Ang2,HIF-1α及VEGF对肝癌血管形成的影响

摘要：目的:探讨促血管生成素2（Ang2）、缺氧诱导因子1α（HIF-1α）及血管内皮生长因子（VEGF）与肝细胞癌血管形成的关系。方法:检测52例肝癌组织中Ang2，HIF-1α及VEGF mRNA及蛋白的表达，对共表达的肝癌组织进行微血管计数。结果:RT-PCR 显示,52例肝癌组织中有38例共表达Ang2mRNA，HIF-1αmRNA 和VEGF mRNA，且两两之间呈明显正相关(分别为r=0.783，P<0.01；r=0.427，P<0.05；r=0.433，P<0.05)；免疫组化发现,52例肝癌组织36例共表达Ang2，HIF-1α和VEGF蛋白。共表达Ang2 mRNA，HIF-αmRNA 和VEGF蛋白的38例肝癌组织中,平均微血管数［(45.4±8.90) 个/HP］,明显高于非共表达组［(13.6±3.30)个/HP］（P<0.05)。结论:Ang2，HIF-1α和VEGF与肝癌的新生血管形成有关；肿瘤组织缺氧可能是其始动因素。     

血管生成素和VEGF在人肝细胞癌血管生成作用机制的研究

目的探讨血管生成素(Ang)及受体Tie-2、血管内皮牛长因子(VEGF)在肝细胞癌血管生成和进展中的作用。方法用RT-PCR和免疫组织化学方法分析28例肝细胞痛(HCC)、10例肝硬化和10例正常肝标本。观察血管生成素及受体、VEGF的表达与HCC肿瘤血管生成和临床病理的关系。结果Ang／Tie-2，VEGF在肝细胞癌表达明显上调，免疫组织化学也显示Ang-2和VEGF，Tie-2蛋白在肝癌表达增强。Ang-2／Ang-1 mRNA比值、VEGF mRNA与肿瘤血管侵犯及CD34染色的微血管密度相关。结论Ang／Tie-2，VEGF、在HCC肿瘤血管生成和进展中起重要作用。     

Survivin在肝癌中的表达和意义及其与血管内皮生长因子的相关性

目的　检测肝细胞癌中凋亡抑制蛋白Survivin的表达 ,研究其与肝癌临床特征的关系 ;同时研究Survivin与血管内皮生长因子 (VEGF)表达的相关性 ,探讨Survivin在肝细胞癌发生发展及转移中的作用及机制。方法　采用免疫组织化学技术和蛋白印迹技术 ,检测 3 8例肝癌组织及癌旁非癌组织中Survivin和VEGF蛋白的表达。结果　 3 8例肝癌组织中 2 3例表达Survivin蛋白 ,其中 18例VEGF表达阳性 ,5例VEGF表达呈阴性或弱阳性 ;15例不表达Survivin蛋白者VEGF的表达 3例阳性 ,12例阴性或弱阳性。而在癌周非癌组织未检测到Survivin蛋白的表达。Survivin的表达与肝癌的发病年龄、性别、肿瘤大小、分化程度无关 (均为P >0 .0 5 ) ,而与肝癌的转移有关 (P <0 .0 5 )。结论　Survivin在肝细胞癌中的表达能促进肝癌的发生发展 ,并可能通过上调VEGF的表达而促进肝癌转移。     

