过氧化物酶体增殖物激活受体γ对糖基化终产物诱导大鼠血管平滑肌细胞增殖的作用

目的观察吡格列酮对糖基化终产物（AGEs）刺激下大鼠血管平滑肌细胞（VSMCs）增殖的作用及对过氧化物酶体增殖物激活受体γ（PPARγ）基因及蛋白表达水平的影响,探讨PPARγ在AGEs诱导VSMCs增殖中的作用。方法（1）MTY法观察不同浓度、不同时间的AGEs对VSMCs增殖的影响及吡格列酮（1．0、10、100μmol／L）与AGEs共孵育对VSMCs增殖的干预作用。（2）用半定量逆转录聚合酶链反应测定VSMCs中PPARγ mRNA的表达。（3）用Western blot法检测PPARγ的蛋白表达。结果AGEs作用导致VSMCs增殖,AGEs抑制PPARγ mRNA和蛋白表达水平,这种抑制作用随着AGEs干预的时间延长和浓度的增加而增强（P〈0．05）。PPARγ激活剂吡格列酮通过增加PPARγ的表达,抑制AGEs诱导的VSMCs增殖。结论PPARγ表达的下降可能是糖尿病易患动脉粥样硬化的重要原因之一。     

吡格列酮对胰岛素诱导血管平滑肌细胞增殖核抗原表达的影响

目的观察吡格列酮（Pio）对胰岛素（Ins）刺激的血管平滑肌细胞（VSMC）增殖的干预作用,及对增殖核抗原（PCNA）基因和蛋白表达水平的影响。方法（1）以四甲基偶氮唑盐比色法观察不同浓度、不同时间的Ins对VSMc增殖的影响,以及Pio和Ins共孵育对VSMC增殖的作用。（2）用半定量逆转录聚合酶链反应测定PCNAmRNA的表达。（3）用Westernblot法检测PCNA蛋白的表达。结果Ins促进VSMC增殖,促增殖效应在72h末达峰值,差异有统计学意义（P〈0．01）;而Pio能抑制Ins诱导的VSMC增殖及PCNAmRNA和蛋白表达水平,最佳浓度100μmol／L（P〈0．01）。结论 吡格列酮抑制胰岛素的促VSMC增殖作用,通过降低PCNA的表达影响VSMC表型转换,有望用于治疗动脉粥样硬化。     

阿齐沙坦对转化生长因子诱导的自发性高血压大鼠血管平滑肌细胞增殖及迁移的影响

目的探讨阿齐沙坦对转化生长因子-β（TGF-β）诱导的自发性高血压大鼠血管平滑肌细胞（VSMCs）增殖及迁移的影响。方法采用组织块贴壁培养法进行血管平滑肌细胞的原代培养,取3～5代细胞用于实验。用MTT法测定细胞增殖情况,用Boyden小室测试细胞迁移情况。采用10ng/ml TGF-β刺激VSMCs,并用阿齐沙坦干预,24h后用Western blot和RT-PCR检测VSMCs中MMP-2、MMP-9及TIMP-1蛋白和mRNA的表达。结果 TGF-β可促进大鼠VSMCs的增殖及迁移,并增加大鼠VSMCs的MMP-2、MMP-9和TIMP-1蛋白表达。阿齐沙坦则可抑制TGF-β诱导的大鼠VSMCs的增殖和迁移,并降低大鼠VSMCs的MMP-2、MMP-9及TIMP-1表达。结论阿齐沙坦可能通过下调MMP-2、MMP-9及TIMP-1的表达来抑制TGF-β诱导的自发性高血压血管平滑肌细胞的增殖及迁移。     

