重组抗肿瘤坏死因子-α人鼠嵌合单克隆抗体对类风湿关节炎患者的疗效及其Th细胞亚群的影响

目的 研究重组抗肿瘤坏死因子-α(TNF-α)人鼠嵌合单克隆抗体(anti-TNF rcMAb)对类风湿关节炎(RA)患者治疗效果及对患者外周血Th1、Th17、调节性T细胞影响.方法 50例经严格筛选的RA患者按随机分配原则分为2组.联合治疗组(40例),给予anti-TNF rcMAb(3 mg/kg)+甲氨蝶呤治疗;对照组(10例)单独接受甲氨蝶呤治疗,分别于0、2、6、14周给药,于0、18周分别观察联合治疗组与对照组的相关临床指标的变化,在相应观察点做ACR20、50、70评分.同时,对比外周血中Th1、Th17、调节性T细胞的表达情况及相关转录因子T-bet、维甲酸相关孤核受体(ROR)C、叉头状转录因子3(Foxp3)的mRNA表达水平变化.采用t检验和x2检验或Ridit作统计学分析.结果 治疗前后,联合治疗组ACR20、50、70较对照组均有所改善,尤其ACR20改善程度与对照组相比,差异有统计学意义(Z=1.671,P=0.000 94).联合治疗组患者外周血Th17细胞无显著变化[(0周(1.1±0.6)％;18周(1.1±0.3)％]、Th1细胞比例降低[0周(7.1±3.9)％;18周(4.2±2.8)％],调节性T细胞比例明显升高[0周(91.5±0.8)％;18周(3.0±0.6)％,t=2.301,P=0.048];对照组Th1比例下降[0周(9.1±3.1)％;18周(5.8±2.6)％],调节性T细胞比例略升高[0周(1.2±0.6％);18周(2.2±0.6)％].2组Th17、Th1细胞的转录因子RORC、T-bet mRNA表达水平降低,调节性T细胞转录因子Foxp3的表达水平均升高.结论 anti-TNF rcMAb联合甲氨蝶呤治疗对RA患者疗效显著,可能通过影响患者外周血Th细胞亚群发挥其治疗作用.     

类风湿关节炎患者外周血Th17细胞/调节性T细胞变化及其临床意义

目的 通过检测类风湿关节炎(RA)患者外周血,Th17细胞和调节性T细胞的变化,探讨其在RA发病机制中的作用及其临床意义.方法 采用流式细胞术(FCM)检测57例RA患者和32名健康对照者外周血单个核细胞(PBMCs)中IL-17+CD4+T细胞(Th17细胞)与Foxp3+CD25+CD4+T细胞(调节性T细胞)占CD4+T细胞的百分比,分析其与RA临床及实验室指标的关系.统计学处理采用t检验和方差分析,相关分析采用Pearson直线相关分析.结果 RA组Th17细胞占CD4+T细胞的百分率较健康对照组明显升高[(4.2±2.2)%和(2.3±1.4)%,P=0.000],调节性T细胞降低[(3.9±1.6)%和(7.0±2.2)%,P=0.000],Th17细胞/涮节性T细胞比值显著升高(1.15±0.62和O.34±0.17,P=0.000).RA早期组与非早期组外周血Thl7细胞、调节性T细胞及,Th17调节性T细胞比值比较,差异无统计学意义(P均>0.05).相关性分析显示RA患者Th17细胞及Th17细胞/调节性T细胞比值与关节压痛数、患者疼痛模拟视觉评分(VAS)、RA28关节疾病活动评分(DAS)28评分等病情活动指标呈正相关(P均<0.05),而调节性T细胞与上述病情活动指标无明显相关性(P均>0.05).单因素回归分析显示Th17细胞、Th17细胞/调节性T细胞比值、DAS28评分及病程对RA患者骨侵蚀有显著影响(P均<0.05).经抗风湿药物治疗后,RA患者Th17细胞阙节性T细胞比值降低.结论 RA患者Th17细胞明显增多,调节性T细胞减少,Th17细胞/调节性T细胞比例明显增高.可能是RA发病的重要原因,通过抗风湿药物治疗可调节Th17细胞/调节性T细胞亚群平衡.

