土贝母苷甲对小鼠B16黑色素瘤和Lewis肺癌转移的抑制作用

目的:本研究旨在探讨土贝母苷甲对小鼠B16黑色素瘤和Lewis肺癌转移的影响。方法:采用裸BALB/c小鼠B16黑色素瘤实验转移和裸BALB/c小鼠Lewis肺癌自发转移模型研究土贝母苷甲对肿瘤转移的影响;采用免疫组织化学法检测土贝母苷甲对转移相关基因CD44v6、ErbB-2和nm23-H1表达的影响。结果:腹腔注射低于全身中毒水平剂量的土贝母苷甲明显减少接种B16黑色素瘤细胞小鼠的肺重和肺转移灶数量,而对小鼠的健康和活力无明显影响;土贝母苷甲(2、3 mg.kg-1.d-1×14 d)和环磷酰胺(50 mg.kg-1.wk-1×2 d)对B16黑色素瘤细胞肺转移的抑制率分别为68.8%、82.8%和49.1%。土贝母苷甲治疗组小鼠Lewis肺癌原发肿瘤的平均瘤重明显低于对照组(P<0.05)。土贝母苷甲(2、3 mg.kg-1.d-1×14 d)和环磷酰胺(50 mg.kg-1.w-1×2 d)治疗组小鼠的肝转移抑制率分别为46.3%、52.0%和54.7%。土贝母苷甲显著下调促转移基因CD44v6和ErbB-2的表达,上调抑转移基因nm23-H1的表达。结论:土贝母苷甲对小鼠B16黑色素瘤的实验性转移和Lewis肺癌的自发性转移都有显著的抑制作用。土贝母苷甲对肿瘤转移的这种抑制作用与其抑制原发肿瘤生长、下调促转移基因CD44v6和ErbB-2及上调抑转移基因nm23-H1的表达有关,提示土贝母苷甲是一个阻止癌扩散和转移的候补化合物。     

3-甲基嘌呤对脂多糖诱导小鼠急性肺损伤的保护作用及其机制研究

目的:研究自噬抑制剂3-甲基嘌呤(3-MA)对脂多糖(LPS)诱导小鼠急性肺损伤的保护作用及其机制。方法:取小鼠随机分为正常对照组、模型(LPS 15 mg/kg)组、药物对照(3-MA 20 mg/kg)组和低、高剂量治疗(LPS 15 mg/kg+3-MA 20、40 mg/kg)组,每组10只。除正常对照组和药物对照组外,其余各组小鼠ip LPS复制急性肺损伤模型,药物对照组和低、高剂量治疗组小鼠分别于建模前1 h ip相应剂量的3-MA。建模6 h后分别测量各组小鼠的肺湿/干质量比(W/D),HE染色观察肺组织病理变化;Western blot法检测肺组织肿瘤坏死因子α(TNF-α)、NF-κB p65、LC3BⅡ/Ⅰ、激活型半胱氨酸氨基蛋白酶3(Cleaved-caspase-3蛋白的表达水平。结果:与正常对照组比较,模型组小鼠的W/D值和TNF-α、NF-κB p65、LC3BⅡ/Ⅰ、Cleaved-caspase-3蛋白表达均增强(P<0.01);与模型组比较,低剂量治疗组小鼠的W/D值和TNF-α、NF-κB p65、LC3BⅡ/Ⅰ、Cleaved-caspase-3蛋白表达均减弱(P<0.05),高剂量治疗组小鼠仅LC3BⅡ/Ⅰ蛋白表达减弱(P<0.01)。结论:在LPS诱导的急性肺损伤小鼠模型中,过度自噬可能通过激活NF-κB通路参与炎症反应并诱导细胞凋亡;3-MA适度抑制自噬可减轻炎症反应并起到保护肺组织的作用。     