环氧合酶2对胰腺癌新生血管生成的调节作用及其机制

目的　探讨环氧合酶 2 (COX 2 )在胰腺癌新生血管生成中的调节作用及其作用机制。方法　应用免疫组织化学染色研究人胰腺癌组织COX 2、血管内皮细胞生长因子 (VEGF)表达 ;同时标记肿瘤新生血管内皮细胞vWF和血管壁Ⅳ型胶原 ,计算肿瘤组织微血管密度 (MVD)。建立裸鼠胰腺癌细胞株PC 3移植瘤 ,观察选择性COX 2抑制剂Celebrex对肿瘤组织MVD的影响 ,并应用免疫组织化学染色和逆转录聚合酶链式反应 (RT PCR)研究裸鼠移植瘤组织VEGF表达变化。结果　COX 2在人胰腺癌组织中表达阳性率为 87 5 % ,VEGF阳性率为 5 8 3%。COX 2强阳性组MVD平均值显著高于COX 2弱阳性 +阴性组 ,P <0 0 1。VEGF阳性组MVD平均值高于VEGF阴性组 ,但无统计学差异 ,P >0 0 5 ;Pearson相关性检验结果表明COX 2与vWF和Ⅳ胶原标记的MVD均有明显的相关性 (相关系数分别为 0 5 99和 0 6 ) ,P <0 0 5。在裸鼠移植瘤的体内实验中 ,与对照组MVD(6 3 89± 13 6 7)相比 ,Celebrex处理组MVD为 32 2 5± 12 99,两者差异显著 ,P <0 0 1。免疫组织化学染色和RT PCR结果表明Celebrex处理组肿瘤组织VEGF表达较对照组明显下调。结论　COX 2与胰腺癌新生血管生成密切相关 ,其高表达促进了胰腺癌新生血管生成 ;可能作用机制是上调促血管生成因子VEGF     

乳腺癌组织中血管内皮生长因子mRNA的表达和微血管计数与淋巴结转移的关系

目的：探讨乳腺癌组织中血管内皮生长因子（VEGF）mRNA的表达，微血管密度（MVD）与淋巴结转移的关系。方法：采用逆转录－聚合酶链反应（RT－PCR）和免疫组织化学链霉卵白素－过氧化物酶（SP）法技术，对47例乳腺癌组织VEGF mRNA、VEGF蛋白的表达及微血管密度进行研究。结果：乳腺癌组织VEGF mRNA的表达高于癌旁组织（55．30％：17．02％）。VEGF mRNA的表达与淋巴结转移呈正相关趋势。VEGF表达和MVD与乳腺癌淋巴结转移密切相关（P＜0．05）。癌组织MVD值明显高于癌旁组织MVD值。结论：VEGF与乳腺癌血管生成密切相关，VEGF和MVD表达增高对乳腺癌淋巴结转移有促进作用。     

血管生成在肝门部胆管癌发生发展中作用的研究

目的　探讨血管内皮细胞生长因子 (vascularendothelialgrowthfactor,VEGF)和血管生成与肝门部胆管癌发生发展的关系。方法　应用逆转录多聚酶链反应 (RT PCR)和免疫组化技术对2 6例肝门部胆管癌、癌周组织及 12例正常组织中VEGFmRNA和蛋白及微血管密度 (MVD)进行检测。结果　 2 6例肝门部胆管癌组织中VEGFmRNA阳性表达率为 77% (2 0 / 2 6 ) ;癌周组织阳性表达率为2 7% (7/ 2 6 ) ;正常组织表达率为 8% (1/ 12 ) ,三者差异有显著性 (P <0 0 1)。VEGFmRNA阳性表达与VEGF蛋白表达具有一致性 ;VEGFmRNA阳性者MVD值显著高于阴性者 (P <0 0 1) ;VEGFmRNA表达和MVD与肝门部胆管癌的分化程度、浸润转移密切相关 (P <0 0 5 ) ,而与肿瘤发生部位、病理类型、大小、临床分型无关 (P >0 0 5 )。结论　VEGF在肝门部胆管癌的发生和浸润转移过程中发挥重要作用 ,肿瘤血管生成与肝门部胆管癌浸润转移密切相关。     

Survivin和血管内皮生长因子在肝细胞癌中的表达及其与肿瘤血管生成的关系

我们采用免疫组织化学方法检测survivin、血管内皮生长因子(VEGF)和微血管密度(MVD)在肝细胞癌(HCC)、癌旁组织以及正常肝组织中的表达，探讨survivin、VEGF的表达与HCC的临床病理特征、新生血管形成的关系。     

