相关(r=0.335,P＜0.001),载脂蛋白A1与载脂蛋白E呈显著正相关(r=0.318,P＜0.001).结论 2型糖尿病患者存在血脂代谢异常情况,且与血清载脂蛋白、瘦素、摄食抑制因子-1之间存在一定相关性.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.