▽交联琼脂糖包膜活性炭(CAAC)血液净化作用的研究

本文报告交联琼脂糖包膜活性炭(CAAC)对某些中毒性药物及与肝性脑病发病可能有关的代谢产物如r-氨基丁酸、内毒素、氨基酸等的体外吸附作用。实验证明对此类物质均有不同程度的吸附功能,符合医用吸附剂的要求,对于肝性脑病血液灌流治疗的开展,特别是急性药物中毒血液灌流的临床应用提供了一定的理论依据。     

几种吸附剂对血浆中亚甲蓝的去除研究

研究交联琼脂糖包嵌活性炭CAAC－Ⅰ和包膜活性炭CAAC－Ⅱ及交联琼脂包嵌凹凸棒CAA对血浆中亚甲蓝（MB）的吸附性能，试图探索可用于有效去除血浆病毒光敏灭活药物MB的血液净化材料，试验表明，CAAC－Ⅰ和CAA对血浆MB的吸附迅速而彻底，CAAC－Ⅱ的吸附较慢，考查了一定MB浓度的血浆流过一定体积的CAA经历的吸附时间和吸附率的关系，对于MB含量为1μmol．L^－1的人血浆，25℃时按1ml.min^-1的速度流过10mlCAA，可以使200ml血浆中的MB降低95％以上。     

暴发性肝损伤肝性脑病大鼠血浆及脑游离氨基酸变化的相关分析

本文测定了D-氨基半乳糖所致暴发性肝损伤肝性脑病大鼠血浆及脑勺浆游离氨基酸含量的变化,并作相应的相关分析。结果表明,正常大鼠血浆及脑内各种氨基酸含量间均无相关。肝性脑病大鼠血浆及脑勺浆多种氨基酸水平均有增高,脑内大多数氨基酸含量与血浆相应氨基酸的变化无相关关系,但一些与肝性脑病发生相关的氨基酸水平与其相应的血浆含量呈显著相关。提示肝性脑病的发生与血脑屏障氨基酸转运功能选择性改变有关。     

连续性血液滤过在重型乙型肝炎治疗中的作用

近年来,非生物型人工肝已被广泛应用于重型肝炎的治疗,临床常用的方法包括血浆置换、血浆吸附、连续性血液净化、血液灌流、分子吸附再循环等.但一些危重患者在血浆置换治疗后很快出现肝性脑病,病情进一步进展.为此,我们对连续性血液滤过在重型乙型肝炎治疗中的作用进行观察和回顾性对比分析.     

内毒素诱发肝硬化大鼠发生肝性脑病的实验研究

目的：观察外源性内毒素诱发肝硬化大鼠发生肝性脑病的可能性及可能机制。方法：采用腹腔内小剂量内毒素一次性注射（３００μｇ／１００ｇＢＷ）诱发肝硬化大鼠发生肝性脑病。结果：小剂量内毒素腹腔内注射可以诱发肝硬化大鼠发生肝性脑病。内毒素注射后,动物一般行为状态及脑电图皆有明显变化,与其他肝性脑病模型或肝性脑病病人类似。同时,血氨和胰高血糖素水平显著升高。血浆内毒素含量与血氨、血胰高血糖素含量之间及血氨与务     

36例肝性脑病的临床分析

目的 分析肝性脑病的诱因.探讨诱因与预后的关系.方法 对36例肝性脑痛临床资料进行分析.结果 肝性脑病的诱因依次为电解质紊乱18例(50.0%)各种感染8例(22.2%),消化道出血5例(13.9%).使用镇静剂2例(5.0%)高蛋自饮食2例(5.0%).原因不明1例(2.8%).诱因的多少和肝能损害的严重程度与肝性脑病的发生发展及预后密切相关.结论 尽快祛除诱因是治疗肝性脑病的关键.     

