联合应用供体未成熟树突状细胞与CD40L mAb诱导大鼠小肠移植免疫耐受

目的:研究供体骨髓来源的未成熟树突状细胞(imDC)联合CD40L mAbi诱导大鼠小肠移植免疫耐受.方法:体外培养供体大鼠树突状细胞(DC),实验动物分为3组,受体于手术前分别预处理后进行小肠移植.A组(n=15):注射生理盐水;B组(n=15):注射供体来源的imDC;C组(n=151:同时注射供体来源的imDC CD40L mAb.观察受体存活时间(n=6),移植小肠病理学检查,用ELISA法检测受体血清IL-2、INF-γ和IL-10水平(n=5).结果:C组受体动物存活时间明显长于A、B两组,统计学有显著差异(22.67±7.09 d vs7.17±1.47 d,11.00±2.61 d,P＜0.01),C组移植小肠炎性细胞浸润、黏膜结构破坏程度、血清IL-2、INF-γ水平均明显低于A、B组,有统计学差异(IL-2:225.4±48.7 ng/Lvs 374.1±13.2 ng/L,353.6±10.4 ng/L;INF-γ:56.9±2.6 ng/Lvs 229.2±20.6,125.4±18.5 ng/L,P＜0.05),血清IL-10水平C组明显高于A、B组,有统计学意义(186.4±10.6 ng/Lvs 91.7±5.4,162.2±8.1 ng/L,P＜0.05).结论:联合应用CD40L mAb和imDC可抑制小肠移植后的排斥反应,诱导受体产生免疫耐受.     

亚硒酸钠作用的树突状细胞体外抗乙型肝炎病毒效应

目的:探讨亚硒酸钠作用的树突状细胞(DCs)体外诱导自体淋巴细胞特异性抗乙型肝炎病毒的效应.方法:从乙型肝炎患者外周单个核细胞(PBMC)中诱导DCs,在DCs成熟前加入营养浓度的亚硒酸钠作用,将成熟后的DCs与自身淋巴细胞体外共培养,3d后收集淋巴细胞,分组(乙肝组,加硒组)加入2.2.15细胞培养液中,分别收集24,48和72h的培养上清,检测其表面抗原(HBsAg)和e抗原的分泌以及其与淋巴细胞共培养产生IFN-γ的含量.结果:经亚硒酸钠作用后的DCs组和正常对照组的DCs与自身淋巴细胞共培养产生IFN-γ的浓度,以及在24,48和72h对2.2.15细胞培养上清中HBeAg分泌的抑制效应明显高于乙肝组(34.22±3.17ng/L,3839±2.43ng/L vs 21.47±2.24ng/L;25.90%±1.85%,23.03%±1.51% vs 18.05%±3.64%;37.26%±5.11%,36.88%±5.92% vs 29.52%±2.63%;38.76%±4.00%,40.76%±5.04% vs 35.59%±3.09%,P<0.05).结论:体外经亚硒酸钠作用后的乙肝患者的DC功能可在一定程度上恢复,增强自身淋巴细胞毒性作用并可提高产生IFN-γ的含量,可有效的起到抗乙肝病毒的效应,为以后基于DC的慢性乙型肝炎的免疫治疗提供新思路.     

隐蔽性高血压患者血管活性物质的变化

目的 探讨隐蔽性高血压患者血浆中血栓素A2(TXA2)、前列环素(PGI2)、神经肽Y(NPY)、降钙素基因相关肽(CGRP)水平变化并评价其对隐蔽性高血压患者血压水平的影响.方法 78例研究对象分为健康对照组(A组,n=30),隐蔽性高血压组(B组,n=18)及原发性高血压组(C组,n=30).检测各组血浆中TXA2、PGI2、NPY、CGRP水平并作比较.结果 B组患者血浆中TXA2(1151.0±144.0)ng/L和NPY(138.1±16.1)ng/L水平高于A组[TXA2:(940.5±172.5)ng/L;NPY:(99.6±19.7)ng/L;P均＜0.01],但是低于C组患者[TXA2:(1416.6±145.2)ng/L;NPY(169.8±26.2)ng/L;P均＜0.01];而B组患者血浆中PGI2和CGRP水平低于A组[PGI2:(171.4±44.0) vs A组:(244.4±51.2)ng/L;CGRP:(56.2±15.6) vs A组:(79.8±17.9)ng/L;P均＜0.01],高于C组患者[PGI2:(171.4±44.0) vs C组:(108.3±41.9)ng/L;CGRP:(56.2±15.6) vs C组:(39.2±16.6)ng/L;P＜0.05或P＜0.01].经多元线性回归分析:B组患者白昼SBP水平与TXA2、NPY水平直线相关(P均＜0.01);白昼DBP水平与TXA2、CGRP水平直线相关(P＜0.05～0.01).结论 隐蔽性高血压病人血管活性物质如TXA2、PGI2、NPY、CGRP较正常血压的人不同,表现为收缩性血管活性因子增多,舒张性血管因子减少,提示这些血管活性物质可能参与了隐蔽性高血压的发病.     

