伊可新滴剂联合普米克令舒治疗毛细支气管炎患儿的疗效及其对血清SIL-2R、CysLTs、Eotaxin的影响

目的探讨伊可新滴剂联合普米克令舒治疗毛细支气管炎患儿的疗效及其对血清可溶性白细胞介素-2受体(SIL-2R)、半胱氨酰白三烯(CysLTs)、嗜酸性粒细胞趋化蛋白(Eotaxin)的影响。方法选取我院2016年1月至2018年4月所收治的90例毛细支气管炎患儿作为研究对象,按照随机数表法分为观察组46例,对照组44例。在常规治疗基础上,对照组给予普米克令舒治疗,观察组在对照组的基础上,给予伊可新滴剂治疗,均连续治疗7 d。比较两组血清SIL-2R、CysLTs、Eotaxin的变化,临床疗效,临床症状改善时间及不良反应。结果治疗后,观察组总有效率高于对照组(93.48%vs.77.27%,P<0.05),血清SIL-2R、CysLTs、Eotaxin低于对照组[(151.23±10.08) pg/ml vs.(165.81±12.42) pg/ml,(24.59±3.07) ng/ml vs.(32.37±4.33) ng/ml,(14.94±2.56) ng/L vs.(22.15±2.88) ng/L,P<0.05],咳嗽、喘憋、肺部湿啰音、哮鸣音、气促改善时间较对照组缩短[(3.16±0.65) d vs.(4.17±0.74) d,(3.49±0.47) d vs.(4.26±0.58) d,(3.94±0.55) d vs.(4.73±0.60) d,(3.28±0.37) d vs.(3.95±0.48) d,(2.98±0.4) d vs.(3.76±0.50) d,P<0.05]。治疗期间两组患儿无明显不良反应发生。结论伊可新滴剂联合普米克令舒在毛细支气管炎患儿的治疗中效果显著,可有效降低血清SIL-2R、CysLTs、Eotaxin的表达,促进疾病恢复,安全性高。     

降钙素原检测在脑卒中患者肺部感染的诊断价值

目的研究血清降钙素原(PCT)在脑卒中后肺部感染患者中的临床价值。方法测定42例脑卒中合并肺部感染患者(感染组)和40例单纯脑卒中患者(对照组)的血清PCT和C反应蛋白(CRP)水平,比较其组间差异。结果入院第1天和第4天,感染组PCT均明显高于对照组[(0.92±0.63)ng/ml vs.(0.18±0.08)ng/ml,(1.37±0.93)ng/ml vs.(0.14±0.07)ng/ml](P<0.01),感染组CRP也明显高于对照组[(12.73±7.49)mg/L vs.(7.12±4.51)mg/L,(13.33±6.67)mg/L vs.(8.22±4.67)mg/L](P<0.05)。PCT诊断肺部感染的敏感度和特异度均高于CRP(P<0.01)。结论血清PCT可以作为脑卒中患者合并肺部感染的诊断指标。     

孟鲁司特对肺炎支原体感染哮喘儿尿白三烯水平的影响

目的 探讨孟鲁司特对肺炎支原体(MP)感染对哮喘患儿尿白三烯水平的影响.方法 哮喘组患儿200例和对照组健康儿童50例,采用被动凝集法检测MP-IgM抗体.哮喘患儿根据MP-IgM抗体检测结果分为4组:A组32例MP-IgM阳性,常规治疗+孟鲁司特治疗;B组32例MP-IgM阳性,常规治疗;C组32例MP-IgM阴性,常规治疗+孟鲁司特治疗;D组32例,MP-IgM阴性,常规治疗.应用ELISA法定最测定患儿治疗前后尿白三烯水平.结果 MP-IgM抗体15阳性(A、B组)患儿治疗前尿白三烯水平明显高于MP-IgM抗体阴性(C、D组)患儿[(0.51±0.26)ng/mlvs.(0.38±0.11)ng/ml](P<0.01).A组和C组治疗后尿白三烯水平均比治疗前明显降低[(0.25±0.20)ng/ml vs.(0.50±0.26)ng/ml](P<0.01)和([0.22±0,10)ng/ml vs.(0.35±0.15)ng/ml](P<0.05).治疗后A组尿白三烯水平明显低于B组[(0.25±0.20)ng/ml vs.(0.42±0.15)3(P<0.01).结论 肺炎支原体感染可明显地诱导哮喘忠儿体内白三烯水平的升高;孟鲁司特可以降低肺炎支原体感染的哮喘患儿体内尿白三烯水平.     

