α_1肾上腺素能受体阻滞剂萘哌地尔治疗慢性非细菌性前列腺炎的临床研究

目的:探讨α1肾上腺素能受体阻滞剂萘哌地尔(Naftopidil)治疗慢性非细菌性前列腺炎的有效性及安全性。方法:采用开放、自身对照、多中心的临床试验方法,应用萘哌地尔25mg,每日1次,对106例慢性非细菌性前列腺炎(NBP)患者进行了为期4周的治疗。以美国国立卫生院慢性前列腺炎症状评分(NIHCPSI)、前列腺液(EPS)WBC计数及最大尿流率(MFR)为疗效指标,对其有效性及安全性进行观察。结果:服药4周后,可评价病例105例。全组患者NIHCPSI总评分治疗前后平均减低12.0分(P<0.001),症状评分平均减低7.9分(P<0.001),生活质量评分平均减低4.1分(P<0.001)。EPS中WBC计数治疗前及治疗后分别为(15.2±15.1)、(9.5±12.0)个/HP(P<0.01)。MFR治疗前及治疗后分别为(19.2±4.8)、(22.7±4.9)ml/s(P<0.01)。按症状改善评价,治愈2例(1.9%),显效32例(30.5%),有效55例(52.4%),无效16例(15.2%)。总显效率为32.4%,总有效率为84.8%。3例有轻度头晕,1例食欲不佳,不良事件发生率3.81%。结论:萘哌地尔治疗慢性非细菌性前列腺炎安全、有效。     

NPHS1两种新突变蛋白分子的细胞内分布

目的：研究NPHS1两种新突变编码蛋白在细胞内的分布与先天性肾病综合征发病机制的关系。方法：构建野生型和两种突变型NPHS1克隆，并转染至COS7细胞内，应用免疫荧光双标记的方法，分别进行细胞内及细胞表面的荧光标记，通过共聚焦显微镜对裂隙膜分子Nephrin在细胞内的分布进行研究。结果：野生型Nephrin表现为细胞内和细胞膜染色模式；V822M和C265R则主要为细胞内内质网染色模式，细胞膜着色几乎缺失。结论：突变的Nephrin蛋白由于错误折叠，不能由内质网被输送至细胞表面，这可能是先天性肾病综合征发病的机制之一。     

持续吸入不同浓度氧气对新生大鼠肺血管内皮生长因子及其受体tuRNA表达的影响

目的 探讨持续吸入不同浓度氧气对新生大鼠肺血管内皮生长因子(VEGF)及其受体1(VEGFRl)和受体2(VEGFR2)mRNA表达的影响.方法 新生足月SD大鼠32只,随机分为对照组和实验组.实验组生后12 h开始持续吸入氧气,按不同的吸入氧浓度,将实验组又分为30%O2组、50%O2组和75%O2组.对照组吸入空气.每组8只.于实验开始后21 d处死实验大鼠,取出右肺下叶,RT-PCR技术检测VEGF、VEGFR1和VEGFR2 mRNA表达,根据2-△△CT的计算方法,实验组基因表达差异用实验组相对于对照组基因表达量的倍数表示.结果 与对照组相比,30%O2对新生大鼠肺VEGF及其受体mRNA表达无影响.75%O2组VEGF mRNA表达是对照组的0.48倍;50%O2组、75%O2组VEGFR1 mRNA分别为对照组的0.18倍和0.06倍;VEGFR2 mRNA分别为对照组的0.22倍和0.10倍,差异均有统计学意义(P<0.05).结论 长时间吸入低浓度氧对新生大鼠肺VEGF及其受体mRNA影响不明届,而持续吸入中等浓度及较高浓度氧可降低VEGF及其受体mRNA的表达.     

Analysis of Vascular Endothelial Growth Factor (VEGF) and a receptor subtype (KDR/flk-1) in the liver of rats exposed to riddelliine: a potential role in the development of hemangiosarcoma

