胸苷磷酸化酶在消化道恶性肿瘤中的表达及预后价值

目的观察胸苷磷酸化酶（TP）在消化道恶性肿瘤的表达以及与肿瘤血管生成的关系，探讨TP对肿瘤预后的价值。方法采用免疫组织化学方法检测181例消化道恶性肿瘤组织和对应的77例邻近正常组织的TP表达和微血管密度（MVD），比较不同肿瘤间及肿瘤与正常组织TP表达差异。分析肿瘤组织TP表达与MVD值的关系。以Kaplan—Meier生存曲线分析胃癌、大肠癌TP表达对预后的意义。结果TP在胃癌、大肠癌、肝癌及胰腺癌的阳性表达率依次为62．2％、63．5％、55．0％和68．2％，且肿瘤组织的表达率均显著高于正常组织（P〈0．05）；TP阳性组的MVD值均显著高于阴性组（P〈0．05）；Kaplan—Meier生存曲线提示：胃癌、大肠癌中TP阳性表达者的预后明显较阴性表达者差（P〈0．05）。结论TP在消化道恶性肿瘤中呈高表达并对肿瘤血管生成有促进作用，对胃癌、大肠癌患者的预后评估有一定价值。     

干扰素-α诱导肾癌细胞胸苷磷酸化酶表达对5-FU化疗敏感性的影响

目的 探讨干扰素-α诱导肾癌细胞胸苷磷酸化酶（thymidine phosphorylase，TP）表达对5-氟尿嘧啶（5-FU）化疗敏感性的影响。方法采用不同浓度的干扰素-α2b处理肾癌细胞株786—0，应用RT—PCR和免疫印迹方法分别检测TP mRNA和TP蛋白水平变化。MTT法检测不同处理组786—0细胞中5-FU的半数抑制浓度（IC50）。建立肾透明细胞癌移植瘤动物模型，观察干扰素-α2b联合5-FU化疗对移植瘤生长的影响，免疫组化检测移植瘤中TP的表达，TUNEL检测肿瘤细胞的凋亡。结果 干扰素-α2b3000和6000IU／ml处理组，TP mRNA表达量（灰度峰值）分别为0．5733±0．0231和0．8233±0．0404，TP蛋白表达量分别为0．6347±0．0719和0．8735±0．0640。干扰素-α对TP的表达有剂量依赖性增强作用（P〈0．01）。在干扰素-α2b作用下，5-FU对786—0半数抑制浓度由（13．9467±3．7140）μmol／L下降至（5．3200±0．1039）μmol／L，化疗敏感性增加（P〈0．01）。联合用药组移植瘤体积为（0．0940±0．0492）cm^3，小于单纯5-FU组的（0．5424±0．1591）cm^3（P〈0．05）。单纯5-FU组和联合用药组移植瘤中肿瘤细胞凋亡指数差异无统计学意义（P〉0．05）。结论 干扰素-α2b诱导的TP增强表达参与了干扰素-α联合5-FU化疗增效作用，TP是干扰素-α2b的靶基因之。     

六氧化四砷对小鼠胃癌生长和转移的抑制作用

目的观察六氧化四砷（As4O6）对小鼠胃癌生长和转移的抑制作用。方法完整组织块SCID鼠胃壁原位种植，建立胃癌转移模型。将裸鼠40只随机分为4组，每组10只。移植后第7天开始，分别给予生理盐水（对照组）、5-氟尿嘧啶（5-Fu组）、As4O6组、5-Fu和As4O6联合应用（5-Fu＋As4O6组），每日1次，共6周。种植后第8周末处死动物，原位肿瘤切除称重，计算抑瘤率、测定肿瘤微血管密度（MVD）和细胞凋亡指数（AI），并检查转移情况，计算转移抑制率。结果与对照组比较，5-Fu组、As4O6组和5-Fu＋As4O6组的抑瘤率分别为46．3％、52．2％和67．9％（均P〈0．05），MVD分别为（12．2±5．2）、（7．1±3．5）（P〈0．05）和（5．6±3．3）（P〈0．05），A1分别为（6．82±4．27）、（10．51±6．19）（P〈0．05）和（14．66±7．54）（P〈0．05），肝转移抑制率分别为25％、55％（P〈0．05）和70％（P〈0．05），腹膜转移抑制率分别为22．9％、61．4％（P〈0．05）和87．1％（P〈0．05）。As4O6组和5-Fu＋As4O6组胃癌生长和转移受到明显抑制，以5-Fu和As4O6联用组效果最明显。结论As4O6通过抑制血管生成对胃癌生长和转移有明显抑制作用，与5-Fu联用可起协同抑制作用。     

