矩阵的LDU分解的初等变换法

医学统计多元分析中 ,常常用到矩阵分解。本文介绍了矩阵 L DU分解的初等变换法。首先 ,我们来看什么叫矩阵的 L DU分解。定义 :如果方程 A可以分解成 A=L DU,其中 L 是单位下三角形矩阵 ,D是对角矩阵 ,U是单位上三角形矩阵 ,则称矩阵 A可作 L DU分解。由文献 [1]我们知道 ,n阶方阵 A可惟一分解为 A=L DU的充要条件是 A的顺序主子式△ k≠ 0 (k=1,2 ,… ,n- 1) ,且存在惟一。L1 =1C2 1 1C31 1?Cn1 1,L2 =11C32 1?C2 1 1,… ,Ln- 1 =1 1Cn,n- 1 1,使A=L1 …Ln- 1b1 1 … b1 n 廱nm=1C2 1 1?? Cn- 1 ,1 Cn- 1 ,2 ?1Cn1 Cn2 …     

靶向程序性死亡分子1信号通路的单克隆抗体的研究进展

程序性死亡分子1 (programmed death-1,PD-1),1种T细胞表面的免疫抑制分子,可与程序性死亡配体1 (programmed death ligand-1,PD-L1)组成信号通路.PD-1/PD-L1信号通路可抑制T细胞活化,并对肿瘤免疫逃逸起关键作用.靶向PD-1信号通路的单克隆抗体包括抗PD-1和PD-L1抗体,它们通过阻断PD-1与PD-L1的相互作用来增强机体内源性抗肿瘤免疫效应,在临床试验中,该类单克隆抗体在各类肿瘤患者中表现出令人惊喜的疗效,成为一类有希望的肿瘤免疫治疗药物.此文就靶向PD-1信号通路的单克隆抗体的生物学功能及其临床应用等方面的研究进展做一综述.     

新型树突状细胞疫苗的构建及功能的初步鉴定

目的:构建可同时实现沉默细胞因子信号抑制因子1(SOCS1)、高迁移率族蛋白B1(HMGB1)刺激和肿瘤相关抗原负载的新型树突状细胞(DC)疫苗。方法:构建沉默SOCS1并共表达HMGB1及肿瘤相关抗原NY-ESO-1的质粒(p/shS1-NY-IRES-sig-HMGB1)。体外诱导单核细胞分化为DC,将p/shS1-NY-IRES-sig-HMGB1转染入DC细胞。同时设立未转染组、shNC/GFP转染组和p/shS1-NY-IRES-sig-HMGB1转染组。PCR和Western blot验证基因及蛋白表达后,酶联免疫吸附(ELISA)法检测DC细胞分泌的肿瘤坏子因子(TNF)-α、白细胞介素(IL)-12、IL-1及IL-6的变化。结果:经测序证实所构建质粒序列与预期序列一致,酶切和PCR验证质粒结构正确。成功将p/shS1-NY-IRES-sig-HMGB1转染入DC细胞,并在基因和蛋白水平验证NY-ESO-1的正确表达,HMGB1可在胞浆内表达。SOCS1 shRNA质粒shS可沉默SOCS1表达。p/shS1-NY-IRES-sig-HMGB1转染组DCTNF-α、IL-12、IL-1及IL-6分泌量较未转染组和shNC/GFP转染组升高(P<0.05)。结论:成功构建可同时实现沉默SOCS1、HMGB1刺激和肿瘤相关抗原负载的新型DC疫苗。     

重组痘苗病毒诱导的抗口蹄疫病毒的保护性免疫力

本文报道利用空斑形成分离重组痘苗病毒的方法来构建表达口蹄疫病毒 ( FMDV)C3Arg85株四种结构蛋白前体的重组痘苗病毒 ,并将其作为活疫苗 ,在小鼠中进行试验。　　将从质粒 p UC1 9- P1中获得的 FMD-VC3Arg85株 P1基因插入 p RB2 1质粒的Sma I位点构成重组质粒 p RB2 1 - P1或p RB2 1 ,再将其转染痘苗病毒 v RB2 1感染的CV- 1细胞构成重组痘苗病毒 v RB1 2 - P2 1和v RB1 2 - P1。以 6 0～ 90日龄雌性 Balb/c小鼠和新生小鼠为试验动物 ,分别腹腔注入 1 0 7空斑形成单位 ( PFU)的 v RB1 2 - P2 1、1 0 7PFU的 v RB1 2 - …     