哮喘大鼠肾上腺皮质功能变化与白细胞介素10水平的关系

目的 探讨哮喘大鼠肾上腺皮质功能变化与白细胞介素10(IL-10)水平的关系.方法 卵蛋白致敏方法制备大鼠哮喘模型,随机分为哮喘急性发作期组(A组)、哮喘缓解期组(B组)、正常对照组(C组)、模型对照组(D组),每组6只.放射免疫分析法测定血浆皮质酮(CORT)、促肾上腺皮质激素(ACTH)以及下丘脑促肾上腺皮质激素释放激素(CRH)的含量;ELASA法检测下丘脑组织和血浆IL-10的水平.结果 与C组比较,A组大鼠脑组织和血浆IL-10水平均下降[(15.45±4.06)Pg·mg-1·prot-1 vs.(28.74±8.91) pg·mg-1·prot-1,和(26.62±6.78)pg/ml vs.(54.86±14.32) pg/ml](P＜0.01);CORT、ACTH以及CRH的含量降低[(1.47±0.11) ng·mg-1·prot-1 vs.(1.84±0.12) pg·mg-1·prot-1,(75.55±8.17)pg/ml vs,(108.34±16.57) pg/ml,和(121.69±17.65) ng/ml vs.(162.01±21.21) ng/m1](P＜0.01).哮喘缓解期大鼠脑组织IL-10水平上升,CRH的含量增高.结论 哮喘大鼠存在肾上腺皮质功能减退可能与下丘脑和血中IL-10水平变化有关.     

自拟复脉方辅助西医治疗急性脑梗死的效果及作用机制探讨

目的探讨自拟复脉方辅助西医治疗急性脑梗死的效果及作用机制。方法选择我院2017年1月至2019年4月收治的急性脑梗死患者共146例,以随机抽签法分为对照组(73例)和观察组(73例)。对照组给予西医规范对症干预,观察组在此基础上加用自拟复脉方治疗。比较两组近期疗效、治疗前后主要症候评分、NIHSS评分、ADL评分、凝血功能指标水平、血液流变学指标水平、过氧化氢酶及相关生长因子水平。结果观察组近期有效率高于对照组(94.52%vs.76.71%,P<0.05)。治疗后,观察组主要症候评分、NIHSS评分、ADL评分、凝血功能指标水平及血液流变学指标水平均改善,观察组偏瘫、口舌歪斜、言语蹇涩/不语、气短乏力症候评分低于对照组[(1.05±0.22)分vs.(1.63±0.38)分,(0.92±0.19)分vs.(1.47±0.35)分,(0.95±0.19)分vs.(1.41±0.36)分,(1.11±0.18)分vs.(1.57±0.30)分,P<0.05];观察组NIHSS评分低于对照组[(8.26±1.49)分vs.(12.49±2.31)分,P<0.05],ADL评分高于对照组[(76.36±10.71)分vs.(63.50±7.45)分,P<0.05];观察组血小板聚集率、vWF、FIB低于对照组[53.82%±7.06%vs.64.64%±8.80%,105.47%±20.83%vs.124.26%±25.69%,(2.09±0.27) g/L vs.(2.62±0.45) g/L,P<0.05],PT、APTT、TT高于对照组[(14.75±1.97) s vs.(12.59±1.61) s,(43.52±8.26) s vs.(37.65±7.49) s,(18.84±2.09) s vs.(16.10±1.32),P<0.05];观察组全血黏度/10 s、全血黏度/100 s、PV、EDR低于对照组[(9.80±0.99) mPa·s vs.(11.54±1.42) mPa·s,(5.31±0.40) mPa·s vs.(6.98±0.63) mPa·s,(1.67±0.38) mPa·s vs.(2.10±0.52) mPa·s,(18.93±2.15) mm·h vs.(23.37±3.31) mm·h]。治疗后,观察组过氧化氢酶和相关生长因子水平均改善,观察组过氧化氢酶、VEGF、bFGF高于对照组[(21.93±5.83) pg/ml vs.(18.79±4.20) pg/ml,(327.51±70.36) pg/ml vs.(285.03±61.84) pg/ml,(35.46±4.22) pg/ml vs.(27.68±3.36) pg/ml]。结论自拟复脉方辅助西医治疗急性脑梗死能够显著减轻临床症状,保护神经损伤,促进生活质量恢复,并有助于改善血液流变学和血液黏稠度指标,可能与该方案对过氧化氢酶、VEGF、bFGF水平调节作用密切相关。     

