预防性应用吡格列酮改善胰岛素抵抗的脂肪内分泌机制

目的探讨吡格列酮改善胰岛素抵抗过程中脂肪内分泌功能的改变。方法45只W istar雄性大鼠随机分为对照组、胰岛素抵抗组和吡格列酮组。胰岛素抵抗动物模型成功建立后,分析各组抵抗素、脂联素和脂联素受体的表达。结果与胰岛素抵抗组比较,吡格列酮组大鼠的体质量、空腹血糖、游离脂肪酸差异不明显,但胰岛素、胰岛素抵抗指数、葡萄糖耐量和胰岛素耐量明显改善（P〈0.01）,脂联素表达明显增高（P〈0.05）。结论脂肪内分泌功能紊乱在高脂诱导胰岛素抵抗的发生中起着重要的作用,预防性应用吡格列酮可明显延缓大鼠胰岛素抵抗的发生,改善脂肪内分泌功能。     

吡格列酮对高脂血症大鼠主动脉脂联素受体表达的影响

目的观察高脂血症大鼠主动脉脂联素受体(adiponectin receptors1/2,AdipoR1/2)的表达改变,探讨吡格列酮对高脂血症大鼠主动脉血管脂联素受体表达的影响。方法清洁级SD大鼠26只,随机分为正常饮食组(9只)和高脂饮食组(17只);高脂饮食组12周后检测空腹血脂,明确造模是否成功,随机分为模型组(8只)和吡格列酮组(9只),后者给予吡格列酮溶液(0.6mg/ml)连续灌胃4周,之后检测血脂水平及主动脉病理,ELISA法检测血清脂联素水平,荧光RT-PCR法检测主动脉脂联素受体AdipoR1和AdipoR2mRNA的表达,Western Bolt法检测脂联受体蛋白表达。结果高脂饲料喂养12周,高脂饮食组TG、TC、LDL水平明显升高(P0.01);给药四周后,吡格列酮组TG、TC水平明显降低(P0.01),模型组主动脉脂联素受体1/2mRNA和蛋白的表达明显下降(P0.01)。与模型组比较,吡格列酮组主动脉AdipoR(1P0.05)和AdipoR2(P0.01)mRNA的表达明显升高,主动脉脂联素受体蛋白的表达明显升高(P0.05),差异有统计学意义。结论脂联素及其受体下降可能介入高脂血症血管损伤,吡格列酮具有抗动脉粥样硬化作用,该作用可能与提高血清脂联素和主动脉血管脂联素受体表达有关。     

吡格列酮对胰岛素抵抗HepG2细胞胰岛素受体底物表达的影响

目的探讨毗格列酮对胰岛索抵抗（IR）HepG2细胞胰岛素受体底物（IRS）蛋白表达的影响。方法胰岛素抵抗HepG2细胞模型建立后,培养液中加入吡格列酮共同孵育,观察吡格列酮对模型细胞葡萄糖掺入率的影响;应用免疫细胞化学染色法观察吡格列酮对IR HepG2细胞IRS-1、IRS-2表达的影响。结果与模型细胞组比较,1×10^-5mol／L吡格列酮显著提高了HepG2细胞的葡萄糖掺入率（P〈0．01）,使IRHepG2细胞IRS-1、IRS-2蛋白的表达显著增加（P〈0．05）。结论吡格列酮的胰岛素增敏作用可能与胰岛素信号转导分子IRS-1、IRS-2蛋白的表达增强有关。     

吡格列酮对2型糖尿病大鼠骨骼肌脂联素受体1表达的影响

目的观察吡格列酮对2型糖尿病大鼠血清脂联素以及骨骼肌脂联素受体1(AdipoR1)表达的影响,探讨吡格列酮对2型糖尿病胰岛素抵抗的改善作用及机制。方法 40只8周龄健康雌性SD大鼠,随机分为正常对照组(n=10)、糖尿病组(n=15)及吡格列酮组(n=15)。用高糖高脂饲料加小剂量链脲佐菌素建立2型糖尿病大鼠模型,成模后吡格列酮组给予10 mg/(kg.d)吡格列酮灌胃,正常对照组和糖尿病组给予同体积生理盐水灌胃,共12周。3个月后股静脉取血,酶联免疫吸附法(ELISA)测定血清脂联素水平,留取大鼠骨骼肌,光、电镜观察骨骼肌结构,免疫组织化学染色法测定骨骼肌AdipoR1蛋白的表达。结果与正常对照组(1.73±0.32 mg/L)比较,糖尿病组血清脂联素(1.01±0.27 mg/L)水平显著降低,而吡格列酮组(1.34±0.43 mg/L)较糖尿病组显著升高,差异有统计学意义(P<0.05)。骨骼肌AdipoR1免疫组织化学染色正常对照组着色深且广泛,糖尿病组较正常对照组染色浅,吡格列酮组较糖尿病组染色深,但较正常对照组浅。光镜及电镜结果显示大鼠骨骼肌结构未见明显异常。结论 2型糖尿病大鼠血清脂联素水平及骨骼肌AdipoR1表达降低并导致糖脂代谢紊乱及胰岛素抵抗。吡格列酮可上调血清脂联素及骨骼肌AdipoR1的表达,从而调节糖脂代谢,改善胰岛素抵抗。     