布拉氏酵母菌散对肝硬化大鼠内毒素血症的影响

目的:研究布拉氏酵母菌散对肝硬化大鼠内毒素血症的影响及其保护机制.方法:采用皮下注射40%CCl4橄榄油溶液+10%酒精饮料诱导肝硬化模型.A组为正常对照组,B组为肝硬化模型组,C组为治疗组.造模成功后,C组用布拉氏酵母菌灌胃[75×108CFU/(kg·d)],A组、B组给予等容量的生理盐水灌胃,连续14 d.采用鲎试剂检测血浆内毒素水平,酶联免疫法检测血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-6(interleukin-6,IL-6)水平,应用自动生化分析仪检测血清丙氨酸氨基转移(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、白蛋白含量变化.结果:C组血浆内毒素水平(0.168 EU/m L±0.012 EU/m L)明显低于B组(0.251 EU/m L±0.011 EU/m L),差异有统计学意义(P0.01);B组血清T N F-α、I L-6浓度比A组明显升高(2.37 ng/L±0.14 ng/L vs 0.64 ng/L±0.12 ng/L、214.51 ng/L±14.13 ng/L vs 106.63 ng/L±9.49 ng/L),差异有统计学意义(P0.01);C组TNF-α、IL-6浓度分别为1.59 ng/L±0.13ng/L、176.45 ng/L±10.81 ng/L,与B组比较明显下降,差异有统计学意义(P0.01);B组A LT、A S T含量分别为133.89 U/m L±8.09U/m L、176.92 U/m L±10.94 U/m L,与A组ALT、AST含量(36.73 U/m L±6.95 U/m L、41.35 U/m L±10.07 U/m L)相比明显升高(P0.01),白蛋白含量(14.50 g/L±1.21 g/L)比A组含量(23.99 g/L±1.92 g/L)下降,差异有统计学意义(P0.01);C组与B组相比较,A LT、A S T含量下降,差异有统计学意义(P0.01),C组白蛋白含量与B组相比,差异无统计学意义(P0.05).结论:肝硬化大鼠存在内毒素血症,布拉氏酵母菌可通过保护肠黏膜屏障降低血浆内毒素水平,减轻肝细胞损伤,可作为慢性肝病的辅助治疗.     

日本血吸虫感染鼠树突状细胞对哮喘抑制作用的实验研究

目的通过过继转移日本血吸虫感染鼠树突状细胞(DC),探讨DC在抑制过敏性哮喘中的作用及机制。方法用CD11c 磁珠分离纯化日本血吸虫感染鼠及正常鼠DC亚群CD11c 细胞。将15只BALB/c小鼠随机分为3组,A组为过继转移日本血吸虫感染鼠DC并诱发过敏性哮喘组,B组为过继转移正常鼠DC并诱发过敏性哮喘组,C组为单纯过敏性哮喘组。A、B两组小鼠经尾静脉过继转移1×106DC,2 h后A、B、C 3组均开始诱发哮喘。4周后处死小鼠,收集肺泡灌洗液,检测细胞因子IL-4I、L-5及IFN-γ水平;取小鼠肺组织作病理切片,观察其炎症变化。结果与B、C组比较,A组肺部炎症明显减轻,按Underwood标准,A、B、C 3组总评分分别为5.00±1.58、11.40±2.07和13.20±2.86,差异有统计学意义(P<0.05)。A、B、C组小鼠肺泡灌洗液IL-4水平分别为(23.25±1.57)pg/ml、(40.70±3.28)pg/ml和(65.23±4.84)pg/ml,差异有统计学意义(P<0.05);IL-5水平分别为(16.20±4.11)pg/ml、(41.41±7.14)pg/ml和(64.75±16.96)pg/ml,IFN-γ水平分别为(6.60±2.34)pg/ml(、6.94±2.19)pg/ml和(5.87±2.44)pg/ml,差异无统计学意义(P>0.05)。结论日本血吸虫感染鼠DC通过影响受体鼠Th2细胞因子的分泌明显抑制过敏性哮喘的发生。     