812树脂炭膜吸附内毒素的实验研究

本文报告了812树脂炭膜对内毒素吸附的实验结果。通过实验证明812树脂炭膜对内毒素有较好的吸附作用。在50及100ng/ml浓度的内毒素溶液中,在室温20～25℃时,6小时的吸附值分别为14.12±2.36ng/100mg及31.04±4.54ng/100mg,吸附率分别为84.75±0.39％及93.14±1.60％。吸附率及吸附值与内毒素浓度和吸附时间有关。通过实验认为此膜可用于人工肝辅助装置以清除内毒素。     

HB-H-6树脂吸附胆红素血浆灌流治疗慢性肝病重度黄疸适用范围

目的进一步评价HB-H-6树脂吸附胆红素血浆灌流在治疗慢性肝病重度黄疸中的价值及最佳适用范围。方法选择2006年10月～2010年7月天津市第三中心医院94例不同病因慢性肝病重度黄疸患者,其中男性68例,女性26例;年龄29～76岁,中位年龄57岁。接受HB-H-6树脂吸附胆红素血浆灌流治疗,比较单次HB-H-6树脂吸附胆红素血浆灌流治疗前后血清胆红素变化;并探讨不同初始胆红素水平及初始凝血酶原活动度(PTA)水平对HB-H-6树脂吸附胆红素能力的影响。结果单次HB-H-6树脂吸附胆红素血浆灌流治疗前血清总胆红素(TBiL)、直接胆红素(DBiL)、间接胆红素(IBiL)分别为(387.80±183.08)、(238.66±103.52)、(127.23±62.00)μmol/L;治疗后分别为(291.80±135.58)、(183.10±76.29)、(92.85±54.25)μmol/L,血浆灌流治疗能显著降低治疗后血清TBiL、DBiL及IBiL的水平(P<0.01);单次HB-H-6树脂吸附胆红素血浆灌流治疗对TBiL、DBiL及IBiL的清除率分别为23.68%±9.14%、21.54%±9.90%及27.09%±16.84%,HB-H-6树脂对IBiL的吸附能力略强于TBiL及DBiL(P<0.01)。HB-H-6树脂吸附胆红素血浆灌流对不同层次的初始TBiL水平均有效,均能引起治疗后胆红素水平的显著降低(P<0.01);初始TBiL水平越高,HB-H-6树脂清除胆红素的绝对值越高(P<0.01);对初始TBiL水平在200μmol/L以上HB-H-6树脂吸附能力明显高于初始TBiL水平在200μmol/L以下时(P<0.01)。HB-H-6树脂吸附胆红素的能力不受初始PTA影响;无明显不良反应。结论 HB-H-6树脂吸附胆红素血浆灌流作为黄疸的人工肝治疗方法之一,安全有效,且适用于TBiL浓度200μmol/L以上的重度黄疸患者。     

血浆灌流治疗高胆红素血症的临床研究

目的 观察使用树脂通过血浆吸附(PA)胆红素治疗肝性高胆红索血症的疗效和安全性.方法 选择临床肝性高胆红素血症患者19例,其中男性18例,女性1例;年龄28～63岁.平均年龄45.5岁.病毒性肝炎乙型亚急性重型11例,慢性重型4例,戊型2例,丙型2例.观察PA治疗前后胆红素变化及临床症状改善情况,评价PA的疗效和安全性.结果 PA术后总胆红素(TBiL)较术前明显下降,吸附率为13.0%～31.2%,不良反应发生率为18.0%(血压下降2例,占9.0%;出血2例,占9.0%).结论 树脂通过PA治疗肝性高胆红素血症有较满意的疗效和较高的安全性,可明显改善患者临床症状及缩短平均住院时间.     