再生障碍性贫血患者hepcidin检测及意义

目的 探讨再生障碍性贫血(AA)患者血清hepcidin的表达及其与血清铁蛋白(SF)间的关系.方法 用ELISA、放射免疫法测定45例AA患者(AA组)血清中的hepcidin及SF水平,并选择60例正常体检者作为对照(C组).结果 AA组hepcidin和SF高于C组[(237.09±44.77)ng/ml vs.(137.12±40.19) ng/ml和(140.78±42.14) μg/L vs.(77.70±16.83)μg/L](P＜0.01);AA组hepcidin和SF水平呈正相关(r=0.982,P＜0.01).输血＞3次的AA患者hepcidin和SF高于输血≤3次者[(245.17±40.09) ng/ml vs.(204.84±25.34)ng/ml和(216.55±55.97) μg/L vs.(156.33±43.64)μg/L](P＜0.01).结论 AA患者hepcidin较正常人显著增高,且与输血次数显著相关.     

参麦注射液预处理对大鼠心肌缺血-再灌注损伤中胰岛素抵抗的影响

目的探讨参麦注射液(SM)对胰岛素(Ins)抵抗是否有改善作用。方法 SD雄性大鼠24只随机均分为两组:A组每天腹腔注射SM 10ml/kg,连续3d;B组注射等量生理盐水。末次给药后30min采用冠脉结扎15min后再松开45min的办法制备大鼠心肌缺血-再灌注(I-R)损伤模型。放射免疫法检测血糖(Glu)、Ins和C肽的浓度,ELISA法检测血浆抵抗素和游离脂肪酸(FFA)含量。结果 A组血浆Glu[(3.64±0.53)mmol/L vs.(4.29±0.62)mmol/L]、Ins[(31.68±0.21)μU/ml vs.(39.17±0.69)μU/ml]、C肽[(9.26±1.87)ng/ml vs.(13.05±2.56)ng/ml]的浓度以及血浆FFA[(326.40±35.63)μmol/L vs.(429.30±29.64)μmol/L]和抵抗素[(13.29±1.16)ng/mlvs.(16.32±1.52)ng/ml](P<0.05)的含量均明显低于B组(P<0.05)。结论 SM预处理能减轻大鼠心肌I-R损伤过程中的Ins抵抗,对心肌产生一定的保护作用。     