CD133与胃癌细胞化疗耐药的关系及其机制

目的探讨CDl33阳性胃癌起始细胞对常规化疗药物氟尿嘧啶（5．FU）的敏感性及其耐药机制。方法免疫磁珠法分选KATO—III、SGC7901和MKN-45胃癌细胞株并分为未分选组、CDl33＋组及CDl33一组。Westernblot法和RT—PCR法分别检测分选后胃癌细胞CDl33、P—gP、Bax和Bcl-2蛋白及mRNA表达水平。免疫荧光法检测各组细胞P-gP及Bcl-2蛋白的表达。CCK-8法和Hoechest染色检测各组细胞对5．FU的敏感性。siRNA干扰MKN45细胞CDl33表达后，检测CDl33、P-gP、Bcl-2、Akt及p-Akt蛋白及mRNA表达。结果CDl33＋组胃癌细胞中CDl33、P—gP及Bcl-2蛋白和mRNA表达水平均显著高于未分选组及CDl33-组（均P〈0．05），而促凋亡因子Bax的表达水平则明显降低（P〈0．05）。在相同药物浓度下，5-Fu对CDl33＋组的抑制率显著低于CDl33一组（P〈0．05）。5-FU处理胃癌细胞后，CDl33＋组胃癌细胞中凋亡细胞比率明显低于CDl33-组及未分选组（P〈0．05）。CDl33特异siRNA干扰胃癌细胞后，干扰组P—gP、Bcl-2和p-Akt蛋白及mRNA表达显著降低（均P〈0．05），而Bax表达水平则显著增加（P〈0．05）。结论CDl33可能通过调节P-gp和Bcl-2的表达来促进胃癌的化疗耐药；在胃癌化疗耐药产生中，CDl33＋细胞可通过P13K／Akt通路起作用。     

胸苷磷酸化酶和二氢嘧啶脱氢酶在原发性肝癌中的表达

目的探讨胸苷磷酸化酶（TP）和二氢嘧啶脱氢酶（DPD）在肝癌中的表达情况。方法选取肝癌手术切除标本20例，取肝癌和癌旁肝组织进行TP和DPD的免疫组织化学染色。运用图像分析系统对结果进行分析。结果TP在肝癌组织中表达的平均阳性单位值为26.696，在癌旁肝组织中表达的平均阳性单位值为30.996，差异有统计学意义（P〈0.05）。DPD在肝癌组织中的表达的平均阳性单位值为11.408，在癌旁肝组织中表达的平均阳性单位值为13.843，差异有统计学意义（P〈0.5）。肝癌组织中TP与DPD表达的平均阳性单位值的比值为4.447，在癌旁肝组织中TP与DPD表达的平均阳性单位值的比值为4.152。TP与DPD的比值（TP／DPD）在肝癌组织中较癌旁高，差异无统计学意义（P〉0．05）。结论肝癌和癌旁肝组织中均有较高水平的TP酶和DPD酶表达，TP与DPD的比值在肝癌组织中较癌旁高。     

凋亡相关基因survivin、caspase-3及cyclin-B1在胃癌发生、发展中的作用

目的 检测凋亡相关基因survivin、caspase-3和cyclin—B1在胃癌组织中的表达，探讨其表达在胃癌发生、发展中的作用。方法 采用RT—PCR方法检测survivin mRNA、caspase-3 mRNA和cyclin-B1 mRNA在30例胃癌组织、10例癌旁正常胃组织标本中的表达。结果 30例胃癌组织中有20例survivin mRNA阳性表达，10例正常胃组织中无survivin mRNA表达；30例胃癌组织和10例正常胃组织中均有caspase-3 mRNA和cyclin—B1 mRNA阳性表达；20例survivin mRNA阳性表达的胃癌组织中caspase-3 mRNA和cyclin-B1 mRNA表达水平明显低于lo例survivin mRNA阴性表达的胃癌组织（P〈0．01）和正常胃组织（P〈0．01）；10例survivin mRNA阴性表达的胃癌组织caspase-3 mRNA和cyclin—B1 mRNA表达水平亦明显低于10例正常胃组织（P〈0．01）。相关性分析表明，survivin的表达与caspase-3（r=-0．923，P〈0．01）和cyclin-B1（r=0．886，P〈0．01）表达呈负相关，caspase-3的表达与cyclin-B1表达呈正相关（r=0．892，p〈-0．01）。结论survivin促进胃癌发生、发展，caspase-3和cyclin-B1抑制胃癌发生、发展。     