小儿烧伤的护理

我院自1996年至今共收治烧伤患儿1022例,现将护理体会总结如下。1病情观察1 1休克期的观察要点:1 1 1神志和精神状态,休克早期表现为口渴、烦躁,继而表情淡漠、软弱无力,如有意识障碍,常表示输液量不够。1 1 2生命体征:烧伤患者应每30分钟测量生命体征1次,特别注意血压、脉率的     

医院业务收入增长因素的分析

笔者运用因素分析法对我院业务收入进行分析。1资料与方法1 1资料来源于我院2001～2002年医院工作报表 ,见表1。1 2计算方法1 2 1用相对数分析其影响的程度 :∑f1x1/∑f0x0=(∑f1x0/∑f0x0)×(∑f1x1/∑f1x0)。1 2 2从绝对差额上分析其影响的程度 :业务收入增减的绝对量=∑f1x1-∑f0x0;工作量变动增减绝对量=∑f1x0-∑f0x0;单位费用变动增减绝对量=∑f1x1-∑f1x0;∑f1x1-∑f0x0=(∑f1x0-∑f0x0) +∑f1x1-∑f1x0。2结果与分析以2001年为基期 ,2002年为报告期 ,医院业务收入因素分析见表2。利用表2数据运用因素指数分析方法计算结果见表3。2 1…     

编码4种间日疟原虫抗原的DNA疫苗质粒的构建和免疫原性

作者从间日疟原虫 (Pv) Sal 株基因组DNA中扩增编码抗原的基因片段 ,经琼脂糖凝胶纯化克隆至 p CR Script质粒后测序。再将上述抗原基因片段插入 VR1 0 1 2、VR1 0 2 0、VR1 0 40质粒载体中获得 8种 DNA疫苗质粒 ;Pv环子孢子蛋白 (Pv CSP) /1 0 1 2、Pv CSP/1 0 40、Pv CSP/1 0 2 0、Pv子孢子表面蛋白 2 (Pv SSP2 ) /1 0 1 2、Pv SSP2 /1 0 2 0、Pv顶部膜抗原 1 (Pv AMA1 ) /1 0 1 2、Pv AMA1 /1 0 2 0和 Pv裂殖子表面蛋白 1 (Pv MSP1 ) /1 0 2 0。　　将 8种疫苗质粒短暂地转染 UM449细胞后 ,用免疫印迹法测定疫苗质…     

已免疫的医务人员对乙型肝炎疫苗加强免疫的应答

1994～ 1 995年 ,作者在美国阿拉斯加选择 1 1 5名已有 3针乙型肝炎疫苗免疫接种史的医务人员 ,他们在免疫后 1 2个月内经放射免疫法检测抗 - HBs水平≥ 1 0 m IU/ml或用酶免疫试验检测抗 - HBs阳性、HBs Ag及抗 -HBc均阴性。将他们按抗 - HBs水平分成 <1 0 m IU/ml和 1 0～ 50 m IU/ml组。两组人员又各自被随机分成两组 ,分别接种 2 .5μg或1 0 μg乙型肝炎疫苗。在加强免疫后 1 0～ 1 4天、1个月、1年分别检测抗 - HBs。　　结果显示 ,所有对象在加强免疫后均出现抗 - HBs水平升高的免疫应答。免疫后 1 4天 ,抗体基值较高组和 1 …     