慢性阻塞性肺疾病患者血清巨噬细胞移动抑制因子的表达

目的探讨慢性阻塞性肺疾病(COPD)患者血清巨噬细胞移动抑制因子(MIF)的表达。方法 COPD患者100例均分为急性加重(A)组和稳定(B)组,同期体检的健康人50例予以对照(C组)。检测并比较三组患者的血清NF-κB、MIF、IL-6和C反应蛋白(CRP)的表达。结果三组血清NF-κB均无统计学差异(P>0.05);三组血浆MIF水平差异无统计学意义(P>0.05)。A组MIF mRNA高于B、C组(0.0314±0.0210vs.0.0130±0.0193、0.0175±0.0063)(P<0.05)。A组巨噬细胞CD4~+MIF~+T细胞和CD8~+MIF~+T细胞占总CD4~+T细胞的百分比均高于B、C组[(77.78±15.75)%vs.(60.39±20.71)%、(62.08±19.65)%和(76.97±19.89)%vs.(59.36±26.18)%、(55.72±28.94)%](P<0.05)。B、A组血清IL-6表达高于C组[(45.46±17.04)ng/L、(31.78±19.65)ng/L vs.(24.82±8.97)ng/L](P<0.05)。A组CRP高于B、C组[(28.23±37.56)mg/L vs.(8.23±17.21)mg/L、(2.82±4.79)mg/L](P<0.05)。结论血清巨噬细胞MIF和IL-6可能与COPD发病有关。     

生大黄治疗急性胰腺炎的临床观察

目的 探讨生大黄治疗急性胰腺炎(AP)的疗效.方法 69例AP患者随机分成两组:对照组33例,仪采用常规治疗;治疗组36例,同时经胃管加用生大黄颗粒剂.于治疗前和治疗第7天检测血自细胞(WBC)、C-反应蛋白(CRP)和血清淀粉酶(AMS),并行APACHEⅡ评分;记录住院大数及费用.结果 治疗组第7天WBC、CRP、AMS及APACHEⅡ评分均明显低于对照组[(8.0±3.7)×109/L vs.(11.3±4.3)×109/L,(20.0±6.7)mg/L VS.(56.2±16.3)mg/L,(124.0±35.4)U/L vs.(256.0±67.6)U/L和(6.3±0.8)分vs.(8.6±1.1)分](P<0.05).与对照组比较.治疗组平均住院日少[(14.2±6.3)d vs.(11.2±4.4)d]、住院费用低(P<0.05).结论 在常规治疗基础上加用生大黄颗粒剂治疗急性胰腺炎具有显著疗效.     

先兆流产患者血清HLA-G、β-HCG、PIBF水平与妊娠结局的相关性分析

目的 分析先兆流产患者血清人类白细胞抗原G(HLA-G)、人绒毛膜促性腺激素(β-HCG)、孕激素诱导阻滞因子(PIBF)水平与妊娠结局的相关性.方法 选取先兆流产患者140例作为先兆流产组,同期入院产检的健康孕妇90例作为对照组.比较两组的HLA-G、β-HCG、PIBF水平,使用ROC曲线分析HLA-G、β-HCG...     

Opposing effects of platelet-activating factor and lyso-platelet-activating factor on neutrophil and platelet activation

Platelet-activating factor (PAF) is a potent, bioactive phospholipid that acts on multiple cells and tissues through its G protein-coupled receptor (GPCR). PAF is not stored but is rapidly generated via enzymatic acetylation of the precursor 1-O-hexadecyl-2-hydroxy-sn-glycero-3-phosphocholine (lysoPAF). The bioactivity of PAF is effectively and tightly regulated by PAF acetylhydrolases, which convert PAF back to lysoPAF. Previous studies report that lysoPAF is an inactive precursor and metabolite of PAF. However, lysoPAF has not been carefully studied in its own context. Here we report that lysoPAF has an opposing effect of PAF in the activation of neutrophils and platelets. Whereas PAF potentiates neutrophil NADPH oxidase activation, lysoPAF dose-dependently inhibits this function. Inhibition by lysoPAF is not affected by the use of a PAF receptor antagonist or genetic deletion of the PAF receptor gene. The mechanism of lysoPAF-mediated inhibition of neutrophils involves an elevation in the intracellular cAMP level, and pharmacological blockade of adenylyl cyclase completely reverses the inhibitory effect of lysoPAF. In addition, lysoPAF increases intracellular cAMP levels in platelets and inhibits thrombin-induced platelet aggregation, which can be reversed by inhibition of protein kinase A. These findings identify lysoPAF as a bioactive lipid with opposing functions of PAF and suggest a novel and intrinsic regulatory mechanism for balance of the potent activity of PAF.     