Abstract：

Objective To analyze the level of Th17 and Treg cells in the peripheral blood of patients with rheumatoid arthritis(RA),and to investigate its role in the pathogenesis of RA and the clinical significance.Methods Flow cytometry(FCM)was used to analyze the ratio of interleukin(IL)-17+CD4+T (Thl7)cells and Foxp3+CD25+CD4+T(Treg)cells in CD4+T cells from the peripheral blood of 57 RA patients and 32 normal controls.T-test and Chi-square test were used for inter-group comparison and Pearson's linear analysis was used for correlation analysis.Resuits Compared with normal controls.the level of both IL-17+CD4+T cells and the ratio of Th17/Treg in RA patients increased significantly.while the level of Foxp3+CD4+CD25+T cells decreased markedly[(4.2±2.2)%vs(2.3±1.4)%,P=0.000;1.15±0.62 I)5 0.34±0.17,P=0.000;(3.9±1.6)%vs(7.0±2.2)%,P=0.000].Compared with early RA(persistent for 2 years or less)patients,the levels of Th17,Treg and the ratio of Th17/Treg in chronic RA(duration for more than 2 years)patients didn't markedly changed(P>0.05).The level of Th17 cells and the ratio of Th17/Treg was directlycorrelated with disease activity parameter (including tender ioint counts,visual analog seale of patients,disease activitv score in 28 joints,etc).Regression analysis discovered that risk factors of bone erosion were the level of Th17 cells,the ratio of Th17/Treg,disease activity score in 28 joints and disease duration.Antirheumatic drugs could decreascthe ratio of Th 17/Treg.Conclusions Treg cells is decreased in RA patients while Th7 cells is increased in patients with RA.Th17/Treg ratio goes up significantly as well.Change of T celt subsets,especially Th17 and Treg cells are important for the pathogenesis of RA.Th17 and Treg cells could aggrevate disease activity and bone destruction throughout the whole disease process.Anti-rheumatic medications is effective by regulating Th17/Treg subset balance.     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对类风湿关节炎患者外周血CD4+CD25+调节性T细胞亚群的调节作用

目的 观察活动期类风湿关节炎(RA)患者外周血CD4+D25+FOXP3+调节性T细胞数量和比例的变化,探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(TNFRⅡ-Fc)对调节性T细胞亚群的调节作用.方法 ①选择40例活动期中重度RA患者,按随机、双盲、平行、安慰剂对照的原则分为TNFR Ⅱ-Fc+甲氨蝶呤联合治疗组和甲氨蝶呤对照治疗组,共治疗12周,采用流式细胞术分析并比较2组患者治疗前后外周血CD4+CD25+ FOXP3+调节性T细胞的表达比例,并同期选择40名健康体检者作平行比较.②比较2组患者治疗不同时期疼痛视觉模拟评分法(VAS)、28个关节疾病活动指数(DAS28)、健康评估问卷(HAQ)平均分.计量资料组间比较采用配对t检验.结果 ①活动期RA患者外周血CD4+CD25+FOXP3+细胞比例显著低于健康对照组[(5.4±1.4)％与(7.5±1.5)％,P＜0.01 ];TNFRⅡ-Fc+甲氨蝶呤联合治疗12周后,CD4+CD25+ FOXP3+细胞比例显著高于治疗前[(7.0±1.2)％与(5.2±1.6)％,P＜0.01].联合治疗组CD4+CD25TOXP3+细胞比例增高的幅度显著高于甲氨蝶呤治疗组[(7.0±1.2)％与( 5.6±0.7)％,P＜0.01].②治疗12周后,联合治疗组VAS评分、DAS28评分、HAQ平均分均优于甲氨蝶呤组,差异有统计学意义(P＜0.01).结论 TNFRⅡ-Fc联合甲氨蝶呤治疗的疗效优于单纯甲氨蝶呤治疗,TNFRⅡ-Fc可提高活动期RA患者血中CD4+CD25+调节性T细胞比例,可能是其治疗RA的一个重要机制.     