GLP-1R激动剂的细胞筛选模型的建立

目的构建靶向GLP-1R的高通量筛选模型。方法构建过表达GLP-1R的重组质粒和响应GLP-1信号通路的报告载体,共转染到HEK293细胞中,筛选得到稳定转染的单克隆细胞株,并用阳性药进行模型验证。结果成功构建了表达GLP-1R的重组质粒pcDNA3.1(+)-HuGLP-1R和响应GLP-1信号通路的报告载体PGL4.22-CRE-vip-GFP,共转染到HEK293细胞,筛选得到稳定转染细胞株CG-HEK293,经GLP-1刺激后,确定GFP的最佳表达时间为8 h,经过不同浓度的GLP-1刺激后,能够剂量依赖性地激活GFP的表达。结论构建了靶向GLP-1R的高通量筛选模型,该模型能够直观、稳定、高通量的筛选靶向GLP-1R的小分子或者GLP-1类似物,为长效的GLP-1类似物的研究和开发奠定了基础。     

检测HCV核心抗原的简便、高度灵敏的酶免疫试验

作者使用 0 .3% Triton X- 1 0 0、1 .5 % 3-〔(3-胆酰胺丙基 ) -二乙铵〕-丙磺酸 (CHAPS)和 1 5 %十二烷基硫酸钠 (SDS)作为预处理液 ,取 5 0 μl与 1 0 0 μl标本混合 ,5 6℃作用 30分钟进行预处理。同时 ,在大肠杆菌中表达重组丙型肝炎病毒 (HCV)核心抗原融合蛋白(HCV基因型 2 a分离株的 1～ 1 6 0氨基酸 )。经过提取纯化得到重组丙型肝炎病毒核心抗原 (HCVc Ag) ,用其制备单克隆抗体(Mc Ab)。在得到的 32株杂交瘤细胞中选择c1 1 - 3和 c1 1 - 7两株 Mc Ab作为包被抗体 ;选择 c1 1 - 1 0和 c1 1 - 1 4两株 Mc Ab与碱性磷酸酶 …     

Sesquiterpenoids from Hedychium yunnanense and Porana discifera, and the structural revision of two sesquiterpenoids from Laggera pterodonta

A new eudesmane-type sesquiterpenoid, hedytriol (1), was isolated from Hedychium yunnanense (Zingiberaceae). By means of chemical and spectroscopic methods, the structure of 1 was determined as ( - )-7aH-eudesmane-1beta, 4alpha, 11-triol. A new ent-eudesmane sesquiterpenoid, disciferitriol (2), was isolated from Porana discifera (Convolvulaceae), which was exactly the enantiomer of hedytriol (1). The structures of pterodondiol (3a) and pterodontriol B (3), previously isolated from Laggera pterodonta, were revised on the basis of X-ray diffraction, as well as chemical transformations.     

环状RNA CDR1as与miR-7在癫痫患者血浆中的表达及与脑电图异常的关系分析#br#

摘要：目的　探讨环状RNA小脑变性相关蛋白1反义转录物（CDR1as）与微小RNA-7（miR-7）在癫痫患者血浆中的表达及与脑电图异常的关系。方法　选取2016年12月—2019年12月在新乡医学院第二附属医院门诊及住院的癫痫患者87例为观察组，并根据脑电图结果分为正常组（6例）、轻度异常组（18例）、中度异常组（37例）及重度异常组（26例）；选取同期健康体检者90例为对照组。实时荧光定量PCR（qPCR）法检测血浆CDR1as、miR-7水平，酶联免疫吸附测定（ELISA）法检测血浆白细胞介素（IL）-2、肿瘤坏死因子（TNF）-α和IL-1β水平；Pearson法分析癫痫患者血浆CDR1as、miR-7水平与IL-2、TNF-α和IL-1β水平的相关性。结果　对照组、正常组、轻度异常组、中度异常组、重度异常组血浆CDR1as、IL-2、TNF-α和IL-1β水平总体呈升高变化，miR-7水平总体呈降低变化，差异均有统计学意义（P＜0.05）。癫痫患者血浆CDR1as水平与IL-2、TNF-α和IL-1β水平呈正相关（P＜0.05），miR-7水平与IL-2、TNF-α和IL-1β水平呈负相关（P＜0.05）。结论　CDR1as、miR-7在癫痫患者血浆中分别呈高表达、低表达，与炎症因子水平、脑电图异常程度密切相关，可能通过影响炎症反应引起脑部异常放电。     