肿瘤血管生成促进因子和抑制因子

在成人多数正常组织中,血管生成促进因子和抑制因子处于相对平衡状态,因此血管系统也就处于相对静止状态.如果这一平衡被打破就可能导致生理性的血管生成(如伤口愈合)或病理性的血管生成(如肿瘤血管生成).     

Perspectives on factor Xa inhibition

Blood coagulation involves a complex cascade of enzymatic reactions, ultimately generating fibrin, the basis of all blood clots. This cascade is comprised of two arms, the intrinsic and extrinsic pathways which converge at factor Xa to form the common pathway. Factor Xa activates prothrombin to thrombin, which in turn catalyzes the conversion of fibrinogen to fibrin. Recently, both natural and synthetic factor Xa inhibitors have shown promising pharmacological effects in animal models of thrombosis. Accordingly, factor Xa has emerged as a compelling target for pharmacological intervention and much recent effort has focused on selective and potent inhibition of this key enzyme. Factor Xa and other enzymes in the coagulation cascade belong to the trypsin-like serine protease family, the various members of which are involved in numerous physiological functions in the body. Hence, to avoid toxicity and adverse side effects, it is important to selectively inhibit the target enzyme. Achieving the needed selectivity has proved challenging due to the high degree of structural homology around the active site of this class of enzymes. This article provides a brief review of the strategies currently being employed to develop oral anticoagulants and, more specifically, the structural features of protein-ligand binding that have been utilized to achieve potency and selectivity toward factor Xa. Additionally, selected lead molecules will be discussed to highlight binding motifs used to attain both potency and selectivity in drug candidates.     

左乙拉西坦联合地西泮对热性惊厥反复发作儿童损伤因子、炎性因子和免疫因子的影响

目的 探讨左乙拉西坦联合地西泮对热性惊厥反复发作儿童损伤因子、炎性因子和免疫因子的影响。方法 选择唐山市妇幼保健院2016年6月-2018年4月收治的热性惊厥患儿100例作为研究对象,按照随机数字表法将患儿分为对照组（n=50）和观察组（n=50）。对照组患儿口服复方地西泮片,40~200 μg/kg,3次/d,共7 d。观察组在对照组的基础上口服左乙拉西坦片,20 mg/kg,2次/d,热退24 h后开始减量,以每2天减半量至第减药期第7天停药。两组患儿出院后,均随访48周,每3个月随访1次。比较两组患儿治疗前后的脑损伤因子、炎性因子、免疫因子水平,同时观察患儿发热、热性惊厥复发情况和不良反应发生情况。结果 治疗后,两组血清神经元特异性烯醇化酶（NSE）、核因子κB（NF-κB）和S100β蛋白水平均显著降低,同组治疗前后比较差异具有统计学意义（P<0.05）;治疗后,观察组血清NSE、NF-κB和S100β蛋白水平均显著低于对照组,两组比较差异具有统计学意义（P<0.05）。治疗后,两组血清肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-10（IL-10）水平均显著降低,同组治疗前后比较差异具有统计学意义（P<0.05）;治疗后,观察组血清TNF-α、IL-1β和IL-10水平均显著低于对照组,两组比较具有统计学意义（P<0.05）。治疗后,两组血清免疫球蛋白（Ig）A、IgG、IgM水平均显著降低,同组治疗前后比较差异具有统计学意义（P<0.05）;治疗后,观察组血清IgA、IgG、IgM水平均显著低于对照组,两组比较具有统计学意义（P<0.05）。在治疗和随访期间,观察组患儿发热、热性惊厥复发情况和不良反应发生情况均优于对照组（P<0.05）。结论 左乙拉西坦联合地西泮治疗小儿热性惊厥可减少脑组织损伤,抑制炎性免疫反应,预防热性惊厥反复发作,安全可靠,值得应用于小儿热性惊厥的临床治疗。     

Conformational analysis of the effects of methylmercury on nerve growth factor and brain derived neurotrophic factor

Methylmercury is a neurotoxicant that is detrimental to the development and physiology of the nervous system. One possible mechanism for methylmercury's toxicity stems from its ability to interfere with the signaling of the neurotrophins nerve growth factor and brain derived neurotrophic factor. In this study, we examine the effect of methylmercury to determine if it interferes with neurotrophin conformation in a manner similar to Hg(2+), or if it occurs via an alternate mechanism. Our findings indicate that although MeHg inhibits neurotrophin signaling, its toxic effects are not mediated via an induced conformational change, as seen with other metal ions, including Hg(2+).     