淫羊藿素抑制外泌体介导的黑色素瘤肺转移及机制初探

本研究从体内外考察淫羊藿素(icaritin,ICT)对外泌体(exosomes,Exo)诱导的小鼠黑色素瘤B16BL6细胞肺转移的影响,并探讨其潜在分子机制。收集B16BL6细胞培养上清液,超速离心法提取Exo,使用透射电镜和Western blotting对Exo进行表征,BCA法对Exo总蛋白进行定量分析。细胞划痕实验考察ICT对Exo诱导的B16BL6细胞迁移能力的影响。建立C57BL/6小鼠黑色素瘤实验性转移模型,动物实验获得南京中医药大学伦理委员会的同意,H&E染色考察ICT体内抑制Exo介导的黑色素瘤转移作用。ELISA及免疫荧光检测转移组织中促炎因子白细胞介素6(interleukin-6,IL-6)、S100钙结合蛋白A8/A9复合物(S100 calcium-binding protein A8/A9 complex,S100A8/A9)、血清淀粉样蛋白A(serum amyloid A,SAA)及纤连蛋白(fibronectin)的表达。免疫组化及Western blotting检测ICT对Exo诱导的转移组织相关蛋白干扰素基因刺激因子(stimulator of interferon gene,STING)、磷酸化STING(p-STING)、TANK结合激酶1(TANK-binding kinase 1,TBK1)和磷酸化的TBK1(p-TBK1)的表达情况。结果表明,所提取的外泌体粒径为(149.33±2.68)nm、多分散系数为(0.192±0.02)、zeta电位为(-32.22±0.50)mV,电镜下呈现茶托样双层膜结构,测得蛋白浓度为(838.66±62.14)μg·mL^-1。ICT浓度为5、10和20μmol·L^-1时,能够抑制Exo诱导的B16BL6细胞迁移。ICT能够抑制Exo介导的黑色素瘤肺转移,抑制肺组织中促炎因子S100A8/A9、SAA和IL-6的表达,能够抑制转移肺组织的p-STING和p-TBK1的表达。本研究结果表明,ICT能够明显抑制Exo诱导的肿瘤转移,且与STING通路的失活有关。     

鲨鱼软骨提取物对C_(57)BL/6J小鼠B_(16)黑色素瘤肺转移的影响

目的：评价鲨鱼软骨提取物（SCAE）对C57BL／6J小鼠B16黑色素瘤肺转移的影响。方法：小鼠经尾静脉接种B16黑色素瘤细胞悬液（5×104／每鼠）后d21，观察SCAE低、中、高剂量及环磷酰胺、生理盐水对照组小鼠肺部转移瘤生长情况。结果：SCAE及环磷酰胺对C57BL／6J小鼠经血道B16黑色素瘤肺转移均有明显的抑制作用，其肺校重及肺转移灶数均低于对照组，但后者主要免疫器官胸腺呈现明显萎缩，而SCAE各剂量组无此毒副作用。     

开口箭皂苷抗黑色素瘤侵袭与转移作用研究

目的研究开口箭皂苷对B16-BL6黑色素瘤肺转移和体外肿瘤细胞穿透人工基底膜的影响。方法小鼠爪下制备黑色素瘤模型,注射不同剂量开口箭皂苷溶液,3周后称量患肢质量并计算肿瘤抑制率,5周后测定小鼠肺、脾、胸腺组织表面肿瘤节结数,Transwell小室实验测定药物对肿瘤细胞侵袭基底膜的影响。结果开口箭皂苷呈剂量依赖性地抑制小鼠黑色素瘤生长,高剂量(45 mg.kg-1)开口箭皂苷可明显减少小鼠肺转移结节数、总转移结节数和转移率(P<0.05);Transwell小室实验中,开口箭皂苷可显著抑制侵袭细胞数(P<0.05),抑制率21.46%。结论开口箭皂苷可能通过抑制黑色素瘤生长、转移及降低基底膜侵袭而发挥抗肿瘤作用。     

胡桃醌对小鼠黑色素瘤细胞B16F10体内迁移的影响

目的:研究胡桃醌对小鼠黑色素瘤细胞B16F10体内迁移的影响.方法:采用小鼠B16/F10黑色素瘤人工肺转移模型研究胡桃醌对肿瘤细胞血道转移的作用.结果:与溶剂对照组相比,4.5、3、1.5和0.75 mg/kg胡桃醌组显著减少小鼠黑色素瘤B16F10血道转移(P＜0.05),其抑制率分别为27.30％、55.35％、31.52％和25.34％;3 mg/kg胡桃醌与阳性对照组相比,抑瘤率无统计学差异(P＞0.05).结论:胡桃醌可抑制小鼠黑色素瘤B16F10血道转移.     