类风湿关节炎患者外周血辅助性T细胞9及白细胞介素-9的变化及临床意义

目的 观察类风湿关节炎(RA)患者外周血中辅助性T细胞9(Th9)及血清中白细胞介素(IL)-9的变化,探讨其与RA临床表现的相关性及其可能的免疫学发病机制.方法 收集36例RA患者和22名健康对照者,RA患者根据病情活动度不同分为病情重度活动组22例、病情中度活动组14例.流式细胞仪检测患者和健康对照者外周血中Th9细胞的变化;酶联免疫吸附试验(ELISA)检测RA患者及健康对照者血浆中IL-9等细胞因子的水平.采用t检验、Spearman相关分析进行统计学分析.结果 RA患者外周血中Th9比例显著高于健康对照组[分别为(0.99±0.50)％,(0.21±0.08)％,P＜0.01];RA患者重度活动组的Th9表达率显著高于中度活动组[分别为(1.18±0.52)％,(0.69±0.25)％,P＜0.01].RA患者外周血IL-9水平高于健康对照[分别为(1.06±0.42) pg/ml,(0.69±0.13) pg/ml,P＜0.01],重度活动组的RA患者IL-9水平[( 1.37±0.47) pg/ml]高于中度活动组[(0.94±0.30) pg/ml],差异有统计学意义(P＜0.05).RA患者外周血Th9的表达与疾病活动指数(DAS )28、红细胞沉降率(ESR)、C反应蛋白(CRP)、关节压痛数、关节肿胀数及类风湿因子(RF)滴度、IL-9的水平呈正相关;RA患者IL-9的水平与DAS28、ESR、关节压痛数、关节肿胀数呈正相关.结论 RA患者外周血Th9细胞比例及血浆中IL-9水平显著升高,且与疾病活动度及相关炎症指标明显相关,提示Th9及IL-9参与RA的发病及病情发展.     

重组人细胞毒T淋巴细胞相关抗原4抗体融合蛋白对类风湿关节炎患者外周血T淋巴细胞的影响

目的 探讨应用重组人细胞毒T淋巴细胞相关抗原(CTLA)-4抗体融合蛋白(rhCTLA-41g)治疗类风湿关节炎(RA)患者的临床疗效及对患者外周血辅助性T细胞17(Th17)和调节性T细胞的影响.方法 48例处于活动期的RA患者按1:1的比例随机分为治疗组和对照组,治疗组接受12周的rhCTLA-4Ig(10mg/kg)治疗;对照组接受12周的安慰剂治疗.以美国风湿病学会RA20％改善标准(ACR20)及疾病活动指数(DAS)28观察临床疗效;同时用流式细胞术检测受试者外周血Th17的变化,反转录聚合酶链反应(RT-PCR)检测外周血单个核细胞中FoxP3表达水平的变化.采用t检验和x2检验进行统计学分析.结果 ①治疗后12周治疗组24例中18例达ACR20改善,达ACR20改善的患者比例为75％,对照组中有1例(4％)达ACR20改善,2组差异有统计学意义(x2=25.176,P＜0.01);治疗后12周DAS28评分治疗组与对照组比较差异有统计学意义(分别为3.0±0.7,6.9±0.7,t=-12.39,P＜0.01).②治疗后治疗组RA患者外周血表达IL17A的单个核细胞为(0.22±0.20)％,对照组为(1.63±0.47)％,治疗组较对照组显著下降,差异有统计学意义(t=5.61,P＜0.05).③治疗组FoxP3 mRNA的表达(0.88±0.18)较对照组(0.24±0.05)明显增高,差异有统计学意义(t=7.56,P＜0.01).结论 rhCTLA-4Ig治疗RA临床表现和实验室指标明显改善,且外周血中TH17细胞及调节性T细胞的失衡程度有明显恢复.     