粟米草皂甙对血管平滑肌细胞增殖的影响及机制探讨

目的观察粟米草皂甙对血管平滑肌细胞（VSMCs）增殖的影响,并探讨其机制。方法将原代培养大鼠胸主动脉VSMCs分为两组,观察组加入不同浓度（1、3、9、27μmol/L）粟米草皂甙,对照组加入等体积稀释后的DMSO培养24、48、72 h。采用MTT法检测VSMCs的增殖抑制率,采用RT-PCR法检测VSMCs中的线粒体转录因子A（mtTFA）mRNA。结果与对照组比较,观察组VSMCs增殖抑制率明显升高（P均〈0.05）,mtTFA mRNA表达下降（P均〈0.05）,且呈一定浓度、时间依赖性。结论粟米草皂甙对大鼠VSMCs细胞增殖有显著的抑制作用,其机制可能与下调mtTFA mRNA表达有关。     

血红素氧合酶-1/一氧化碳系统对胰岛素样生长因子-Ⅰ诱导的兔血管平滑肌细胞增殖的抑制作用

目的研究血红素氧合酶-1／一氧化碳（HO-1／CO）系统对胰岛素样生长因子-I（IGF-I）诱导的血管平滑肌细胞（VSMCs）增殖的影响及分子机制。方法体外培养兔主动脉VSMCs,用IGF-I诱导其增殖,用氯化血红素和锌原卟啉-9,分别诱导和阻断HO-1的表达,从而促进和抑制CO生成,通过RT．PCR及Western blot检测HO-1mRNA和蛋白的表达,采用酶联免疫法测定培养上清液中碳氧血红蛋白含量,应用同位素^3H-TdR掺入试验检测VSMCs增殖,采用流式细胞技术检测细胞增殖周期。结果氯化血红素显著诱导VSMCs HO-1 mRNA及蛋白的表达,显著增加VSMCs培养上清液中CO的生成量,呈剂量依赖趋势;梯度浓度的氯化血红素对IGF-I增高的VSMCs ^3H-TdR掺入量抑制率分别为29．6％、45．0％和54．1％,显著抑制细胞周期进程,导致G0／G1细胞显著增多,S期和G2／M期细胞显著减少（P均〈0．01）,与加入的氯化血红素及上清液中碳氧血红蛋白含量呈剂量依赖趋势;锌原卟啉-9则导致相反的结果。结论内源性CO通过抑制VSMCs的DNA合成及细胞周期进程直接参与VSMCs的增殖调节;HO-1表达上调是细胞对抗氧化应激和损伤的保护性反应;HO-1 mRNA及蛋白表达增加是内源性CO抑制VSMCs增殖的基础。     

辛伐他汀减轻糖基化终末产物对内皮细胞环氧化酶2表达的影响

目的 探讨辛伐他汀对糖基化终末产物（AGEs）诱导内皮细胞环氧化酶2（COX-2）表达的影响。 方法 体外以不同浓度的糖基化白蛋白（AGE-BSA）、辛伐他汀单独或联合作用于人脐静脉内皮细胞,检测细胞COX-2 mRNA的表达及培养上清液中前列腺素E2（PGE2）的含量。 结果 AGE-BSA诱导内皮细胞COX-2 mRNA的表达,作用呈剂量和时间依赖方式。辛伐他汀可降低AGE-BSA诱导的COX-2 mRNA表达及PGE2产物浓度。 结论 AGEs促进内皮细胞COX-2表达,辛伐他汀可减轻此作用。     

吡格列酮对瘦素诱导的血管平滑肌细胞PCNA及瘦素受体表达的影响

观察吡格列酮对瘦素诱导的血管平滑肌细胞(VSMCs)增殖的干预作用,分别检测VSMCs中增殖细胞核抗原(PCNA)和瘦素受体(OB-R)mRNA和蛋白表达水平的变化.结果 表明吡格列酮可抑制瘦素刺激的VSMCs增殖以及PCNA和OB-R的表达,抑制效应的最佳浓度为100 μmol/L(P<0.01).     

