雷帕霉素对急性肝功能衰竭大鼠Toll样受体-4表达的影响

目的 探讨雷帕霉素抑制Janus激酶/信号转导和转录激活子(JAK/STAT)通路对急性肝功能衰竭大鼠Toll样受体(TLR)-4基因表达的影响.方法采用腹腔注射D-氨基半乳糖(D-GalN)800 mg/kg和脂多糖(LPS)8 μg/只,建立急性肝功能衰竭大鼠模型,分别在注射D-GalN和LPS后2、6、12、24、48 h 5个时间点留取大鼠血及肝脏标本.SD大鼠分为对照组(n=6)、急性肝功能衰竭模型组(n=30)、STAT抑制剂雷帕霉素(RPM)干预组(n=30),在各不同时间点检测ALT、AST.ELISA法检测血清TNF-α、IL-6水平,RT-PCR法检测大鼠肝组织TLR-4 mRNA表达.数据行t检验.结果急性肝功能衰竭组大鼠在造模后2 h TNF-α、IL-6水平均显著升高,6 h达峰值,RPM可明显抑制TNF-α、IL-6水平.急性肝功能衰竭组大鼠6、12、24、48 h肝组织中TLR-4 mRNA分别为0.745±0.135、1.092±0.175、1.115±0.152和0.812±0.130,RPM干预后分别为0.545±0.118、0.798±0.124、0.857±0.109和0.595±0.152,各时间点两组比较,差异均有统计学意义(t值分别为2.726、3.349、3.382和2.567,均P＜0.05).TLR-4 mRNA表达与ALT、AST均呈正相关(r值分别为0.722、0.712,均P＜0.01).结论抑制JAK/STAT通路可明显下调急性肝功能衰竭大鼠肝组织TLR-4表达,JAK/STAT通路可能参与急性肝功能衰竭过程中TLR-4mRNA表达的调控.     

慢性乙型肝炎患者高迁移率族蛋白1mRNA的表达及其临床意义

目的:通过检测慢性乙型肝炎患者外周血单个核细胞(PBMCs)高迁移率族蛋白1(HMGB1) mRNA的表达情况,研究HMGB1在乙型肝炎中的临床意义．方法:应用逆转录聚合酶链反应(RT-PCR) 对54例慢性乙型肝炎患者和10例健康对照者PBMCs HMGB1 mRNA的表达进行检测, 同时应用ELISA法检测外周血浆肿瘤坏死因子α(TNF-α)和内毒素(LPS)水平,比较各组HMGB1 mRNA表达水平的差异及其与 TNF-α、LPS、总胆红素(TBIL)、凝血酶原活动度(PTA)的关系．结果:PBMCs HMGB1 mRNA的表达水平在慢性重型肝炎组分别高于慢性肝炎组(0．89± 0．06 vs 0．70±0．10,P<0．01)和正常对照组 (0．89±0．06 vs 0．58±0．08,P<0．01),慢性肝炎组高于正常对照组(0．70±0．10 vs 0．58±0．08． P<0．01)．在23例慢性重型肝炎患者中,11例未恢复患者PBMCs HMGB1 mRNA表达水平明显高于12例恢复的患者(0．93±0．04 vs 0．85± 0．05,P<0．01)．其中12例已恢复的慢性重型肝炎患者,患者恢复期PBMCs HMGB1 mRNA 的表达水平较发病期明显下降(0．72±0．07 vs 0．85±0．05,P<0．01)．HMGB1 mRNA表达水平与外周血浆LPS、TNF-α及TBIL均呈显著正相关(r=0．74,0．64,0．71,均P<0．01),与PTA呈负相关(r=-0．82．P<0．01)．结论:HMGB1在乙型肝炎发病过程中可能起重要作用,HMGB1 mRNA的表达水平高低与病情轻重密切相关．     