TLR4/NF-κB信号转导通路介导吡格列酮在内脂素诱导内皮细胞炎症损伤过程中作用机制的探讨

目的 观察吡格列酮对内脂素诱导人脐静脉内皮细胞（HUVECs）炎症损伤过程中的影响,探讨吡格列酮改善内皮功能的信号转导机制。方法 将HUVECs随机分组,给予不同浓度的内脂素进行诱导,运用蛋白印迹法（Western blotting）检测各组细胞Toll样受体4（TLR4）、细胞间黏附分子-1（ICAM-1）、核因子-κB（NF-κB）和NK-κB抑制蛋白α（IκB-α）的表达;再给予过氧化物酶体增殖物激活受体γ（PPARγ）激动剂吡格列酮,观察各组指标表达变化。结果 与正常对照组相比,内脂素呈浓度依赖性地增加ICAM-1含量,下调IκB-α蛋白的表达,同时上调TLR4的表达,差异具有统计学意义 （P＜0.05）,且当内脂素浓度为1×10-5mol/L时效果最显著。而吡格列酮呈浓度依赖性地抑制内脂素所诱导的上述效应,差异具有统计学意义（P＜0.05）,当吡格列酮浓度为20μmol/L时效果最显著。结论 吡格列酮对内脂素诱导的HUVECs炎症损伤有保护作用,其机制可能与抑制TLR4/NF-κB信号转导通路有关。     

吡格列酮对2型糖尿病并发心血管病患者血清脂联素与胰岛素抵抗的影响

目的探讨吡格列酮对2型糖尿病并发心血管病患者血清脂联素与胰岛素抵抗(IR)的影响。方法随机选取2型糖尿病合并冠心病患者60例,正常对照组30例。分别检测血清脂联素、瘦素、肿瘤坏死因子(TNF-α)、游离脂肪酸(FFA)、空腹血糖(FPG)和胰岛素、体重指数(BMI)、血压(BP)、总胆固醇(TC)、甘油三酯(TG)等指标,计算胰岛素敏感指数(ISI)和胰岛素抵抗指数(HOMA-IR)。再将60例2型糖尿病并发心血管病患者分成2组,吡格列酮治疗组32例,常规治疗组28例,吡格列酮治疗组用吡格列酮治疗8w,治疗前后均检上述指标。结果(1)2型糖尿病合并冠心病患者与对照组比较,血清脂联素水平降低(P<0.01),吡格列酮治疗组与常规治疗组比较,血清脂联素无差异(P>0.05);(2)应用吡格列酮治疗后,患者血清脂联素水平显著升高(P<0.01),TNF-α、FFA、胰岛素水平下降(P<0.01),IR明显改善。结论吡格列酮能增加2型糖尿病并发心血管病患者血清脂联素水平,改善IR。     

复方丹参滴丸对胰岛素抵抗大鼠的保护作用及其机制研究

目的观察复方丹参滴丸对胰岛素抵抗大鼠糖脂代谢的作用,探讨其改善胰岛素抵抗的机制。方法隔日1次肌肉注射地塞米松1mg/kg诱导SD大鼠产生胰岛素抵抗,并随机分为正常对照组、模型对照组、吡格列酮组、丹参注射针组及复方丹参滴丸浸膏组。给药8周后分别检测空腹血糖、空腹胰岛素、一氧化氮合酶、一氧化氮、胸主动脉肌层/管壁厚度,并采用ELISA法测定脂联素浓度及实时PCR法测定大鼠骨骼肌细胞膜葡萄糖转运蛋白-4 mRNA表达。结果造模成功大鼠胰岛素抵抗指数增加,一氧化氮合酶生成减少,一氧化氮降低,胸主动脉肌层/管壁厚度明显增加,脂联素分泌减少,肌细胞膜葡萄糖转运蛋白-4 mRNA表达降低。而经上述3种药物干预后,大鼠的胰岛素抵抗指数均有不同程度降低,一氧化氮合酶及一氧化氮生成增加,胸主动脉肌层/管壁厚度明显降低,脂联素分泌及肌细胞膜葡萄糖转运蛋白-4 mRNA表达增强（P〈0.05或P〈0.01）,且吡格列酮组及复方丹参滴丸浸膏两组间作用无统计学意义（P〉0.05）;丹参注射针组作用较弱（P〈0.05）。结论复方丹参滴丸通过多靶点调节糖脂代谢而发挥改善胰岛素抵抗的作用,并与其促进脂联素分泌、增强骨骼肌细胞膜葡萄糖转运蛋白-4 mRNA表达密切相关。     

吡格列酮对2型糖尿病患者血清脂联素的影响及其意义

目的 探讨吡格列酮对2型糖尿病(T2DM)患者血清脂联素水平影响.方法 用ELISA法检测67例T2DM患者和52例非糖尿病对照组的血清脂联素水平,用随机双盲法比较47例T2DM患者用安慰剂和吡格列酮干预治疗8 w后的血清脂联素、血糖、胰岛素抵抗(IR)水平.结果 T2DM患者组与对照组比较,血清脂联素水平降低(P<0.05);应用吡格列酮治疗后,患者血清脂联素水平显著升高(P<0.05),血糖降低(P<0.05),IR明显改善,而常规组治疗前后无显著性差异(P>0.05).结论 吡格列酮能提高2型糖尿病患者血清脂联素水平,降低血糖水平及改善胰岛素抵抗.     