类风湿关节炎患者外周血白细胞介素1受体相关激酶1与疾病活动及CD4+T细胞亚群分析

目的探索RA患者外周血白细胞介素1受体相关激酶1(IRAK1)的表达, 并分析其与疾病活动及CD4+ T细胞亚群的相关性。方法①采用ELISA检测77例RA组患者和24名健康对照组外周血中IRAK1的活性表达量;②收集RA患者的一般资料及临床观察指标(包括DAS28评分、ESR、CRP、外周血CD4+ T细胞亚群等);③采用独立样本t检验或Mann-whitneyU检验进行两组间的比较;采用Spearman秩相关及多元线性回归分析IRAK1的表达水平与各临床观察指标的相关性。结果① RA组外周血IRAK1的表达相比于健康对照组显著升高(P<0.001)。② RA组外周血CD4+ T细胞亚群, 较健康对照组相比, 调节性T细胞(Treg)绝对值、Treg%均降低(P<0.001), 辅助性T细胞17(Th17)绝对值、Th17%、Th17/Treg比值均升高(P<0.001), 且Th1/Th2比值明显升高(P<0.05)。③随着RA患者疾病活动度的增加, IRAK1的活性表达量也增加, RA组外周血IRAK1的表达与ESR、受累关节的个数、DAS28评分呈正相关...     

活动性类风湿关节炎调节性T细胞程序性细胞死亡蛋白-1/程序性死亡配体1表达及与临床指标的相关性

目的探讨程序性细胞死亡蛋白-1/程序性死亡配体1(PD-1/PD-L1)在活动性类风湿关节炎(rheumatoid arthritis,RA)患者外周血调节性T细胞表面表达变化及临床意义。方法用流式细胞术分别检测62例活动期RA患者外周血CD4~+CD25~+T细胞和CD4~+CD25~-T细胞群PD-1和PD-L1的阳性率,并设立39例健康体检者作为健康对照组,分析PD-1/PD-L1与实验室各指标和病情活动性的相关性。结果 PD-1在24例高度活动组和38例中低度活动组RA患者CD4~+CD25~+T细胞的表达水平分别为[(2.27±0.56)%和(1.83±1.08)%],高于健康对照组(1.42±0.49)%,差异有统计学意义(P0.01)。PD-L1在高度活动组和中低度活动组RA患者CD4~+CD25~+T细胞的表达水平分别为[(2.06±0.62)%和(1.83±0.63)%],亦高于健康对照组(0.80±0.43)%,与对照组相比差异有统计学意义(P0.001)。PD-1在CD4~+CD25~+T细胞表达水平与DAS28呈正相关(r=0.477,P0.01),PD-L1在CD4~+CD25~-T细胞表达水平与DAS28无相关性(r=0.078,P=0.549)。结论 PD-1/PD-L1在活动性RA患者调节性T细胞表达存在差异,其与DAS28相关性提示PD-1/PD-L1信号通路可经调节性T细胞调控参与RA的发生。     

肿瘤坏死因子-α拮抗剂对类风湿关节炎和强直性脊柱炎患者血清白细胞介素-17和外周血 Th17细胞比例的影响

目的初步探讨外周血 Th17细胞亚群的比例以及 IL-17的表达水平在 RA 和 AS 患者接受 TNF-α拮抗剂治疗前后的改变及其意义。方法选择 RA 患者27例和 AS 患者22例,2种疾病中各有14例患者接受 TNF-α拮抗剂治疗40周。对照组24名来源于健康献血者。采用流式细胞术检测外周血 CD4+T 细胞中 Th17细胞亚群的比例,ELISA 检测外周血 IL-17表达水平。符合正态分布数据采用2个独立样本 t 检验,不符合正态分布则采用 Wilcoxon 秩和检验,患者治疗前后的比较采用配对 t 检验。结果治疗前,RA 和 AS 患者外周血 CD4+ T 细胞中 Th17细胞亚群的比例显著高于健康对照组[RA 1.03%（0.66%,1.78%）与健康对照0.50%（0.43%,0.67%）,Z=-3.236,P<0.01;AS（1.16±0.09）%与健康对照（0.59±0.06）%,t=5.226,P<0.01]。同样,IL-17的表达水平在2组疾病中也显著升高[RA（32.3±2.5） pg/ml,健康对照（14.3±2.5） pg/ml,t=5.070,P<0.01;AS 28.98（23.84,36.14） pg/ml,健康对照11.84（5.33,22.12） pg/ml,Z=-4.103,P<0.01]。 TNF-α拮抗剂治疗后,2组疾病 CD4+T 细胞中 Th17细胞亚群比例无明显变化[RA 驻（0.1045±0.2126）%;AS 驻（0.0025±0.1838）%],但 IL-17表达水平则明显下降[RA 驻（-13.5±5.0） pg/ml;AS 驻（-16.0±1.9） pg/ml]。结论 Th17细胞及其分泌的细胞因子 IL-17在 RA 和 AS 的发病机制中起重要作用,TNF-α拮抗剂对 AS 和 RA 患者 Th17细胞亚群炎症细胞因子的分泌功能有明显的抑制作用,但40周的治疗仍不能降低 Th17细胞比例,这可能是 TNF-α拮抗剂短期治疗后疾病复发的原因之一。     