细胞周期蛋白D1和P21WAF1在胃癌中的表达及其与化疗药物敏感性的关系

目的检测细胞周期蛋白（cyclin）D1、P21WAF1在胃癌组织中的表达,并探讨其与化疗药物敏感性的关系。方法采用MTT比色法观察80例胃癌原代培养细胞在体外对化疗药物羟基喜树碱（HCPT）、顺铂（DDP）、阿霉素（ADM）、氟尿嘧啶（5-Fu）及丝裂霉素（MMC）的敏感性;免疫组织化学染色检测cyclin D1和P21WAF1蛋白在胃癌组织中的表达情况。结果胃癌细胞对不同化疗药物敏感性不同：5-FU、MMC和DDP对胃癌细胞的抑制率显著高于ADM和HCPT（P〈0．05）。胃癌组织中cvclin D1和P21WAF1蛋白的阳性率分别为70．0％和47．5％。cyclin D1阳性表达者对5-Fu和HCPT的敏感性显著高于阴性表达者（P〈0．05）,而P21WAF1阴性表达者对MMC、5-FU和DDP的敏感性显著高于阳性表达者（P〈0．05）。结论cyclin D1和P21WAF1蛋白与胃癌对化疗药物敏感性有关．检测其表达对于化疗药物的选择具有一定的参考价值。     

抑癌基因Runt相关转录因子3在胃癌中的表达及其与临床病理学因素的关系

目的探讨胃癌组织中Runt相关转录因子3（Runx3）基因的表达情况及其与胃癌临床病理学因素的关系。方法采用逆转录聚合酶链反应（RT—PCR）和蛋白印迹（Western blot）法分别检测52例胃癌组织和配对的正常胃黏膜组织中Runx3 mRNA以及蛋白的表达水平，并分析Runx3表达与胃癌临床病理学因素的关系。结果59．6％（31／52）的胃癌组织出现Runx3 mRNA表达缺失，48．1％（25／52）出现Runx3蛋白表达缺失，其缺失率均明显高于对应的正常胃黏膜组织（P〈0．05）。Runx3的表达缺失与肿瘤大小、组织分化程度、浸润深度、淋巴结转移及TNM分期有关（P〈0．05，P〈0．01）。Runx3 mRNA表达与蛋白表达呈正相关（r=0．840，P〈0．01）。结论Runx3基因与胃癌的发生、发展密切相关，有望成为胃癌诊断和治疗的新靶点。     

保罗样激酶1mRNA及蛋白质在胃癌中的表达意义

目的 探讨保罗样激酶1（plk1）在胃癌组织中mRNA及蛋白质的表达，并探讨其表达水平与临床病理指标的关系。方法 采用实时定量多聚酶链反应及免疫印迹（Western blot）分别检测了60例胃癌患者新鲜切除胃癌组织及其对应正常胃粘膜组织中plk1 mRNA及蛋白质的表达。结果胃癌组织中plk1 mRNA及蛋白质水平均明显高于正常组织（P〈0．05，P〈0．01）；并且其水平与胃癌的分化程度和浸润深度有关（P〈0．05）；蛋白质表达水平与胃癌的分化有关（P〈0．05）。结论 plk1的过表达可能在胃癌发生发展中起促进作用；其表达程度可望作为胃癌的某些生物学行为新的判定指标。     

转移抑制基因Kiss-1和KAI-1在胃癌组织中表达的原位杂交研究

目的研究胃癌及其癌旁组织Kiss-1和KAI-1转移抑制基因信使核糖核酸（Kiss-1mRNA和KAI-1 mRNA）的表达水平及其临床意义。方法将49例胃癌组织和20例癌旁组织常规制作石蜡包埋切片．用Kiss-1 mRNA和KAI-1 mRNA染色方法作为原位杂交染色法。结果胃癌组织中Kiss-1 mRNA和KAI-1 mRNA表达阳性率明显低于癌旁组织（P〈0．01）；正常至轻度不典型增生癌旁组织两者Kiss-1 mRNA和KAI-1 mRNA表达阳性率及其评分明显高于中至重度不典型增生病例（P〈0．05，P〈0．01）。侵袭深度T1～T2、区域淋巴结无转移、第1站淋巴结转移及无远处转移的胃癌Kiss-1 mRNA和KAI-1 mRNA表达阳性率及其评分明显高于侵袭深度T3～T4、区域淋巴结有转移、第2站或第3站淋巴结转移及有远处转移的病例（P〈0．05，P〈0．01）；但两者的表达与胃癌其他临床病理特征无明显关系。胃癌组织中Kiss-1 mRNA表达评分与KAI-1 mRNA表达评分呈密切正相关（r=0．53，P〈0．01）。结论Kiss-1 mRNA和KAI-1 mRNA表达可能是反映胃癌侵袭和转移潜力及预后的重要生物学标记物，对胃良性病变者检测Kiss-1 mRNA和／或KAI-1 mRNA可能对早期发现及预防胃癌发生有重要临床意义。     

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。