支气管哮喘患儿外周血树突状细胞上前列腺素D2受体改变研究

目的 研究不同病期支气管哮喘(简称哮喘)患儿单核细胞衍生的树突状细胞(dendriticcells,DC)上前列腺素D2受体(DP/CRTH2)结合容量改变,探讨其对Th2极化的影响.方法 随机病例对照研究.分哮喘急性发作期组32例.平均年龄(6.1±3.5)岁.缓解期组30例,平均年龄(5.8±2.6)岁,正常对照组34例,平均年龄(7.2±3.8)岁.用放射配体结合分析法测定外周血DC上DP1/CRTH2结合容量;用酶联免疫吸附试验(ELISA)法测定外周血白介素4(IL-4)、IL-5和γ干扰素(IFN-γ).结果 哮喘发作期和缓解期组DC上总结合和CRTH2受体结合容量比正常对照组显著增加,DP总结合为:(532.42±123.87)fmol/106细胞、(491.78±110.64)fmol/106细胞、(274.61±87.16)fmol/106细胞;CRTH2为:(355.66±99.19)fmol/106细胞、(316.83±81.42)fmol/106细胞、(123.74±49.27)fmol/106细胞;而DP1差异无统计学意义(P<0.01).发作期和缓解期组Th2细胞因子IL-4、IL-5比正常对照组显著增加,IL-4为:(12.76±3.54)ng/L、(11.44±2.65)ng/L、(7.49±1.45)ng/L;IL-5为:(36.28±10.21)ng/L、(32.11±11.56)ng/L、(18.484±5.65)ng/L(P<0.01);发作期和缓解期组Th1细胞因子IFN-γ比正常对照组显著减少,IFN-γ为:(7.47±2.49)ng/L、(7.56±1.41)ng/L、(13.13±1.44)ng/L(P<0.01).结论 哮喘患儿发作期和缓解期外周血DC上CRTH2受体表达和Th2细胞因子IL-4、IL-5分泌增加.     

硒对4-羟基壬烯酸和β淀粉样蛋白诱导的神经细胞凋亡抗氧化保护作用

目的探讨硒对4-羟基壬烯酸(HNE)和β淀粉样蛋白(Aβ)诱导的神经细胞凋亡率的影响及其作用机制。方法取原代大鼠胚胎海马神经细胞置常规培养液中培养后为未处理1组和未处理2组;细胞置于0、100和200nmol/L亚硒酸钠中,加HNE处理24h,分别为对照1组、亚硒酸钠A、B组;细胞置于0、200、500和1000nmol/L亚硒酸钠中,加入Aβ处理24h,分别为对照2组、亚硒酸钠C、D和E组;将SH-SY5Y置于培养液中培养为空白组;细胞置于0、50、100和200nmol/L亚硒酸钠中,加入HNE处理24h,分别为对照3组、亚硒酸钠A1、B1和C1组。采用锥虫蓝染色和细胞形态学检测细胞凋亡率,采用荧光染料H2DCF-DA检测细胞活性氧水平。结果与未处理1组和未处理2组比较,对照1组、对照2组细胞凋亡率明显增加;与对照1组和对照2组比较,亚硒酸钠A、B、C、D和E组细胞凋亡率明显降低(P<0.05,P<0.01)。与空白组比较,对照3组细胞活性氧水平明显升高;与对照3组比较,亚硒酸钠A1、B1和C1组活性氧水平明显降低(P<0.01)。结论硒能够通过抗氧化应激作用抑制HNE和Aβ诱导的神经细胞凋亡。     

生物人工肝用C3A细胞在零下非结冰时的保存

目的:探讨零下非结冰保存肝细胞的效果及其与细胞凋亡的关系.方法:UW液保存的C3A细胞悬液分为3组:-0.8℃组(零下非结冰组),0℃组(0℃非结冰组),4℃组(对照组).低温保存24、48及72 h后,采用流式细胞术分别测定细胞存活率及凋亡率,同时测定LDH、乳酸释放,细胞内ATP含量、尿素合成功能及白蛋白分泌功能,同时观察细胞形态.结果:零下非结冰组较0℃非结冰组及对照组明显提高了低温保存72 h的C3A细胞的存活率(86.49%±2.80%vs 81.50%±2.83%.77.83%±3.40%,均P<0.05),降低了细胞凋亡率(1.26%±0.84%vs 5.34%±1.20%,9.16%±1.99%,均P<0.05);明显抑制了低温保存72 h乳酸以及LDH释放(乳酸:10.38μg/106 Cells±1.40 μg/106 cells vs 12.02 μg/106cells±1.64μg/106 cells,17.41μg/10°cells±2.40μg/106cells:LDH:80.10 U/L±11.10 U/L vs 12004U/L±14.32 U/L,148.98 U/L±15.37 U/L,均P<0.05);更好地维持了低温保存72 h C3A细胞内ATP含量、尿素合成功能、及白蛋白分泌功能(均P<0.05).形态上,零下非结冰组保存细胞死亡比例少,细胞接触良好,未见对照组及0℃非结冰组细胞膜周围出现"毛刺"样改变及细胞内的"空泡样"改变.结论:在零下非结冰条件下保存肝细胞,建立一个"血库样"(ready to use)肝细胞库,可以有效促进生物人工肝的发展.     

