PUMA和BIM表达与结直肠癌浸润转移及预后的关系

目的 研究BH3-only蛋白家族中p53上调凋亡调控因子(PUMA)和与bcl-2相互作用的细胞死亡调解因子(BIM)在结直肠癌组织中的表达及其与结直肠癌侵袭、转移和预后关系.方法 采用免疫组化染色方法(EnVision),检测PUMA和BIM蛋白在30例正常大肠黏膜、30例大肠腺瘤及142例结直肠癌组织中的表达.分析PUMA、BIM蛋白表达与患者临床病理特征、预后及化疗耐药相关蛋白[P-糖蛋白(P-gp)、谷胱甘肽S转移酶-π(GST-π)]的相关性.结果 PUMA蛋白在结直肠癌组织中的阳性表达率为82.4％,低于其在大肠腺瘤和正常大肠黏膜组织中的阳性表达率(均为96.7％)(x2=3.93、3.93,P＜0.05).BIM蛋白在结直肠癌组织中的阳性表达率为62.7％,明显低于其在大肠腺瘤组织中和正常大肠黏膜的阳性表达率(90.0％和96.7％)(x2 =8.42、13.29,P＜0.01).PUMA蛋白与BIM蛋白在结直肠癌组织中的表达呈正相关(r=0.747,P=0.000).PUMA蛋白的表达与肿瘤的分化程度(x2 =11.87)、浸润深度(x2=11.59)、淋巴结转移(x2=12.82)、TNM分期(x2=33.47)以及P-gp表达(x2=18.30)有关(P＜0.05),而与患者的年龄、性别、肿瘤大小、病理组织学类型以及GST-π表达无关(P＞0.05).BIM蛋白的表达与分化程度(x2=16.19)、淋巴结转移(x2=14.95)、TNM分期(x2=52.66)以及P-gp表达(x2 =10.60)有关(P＜0.05),而与患者的年龄、性别、肿瘤大小、浸润深度、病理组织学类型以及GST-π表达无关(P＞0.05).PUMA、BIM阳性表达者的术后1、3、5年生存率明显高于阴性表达者(x2=6.10、27.60,P＜0.05).淋巴结转移(RR=0.238)、TNM分期(RR=7.895)、PUMA(RR=1.691)和BIM蛋白的表达(RR =0.440)可作为结直肠癌独立的预后指标(P＜0.05).结论 PUMA、BIM在结直肠癌中的表达与结直肠癌的侵袭、转移和预后明显相关.PUMA和BIM蛋白表达降低的结直肠癌患者病期晚、预后差.     

Claudin-4及Clusterin在大肠癌组织中的表达及临床意义

目的:研究紧密连接蛋白-4(Claudin-4)和Clusterin在大肠癌组织中的表达及临床意义。方法:采用免疫组织化学方法检测70例大肠癌、25例腺瘤、20例正常大肠黏膜中Claudin-4、Clusterin的表达。结果:Claudin-4在大肠癌组织中的表达(68.6%)明显高于腺瘤组织(40.0%,P0.05),腺瘤组织中的表达明显高于正常大肠黏膜组织(10.0%,P0.05)。Claudin-4的表达与有无淋巴结转移、Dukes分期、浸润深度密切相关(P0.05)。Clusterin在大肠癌组织中的表达(70.0%)明显高于腺瘤组织(44.0%,P0.05),腺瘤组织中的表达明显高于正常大肠黏膜组织(15.0%,P0.05)。Clusterin的表达与肿瘤分化程度、浸润深度、Dukes分期、有无淋巴结转移有关(P0.05)。Claudin-4与Clusterin在大肠癌组织中的表达呈正相关(P0.05)。结论:Claudin-4和Clusterin在大肠癌的发生、发展中起重要作用,可能成为大肠癌新的分子标志物或治疗的新靶点。     