雨蛙素诱导的急性胰腺炎体外细胞模型的信号转导通路研究

目的 观察急性胰腺炎(AP)体外细胞模型Janus激酶/信号转导和转录激活子(JAK/STAT)信号转导通路及细胞因子表达的变化,探讨其机制.方法 应用雨蛙素处理大鼠胰腺外分泌细胞株AR42J细胞建立AP体外模型,再用雷帕霉素(RPM)及AG490干预.采用Western blotting检测细胞JAK1、磷酸化JAK1(P-JAK1)、STAT1、P-STAT1及TNF-α、IL-1β、IL-6蛋白表达水平;RT-PCR检测TNF-α、IL-1β、IL-6 mRNA表达;台盼蓝染色测定细胞存活率.结果 未经雨蛙素处理的AR42J细胞的JAK1、P-JAK1、STAT1、P-STAT1及TNF-α、IL-1β、IL-6蛋白的相对表达量分别为0.09±0.04、0.14±0.08、0.21±0.09、0.12±0.12、0.10±0.02、0.08±0.03、0.02±0.02.雨蛙素处理后,AR42J细胞上述蛋白的表达呈时间依赖性增加,24 h时的表达量分别为0.53±0.09、0.53±0.13、0.56±0.09、0.55±0.10、0.25±0.04、0.25±0.09、0.27±0.07,均较雨蛙素未处理组显著增加(P＜0.05).再分别应用RPM和AG490抑制24 h后,细胞TNF-α、IL-1β、IL-6蛋白表达量显著降低到0.17±0.03和0.17±0.01、0.15±0.05和0.14±0.07、0.19±0.04和0.19±0.05,它们的mRNA表达量也显著降低(P值均＜0.05);RPM和AG490抑制组的细胞存活率分别为(72.4±11.2)%、(69.7±9.8)%,均显著高于单用雨蛙素处理细胞组的(42.2±12.3)%(P＜0.05).结论 JAK1/STAT1信号通路早期参与雨蛙素诱导的AP细胞促炎症细胞因子释放.早期抑制JAK1/STAT1信号通路有利于控制AP的炎症反应.     

STAT1/SOCS1在高迁移率族蛋白1诱导的大鼠滑膜细胞中的表达

目的 探讨高迁移率族蛋白(HMGB)1对滑膜细胞增殖的影响及机制.方法 ①常规培养的滑膜细胞,随机分为正常对照组和肿瘤坏死因子(TNF)-α组,培养6、12 h和24 h,反转录-聚合酶链反应(RT-PCR)免疫细胞化学法(ICC)检测HMGBI mRNA及蛋白在滑膜细胞中的表达变化;②常规培养的滑膜细胞,随机分为正常对照组、HMGB1组,分别培养6、12 h和24 h,RT-PCR检测磷酸化信号转导和转录激活因子(p-STAT1)mRNA表达;ICC和流式细胞术(FCM)检测p-STAT1、细胞激酶信号抑制剂(SOCSl)蛋白的表达;ICC检测PCNA蛋白的表达.结果 ①TNF-α刺激6、12、24 h显著上调HMGB1mRNA的表达[0.86,0.92,1.06 vs 0.70,P<0.01];其蛋白表达亦增强,HMGB1蛋白不仅表达于细胞核,而且出现于胞质中;② HMGB1作用6、12、24 h显著增强STAT1 mRNA及蛋白的表达量[0.30,0.69,1.05 vs 0.24,P<0.01]及[1.34±0.09,1.55±0.16,1.74±0.13 vs 1.00±0.15,P<0.01];SOCS1蛋白量分别为1.43±0.10、1.58±0.05和1.24±0.15,呈先升高后下降.③ p-STAT1与SOCS1蛋白表达呈负相关(r=-0.484,P=0.04).结论 HMGB1是滑膜细胞增殖过程中的重要细胞因子,其可能通过上调STAT1的表达和活性,促进细胞增殖.     