白芍总苷通过白细胞介素 -6/信号转导及转录激活蛋白 3信号通路对脂多糖诱导的急性肺炎小鼠炎症反应的影响

目的探讨白芍总苷( TGP)通过白细胞介素 -6/信号转导及转录激活蛋白 3(IL-6/STAT3)信号通路对脂多糖诱导的急性肺炎小鼠炎症反应的影响。方法本研究起止时间为 2019年 10月至 2020年 2月。选择 SPF级雄性小鼠 50只,采用随机数字表法将小鼠随机分为五组,对照组、急性肺炎模型组、 TGP低剂量组、 TGP中剂量组和 TGP高剂量组。采用苏木精 -伊红( HE)染色观察各组小鼠肺组织病理形态学;采用酶联免疫吸附测定( ELISA)检测各组小鼠肺组织肿瘤坏死因子 -α(TNF-α)、白细胞介素( IL)-1β含量;采用蛋白质印迹( Western blotting)检测各组小鼠肺组织 IL-6、STAT3、磷酸化信号转导及转录激活蛋白 3(p-STAT3)的蛋白表达水平;采用实时荧光定量 PCR(qRT-PCR)检测各组小鼠肺组织 IL-6、STAT3 mRNA表达水平。结果模型组小鼠肺组织结构被破坏,肺泡间隔增厚,大量炎性细胞浸润; TGP药物组病理改变较模型组均存在不同程度改善,白芍总苷高剂量组肺组织仅存在少量炎性细胞浸润。与对照组( 45.12±9.73)ng/L、(21.38±2.13)ng/L相比,模型组及 TGP各剂量组小鼠肺组织 TNF-α(89.30±9.26)ng/L,(84.32±5.08)ng/L,(75.36±4.67)ng/L,(64.06±5.90)ng/L、IL-1β含量( 59.69±3.60)ng/L,(56.87±     

GHGKHKNK八肽抑制小鼠恶性黑色素瘤B16-F10转移及其机制的实验研究

目的：探讨GHGKHKNK八肽抑制小鼠恶性黑色素瘤B16-FIO细胞转移及其机制。结果：1．不同剂量的GHGKHKNK八肽对小鼠恶性黑色素瘤细胞B16-FIO的克隆形成均有抑制作用,与对照组相比较均有显著性差异（P〈0．05）2．不同剂量的GHGKHKNK八肽在体外作用24h后可以显著抑制小鼠恶性黑色素瘤B16-FIO细胞的侵袭,穿膜细胞数与对照组比较具有显著性差异（P〈0．05）。3．GHGKHKNK八肽在24h时5．5&#215;10^-4mol／L、5．5&#215;10^-5mol／L、5．5&#215;10^-6mol／L对小鼠恶性黑色素瘤细胞B16-F10黏附抑制率与对照组相比较均有显著性差异（P〈0．05）。4．经GHGKHKNK八肽作用后,小鼠恶性黑色素瘤细胞ICAM-1、LN—R表达降低表达降低,E-cadhesion表达增强。与对照组比较明显差异P〈0．05．5．GHGKHKNK八肽对B16一F10人工肺转移的抑制作用的实验结果显示：GHGKHKNK八肽各剂量组和环磷酰胺组肺转移灶的平均数目与生理盐水组照组相比较有明显差异（P〈0．05）：GHGKHKNK八肽500ug／kg／d、50ug／kg／d剂量组与环磷酰胺组对比有显著性差异（P〈0．05）。结论：i．GHGKHKNK八肽在体外能抑制小鼠恶性黑色素瘤细胞的体外克隆形成能力,能显著抑制小鼠恶性黑色素瘤B16-F10细胞的侵袭。提示HGKHKNK八肽可能通过抑制小鼠恶性黑色素瘤细胞的侵袭和增殖而抗肿瘤细胞的转移。2．GHGKHKNK八肽抑制小鼠小鼠恶性黑色素瘤细胞B16-FIO与人工基底膜的黏附,提示GFIGKHKNK八肽可能通过抑制细胞与基底膜的黏附来抑制肿瘤细胞的转移。3．GHGKHKNK八肽能够下调细胞间黏附因子1（ICAM-1）和层黏连蛋白受体（LN—R）在细胞内的表达,提示GHGKHKNK八肽可能通过抑制细胞间黏附因子的表达而抑制肿瘤细胞的转移。4．GHGKHKNK八肽能显著抑制小鼠恶性黑色素瘤细胞B16-F10在小鼠体内的肺转移。     