Biological activity of tropolone

Tropolone (1). showed strong insecticidal activity on Tyrophagus putrescentiae and Dermatophagoides farinae. The insecticidal effect of 1 on both insects was stronger than that of hinokitiol (2, 4-isopropyltropolone: major component of Thujopsis dolabrata SIEB. et ZUCC. hondai MAKINO). The insecticidal activity of both compounds was higher than that of N,N-diethyl-m-toluamide (DEET), used as a positive control. Compound 1 had potent insecticidal activity against Coptotermes formosanus, although its activity was much lower than that of commercial chloropyrifos. Like 2, 1 showed the inhibitory activity toward metalloproteases such as carboxypeptidase A, collagenase and thermolysin and their inhibitory activities were much higher than that of 1,10-phenanthroline, used as a positive control. The inhibitory activity of 1 on carboxypeptidase A was especially high, its 50% inhibitory concentrations (IC(50)) being 2.73 x 10(-6) M. This inhibitory activity was as high as that of 2 (IC(50): 2.76 x 10(-6) M). Compound 1 inhibited the growth of seven kinds of plant-pathogenic fungi and their minimum inhibitory concentration (MIC) values were in the range of 6.0-50.0 microg/ml. In particular, 1 showed strong antifungal activity on Pythium aphanidermatum IFO-32440 (MIC: 6.0 microg/ml).     

Protection from apoptotic cell death by cilostazol, phosphodiesterase type III inhibitor, via cAMP-dependent protein kinase activation.

This study aimed to elucidate whether the effect of cilostazol to suppress apoptotic cell death is directly coupled to cAMP-dependent protein kinase activation in human umbilical vein endothelial cells (HUVECs). After exposure of HUVECs to LPS (1 microgml(-1)) for 18 h, the endothelial cells irregularly aggregated with loss of cobblestone appearance, which was reversed by cilostazol (1-100 microM), as well as by cilostamide (cilostazol analog), and cilostazol metabolites (OPC-13015 and OPC-31213), respectively. LPS-stimulated production of reactive oxygen species (ROS) was significantly reduced by cilostazol (0.1-10 microM). In line with these, LPS (1 microgml(-1))- and TNF-alpha (200 ngml(-1))-induced DNA fragmentation, assessed by agarose gel electrophoresis, was significantly reduced by treatment with cilostazol (10 microM) as well as by dibutyryl cAMP (100 microM). This effect was reversed by cAMP-dependent protein kinase inhibitor, Rp-cAMPs (200 microM). Further, LPS (1 microgml(-1))-induced decrease in Bcl-2 and increase in Bax protein expression were fully reversed by cilostazol (10 microM) and dibutyryl cAMP (100 microM), all of which were antagonized by Rp-cAMPs (200 microM). Taken together, cilostazol effectively protected HUVECs from LPS- and TNF-alpha-induced cell death associated with oligonucleosomal DNA fragmentation via activation of cAMP-dependent protein kinase.     

271例甲型H1N1流感C-反应蛋白与白细胞的关系探讨

目的:探讨甲型H1N1流感C-反应蛋白(CRP)与白细胞(WBC)的关系。方法:回顾性分析271例住院患者不同临床类型、不同疾病阶段CRP与WBC的关系。结果:①甲型H1N1流感患者感染初期CRP升高常见,且升高程度随着病情的加重而更明显。②轻症患者CRP升高幅度<3倍正常值上限(ULN),重症患者CRP升高幅度达10倍ULN,危重症患者CRP升高幅度达20倍ULN。③Pearson相关分析显示,感染初期CRP与年龄、WBC及中性粒细胞百分率(GR%)均呈正相关。当校正了年龄因素后,偏相关分析发现CRP仍与WBC呈正相关,与GR%的相关性消失。结论:甲型H1N1流感患者CRP升高常见,轻度升高(<3倍ULN)与病毒感染所致的炎症反应有关,明显升高(≥10倍ULN)提示合并细菌感染。     

Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man.