DLL4和血管内皮生长因子在肝细胞癌的表达及其在肿瘤血管生成的作用

目的 探讨Delta样配体(DLL4)及血管内皮生长因子(VEGF)在肝细胞癌中的表达及其与血管生成的关系.方法 免疫组织化学法检测75例肝细胞癌(HCC)中DLL4和VEGF的表达,用CD34进行微血管内皮细胞染色,计算微血管密度(MVD),分析其相关性.结果 DLL4和VEGF表达在HCC组明显高于肝硬化组和正常肝组(P＜0.01),与HCC的临床病理学分级相关(P＜0.01),HCC组中的CD34表达与DLL4的表达呈明显负相关(P＜0.05,r=-0.778);与VEGF的表达呈明显正相关(P＜0.05,r=0.747),32例共表达DLL4和VECF蛋白者,其平均微血管数(19.70±5.82)个/HP,明显高于非共表达组(7.60±2.12)个/HP(P＜0.01).结论 DLL4、VEGF在肝细胞癌血管生成中可能起重要作用.     

肝细胞癌门静脉主干癌栓中血管内皮细胞生长因子的表达及其意义

目的探讨血管内皮细胞生长因子(VEGF)与肝细胞癌门静脉主干癌栓(PVTT)形成的关系.方法采用原位杂交等技术检测16例肝癌PVTT(A1组)中及其原发癌(A2组)和20例临床无转移的肝癌(B组)组织中的VEGF表达.结果 A1组和A2组VEGF mRNA及其蛋白表达阳性率均高于B组(P＜0.01),A1组细胞平均光密度高于A2组(P＜0.01).A1组的微血管密度高于A2组,A2组又高于B组(P＜0.01).在A1组和A2组,VEGF mRNA及其蛋白表达和微血管密度之间呈良好的相关关系(P均＜0.01).结论 VEGF在肝癌的侵袭、转移中起重要作用,是PVTT形成的主要因素; 微血管密度和肝癌的进展密切相关.     

兔肝癌肝动脉栓塞后肿瘤血管生成的变化

目的　观察肝癌肝动脉栓塞后肿瘤组织血管生成的变化。方法　建立兔肝癌模型 ,随机分栓塞组 (n =10 )和对照组 (n =10 )。于接种后 14d经肝动脉注入超液化碘油 (栓塞组 )或等量生理盐水 (对照组 )。栓塞后第 7天取肿瘤 ,免疫组织化学方法检测肿瘤组织微血管密度 (MVD)及血管内皮生长因子 (VEGF)蛋白的表达 ,逆转录 聚合酶链反应 (RT PCR)检测VEGFmRNA的表达。结果　栓塞组MVD (2 8.6± 10 .6)与对照组 (16.3± 6.9)比较差异有非常显著性 (t =3 .0 83 ,P <0 .0 1) ;栓塞后VEGF蛋白 (t =3 .0 75 ,P <0 .0 1)及VEGF165mRNA (t =3 .95 4,P <0 .0 0 1)表达水平显著增高 ;在栓塞组和对照组 ,VEGF蛋白表达均与MVD呈正相关 (r分别为 0 .69和 0 .72 ,P <0 .0 5 )。结论　肝动脉栓塞术可通过促使肿瘤细胞VEGF表达上调 ,从而促进肿瘤的血管生成 ,如果将介入栓塞与抗血管生成治疗相结合 ,可望提高栓塞治疗效果     

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.     

Tendon and Ligament Healing and Current Approaches to Tendon and Ligament Regeneration

Ligament and tendon injuries are common problems in orthopedics. There is a need for treatments that can expedite nonoperative healing or improve the efficacy of surgical repair or reconstruction of ligaments and tendons. Successful biologically-based attempts at repair and reconstruction would require a thorough understanding of normal tendon and ligament healing. The inflammatory, proliferative, and remodeling phases, and the cells involved in tendon and ligament healing will be reviewed. Then, current research efforts focusing on biologically-based treatments of ligament and tendon injuries will be summarized, with a focus on stem cells endogenous to tendons and ligaments. Statement of clinical significance: This paper details mechanisms of ligament and tendon healing, as well as attempts to apply stem cells to ligament and tendon healing. Understanding of these topics could lead to more efficacious therapies to treat ligament and tendon injuries. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:7–12, 2020