三七总皂苷对B16黑色素瘤生长及转移的作用

目的观察三七总皂苷（PNS）对B16黑色素瘤生长及转移的作用,及其对B16黑色素瘤表达缝隙连接蛋白Connexin32的影响。方法实验采用B16黑色素瘤自发性肺转移模型,来观察PNS对B16黑色素瘤生长及转移的影响。免疫组织化学检测Connexin32在黑色素瘤原发灶的表达情况。结果（1）PNS对黑色素瘤生长有较好的抑制作用,其中PNS高剂量组抑瘤率可达50．85％。（2）与模型组相比PNS中、高剂量组能有效抑制黑色素瘤的肺转移,转移灶数量与对照组相比有明显减少。（3）免疫组织化学检测,发现PNS各用药组均能增强黑色素瘤原发灶细胞膜上Connexin32的表达。结论PNS能够抑制B16黑色素瘤的生长和转移,并能有效增强肿瘤细胞膜上Connexin32的表达。     

强力枇杷露治疗慢性支气管炎模型小鼠作用机制研究

目的 探讨强力枇杷露治疗慢性支气管炎模型小鼠的作用机制。方法 将72只NIH小鼠随机分为空白对照组(A组,12只,等体积纯净水)和模型组(60只),采用烟熏联合脂多糖吸入法复制慢性支气管炎模型小鼠建模45 d后,将模型组小鼠随机分为模型对照组(B组,等体积纯净水),盐酸氨溴索组(C组,10 mL/kg),强力枇杷露低、中、高剂量组(D₁组、D₂组、D₃组,7.5,15,30 mL/kg),各12只,雌雄各半。各组小鼠按30 mL/kg灌胃给药,每日1次,连续14 d。末次给药24 h后,采集小鼠血清,测定白细胞介素6(IL-6)、白细胞介素8(IL-8)水平;取右肺组织,测定肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)及超氧化物歧化酶(SOD)含量;对左肺支气管组织进行病理组织学检查。结果 与B组比较,D₁组小鼠肺组织MDA含量显著降低(P <0.01);D₂组小鼠血清IL-8的水平、肺组织MDA含量均显著降低(P <0.05);D₃组小鼠...     

Role of the liver in the disposition of intravenous nitroglycerin in the rat

Previous studies have indicated that the liver is the main site of nitroglycerin (NTG) elimination when the drug is systematically infused. To examine this hypothesis, we measured the apparent systemic clearance (Cls) of nitroglycerin in anesthesized rats receiving a constant intravenous infusion at a dose of 100 micrograms per kg per min. Animals were divided into shunt and sham groups; the former had undergone a portal vein ligation 10 days prior to the study, while the latter was subjected to a sham operation. On the study day, half of the animals of each group also received probenecid at 200 mg/kg, i.v., a drug previously reported to inhibit organic nitrate ester reductase (ONER) activity in rat liver. Arterial NTG samples were obtained at 41, 43 and 45 min of infusion in all four experimental groups; Cls was 439 +/- 32 ml per kg per min (mean +/- S.E.) in sham, 460 +/- 44 in sham and probenecid, 477 +/- 39 in shunt, and 461 +/- 34 in shunt and probenecid animals. During NTG infusion, hepatic blood flow (measured with a constant infusion of indocyanine green) was decreased markedly in shunted rats as was liver/body weight, indicating hepatic atrophy. The specific activity of hepatic ONER was similar in all four groups. In spite of marked differences in hepatic blood flow and hepatic mass, the Cls was similar in all four groups. The liver does not appear to be a major site for the elimination of systemic nitroglycerin as hitherto assumed.     