维持性血液透析患者外周血单个核细胞核因子κB活性与微炎症、氧化应激状态及心血管疾病的关系

目的:探讨维持性血液透析(MHD)患者外周血单个核细胞(PBMC)核因子κB (NF-κB)活性与微炎症、氧化应激状态及心血管疾病(CVD)的关系. 方法:选取MHD治疗3个月以上的患者(32例),以体检健康者(12例)为对照组.采用ELISA法检测受试者PBMC的NF-κB活性,比色法检测血清总抗氧化能力(TAOC)及丙二醛(MDA).Pearson相关和线性回归分析PBMC的NF-κB活性与其他指标的相关性.二分类Logistic回归分析NF-κB活性与CVD的关系. 结果:MHD患者PBMC的NF-κB活性[(1 142.4±413.0)ng/mg核蛋白vs(208.3±39.5) ng/mg核蛋白,P＜0.05]、血清高敏C反应蛋白(hsCRP)(3.2 mg/L vs0.5 mg/L,P＜0.05)、TAOC[ (21.9±6.6)U/ml vs (15.7±2.3)U/ml,P＜0.05]和MDA[ (6.80±0.86) nmol/ml vs (3.89±0.51) nmol/ml,P＜0.05]皆显著高于对照组.单次HD后MHD患者PBMC的NF-κB活性显著升高[(2 076.5±690.1)ng/mg核蛋白vs(1 142.2 ±413.0)ng/mg核蛋白,P＜0.05],TAOC显著降低[(13.6±5.0) U/ml vs(21.9±6.6)U/ml,P＜0.05].Pearson相关分析显示PBMC的NF-κB活性与白细胞计数(r=0.454,P＜0.05)、血清hsCRP(r =0.590,P＜0.05)及MDA(r=0.390,P＜0.05)呈正相关.线性回归分析显示白细胞计数(β=0.338,P＜0.05)、血清hsCRP(β =0.440,P＜0.05)及MDA(β=0.319,P＜0.05)皆与PBMC的NF-κB活性独立相关.Logistic回归分析显示PBMC的NF-κB活性升高(＞1 170.0 ng/mg核蛋白)是CVD的独立危险因素(OR=8.47,P＜0.05). 结论:MHD患者PBMC的NF-κB活性显著升高,且与微炎症、氧化应激状态及CVD相关,可作为患者的炎症标志物.     

DC-exosomes联合顺铂对人胶质瘤U251细胞增殖和凋亡的影响

目的观察利用人树突细胞(DC)制备的治疗性疫苗DC-exosomes联合顺铂对人脑胶质瘤U251细胞增殖与凋亡的影响。方法将传代的U251细胞随机分为四组,A组加常规培养液,B、C、D组分别加DC-exosomes激活的淋巴细胞(2×106/mL)0.5 mL、顺铂(1 mg/mL)0.01 mL、DC-exosomes激活淋巴细胞(2×106/mL)0.5 mL+顺铂(1 mg/mL)0.01 mL培养2 d;用MTT法检测U251细胞光密度值(OD值)观察细胞增殖情况,用流式细胞仪检测U251细胞凋亡率。结果加入MTT培养12、24、36、48、60 h,A组细胞OD值分别为1.38±0.01、1.36±0.02、1.34±0.03、1.32±0.05、1.30±0.03,B组分别为1.30±0.02、1.10±0.03、0.90±0.04、0.75±0.03、0.62±0.03,C组分别为1.00±0.04、0.80±0.02、0.55±0.04、0.30±0.03、0.15±0.04,D组分别为0.75±0.04、0.50±0.04、0.38±0.02、0.21±0.02、0.05±0.03;B、C、D组与A组比较,P均<0.05;D组与B、C组比较,P均<0.05。培养24 h时,A、B、C、D组细胞凋亡率分别为0.5%±0.3%、18.6%±1.7%、36.9%±4.3%、57.5%±2.1%。B、C、D组与A组比较,P均<0.05;D组与B、C组比较,P均<0.05。结论 DC-exosomes疫苗联合顺铂可抑制人脑胶质瘤U251细胞增殖,并诱导其凋亡。     

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.     

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.     

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.     

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     

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。     

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。