银杏叶提取物抗大鼠肝纤维化中激活素A和肝细胞凋亡的作用

目的：观察银杏叶提取物(GBE)对大鼠肝纤维化的防治效果及其机制．方法：♂SD大鼠30只随机分为3组：正常对照组(n=10)、模型组(n=10)及GBE干预组(n= 10),模型组及GBE干预组给予500 mL/L CCl_4 ip,1 mL/kg,每周2次,共8 wk,干预组每天同时给予GBE灌胃,0．4 g/kg．实验结束后,心脏取血分离血清行肝功能生化指标检测,处死动物取肝脏液氮冻存及甲醛固定,常规行HE染色,免疫组化检测Activin A,RT-PCR检测Activin A mRNA的表达,TUNEL法检测肝细胞凋亡．结果：光镜下组织学检查纤维化分级GBE干预组低于模型组(P＜0．05),肝功能生化指标检测GBE干预组优于模型组(分别为ALT：2806．9±576．1 nkat/L vs 4452．9±709．5 nkat/L：AST：5314．2±1042 nkat/L vs 15 743．4±625．8 nkat/ L；ALB：31．0±2．1 g/L vs 21．7±1．8 g/L；P均＜0．05),免疫组化和RT-PCR检测Activin A的表达GBE干预组低于模型组(免疫组化：4．2±0．8 vs 11．4±1．2；RT-PCR：0．42±0．09 vs 0．78±0．15：P均＜0．01),凋亡指数(AI)GBE干预组低于模型组(7．56±3．36 vs 16．06±8．84,P＜0．01)．结论：GBE对CCl_4诱导的大鼠肝纤维化有良好的防治作用,其作用机制可能与肝组织Activin A表达降低及肝细胞凋亡减少有关．     

姜黄素对大鼠脑缺血后Janus蛋白酪氨酸激酶2信号转导和转录激活子3信号通路的影响

目的探讨姜黄素对大鼠脑缺血损伤后Janus蛋白酪氨酸激酶2(JAK2)/信号转导和转录激活子3(STAT3)信号通路的影响。方法将68只SD大鼠随机分为假手术组、脑缺血组、姜黄素组(尾静脉注射姜黄素40mg/kg)和对照组(注射等量生理盐水),每组17只,后3组建立大鼠局灶性脑缺血模型,观察各组大鼠神经行为学变化,ELISA检测大鼠脑组织TNF-α、白细胞介素(IL)-1β、IL-6表达,Western blot检测大鼠脑组织JAK2、磷酸化JAK2(p-JAK2)、STAT3、磷酸化STAT3(p-STAT3)、高迁移率族蛋白1(HMGB1)表达。结果与脑缺血组比较,姜黄素组大鼠神经行为学评分减低[(1.53±0.62)分vs(2.94±0.87)分,P0.05];与脑缺血组比较,对照组TNF-α、IL-1β和IL-6无明显变化(P0.05),姜黄素组大鼠TNF-α[(57.63±10.27)ng/L vs(99.35±8.97)ng/L]、IL-1β[(33.67±9.10)ng/L vs(58.43±7.22)ng/L]和IL-6[(31.97±6.91)ng/L vs(49.23±6.28)ng/L]表达降低(P0.01),p-JAK2/JAK2、p-STAT3/STAT3相对含量及HMGB1表达降低(P0.05,P0.01)。结论姜黄素可保护大鼠缺血后脑损伤,其机制可能是通过抑制JAK2/STAT3信号通路,减少HMGB1表达,减轻炎性反应。     

腹腔注射左旋精氨酸诱导急性坏死性胰腺炎大鼠模型

目的:通过大剂量左旋精氨酸(1-arginine) ip诱导大鼠急性胰腺炎(acute necrotizing pancreatitis,ANP)模式,探讨此模型制备的方法和机制．方法:将60只SD大鼠随机分为正常对照组(C组,n=24),ANP模型组(A组,n=36)．C组接受生理盐水对照;A组用60 g/L左旋精氨酸分3次ip建立ANP模型．分别观察两组大体病理变化、光镜下病理评分、血清淀粉酶水平．结果:1-arginine ip后24 h可观察到集中于小叶边缘区的大片胰腺组织坏死、腺小叶结构消失,A组的病理评分(4 h:4．45±1．33 vs 0．50±0．55．P<0．01;12 h:5．33±1．66 vs 0．67±0．82．P<0．01;24 h:7．89±1．67 vs 0．67±0．82,P<0．01;36 h:8．33±1．12 vs 0．67±0．82, P<0．01)、血清淀粉酶(4 h:8296．16±1028．21 nkat／L vs 6315．10±816．83 nkat／L,P<0．01;12 h: 11 255．92±2565．18 nkat／L vs 5867．84±632．29 nkat／L,P<0．01;24 h:54 424．22±27 125．09 nkat／L vs 6078．05±1070．88 nkat／L．P<0．01; 36 h:28 494．53±12 278．62 nkat／L vs 6286．26±1074．38 nkat／L,P<0．01)各时点都比C组明显升高．结论:采用分3次ip 60 g／L左旋精氨酸方法可成功诱导ANP模型．     