HACCP在学校集体食堂卫生管理中的应用研究

目的 通过HACCP在学校集体食堂管理中的应用,提高食品卫生水平,保障学生的身体健康。方法 HACCP原则。结果 食品卫生达到较高水平,极大地减少了食物中毒的发生。结论 提示HACCP原则可在学校集体食堂的卫生管理中发挥有效作用。     

半导体激光治疗老年人压疮疗效观察

目的探讨半导体激光局部照射治疗老年人压疮疗效.方法:收集2012年1月-2015年6月48例压疮患者,分为半导体组和常规组各24例.常规组采用常规治疗,半导体组采用半导体激光加常规治疗,10 d为1个疗程,不超过3个疗程.疗程结束后比较两组疗效.结果:半导体组压疮愈显率为83.33％,创面愈合时间为(12.75±5.51)d,常规组分别为54.17％和(19.63±8.65)d,组间差异有统计学意义(P＜0.05),两组均未见不良反应.结论:半导体激光加常规治疗压疮效果肯定,无明显不良反应,且操作简便.     

脑卒中恢复期患者社区综合康复的疗效观察

目的：探讨社区开展康复活动对于脑卒中患者肢体功能康复的影响。方法：选取2014年4至10月参与社区“陈睿健康工作室”康复活动的脑卒中恢复期患者50例作为观察组,选取同期延吉社区卫生服务中心门诊的50例脑卒中恢复期患者作为对照组（进行门诊随访、服药、自我康复）。采用知识、信念、行为（KAP）量表对观察组患者进行问卷调查。采用简化Fugl-Meyer肢体运动功能评分表（Fugl-Meyer assessment of motor function,FAM）比较两组患者入组时和入组6个月时的肢体功能恢复情况及对家庭医生（门诊医师）的满意度。结果：入组6个月时,两组患者的FAM均有所改善,观察组FAM得分[上肢（50.92±7.05）分,下肢（33.01±1.37）分]较对照组[上肢（34.85±6.55）分,下肢（25.20±4.88）分]更高,差异有统计学意义（t上肢=11.8215,t下肢=10.8595,P均＜0.01）。观察组患者的满意率为92%（46/50）,明显高于对照组的30%（15/50,P＜0.05）。结论：在社区开展康复活动可以促进脑卒中患者肢体功能的康复,提高患者的满意度。     

Evaluation of the safety of enalapril in the treatment of heart failure in the very old

Summary We have introduced enalapril, in doses equal to or less than the 2.5 mg currently recommended, as an adjuvant to digoxin and diuretics in 17 patients of mean (SD) age 83 (5) years with severe heart failure. Only eleven patients tolerated its introduction. Unlike those reported in younger patients, all but one of the adverse drug reactions occurred 8 h or more after the first dose. Aged patients started on ACE inhibitors should be observed in hospital until stabilized on a maintenance dose. Three patients had an adverse reaction which differed in nature from those previously reported: acute confusional state, ataxia and mesenteric ischaemia.Ten patients were discharged on 5 mg or 10 mg maintenance doses of enalapril. In nine of them improvement on triple therapy was sustained for a minimum of three months. ACE inhibition was lost in the other patient when her compliance with enalapril therapy fell to around 75%: monitoring compliance is essential when ACE inhibitors are used in low dosages.Enalapril was withdrawn during follow up in three patients because of symptoms of mesenteric ischaemia and in four because of dramatic deterioration of renal function. One of the latter was found subsequently to have severe bilateral atheromatous renal artery stenosis. When isosorbide dinitrate was substituted for enalapril, symptoms of mesenteric ischaemia resolved and renal function returned to baseline. Continuing surveillance for adverse effects is essential in patients of this age group with severe heart failure, and the risk of occult renal artery stenosis requires regular biochemical screening during follow up.The benefit to cost ratio of ACE inhibitors might be improved in aged patients by their use at an earlier stage in the natural history of heart failure, when perfusion of essential organs is not grossly impaired, but carefully monitored trials would be necessary to establish this.     