812树脂活性炭膜用于人工肝肾的初步报告

著者等已报告812树脂活性炭膜的研制,系活性炭粉与二甲基亚砜、812树脂混合构成,具有吸附和超滤两种功能,及较好血液相容性。本文报告该膜用于人工肝肾方面的体外与体内实验结果。用急性肝衰竭和黄疸家犬作直接血液灌流,证明在2小时能清除血浆氨54.36％、胆红素33.82％,血浆支链氨基酸与芳香氨基酸比值(BCAA:AAA)由1.7升至3.0。在超滤液中未检出蛋白,其中钠、钾、氯等电解质与血浆水平相同。本文实验表明812树脂活性炭膜可以用于人工肝、肾辅助装置。     

卵巢癌患者血清HE4、CA125和血浆LPA水平变化及其临床意义

目的:探讨血清HE4、CA125和血浆LPA水平在卵巢癌患者中的变化及其临床意义.方法:分别应用单克隆夹心ELISA、放射免疫分析和化学法定量检测50例卵巢癌患者血清HE4、CA125和血浆LPA含量,并与正常对照组比较分析.结果:卵巢癌Ⅲ/Ⅳ期患者血清CA125和血浆LPA水平均显著高于Ⅰ/Ⅱ期(P<0.01),而血...     

DAPT 调节Treg / Th17 细胞免疫平衡抑制动脉粥样硬化

目的:观察Notch 信号抑制剂分泌酶抑制剂( DAPT)对动脉粥样硬化小鼠病理改变及Treg/ Th17 细胞免疫平衡的影响。方法:将24 只ApoE 基因敲除C57BL 小鼠随机分为空白组、模型组和DAPT 组。空白组用普通饲料饲养,模型组和DAPT 组用高脂饲料饲养。饲养5 周后,DAPT 组小鼠以100 mg/ (kg•d)皮下注射DAPT(溶于DMSO 中),其余两组皮下注射等量DMSO。5 周后,采用病理染色分析各组小鼠动脉病理改变,ELISA 检测血浆中IL-17 水平,采用流式细胞术检测各组小鼠脾脏Treg/ Th17 细胞比例。结果:HE 染色结果显示,模型组有明显粥样斑块形成和泡沫细胞形成,DAPT 组动脉病变程度比粥样动脉硬化模型组明显减轻。正常组、模型组和DAPT 组各组血浆中IL-17 水平分别为(293.94±28.59)、(454.05±172.68)和(335.40±89.57)pg/ ml;DAPT 降低AS 小鼠血浆IL-17 水平(P<0.05)。空白组、模型组和DAPT 组各组小鼠Treg 细胞百分比分别为(3.0±0.56)%、(2.54±0.38)%和(4.73±0.64)%;DAPT 降低AS 小鼠血浆IL-17 水平(P<0.05)。空白组、模型组和DAPT 组各组小鼠Th17 细胞亚群分别为(3.46±0.23)%、(4.52±0.85)% 和(1.38±0.37)%。结论:DAPT 降低AS小鼠血浆IL-17 的水平,抑制Th17 细胞亚群分化,而促进Treg 细胞分化,通过改变Treg/ Th17 细胞疫平衡从而减轻动脉粥样硬化。     

Bulk Acyclic Diene Metathesis Polycondensation

Bulk acyclic diene metathesis (ADMET) polymerization performed in the melt at temperatures up to 175 °C is completed using a cyclic (alkyl)(amino) carbene (CAAC) ruthenium‐based Grubbs catalyst. High temperature stability is investigated at temperatures well above conventional ADMET chemistry, leading to the highest weight‐average molecular weights ever achieved for any ADMET polymer. A study of isomerization tendency (double bond migration) is done via self‐metathesis of a small molecule model compound using CAAC catalysts. Minimal olefin isomerization is observed using appropriate catalyst ratios and temperatures.     

Gradual loss of pancreatic beta-cell insulin, glucokinase and GLUT2 glucose transporter immunoreactivities during the time course of nutritionally induced type-2 diabetes in Psammomys obesus (sand rat)