The pharmacokinetics of caffeine (CA), paraxanthine (PX), theobromine (TB) and theophylline (TP) were studied in six healthy male volunteers after oral administration of each compound on separate occasions. The total plasma clearances of CA and PX were similar in value (2.07 and 2.20 ml min-1 kg-1, respectively) as were those for TP and TB (0.93 and 1.20 ml min-1 kg-1, respectively). The unbound plasma clearances of CA and PX were also similar in magnitude (3.11 and 4.14 ml min-1 kg-1, respectively) as were those of TP and TB (1.61 and 1.39 ml min-1 kg-1, respectively). The half-lives of TP and TB (6.2 and 7.2 h, respectively) were significantly longer than those of CA and PX (4.1 and 3.1 h, respectively). The volume of distribution at steady state of TP (0.44 l kg-1) was lower than that of the other methylxanthines (0.63-0.72 l kg-1). The unbound volume of distribution of TP (0.77 l kg-1) was however the same as that of TB (0.79 l kg-1) whereas the unbound volume of distribution of PX (1.18 l kg-1) was similar to that of CA (1.06 l kg-1).     

慢病毒转染调控FoxM1表达对人肝内胆管细胞癌增殖、侵袭及MMPs表达的影响

目的 通过实验探讨慢病毒转染调控FoxM1表达对人肝内胆管细胞癌（ICC）增殖、侵袭能力及基质金属蛋白酶（MMP）-9和MMP-2表达的影响。方法 Western blot检测ICC细胞株HCCC-9810、RBE及SSP-25的FoxM1蛋白表达水平,选取表达量较低者作为上调FoxM1细胞株,较高者作为下调细胞株;将分别携带FoxM1质粒和shRNA的慢病毒载体转染目标上调和下调ICC细胞株,建立稳定上下调FoxM1的细胞株（Western blot验证）;MTT法检测转染后细胞增殖力,Transwell侵袭实验检测细胞侵袭能力;qPCR检测各组稳定转染细胞株MMP-9及MMP-2mRNA表达水平。结果 SSP-25的FoxM1蛋白表达最高,HCCC-9810最低,由此选取SSP-25作为下调FoxM1表达目标细胞株,HCCC-9810作为上调FoxM1表达目标细胞株。慢病毒转染成功构建稳定上调（HCCC-9810-FoxM1组）及下调FoxM1细胞株（SSP-25-shFoxM1组）;HCCC-9810-FoxM1组增殖及侵袭能力明显高于HCCC-9810-Control组（均P&...     

Decreased apoptosis during CAR-mediated hepatoprotection against lithocholic acid-induced liver injury in mice

Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that is regulated by the constitutive androstane receptor (CAR). Activation of CAR can protect the liver against bile acid-induced toxicity and it may have a role in cell death via apoptosis by altering expression of Bcl-2 family proteins such as myeloid cell leukemia-1 (Mcl-1). Our aim was to determine if activation of CAR reduces hepatocellular apoptosis during cholestasis as a mechanism of hepatoprotection. CAR^+/+ (WT) and CAR^−/− (CAR-null) mice were pre-treated with compounds known to activate CAR prior to induction of intrahepatic cholestasis using the secondary bile acid lithocholic acid (LCA). Pre-treatment with the CAR activators phenobarbital (PB) and TCPOBOP (TC), as well as the non-CAR activator pregnenolone 16α-carbontrile (PCN), protected against LCA-induced liver injury in WT mice, whereas liver injury was more extensive without CAR (CAR-null). Unexpectedly, expression of anti-apoptotic Mcl-1 and Bcl-x_L was not increased in hepatoprotected mice. Compared to unprotected groups, apoptosis was decreased in hepatoprotected mice as evidenced by the absence of cleaved caspase 3 (cCasp3). In contrast to the cytoplasmic localization in the injured livers (LCA and oltipraz), Mcl-1 protein was localized in the nucleus of hepatoprotected livers to potentially promote cell survival. This study demonstrates that although apoptosis is reduced in hepatoprotected mice pre-treated with CAR and non-CAR activators; hepatoprotection is not directly a result of CAR-induced Mcl-1 expression.     