GPRC5A和SOCS3在大肠癌中的表达及临床意义

目的:研究G蛋白偶联受体C家族5A(GPRC5A)和细胞因子信号转导抑制因子-3(SOCS3)在大肠癌中的表达及临床意义。方法:应用免疫组织化学(SP法)检测GPRC5A和SOCS3在45例大肠癌、25例大肠腺瘤及22例正常大肠黏膜组织中的表达。结果:1)GPRC5A在大肠癌组织中的表达(22.2%)明显低于腺瘤组织(52.0%,P0.05),腺瘤组织中的表达明显低于正常大肠黏膜组织(81.8%,P0.05)。GPRC5A的表达与有无淋巴结转移、Dukes分期、浸润深度密切相关(P0.05)。2)SOCS3在大肠癌组织中的表达(24.4%)明显低于腺瘤组织(56.0%,P0.01),腺瘤组织中的表达明显低于正常大肠黏膜组织(86.4%,P0.05)。SOCS3的表达与肿瘤分化程度、浸润深度、Dukes分期、有无淋巴结转移有关(P0.05)。3)GPRC5A与SOCS3在大肠癌组织中的表达呈正相关(r=0.503,P0.05)。结论:GPRC5A和SOCS3的低表达参与了大肠癌的发生、发展,联合检测两蛋白可能作为临床判断大肠癌的恶性程度及预后的参考指标,并有望成为基因治疗的新靶点。     

Livin与Caspase-9在大肠癌组织中的表达及临床意义

目的:研究Livin和Caspase-9在大肠癌组织中的表达及意义。方法:采用免疫组织化学SP法检测60例大肠癌、20例腺瘤、18例正常大肠黏膜中Livin、Caspase-9的表达情况。结果:Livin在大肠癌组织中的表达(68.3%)明显高于腺瘤组织(40.0%)(P<0.05),腺瘤组织中的表达明显高于正常大肠黏膜组织(5.9%)(P<0.05)。Livin的表达与肿瘤有无淋巴结转移、Dukes分期、是否放化疗密切相关(P<0.05)。Caspase-9在大肠癌组织中的表达(25.0%)明显低于腺瘤组织(50.0%)(P<0.05),腺瘤组织中的表达明显低于正常大肠黏膜组织(83.3%)(P<0.05)。Caspase-9的表达与肿瘤分化程度、有无淋巴结转移密切相关(P<0.05)。Livin与Caspase-9在大肠癌组织中的表达呈负相关(P<0.05)。结论:Livin和Caspase-9在大肠癌的发生、发展中起着重要作用,可能会成为大肠癌的分子标志物或治疗的新靶点。     

联合检测大肠癌组织中PTEN与CyclinD1的表达及DNA含量的临床意义

目的:探讨大肠癌组织中PTEN和CyclinD1的表达及与DNA含量联合检测的关系及意义.方法:应用免疫组织化学SP法检测58例大肠癌及14例癌旁正常大肠黏膜组织中PTEN和CyclinD1蛋白表达;应用流式细胞术检测以上组织中PTEN和CyclinD1的DNA含量;分析它们之间及与肿瘤分期、分级的关系.结果:PTEN蛋白在大肠癌组织中的表达(65.52%)显著低于癌旁正常组织(100%),CyclinD1蛋白在大肠癌组织中的表达(60.34%)显著高于癌旁正常组织(1.72%),两种蛋白在大肠癌组织中的表达呈负相关(r =-0.71);大肠癌组织的异倍体率(68.97%)显著高于癌旁正常组织(0);PTEN阳性组的DNA指数(DNA index,DI)、S期细胞比率(S-phase fraction ,SPF)均低于阴性组(P<0.05),CyclinD1阳性组的DI及SPF均高于阴性组(P<0.05);两者的表达与肿瘤病理分级、Dukes分期及淋巴结转移相关;淋巴结转移患者的异倍体率及SPF均高于无淋巴转移患者(P<0.05).结论:PTEN和CyclinD1基因的异常改变可能参与大肠黏膜细胞的恶性转化过程,两者的变化存在相关性;DNA含量的变化可能与淋巴结转移有关.联合检测PTEN、CyclinD1蛋白及DNA含量可作为评估大肠癌病理生物学行为和预后的重要指标.     