The Psammomys obesus (sand rat) is a well-established model of nutritionally induced non-insulin-dependent type-2 diabetes. When fed a high-energy (HE) diet, the diabetes-prone animals develop hyperinsulinaemia and hyperglycaemia. Within 1 week, all animals become hyperinsulinaemic. However, a loss of immunostaining for insulin as well as for the GLUT2 glucose transporter in the plasma membrane and the glucokinase in the cytoplasm of the pancreatic beta cells became evident only when the animals subsequently developed hyperglycaemia. After 1 week of HE diet feeding, the pancreatic beta-cell volume was reduced by one-third in hyperglycaemic Psammomys. Insulin immunostaining as well as GLUT2 glucose transporter immunostaining in the plasma membrane and glucokinase immunostaining in the cytoplasm were reduced by more than 50%. After 3 weeks of HE diet feeding, all changes observed after 1 week were even more pronounced, with reductions in the range of 70-95%. The reduction of the total beta-cell volume of the pancreas due to beta-cell death and the diminution of insulin content of the remaining beta cells in the islets during the HE diet feeding was accompanied by a parallel fall of the pancreas insulin content. For all changes observed, there was a significant correlation with the increase of the blood glucose concentration (r>0.9) but not with the increase of the plasma insulin concentration (r>0.2). Thus, increasing glycaemia appears to be the factor responsible for the deterioration of the pancreatic beta-cell function and the resulting loss of the insulin secretory capacity in Psammomys. The final result of this development is an irreversible diabetic state due to the feeding of the HE diet.     

HE1/NPC2 status in human reproductive tract and ejaculated spermatozoa: consequence of vasectomy

We have previously demonstrated that the amount of HE1/NPC2 mRNA and protein expressed in the human epididymis is decreased under vasectomy. In this study, western blot analyses showed that many vasovasostomized men are characterized by high HE1/NPC2 levels in spermatozoa when compared with fertile donors. HE1/NPC2 association with sperm from vasovasostomized men was not related to low motility per se as spermatozoa from asthenospermic men have HE1/NPC2 levels similar to those in normal fertile semen samples. Spermatozoa from vasovasostomized men with high amount of HE1/NPC2 are characterized by higher concentration of cholesterol and more lipid raft domains. HE1/NPC2 is secreted in different glycoforms by different tissues of human male reproductive tract. These forms are due to variation in N-glycosylation, and only the deglycosylated form is associated with spermatozoa from some vasovasostomized men. Compared with normal men, seminal plasma of vasectomized men is characterized by a major decrease in immunodetectable HE1/NPC2 without change in the glycosylation pattern. Following surgical vasectomy reversal, seminal plasma HE1/NPC2 was found in similar amounts to the ones characterizing normal men. Considering the potential role of HE1/NPC2 in cholesterol transport during sperm maturation, unusual high levels of this protein associated with spermatozoa of vasovasostomized men may reflect epididymal sequelae occurring when the vas deferens is obstructed.     

促分泌酶抑制剂对毛细支气管炎模型大鼠体内Th17 细胞分化的影响

目的:研究酌鄄促分泌酶抑制剂阻断Notch 信号对毛细支气管炎(简称毛支)模型大鼠Th17 细胞发育和分化的影响,为毛支治疗寻找新的药物提供理论基础。方法:按随机对照原则将SD 大鼠分为正常组、毛支组和酌鄄促分泌酶抑制剂组,滴鼻法成功建立毛支模型,而后尾静脉注射酌鄄促分泌酶抑制剂MW167,通过HE 染色观察肺组织病理改变,ELISA 检测血浆中白介素17(IL鄄17)的水平,实时荧光定量PCR 检测肺组织和外周血单个核细胞中ROR酌t mRNA 的表达,Western blot 检测肺组织中Notch 信号、ROR酌t 的蛋白表达。结果:与毛支组相比,MW167 组肺组织病理学改变减轻;血浆IL鄄17 水平也较毛支组降低;肺组织及外周血单个核细胞ROR酌t mRNA 在MW167 注射组表达均减弱;MW167 组肺组织Notch 信号和ROR酌t 蛋白的表达也显著降低。结论:静脉注射酌鄄促分泌酶抑制剂能够通过阻断Notch 信号通路抑制Th17 细胞的分化,缓解毛支模型大鼠的气道炎症,对毛支有潜在的治疗价值。     