叉头状转录因子O1与吡格列酮干预对肝癌HepG-2细胞葡萄糖消耗的影响

目的研究叉头状转录因子O1（FoxO1）及吡格列酮干预对高胰岛素诱导的肝癌HepG-2细胞葡萄糖消耗的影响及机制。方法1×10^-6mol／L胰岛素培养HepG．2细胞24h后,诱发培养基葡萄糖消耗减少建立细胞模型,将细胞分为对照组、空白质粒组、FoxOlsiRNA载体组、1×10^-5mol／L吡格列酮组。以普通培养基培养的细胞作为空白对照组。37℃、5％CO2培养箱中孵育24h,葡萄糖氧化酶法检测培养基中葡萄糖含量,逆转录-聚合酶链反应（RT—PCR）检测FoxO1mRNA和过氧化物酶体增殖物激活受体-γ（PPAR-γ）mRNA表达,Westernblot法检测PPAR-γ蛋白表达。将FoxO1mRNA、PPAR-γ mRNA、PPAR-γ蛋白表达与葡萄糖消耗量进行相关分析和曲线拟合。采用单因素方差分析及多样本均数两两比较进行统计学分析。结果高胰岛素培养24h较未诱导细胞培养基的葡萄糖消耗降低[分别为（1．36±0．03）和（2．93±0．05）mmol／L,P〈0．01],细胞Fox01mRNA升高（分别为0．513±0．016和0．425±0．011,P〈0．05）,PPAR-γmRNA降低（分别为0．260±0．025和0．441±0．012,P〈0．05）,PPAR-γ蛋白降低（分别为0．312±0．032和0．600±0．046,P〈0．05）。在抑制FoxO1和吡格列酮干预后此趋势有所缓解,逐渐接近于空白对照组。FoxO1mRNA、PPAR-γ mRNA和PPAR-γ蛋白表达与葡萄糖消耗量高度相关。结论FoxO1表达升高或降低对葡萄糖代谢产生不利影响;增强PPAR-γ表达可有效恢复高胰岛素诱导的高糖,增加肝细胞的胰岛素敏感性。     

肿瘤坏死因子α、吡格列酮对3T3-L1脂肪细胞脂联素mRNA表达的影响

目的观察吡格列酮（PIO）和肿瘤坏死因子α（TNF-α）对3T3-L1脂肪细胞脂联素mRNA表达的影响。方法以不同浓度PIO和TNF-α于各时段处理3T3-L1细胞,用RT-PCR技术检测各条件下脂联素mRNA的表达。结果（1）3T3-L1前体脂肪细胞无脂联素mRNA表达。（2）TNF-α抑制分化及成熟的3T3-L1脂肪细胞脂联素mRNA表达。（3）PIO增强分化及成熟的3T3-L1脂肪细胞脂联素mRNA表达。（4）PIO能改善TNF-α对脂联素mRNA表达的抑制。结论在分化及成熟的脂肪细胞中,TNF-α抑制脂联素mRNA表达,而PIO增强其表达;PIO促进前体脂肪细胞分化及激活脂联素表达;PIO改善TNF-α对成熟脂肪细胞脂联素的抑制。     

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.     

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。     

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。     

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。     

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     

CagA-Hp抗体IgG与胃炎的组织学分析

研究幽门螺杆菌(Hp)感染与胃炎的关系。方法对204例慢性胃炎患者胃粘膜进行观察分析,并测定其中137例Hp阳性患者血清CagA-Hp抗体IgG水平,与组织学对照。结果慢性萎缩性胃炎伴肠上皮化生患者血清CagA抗体IgG明显高于对照组(P＜0.01);其他类型胃炎患者血清CagA抗体IgG水平无明显增高(P＞0.05)。结论CagA-Hp可能是导致慢性萎缩性胃炎伴肠上皮化生的因素之一,对这类患者应密切随访观察。     

慢阻肺急性加重期患者预后的影响因素分析

目的探讨慢性阻塞性肺病急性加重期(AECOPD)患者预后的相关危险因素。方法回顾性调查、收集58例AECOPD患者可能影响其预后的相关因素,并对其分别进行单因素分析。并进行Logistic多元逐步回归进行多因素分析,筛选影响AECOPD患者预后的独立危险因素。结果单因素分析后将结果 P0.1的因素纳入多因素Logistic回归,分析发现是否合并呼吸衰竭、气促程度、白细胞计数、APACHEⅡ、应用抗氧化剂、慢阻肺治疗依从性为影响AECOPD患者预后不佳的独立因素(P0.05)。结论根据AECOPD患者预后的独立危险因素,及早判断,选择合适的后续治疗方案,对提高其生存率及生存质量具有重要意义。