大肠癌中HSP70和HSP90α表达与其生物学行为的关系

目的探讨热休克蛋白(HSP)70和HSP90α的表达与大肠癌生物学行为及预后的关系。方法应用免疫组织化学(SP法)检测HSP 70和HSP 90α在58例大肠癌和24例大肠腺瘤及20例正常大肠黏膜组织中的表达。结果大肠癌组织中HSP 70和HSP 90α阳性表达率分别为81.0%和77.6%,均明显高于大肠腺瘤及正常大肠黏膜组织(P<0.05)。两种蛋白表达与大肠癌的分化程度,淋巴结转移,Dukes分期,浸润肌层的深度有关;该4因素的分组间均有统计学差异(均P<0.05),且两者表达呈正相关(r=0.331,P<0.05)。HSP 70和HSP 90α表达阳性者术后3年生存率明显低于阴性者(P<0.05)。结论 HSP 70和HSP 90α的异常表达参与了大肠癌的发生、发展;对两者的检测可作为临床判断大肠癌的恶性程度、转移及预后的参考指标。     

Skp2、p27kip1在大肠癌中的表达及其临床意义

目的研究Skp2、p27kip1在大肠癌组织中的表达,探讨它们之间的关系及其临床意义。方法采用免疫组化方法检测Skp2、p27kip1蛋白在83例大肠癌、18例大肠腺瘤和20例大肠正常黏膜中的表达。结果大肠癌组织中Skp2蛋白阳性率(28.65±12.60)%,显著高于大肠腺瘤组织(17.28±10.66)%(P<0.01)和大肠正常黏膜组织(6.60±5.54)%(P<0.01)。Skp2蛋白表达与细胞分化程度、肿瘤分期及淋巴结转移呈正相关(P<0.01)。大肠癌组织中p27kip1蛋白阳性率(24.61±11.27)%,显著低于大肠腺瘤组织(49.94±13.22)%(P<0.01)和大肠正常黏膜组织(65.40±15.74)%(P<0.01)。p27kip1蛋白表达与细胞分化程度、肿瘤分期及淋巴结转移呈负相关(P<0.01)。大肠癌组织中Skp2与p27kip1表达呈负相关(r=-0.430,P<0.01)。结论大肠癌中Skp2蛋白的过度表达与p27kip1蛋白降解有关,提示Skp2蛋白可能在大肠癌的发生发展中起重要作用。     

24 大肠癌组织中EphA2，VEGF和MMP9蛋白的表达及其相关性研究

为探讨大肠癌组织中EphA2，VEGF和MMP9蛋白的表达及其与大肠癌生物学行为的关系。笔者应用免疫组织化学S-P法检测69例大肠癌组织及30例远癌肠黏膜中EphA2，VEGF，MMP9蛋白的表达。结果示,大肠癌组织中EphA2蛋白（100%）表达显著高于远癌肠黏膜（80.0%）（P<0.01）,且与Dukes分期、肿瘤组织分化程度及肉眼类型有关（P<0.05），而与年龄无关（P>0.05）。VEGF蛋白及MMP9蛋白在大肠癌中的表达均显著高于远癌肠黏膜(均P<0.01)，与Dukes分期有关（P<0.05），但与年龄、肿瘤组织分化程度及肉眼类型等无关（均P>0.05）。EphA2蛋白在大肠癌中的表达与VEGF，MMP9呈正相关（r1=0.404，P1=0.000;r2=0.282，P2=0.000）。提示联合检测EphA2,VEGF和MMP9有助于对大肠癌侵袭及转移能力的评估，对大肠癌的预后判断可能具有一定的临床意义。     

大肠良恶性肿瘤中PTEN的蛋白表达及其临床意义

目的　探讨抑癌基因PTEN在大肠良恶性肿瘤组织中的表达及其临床意义。方法　应用S -P免疫组织化学方法检测 2 8例正常大肠黏膜组织 ,3 2例大肠腺瘤的腺体及腺体旁组织 ,12例大肠息肉及息肉旁组织 ,48例大肠癌的癌组织及癌旁组织中PTEN蛋白的表达情况。结果　PTEN蛋白在所有大肠肿瘤组织的表达与其在正常粘膜组织及肿瘤旁组织表达相比均有显著性差异 ;PTEN蛋白在所有大肠肿瘤组织的表达水平 ,尤其在大肠息肉和大肠癌中 ,均显著低于正常大肠组织及其相应的肿瘤旁组织 ,且与肿瘤的大小呈显著负相关 ;癌组织中PTEN蛋白表达与癌组织分化程度呈显著正相关 ,而与其临床Dukes分期、淋巴结转移和远处脏器转移无关。结论　抑癌基因PTEN在大肠息肉 (尤其是腺瘤性息肉 )和大肠癌的发生发展中起着重要作用 ,检测PTEN蛋白表达可能对大肠息肉 (尤其是腺瘤性息肉 )和大肠癌的早期诊断、指导临床术后的进一步治疗及预后的判断有一定价值。     