基于背景估计和SVM分类器的眼底图像硬性渗出物检测方法

硬性渗出物是糖尿病视网膜病变(DR)的早期病症,是糖尿病性黄斑水肿的最主要表现,因此对硬性渗出物的准确检测具有重要的临床意义。提出一种基于背景估计和SVM分类器的眼底图像硬性渗出物检测方法。首先通过背景估计,得到包含亮目标的前景图;然后利用基于Kirsch算子的边缘信息确定硬性渗出物的候选区域,再移除视盘;最后对候选区域进行形状特征、直方图统计特征以及相位特征的提取,采用SVM对候选区域进行分类,完成硬性渗出物的精确提取。对DIARETDB1和HEI MED公共数据库中共248幅眼底图像进行实验,图像水平达到灵敏度97.3%和特异性90%,病灶水平达到灵敏度84.6%和阳性预测值944%。实验表明,所提出的方法能够实现眼底图像中硬性渗出物的自动检测。     

植物甾醇酯对大鼠主动脉衰老及相关基因表达的影响

目的:探讨植物甾醇酯延缓大鼠主动脉衰老的作用及其机制。方法:将42只12月龄雌性SD大鼠随机均分为对照组、模型组和植物甾醇酯干预组,分别喂食基础饲料、高脂饲料和高脂加2%植物甾醇酯(W/W)饲料6个月。采用HE染色法和Masson染色法对主动脉横截面石蜡切片进行染色,观察主动脉组织的病理学改变,对血管壁平滑肌细胞和胶原纤维的绝对面积进行图像分析。检测血浆脂质蛋白、晚期糖基化终末产物(AGEs)、丙二醛(MDA)的含量以及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的活性。分别采用real-time PCR和Western blot的方法评估主动脉组织沉默信息调节因子1(SIRT1)和过氧化物酶体增殖物激活受体γ(PPARγ)的mRNA和蛋白表达水平。结果:与模型组相比,植物甾醇酯干预组的血浆总胆固醇和低密度脂蛋白胆固醇水平显著降低,高密度脂蛋白胆固醇的水平相反(P0.05),甘油三酯的水平没有统计学差异;主动脉内膜和中膜的增厚以及平滑肌细胞的迁移均得到改善;主动脉平滑肌细胞和胶原纤维的含量显著下降(P0.05);血浆AGEs的含量显著降低(P0.05);机体的抗氧化功能有所提升,血浆MDA的含量显著减少(P0.05),SOD和CAT活性的差异没有统计学意义;PPARγ的表达下调,SIRT1的表达上调(P0.05)。结论:植物甾醇酯能够延缓大鼠主动脉的衰老。其机制可能与降低机体活性氧的生成有关。植物甾醇酯可能通过激活SIRT1或抑制PPARγ的表达而发挥作用。     

Memory impairment in patients with cirrhosis

BACKGROUND AND AIM: Subclinical hepatic encephalopathy (HE) in cirrhotic patients is usually characterized by memory impairment and psychomotor slowing. Our aim was to investigate memory status in cirrhotic patients with and without clinically overt HE. MATERIAL AND METHODS: Thirty-two cirrhotic patients (10 female and 22 male) aged 49 +/- 17 years and 20 healthy subjects (six female and 14 male) aged 46 +/- 12 years were included in the study. Memory status was defined by Wechsler Memory Scale, verbal memory process and complex memory process tests. RESULTS: Grade-1 HE was detected in 7 (22%) patients with cirrhosis. We detected 36 to 92% decrement in various memory tests in cirrhotic patients without HE as compared to healthy subjects. The scores for all psychometric testing results were significantly lower in cirrhotic patients without HE as compared to healthy subjects. We detected 42.9 to 100% decrement in various memory tests in cirrhotic patients with HE than cirrhotic patients without HE. However, there was no statistical significant difference between cirrhotic patients with and without HE. There was no statistical significant difference in cirrhotic patients with Child-Pugh A, B, and C. CONCLUSION: In conclusion, memory status was influenced in which patients with cirrhosis yet has a normal mental and neurological status to routine clinical examination (subclinical HE). Occasionally, decreased memory performance may adversely affect the satisfaction and lifestyle of these patients. Therefore, subclinical HE is an important social problem.