iNOS及ERK1/2信号转导通路在17β-雌二醇抑制血管平滑肌细胞增殖中的作用

目的: 观察诱导型一氧化氮合酶（inducible nitric oxide synthase,iNOS）及细胞外信号调节激酶1/2（ERK1/2）信号转导通路在17β-雌二醇（17β-estradiol,E2）抑制血管平滑肌细胞（vascular smooth muscle cells,VSMCs）增殖中的作用。方法: 采用MTT比色法和Western blot技术,检测E2预处理前后胎牛血清（fetal calf serum,FCS）对VSMCs中DNA合成、iNOS表达及磷酸化的ERK1/2蛋白表达的影响。结果: E2作用24 h,可明显抑制FCS诱导的VSMCs增殖。Western blot的结果显示,FCS孵育VSMCs后,iNOS蛋白的表达下降,磷酸化的ERK1/2蛋白表达增加。E2预处理后,可增加iNOS蛋白的表达,抑制磷酸化ERK1/2蛋白表达。若提前应用iNOS阻断剂L-精氨酸甲酯（L-NAME）孵育VSMCs,可部分逆转E2诱导的磷酸化的ERK1/2蛋白表达下降的效应。结论: E2可抑制FCS诱导的VSMCs增殖,其作用可能与增加iNOS蛋白的表达,抑制磷酸化的ERK1/2表达有关。     

血管紧张素II对心脏成纤维细胞Ets-1表达的影响及机制研究

目的 研究血管紧张素II（AngII）对大鼠心脏成纤维细胞(CFs)转录因子Ets-1及其下游促纤维化因子表达和细胞增殖的调节及相关的分子机制。方法 将原代培养的大鼠CFs分为对照组,AngII处理不同时间组以及不同剂量组,采用实时定量RT-PCR及western blotting实验技术检测AngII对Ets-1mRNA及蛋白表达的影响。用AngII受体拮抗剂、MAPKs、PKC及PTK抑制剂预处理CFs,测定其对AngII诱导的Ets-1、结缔组织生长因子(CTGF)、纤溶酶原激活物抑制因子-1(PAI-1)表达及细胞增殖的影响。结果 在CFs中,AngII可呈时间及浓度依赖性诱导Ets-1表达(P<0.05),对其mRNA稳定性则无显著影响。血管紧张素II1型受体(AT1R)拮抗剂losartan、ERK抑制剂PD98059、JNK抑制剂SP600125及PKC抑制剂BIM预处理可显著抑制AngII诱导Ets-1过表达(P<0.05),下调CTGF及PAI-1蛋白表达,抑制AngII诱导的CFs增殖(P<0.05)。结论 AngII通过AT1R及PKC,ERK、JNK信号通路介导诱导CFs Ets-1基因的表达。而且,转录因子Ets-1可能是心肌纤维化过程的一个重要介导因素,其发挥作用的主要途径可能是通过参与调控CFs增殖及促纤维化因子CTGF及PAI-1的表达。     

氨基胍对糖基化终产物干预后人肾系膜细胞MMP-2表达的影响

目的观察盐酸氨基胍（AG）对糖基化终产物（AGEs）干预后人肾系膜细胞（HRMC）基质金属蛋白酶2（MMP-2）表达的影响。方法运用糖基化终产物-牛血清白蛋白（AGE-BSA）干预HRMC,以及不同浓度AG单独或与AGE-BSA共同干预HRMC24小时;RT-PCR和Western blot分别检测HRMC MMP-2mRNA和蛋白表达。结果AGE-BSA明显降低HRMC MMP-2mRNA和蛋白表达（P〈0.05）,AG以浓度依赖的方式恢复AGE-BSA下调的HRMC MMP-2mRNA和蛋白表达（P〈0.05）。结论AG可能通过拮抗AGEs对MMP-2表达的抑制效应而发挥其肾脏保护作用。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

治疗高血压药物的经济学评价

重视高血压治疗中的经济学评价,对利用我国有限的卫生资源来遏制高血压对人民群众的危害有着重要的现实意义。药物经济学对于药物治疗的成本和治疗的结果给予同样的关注。因为治疗高血压的费用,不仅涉及药物价格,还包括患者的危险水平,降压疗效和对临床终点事件的影响,以及治疗的依从性和安全性。因此药物经济学更强调整体成本和价-效比。低危病人,若非药价低廉,治疗的价-效比不够理想。而在高危的患者,价-效比越小越经济而不是药费越便宜越好。