大鼠急性胰腺炎早期肺损伤机制及前列腺素E1的保护作用

目的:探讨实验性急性胰腺炎(acute pancreatitis,AP)合并肺损伤的发生机制及前列腺素E1(PGE1)的保护作用．方法:健康成年SD大鼠78只,随机平均分为假手术组(SO组)、AP组和PGE1组,采用十二指肠闭袢法建立大鼠AP模型．PGE1组制模后即刻经颈静脉持续每分钟输入PGE160 ng／kg．观察胰腺和肺组织的病理组织学改变,测定血清淀粉酶、肺组织中性粒细胞髓过氧化物酶 (MPO)活性、脂质过氧化产物(LPO)水平及肺毛细血管通透性(LCP),免疫组织化学ABC法检测肺组织细胞黏附分子-1(ICAM-1)的表达．结果:制模后12和24 h,AP组大鼠胰腺和肺组织病理损伤持续加重,肺组织MPO(12 h: 5．65±0．80 vs 1．22±0．71 kat／g,P<0．01;24 h: 7．22±1．05 vs 1．48±0．57 kat／g,P<0．01)和 LPO(12 h:1．44±0．63 vs 0.38±0．07μmol／g． P<0．01;24 h:3．64±0．83 vs 0．44±0．15 μmol／ g,P<0．01)水平以及LCP(12 h:145．4±23．0 vs 47．3±5．5 μg／g组织湿重,P<0．01)明显高于SO组,AP组大鼠肺组织ICAM-1表达呈阳性或强阳性,而SO组呈阴性;与AP组比较, PGE1组的胰腺病理损伤虽未减轻,但肺组织 MPO(12 h:2．96±1．04 vs 5．65±0．80 kat／g, P<0．05;24 h:3．68±1．15 vs 7．22±1．05 kat／g, P<0．05)和LPO (12 h:0．86±0.34 vs 1．44± 0．63 μmol／g,P<0．05;24 h:1．69±0．45 vs 3．64 ±0．83 μmol／g,P<0．05)水平以及LCP(12 h: 105．9±23．9 vs 145．4±23．0 μg／g组织湿重, P<0．05)明显降低,ICAM-1表达下调．肺间质出血、水肿和中性粒细胞(PMN)浸润明显减轻．结论:肺组织ICAM-1过度表达、PMN浸润和氧自由基大量释放与AP早期肺损伤的发生关系密切．PGE1通过降低肺组织ICAM-1表达, 抑制PMN活化和氧自由基释放,从而减轻AP 早期肺损伤．     