PTEN和缺氧诱导因子-1α在大肠腺瘤-腺癌序列中的表达及意义

目的:观察大肠腺瘤和腺癌组织中PTEN、缺氧诱导因子-1α(HIF-1α)表达情况,探讨两者在大肠腺瘤一腺癌序列发生发展中的作用及相互关系.方法:采用原位杂交技术检测18例大肠腺瘤和62例大肠腺癌组织中PTEN-mRNA、HIF-1αmRNA,用免疫组织化学S-P方法检测VEGF蛋白的表达.比较三者与大肠癌Dukes分期、淋巴结转移、肝转移及组织学分级等病理特征的关系.结果:18例大肠腺瘤PTEN-mRNA、HIF-1αmRNA、VEGF蛋白阳性表达率分别为77.8%(14/18),38.9%(7/18),33.3%(6/18),大肠腺癌分别为51.6%(32/62),67.7%(42/62),59.7%(37/62).腺瘤组织HIF-1αmRNA、VEGF阳性表达率均低于腺癌细织(P ＜0.05),腺瘤组织PTEN-mRNA阳性表达率显著高于腺癌组织(P ＜0.05).大肠腺癌细织中PTEN-mRNA吸光值随Dukes分期增高而逐渐降低,A期(0.1782±0.0271),B期(0.1538±0.0397)分别与C+D期(0.1470±0.0524)比较差异均具有显著性(P ＜0.05).HIF-1αmRNA、VEGF蛋白吸光值随Dukes分期增高而逐渐升高,A期,HIF-1α(0.1029±0.045),VEGF(0.1207±0.0436)分别与B期(0.1656±0.0329、0.1572±0.0514)比较差异均具有显著性(P ＜0.05).A期,B期分别与C+D期(0.2335±0.0748、0.2219±0.0803)比较差异具有高度显著性(P＜0.01).PTEN-mRNA表达分别与HIF-1α、VEGF呈显著负相关(rs=-0.36,P＜0.05:rs=-0.68,P ＜0.05),HIF-1αmRNA与VEGF呈显著正相关(rs=0.71,P＜0.05).结论:抑癌基因PTEN的丢失或表达下调,HIF-1α及其靶基因VEGF的过度表达在大肠腺瘤-腺癌序列的发生发展浸润转移中起促进作用.     

Presenteeism and Absenteeism Before and After Total Hip and Knee Arthroplasty

BackgroundAbsenteeism is costly, yet evidence suggests that presenteeism—illness-related reduced productivity at work—is costlier. We quantified employed patients’ presenteeism and absenteeism before and after total joint arthroplasty (TJA).MethodsWe measured presenteeism (0-100 scale, 100 full performance) and absenteeism using the World Health Organization’s Health and Work Performance Questionnaire before and after TJA among a convenience sample of employed patients. We captured detailed information about employment and job characteristics and evaluated how and among whom presenteeism and absenteeism improved.ResultsIn total, 636 primary, unilateral TJA patients responded to an enrollment email, confirmed employment, and completed a preoperative survey (mean age: 62.1 years, 55.3% women). Full at-work performance was reported by 19.7%. Among 520 (81.8%) who responded to a 1-year follow-up, 473 (91.0%) were still employed, and 461 (88.7%) had resumed working. Among patients reporting at baseline and 1 year, average at-work performance improved from 80.7 to 89.4. A Wilcoxon signed-rank test indicated that postoperative performance was significantly higher than preoperative performance (P < .0001). The percentage of patients who reported full at-work performance increased from 20.9% to 36.8% (delta = 15.9%, 95% confidence interval = [10.0%, 21.9%], P < .0001). Presenteeism gains were concentrated among patients who reported declining work performance leading up to surgery. Average changes in absences were relatively small. Combined, the average monthly value lost by employers to presenteeism declined from 15.3% to 8.3% and to absenteeism from 16.9% to 15.5% (ie, mitigated loss of 8.4% of monthly value).ConclusionAmong employed patients before TJA, presenteeism and absenteeism were similarly costly. After, employed patients reported increased performance, concentrated among those with declining performance leading up to surgery.     