Influence of dichlorodiphenylchloroethylene on vascular endothelial growth factor and insulin-like growth factor in human and rat ovarian cells

1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p′-DDE, DDE), a metabolite of DDT is a persistent hormonally active environmental toxicant present in human serum and follicular fluid. The objective of this study was to investigate the effects of DDE on the expression of the ovarian vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF-1) in primary cultures of human granulosa cells and in the rat ovary. Granulosa cells were obtained at the time of oocyte retrieval for in vitro fertilization and cultured with environmentally relevant concentrations of DDE. Immature female rats were treated with 100 μg DDE/kg body weight or vehicle at 28 and 31 days of age and then euthanized at 50 days of age for collection of ovarian tissue. Expression of VEGF, the VEGF receptor fetal liver kinase (Flk-1) and IGF-1 were determined by Western blotting analysis of protein lysates from granulosa cell cultures and by immunohistochemistry in the rat ovary. DDE at concentrations of 100–1000 ng/mL increased the expression of VEGF, Flk-1 and IGF-1 in vitro in primary cultures of human granulosa cells, with the highest expression occurring at 1000 ng/mL. Similarly, acute administration of DDE resulted in a significant increase in immunoreactive VEGF, Flk-1 and IGF-1 in the rat ovary. We conclude that DDE, at levels, which have been detected in humans, alters the expression of the ovarian growth factors VEGF and IGF-1 both in vivo and in vitro. This alteration in expression of growth factors may lead to altered ovarian function as seen in polycystic ovaries and impaired fertility.     

猪凝血因子Ⅹ及凝血因子Ⅹa的制备工艺研究

目的从猪血中制备猪凝血因子Ⅹ(FⅩ)及凝血因子Ⅹa(FⅩa)。方法采用柠檬酸钡吸附、硫酸铵分级沉淀、DEAE 纤维素离子交换色谱等方法制备FⅩ,并优化FⅩ的激活条件,从而制备FⅩa。通过SDS PAGE进行FⅩ和FⅩa的检测。结果建立了FⅩ和FⅩa的制备工艺,收率分别为每1ml血浆34,12 μg;采用胰蛋白酶激活FⅩ,激活条件为:0 .0 2 %酶浓度、pH 8.0、37℃下作用70min。结论此工艺操作简单,收率高,适合于规模化生产     

Effect of vascular endothelial growth factor and epidermal growth factor on iatrogenic apoptosis in human endothelial cells

To study the effect of growth factors on iatrogenic apoptosis, we examined the influence of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) on staurosporine-induced apoptosis in primary cultures of human umbilical vein endothelial cells (HUVEC). Apoptosis was evaluated by a cell viability test, the TUNEL-POD assay and the activation of the pro-apoptotic caspase-3. Staurosporine (10-100nM) caused the activation of caspase-3. This effect was manifest after 2hr of incubation and reached its maximum after 5hr. Severe loss of viability followed within 18hr. VEGF or EGF (10-100ng/mL) added together with staurosporine decreased the activation of caspase-3. The loss of viability was 24hr delayed. The action of growth factors was observed at 1% serum concentration but also at concentration optimal for HUVEC survival (10%, v/v). Furthermore, the inhibition of PI-3 kinase (PI-3K) by wortmannin or LY294002 as well as the inhibition of MEK by PD098059 or U0126 prevented the protective effect of VEGF and EGF. Western blotting analysis showed that after 3hr of incubation with staurosporine the level of the anti-apoptotic protein Mcl-1 decreased and this effect was reverted by VEGF. It is concluded that VEGF and EGF antagonize the pro-apoptotic action of staurosporine by the combined signalling of PI-3K and ERKs pathways.