雷帕霉素在肝脏缺血再灌注损伤中对自噬相关蛋白 ULK1、LC3表达的影响

目的研究雷帕霉素在肝脏缺血再灌注损伤中对自噬相关蛋白ULK1、LC3表达的影响及意义。方法建立3组大鼠肝脏缺血再灌注损伤模型,实验组(n=10)、对照组(n=10)、假手术组(n=10)。分别于术后24、72 h取材:检测血清ALT和AST水平、肝脏病理以及ULK1、LC3 mRNA水平、蛋白水平。计量资料多组间比较采用方差分析,进一步两两比较采用LSD-t检验。结果肝脏缺血再灌注损伤24 h后血清ALT、AST水平升高,肝脏病理结构损伤(F值分别为1531. 83、1799. 97,P值均0. 05),实验组血清ALT[(354. 58±28. 40) U/L vs (556. 15±19. 32) U/L]、AST[(384. 37±8. 98) U/L vs (575. 96±30. 21) U/L]水平较对照组降低(P值均0. 05),肝脏病理结构损伤减轻;术后72 h后实验组血清ALT[(271. 81±8. 63) U/L vs (466. 33±30. 00) U/L]、AST[(358. 92±13. 20) U/L vs (497. 05±40. 14) U/L]水平低于对照组(P值均0. 05)。而术后72 h实验组、对照组血清ALT、AST水平均低于术后24 h(ALT:t=8. 87、7. 92; AST:t=5. 04、5. 34,P值均0. 05)。术后24 h和72 h实验组ULK1、LC3 mRNA水平、蛋白水平较假手术组升高(P值均0. 05),24 h实验组ULK1 mRNA水平(13. 23±6. 58 vs 4. 91±1. 64)、LC3 mRNA水平(7. 82±1. 65vs 3. 70±1. 10)、ULK1蛋白水平(1. 62±0. 19 vs 1. 17±0. 33)、LC3蛋白水平(1. 62±0. 19 vs 0. 84±0. 10)较对照组增加(P值均0. 05); 72 h实验组ULK1 mRNA水平(10. 58±3. 31 vs 4. 83±2. 66)、LC3 mRNA水平(6. 42±1. 13 vs 2. 71±0. 81)、ULK1蛋白水平(1. 29±0. 24 vs 0. 90±0. 29)、LC3蛋白水平(1. 40±0. 73 vs 0. 64±0. 08)较对照组增加(P值均0. 05)。肝脏缺血再灌注损伤72 h后实验组、对照组血清ALT、AST水平较术后24 h降低,并且肝脏病理结构损伤减轻,ULK1、LC3 mRNA水平、蛋白水平降低(P值均0. 05)。结论肝脏缺血再灌注损伤后ULK1、LC3表达增加,雷帕霉素可能在肝脏缺血再灌注损伤过程中通过上调细胞自噬保护肝脏功能。     

重症急性胰腺炎大鼠肺组织中LIF的表达变化及意义

目的:观察重症急性胰腺炎(SAP)大鼠白血病抑制因子(LIF)在肺组织中表达的时相变化, 探讨LIF在SAP病程及肺损伤中的意义．方法:36只♂SD大鼠随机分为正常对照组(N 组,n=6)、假手术组(Sham组,n=6)和重症急性胰腺炎组(SAP组,n=24)．采用胰管逆行灌注50 g/L牛磺胆酸钠的方法复制大鼠SAP模型．用RT-PCR法检测肺组织中LIF mRNA的表达水平,免疫组织化学方法检测NLIF在肺组织中的表达变化．结果:SAP组3 h后肺组织LIF mRNA的表达量明显高于对照组和假手术组(灰度值:1．018± 0．065 vs 1．451±0．067,1．322±0．072,P<0,05), 并且6,12,24 h持续升高(0．853±0．058,0．635 ±0．064,0．582±0．089)(P<0．01)．同样,SAP组 LIF蛋白表达在3和6 h后明显高于对照组和假手术(127．36±2．76,122．53±2．43 vs 159．46 ±2．78,156．35±3．12,P<0．05),并且12,24 h后也维持在很高的水平(109．37±2．87,102．42± 2．27)．结论:LIF作为促炎症因子参与了SAP肺组织的炎症反应．     

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     

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.     

Angiographic diagnosis of the degree of serosal invasion of carcinoma of the colon

Angiography using Prostaglandin El^® was performed on 38 patients with carcinoma of the colon in order to diagnose the degree of serosal cancer invasion. The findings at angiography were classified into four groups:1) AG-S3, abnormal change (irregularity and/or encasement) up to marginal vessels; 2) AG-S2, abnormality up to vasa recta; 3) AG-S1, abnormality of penetrating branches of vasa recta within the wall of the colon; and 4) AG-S0, no distinct findings of abovementioned vessels. These angiographic findings were compared with both macroscopic and microscopic serosal cancer invasion. Angiographic diagnosis is in accord with the macroscopic findings in 84.2 percent of cases. Angiographic diagnosis is in accord with the microscopic findings in 32.4 percent of cases. Macroscopic findings confirm the angiographic diagnosis precisely but the conflict with microscopic findings should not be overlooked. This may be the result of inflammatory change, adhesion, and fibrosis around carcinoma of the colon.     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.