Riddelliine alters hepatocellular and endothelial cell kinetics and function including stimulating an increase in hepatocytic vascular endothelial growth factor (VEGF) in the absence of increased serological levels of VEGF (Nyska etal. 2002). The objective of this study was to further assess hepatic VEGF and KDR/flk-1 synthesis and expression by hepatic cells under riddelliine treatment conditions. Forty-two male F344/N rats were dosed by gavage with riddelliine (0, 1.0, and 2.5 mg/kg/day) for 6 weeks. Seven animals/group were sacrificed after 8 consecutive daily doses; remaining rats were terminated after 30 daily doses, excluding weekends. Hepatic tissues were evaluated by immunohistochemistry and in situ hybridization. The results showed that VEGF mRNA expression was observed in control and treated animals; however, qualitative differences were noted. Treated animals exhibited VEGF mRNA in clustered, focal hepatocytes and bile duct epithelium, whereas VEGF mRNA in hepatocytes from vehicle control rats was distributed evenly across all hepatocytes. Results evaluating the distribution of the VEGF cognate receptor, KDR/flk-1 showed that randomly distributed, rare sinusoidal endothelium, including those demonstrating karyomegaly and cytomegaly expressed KDR/flk-1. Phosphorylation of KDR/flk-1 at pTyr996 and pTyr1054/1059, but not pTyr951, was also detected, evidence that endothelial cell KDR/flk-1 was activated. These results suggest that both hepatocytes and endothelial cells are targets of riddelliine-induced injury. We speculate that damage to both populations of cells may lead to dysregulated VEGF synthesis by hepatocytes and activation of KDR/flk-1 by endothelium leading to the induction of sustained endothelial cell proliferation, culminating in the development of hepatic hemangiosarcoma.     

选择性5-HT1A受体拮抗剂WAY-100635抑制帕金森病模型大鼠腹内侧前额叶皮质的神经活动

目的腹内侧前额叶皮质在随意运动的起始和控制、情感以及认知中具有重要作用。然而,黑质-纹状体通路变性后腹内侧前额叶皮质的神经活动和5-HT_(1A)受体的作用仍不清楚。本研究观察了6-羟基多巴胺(6- hydroxydopamine,6-OHDA)损毁黑质致密部(substantia nigra pars compacta,SNc)后大鼠腹内侧前额叶皮质神经活动的变化和体循环给予选择性5-HT_(1A)受体拮抗剂WAY-100635后神经元活动的改变。方法采用在体玻璃微电极细胞外记录方法,记录正常大鼠和SNc单侧损毁大鼠的腹内侧前额叶皮质神经元的活动。结果6-OHDA损毁SNc大鼠的腹内侧前额叶皮质神经元放电频率显著增加,放电形式没有明显改变。体循环给予WAY-100635 (0.1 mg/kg,i.v.)不改变正常大鼠腹内侧前额叶皮质神经元的平均放电频率和放电形式,而显著降低了SNc损毁大鼠前额叶皮质神经元的平均放电频率。结论黑质-纹状体通路的变性可导致腹内侧前额叶皮质神经活动增强,5-HT_(1A)受体拮抗剂WAY-100635可以抑制这种活动增强,提示可能存在腹内侧前额叶皮质5-HT_(1A)受体功能失调。     

KiSS-1和E钙黏蛋白在贲门癌组织中的表达及临床意义

目的检测KiSS-1及上皮细胞E钙黏蛋白（E—cadherin）在贲门癌组织中的表达，探讨其临床意义及两者的相关性。方法采用免疫组织化学方法检测80例贲门癌、20例正常贲门组织中KiSS-1及E钙黏蛋白的表达情况。分析其与相关临床病理参数的关系以及两者表达的相关性。结果KiSS-1的表达与贲门癌的临床分期、淋巴结转移呈负相关（均P〈0．05），与分化程度无相关性（均P〉0．05）；E钙黏蛋白的表达与贲门癌的临床分期、淋巴结转移、分化程度均呈负相关（均P〈0．05）。Spearman等级相关分析显示，KiSS-1与E钙黏蛋白在贲门癌中的表达呈正相关（rs=0．722，P〈0．05）。结论KiSS-1与E钙黏蛋白可能在抑制贲门癌的侵袭和转移过程中起重要作用。     