Determination of aflatoxins in imported rice to Iran

Aflatoxins (AFs) are highly toxic and carcinogenic secondary fungal metabolites and have been detected in various food commodities including cereals. Rice were imported to Iran during March 2006–March 2007 analyzed for aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) using immunoaffinity column and quantitated by HPLC. In this regard, 71 rice samples were collected. After dividing samples to sub-samples, AF analyses were done. Among 71 samples analyzed, AFB1 was detected in 59 samples (83% of the total). The mean of AFB1 was 1.89 ng/g for all samples (with the not detected samples taken as zero). Total AF (AFT) was detected in 59 samples (83% of the total). The mean of AFT was 2.09 ng/g for all samples. AFB1 level in two samples (2.8%) was above the maximum tolerated level (MTL) of AFB1 in Iran (5 ng/g). Regarding AFT, the mean contamination level (2.09 ng/g) was lower than MTL of AFT in rice in Iran as well as lower than maximum level of EU for AFT (4 ng/g), and only nine samples had levels above the MTL of EU in AFT.     

Disopyramide pharmacokinetics and metabolism: effect of inducers.

1. The disposition of orally administered disopyramide was studied in a population of smokers (n = 6) and non-smokers (n = 8) before and during phenobarbitone treatment (100 mg daily for 21 days; Cp 21st day = 13.9 +/- 2.0 micrograms ml-1). The comparative inducibility of these populations by phenobarbitone was assessed as was the inductive effect of cigarette smoking, per se. Furthermore, the determinants of the intensity of the inductive effect were examined, as well as the effect of the barbiturate on the binding of disopyramide to alpha 1-acid glycoprotein (AGP). 2. Smokers and non-smokers exhibited similar half-lives (6.48 +/- 1.49 vs 6.66 +/- 1.02 h), apparent total body clearances (0.100 +/- 0.020 vs 0.117 +/- 0.034 l h-1 kg-1), mean renal clearances (0.043 +/- 0.0093 vs 0.057 +/- 0.013 l h-1 kg-1) and apparent intrinsic metabolic clearances (0.057 +/- 0.015 vs 0.060 +/- 0.024 l h-1 kg-1) before phenobarbitone treatment. 3. Both populations responded comparably to barbiturate exposure in that apparent intrinsic metabolic clearance more than doubled. Interestingly, the magnitude of this increase was highly dependent on the observed baseline apparent intrinsic metabolic clearance, (r' = 0.81; P less than 0.001). 4. Phenobarbitone treatment of non-smokers resulted in an increase in the AUC of the active metabolite N-despropyl disopyramide (MND), but not significantly (3.8 +/- 1.6 vs 4.1 +/- 2.3 micrograms ml-1 h). Similar results were observed in smokers (3.5 +/- 1.4 vs 3.9 +/- 2.0 micrograms ml-1 h, respectively). 5. The percent of administered dose recovered in urine as disopyramide in non-smokers was significantly decreased upon phenobarbitone treatment (43 +/- 6% vs 25 +/- 5%), whereas the percent of dose recovered as MND increased significantly in this group (25 +/- 6% vs 31 +/- 5%). The population of smokers responded similarly. 6. At doses typically used to achieve hepatic microsomal enzyme induction in man, phenobarbitone treatment caused no significant change or trend towards a change in serum AGP concentrations as measured using the radial immunodiffusion method in nonsmokers (67.4 +/- 19.9 mg dl-1 vs 68.0 +/- 40.7 mg dl-1) or smokers (64.5 +/- 15.7 vs 67.9 +/- 14.9). Similarly, when AGP concentration was estimated in serum from non-smokers using a nephelometric method no effect attributable to phenobarbitone was observed (47.9 +/- 1.3 vs 47.9 +/- 16.8 mg dl-1). Consistent with this observation, disopyramide free fraction was not affected by barbiturate treatment.