Effect of the Immunomodulator Tilorone on the in Vivo Acetylation of Procainamide in the Rat

Interferon and interferon inducers have been found to inhibit cytochrome P-450-dependent metabolism in animals and man. The effect of these agents on the acetylation of drugs has not been previously reported. Since these agents stimulate the reticuloendothelial system, together with the abundance of N-acetyltransferase in the reticuloendothelial system, it was hypothesized that these immunomodulators may affect drug acetylation. To test this hypothesis, the effect of tilorone (a synthetic interferon inducer) on the in vivo acetylation of procainamide was examined in the rat. Pretreatment with tilorone hydrochloride (50 mg/kg) 48 hr prior to the administration of procainamide hydrochloride (50 mg/kg) resulted in a 32% increase in the urinary recovery of N-acetylprocainamide and a 35% increase in the metabolic clearance of procainamide to N-acetylprocainamide. These data indicate that interferon inducers increase the N-acetylation of drugs in vivo.     

药物经济学成本-效果分析应用的相关问题探讨

目的探讨药物经济学成本-效果分析(CEA)应用的相关问题。方法运用文献计量学方法、数学证明方法等。结果与结论在运用CEA进行药品的经济性评价时,尤其需要重视临床治疗指标的选择、成本的确定、增量分析的使用和与最小成本分析的比较。     

替普瑞酮治疗老年慢性浅表性胃炎的疗效分析

目的分析替普瑞酮治疗老年慢性浅表性胃炎的疗效。方法100例老年慢性浅表性胃炎患者,通过计算机随机表数字法分为对照组和实验组,每组50例。对照组患者选择西咪替丁作为本次治疗药物,实验组患者选择替普瑞酮作为本次治疗药物。比较两组患者临床疗效、不良反应发生情况以及生活质量。结果实验组治疗总有效率92.00%高于对照组的76.00%,差异具有统计学意义(P<0.05)。实验组不良反应发生率6.00%低于对照组的20.00%,差异具有统计学意义(χ^2=4.332,P=0.037<0.05)。实验组患者治疗后的生活质量评分(68.68±4.11)分高于对照组的(57.73±3.48)分,差异具有统计学意义(t=14.377,P=0.000<0.05)。结论对于老年慢性浅表性胃炎疾病患者,选择替普瑞酮进行治疗不仅疗效更为理想,而且还不易增加患者的用药不良反应,有利于提高患者的生活质量,建议进一步推广。     

Adenosine mechanisms in the regulation of breathing in the rat

The central respiratory effects of various adenosine (A) analogues were studied in halothane-anesthetized rats. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injections of the A analogues (2-Cla, L-PIA, CHA and NECA) reduced minute ventilation (VE) due to decreases in respiratory frequency (f) as well as tidal volume (VT). Dose-dependent effects were seen after i.c.v. L-PIA in both normal and vagotomized rats. Analysis of the A-induced changes using the occluded breath technique revealed an increase in expiratory time (TE) as well as a decrease in inspiratory drive. NECA, a relatively specific A2 agonist seemed to be somewhat more potent in eliciting respiratory depression than a relatively specific A1 agonist like L-PIA. Pretreatment with the methylxanthine theophylline completely antagonized the respiratory depression induced by L-PIA. It is concluded that central A receptors are involved in the central regulation of breathing and that A interacts with the respiratory control system mainly by decreasing inspiratory neural drive and prolonging expiratory time.     

Nifedipine in the treatment of hypertension in the elderly

The effect of nifedipine monotherapy, retard tablets, 20 mg bid, was evaluated in 23 hypertensive patients, mean age, 79 +/- 2 years. Twenty-one patients completed an eight-week study. Blood pressure (BP) decreased to 160/90 mm Hg in 15 patients; in four additional patients diastolic BP dropped by 15% to 28%. In a subset of five patients with isolated systolic hypertension, a significant reduction in systolic BP was noted. Side effects were relatively mild and only two patients discontinued the study. The results suggest that nifedipine monotherapy offers an alternative, logic, therapeutic approach to hypertension in the elderly.