急性病毒性心肌炎患者Th17细胞作用初步研究

目的:初步探讨急性病毒性心肌炎患者辅助性T细胞(T help,Th)17细胞在其发病中的作用.方法:选择2008年3-11月在我院住院的急性病毒性心肌炎(AVMC)患者13例、扩张型心肌病(DCM)患者18例,采用ELISA法分别检测其外周血Th17细胞分泌的细胞因子白细胞介素(IL)-17和抗心肌抗体(AHA)的表达、三色流式细胞术检测CD4+T细胞中Th17/Th1/Th2细胞亚群的比例、实时定量PCR法检测B细胞表面IL-17R基因水平,同时选取16例健康人为对照(对照组)结果:AVMC和DCM患者Th1细胞亚群[(10.7±1.4)%、(5.2±1.1)%]、B细胞总数[(21.8±2.1)%、(16.4±1.6)%]及其IL-17R mRNA表达水平(132.4±12、37.5±6.4)较对照组[(3.1±0.8)%,(10.9±1.5)%,16.6±5.7]均有升高,但以AVMC患者更为明显(均P<0.01),且AVMC患者外周血IL-17和Th17细胞亚群也有显著增高[89.2±11.6,(5.5±2.1)%],Th2细胞无明显变化,AHA阳性率为12/13(92.3%);而DCM患者Th2细胞[(6.0±3.2)%]增多超过Th1细胞,IL-17含量和Th17细胞比例与对照组相比差异均无统计学意义,AHA阳性率为10/18(55.6%),表达水平也低于AVMC组.对照组AHA检测均为阴性.结论:Th17细胞可能在AVMC急性炎症和B细胞产生AHA方面均有重要作用.     

抗病毒治疗对慢性丙型肝炎患者Treg/Th17细胞比例变化的影响

目的 了解抗病毒治疗对慢性丙型肝炎患者调节性T细胞(Treg) /Th17细胞比例变化的影响.方法 32例慢性丙型肝炎患者进行聚乙二醇干扰素α-2a联合利巴韦林治疗,20例健康人作为对照.在抗病毒治疗前和随访24周时,采用流式细胞仪检测患者外周血Treg和Th17细胞频率,ELISA法检测患者IL-17的水平,观察Treg/Th17细胞比例变化与患者获得持续性病毒学应答(SVR)的关系.统计学处理采用t检验.结果 抗病毒治疗前患者外周血中Th 17、Treg细胞频率和Treg/Th17比例明显高于对照组[(4.58±0.86)％与(2.48±0.60)％,t=2.399,P＜0.05;(8.58±2.20)％与(4.70±1.30)％,t=7.990,P＜0.01;(1.82±0.40)与(1.60±0.35),t=2.088,P＜0.05].抗病毒治疗后Th 17、Treg细胞频率和Treg/Th17比例分别为(5.35±0.79)％、(6.46±1.29)％、(1.25±0.21).获得SVR患者Th17细胞频率为(6.27±1.15)％,明显高于未获得SVR的(4.05±0.82)％(t=10.103,P＜0.01).获得SVR患者Treg细胞频率和Treg/Th17比例为(4.90±1.39)％、(0.80±0.15),明显低于未获得SVR的(7.42±1.95)％、(1.83±0.42)(t=5.718,8.752,P＜0.01).获得SVR患者IL-17水平为(143.5±31.2)pg/mL,明显高于未获得SVR患者组的(121.4±30.1 )pg/mL(t=2.028,P＜0.05).结论 慢性丙型肝炎患者Treg/Th 17细胞比例高于对照组,抗病毒治疗后Treg/Th17细胞比例下降,获得SVR患者下降更为明显.     

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。