肝细胞癌中Ephrin-A1及其受体的表达与血管生成的关系

目的:探讨Ephrin-A1 及其受体与肝细胞癌血管生成之间的关系。方法:采用免疫组织化学SP法和逆转录聚合酶链反应(RT-PCR)检测52例肝细胞癌（肝癌组）和癌旁组织（癌旁组）标本中Ephrin-A1及其受体EphA1和EphA2蛋白及mRNA的表达情况，并分析其与肝细胞癌的临床病理因素及微血管密度(microvessel density, MVD)之间的关系。结果:在52例肝癌组中 Ephrin-A1及其受体EphA1，EphA2的蛋白阳性表达率分别为59.6%(31/52)，53.8%(28/52)和17.3%(9/52),而癌旁组织中的蛋白阳性表达率分别为23.1%(12/52)，28.9% (15/52)以及21.2%(11/52)。Ephrin-A1及其受体EphA1在两组中的差异有统计学意义(P<0.05)，而EphA2在两组间的差异无显著性（P>0.05）。Ephrin-A1及其受体EphA1mRNA在肝癌组的阳性表达率为67.3%(35/52)和73.7%(38/52)，明显高于癌旁组中的阳性表达42.3%(22/52)和48.1% (25/52) (P<0.05)，而EphA2mRNA在两组间的差异无显著性（P>0.05）。Ephrin-A1蛋白的高表达与患者的甲胎蛋白(AFP)水平及有无门静脉癌栓有关(P<0.05)。Spearman等级相关分析显示，在肝癌组中Ephrin-A1的表达与EphA1的表达呈正相关(r=0.671,P<0.01);而Ephrin-A1与EphA2的表达无相关性;肝癌组中Ephrin-A1的表达与MVD呈正相关(r=0.826,P<0.01)。结论:Ephrin-A1通过与其受体EphA1相结合，促进肝细胞癌的血管生成，从而促进肝细胞癌的生长、浸润和转移; Ephrin-A1及其受体EphA1有望成为肝癌抗血管生成治疗新的靶点。     

Intrahippocampal Injection of Endothelin-1: A New Model of Ischemia-induced Seizures in Immature Rats

Summary:  The goal of this study was to develop a new model of ischemia-induced seizures in immature rats using injection of vasoconstrictor Endothelin-1 (ET-1) into the brain. ET-1 (10, 20, or 40 pmol) was infused into the left dorsal hippocampus of freely moving Wistar rats 12 (P12) and 25 (P25) days old. Animals were then video/EEG-monitored for 100 min and monitoring was repeated 22 h later. Parameters of electrographic seizures (frequency and mean duration) as well as pattern of their behavioral correlates were evaluated. The pattern of behavioral seizures was used to develop model-specific scoring system. Cresyl violet and Fluoro Jade-B-staining were used to evaluate brain damage. Extension of the lesion was correlated with seizure severity. After ET-1-injection, seizures occurred in 83–100% animals of all age-and-dose groups and persisted for 24 h except P12 rats with 10 pmol. There were no differences in average seizure duration (18–40 s) or seizure frequency (3–7 seizures/100 min) among individual dose-groups. Between the 1st and 2nd observation period, total seizure duration decreased in 71% of P12 and 47% of P25 rats. Electrographic seizure activity was most frequently accompanied by clonus, incidence of more severe convulsions (barrel rolling or generalized clonic seizures) increased with dose of ET-1. Morphologic examination did not reveal any dose-related difference in damage severity, hippocampal damage was however more extensive in P12 compared to P25 animals. Seizure severity correlated positively with severity of the damage in both age groups. Our study presents focal injection of ET-1 into the brain as a new and practical model of ischemia-induced seizures in immature rats.     

新生儿医院感染原因探讨及干预对策

目的：分析新生儿医院感染相关危险因素及干预对策.方法：通过对榆林市第一医院2006年5月至2010年5月收治的1428例住院新生儿医院感染发生情况.结果：新生儿患者医院感染率从2006年5月至2008年5月的3.20%,下降到2008年5月至2010年5月的1.99%.结论：对新生儿室医疗护理工作中各种医院感染相关危险因素采取相应的干预对策后,新生儿患者的医院感染率明显降低,提高了医疗护理质量.     

Infection dynamics and virus-induced apoptosis in cell culture-based influenza vaccine production—Flow cytometry and mathematical modeling

Cell culture-based influenza vaccine manufacturing is of growing importance. Depending on virus strains, differences in infection dynamics, virus-induced apoptosis, cell lysis and virus yields are observed. Comparatively little is known concerning details of virus–host cell interaction on a cellular level and virus spreading in a population of cells in bioreactors. In this study, the infection of MDCK cells with different influenza A virus strains in lab-scale microcarrier culture was investigated by flow cytometry. Together with the infection status of cells, virus-induced apoptosis was monitored. A mathematical model has been formulated to describe changes in the concentration of uninfected and infected adherent cells, dynamics of virus particle release (infectious virions, hemagglutinin content), and the time course of the percentage composition of the cell population.