The German emergency and disaster medicine and management systemdhistory and present

As well for optimized emergency management in individual cases as for optimized mass medicine in disaster management, the principle of the medical doctors approaching the patient directly and timely, even close to the site of the incident, is a long-standing marker for quality of care and patient survival in Germany. Professional rescue and emergency forces, including medical services, are the “Golden Standard” of emergency management systems. Regulative laws, proper organization of resources, equipment, training and adequate delivery of medical measures are key factors in systematic approaches to manage emergencies and disasters alike and thus save lives. During disasters command, communication, coordination and cooperation are essential to cope with extreme situations, even more so in a globalized world. In this article, we describe the major historical milestones, the current state of the German system in emergency and disaster management and its integration into the broader European approach.     

Differences in Osteocyte Density and Bone Histomorphometry Between Men and Women and Between Healthy and Osteoporotic Subjects

Bone defects related to osteoporosis develop with increasing age and differ between males and females. It is currently thought that the bone remodeling process is supervised by osteocytes in a strain-dependent manner. We have shown an altered response of osteocytes from osteoporotic patients to mechanical loading, and osteocyte density is reduced in osteoporotic patients, which might relate to imperfect bone remodeling, leading to lack of bone mass and strength. Hence, information on osteocyte density will contribute to a better understanding of bone biology in males and females and to the assessment of osteoporosis. Osteocyte density as well as conventional histomorphometric parameters of trabecular bone were determined in cancellous iliac crest bone of healthy postmenopausal women and men and of osteoporotic women and men. Osteocyte density was higher in healthy females than in healthy males and lower in osteoporotic females than in healthy females. Bone mass was reduced in osteoporotic patients, both male and female. In females, trabecular number was reduced, whereas in males, trabecular thickness was reduced and eroded surface was increased. There were no correlations between the parameter groups bone architecture, bone formation, bone resorption, and osteocyte density. These results are consistent with impaired osteoblast function in osteoporotic patients and with a different mechanism of bone loss between men and women, in which osteocyte density might play a role. The reduced osteocyte numbers in female osteoporotic patients might relate to imperfect bone remodeling leading to lack of bone mass and strength. M. G. Mullender and S. D. Tan contributed equally to this work.     

肝内胆管囊腺瘤和囊腺癌的CT、MRI及病理表现

目的探讨肝内胆管囊腺瘤和囊腺癌的CT、MRI和病理特点。方法回顾性分析经手术病理证实的6例肝内胆管囊腺瘤和2例肝内胆管囊腺癌的影像及临床病理资料，将病变的影像表现与其病理大体形态及组织学表现作对照分析。结果6例肝内胆管囊腺瘤，女4例、男2例；2例肝内胆管囊腺癌均为女性病人；8例病人平均年龄55岁。所有病灶均表现为多房囊性肿块，肿瘤囊腔各分房内常为多种液体成分，在CT上可表现为不同密度、在MRI上可表现为不同信号强度。囊内出现多发大小不等的壁结节在胆管囊腺癌内更常见，囊内有分隔但无壁结节只见于胆管囊腺瘤。在7例CT扫描中，4例胆管囊腺瘤和1例胆管囊腺癌可见囊壁或分隔上钙化，囊壁、囊内分隔及囊内结节均为轻、中度延迟增强。肿瘤中出现卵巢样间质见于3例胆管囊腺瘤和1例胆管囊腺癌，且均为女性病人。结论肝内胆管囊腺瘤和囊腺癌是肝脏不常见的囊性肿瘤，影像上多房、囊内有分隔且各分房囊内密度或信号不一致，高度提示肝内胆管囊腺瘤或囊腺癌的诊断，如囊内伴有多发大小不等的结节，则进一步提示囊腺癌的可能。但影像学表现不能区分肿瘤中有无卵巢样间质。