结直肠癌Dukes B、C、D期患者血清比较蛋白质组学研究

目的建立用于诊断结直肠癌患者Dukes分期的分类树模型。方法用表面增强激光解吸电离飞行时间质谱（SELDI—TOF—MS）技术检测32例Dukes B期、24例Dukes C期和26例Dukes D期结直肠癌患者血清差异蛋白，用BioMaker Pattern软件在学习模式下建立用于判断结直肠癌患者Dukes分期的分类树模型，并用该模型在双盲模式下对随机选取的30例结直肠癌血清标本（Dukes B、C、D期各10例）进行检测以验证其诊断的准确性。结果在捕获的31个差异蛋白中，建立了以14个差异蛋白组成的分类树模型，该模型在学习模式下的诊断准确率为89．0％（73／82），在双盲模式下的诊断准确率为76．7％（23／30）。结论该分类树模型对判断结直肠癌患者Dukes分期有一定的诊断价值，可以为结直肠癌患者治疗方案的选择提供依据。     

数据库建设第六部分：结直肠癌分期的标签与结构化

目的对华西肠癌数据库(DACCA)中结直肠癌分期的构成、定义及解读进行阐述。方法采用文字描述的形式。结果在华西DACCA中,选择作为结直肠癌分期模块项目中的总体分期包括术中分期、cpi综合分期、TNM分期;分类分期包括病理、临床和影像的T、N、M分期;风险因素包括沾染情况和高危因素。然后分别对这些项目进行了细分,并对这些条目的定义、填写形式、标签与结构化、纠错与更新以及在对DACCA中的数据进行分析时如何使用这些特征进行了详细阐述。结论通过对目前华西DACCA中已有的结直肠癌分期模块中的一部分项目的详细描述及规范,为结直肠癌的规范化治疗提供了参考依据,同时为想做结直肠癌数据库建设的同行们提供了经验。     

数据库建设第五部分：结直肠癌的肿瘤特征——模块的设计（一）

目的对华西肠癌数据库(DACCA)中结直肠癌的肿瘤特征模块的构成、定义及解读进行阐述。方法采用文字描述的形式。结果在华西DACCA中,选择作为结直肠癌的肿瘤特征模块的项目包括:癌前病变、癌家族、肿瘤部位、缘距、肿瘤形态、大小、方位、发生、分化、肿瘤病理性质、Ki67、梗阻、套叠、穿孔、疼痛、水肿、出血,本研究中对其中癌前病变、癌家族、肿瘤部位及缘距的具体定义、癌前病变的分类、肿瘤部位划分、癌家族的填写形式以及这些项目的标签与结构化、纠错与更新以及在对DACCA中的数据进行分析时如何使用这些肿瘤特征的方式进行了详细阐述。结论通过对目前华西DACCA中已有的结直肠癌的肿瘤特征模块中的一部分项目(余下部分项目在后期相应章节内容中描述)进行了详细描述及规范,为结直肠癌的规范化治疗提供参考依据,同时为想做结直肠癌数据库建设的同行们提供经验。     

磷脂爬行酶1在结直肠癌中的表达及其意义

目的 探讨磷脂爬行酶1(PLSCR1)的表达与结直肠癌生物学行为及预后的关系.方法 应用免疫荧光细胞化学方法分析PLSCR1在结直肠癌细胞株Lovo与HR8348中的表达情况,同时应用免疫组织化学方法分析PLSCR1在70例结直肠癌、30例正常黏膜、10例肝转移癌标本中的表达情况.结果 PLSCR1在结直肠癌细胞株Lovo与HR8348中的表达较强,PLSCR1主要定位在结直肠癌细胞株的细胞膜.PLSCR1在结直肠癌和肝转移癌组织中的表达率显著高于正常黏膜(P<0.05).PLSCR1阳性表达与远处转移相关(P<0.05),PLSCR1表达阳性者术后5年生存率相对较低(P<0.05).结论 PLSCR1的异常表达在结直肠癌的发生、进展和转移过程中可能发挥着重要作用.     

人结直肠癌裸鼠原位移植模型的建立及生物学特性的研究

目的 建立人结直肠癌裸鼠原位移植动物模型,并对其生物学特性进行检测,为探讨人结直肠癌的治疗提供实验工具.方法 应用外科手术裸鼠盲肠浆膜下原位移植的方法建立人结直肠癌裸鼠原位移植动物模型,并通过免疫组化法检测其生物学特性.结果 原位移植动物模型的成功率为100％,成功建立了人结直肠癌裸鼠原位移植模型,免疫组化检测发现肿瘤组织中增生细胞核抗原及Survivin高表达,该模型很好地模拟了人结直肠癌的生物学特征.结论 人结直肠癌裸鼠原位移植动物模型的建立为研究结直肠癌发生发展、转移机制及治疗提供了理想的实验动物模型.     

辛伐他汀对结直肠癌患者IL-6与IL-8血清表达及癌细胞分泌影响的研究

目的:研究辛伐他汀对结直肠癌患者IL-6及IL-8血清表达和癌细胞分泌的影响,初步探讨辛伐他汀在结直肠癌中的治疗机制。方法:应用ELISA检测结直肠癌患者与健康对照者血清中IL-6及IL-8水平,应用RT-PCR比较IL-6与IL-8在结直肠癌及癌旁组织的表达情况;应用ELISA检测结直肠癌患者辛伐他汀治疗后血清IL-6与IL-8的变化规律。应用ELISA检测辛伐他汀干预后结直肠癌细胞株(HT-29与Ca-co-2)上清中IL-6与IL-8变化。结果:结直肠癌患者血清IL-6与IL-8水平显著高于健康对照者(P<0.05)。IL-8 mRNA表达水平在癌组织明显高于癌旁组织(P<0.05);而IL-6 mRNA在癌组织与癌旁组织表达差异无统计学意义(P>0.05)。结肠癌患者应用辛伐他汀(80 mg/d)治疗14 d后,血清IL-6水平显著降低(P<0.05),而IL-8无明显变化(P>0.05)。应用浓度达到5μmol/L以上辛伐他汀干预结直肠癌细胞株HT-29与Caco-2后,其IL-6及IL-8分泌明显下降(P<0.05)。结论:辛伐他汀可以降低结直肠癌患者血清IL-6的水平,并可以抑制结直肠癌细胞IL-8与IL-6分泌。     

阿司匹林用于结直肠癌预防:证据、争论与未来方向

结直肠癌是最常见的恶性肿瘤之一,相对较差的预后和生存质量给社会带来沉重的卫生经济负担。近年来,阿司匹林用于结直肠癌预防的研究不断涌现,本篇将综合目前关于阿司匹林用于结直肠癌预防的主要观察性研究、随机对照临床试验研究等证据,分析研究结论,指出使用阿司匹林进行结直肠癌预防存在的证据缺口、指南的推荐情况以及未来的研究方向。笔者认为,目前使用阿司匹林进行结直肠癌预防的关键证据依然存在不足,决定是否使用阿司匹林进行结直肠癌预防时,应该综合病人的危险因素、治疗意愿以及效益-风险比等多种因素进行全面的评估,以期在最低的风险水平达到最好的预防效果。未来,还需对阿司匹林预防结直肠癌的作用机制、最佳剂量、并发症处理等进行进一步的研究。     

microRNA-451在结直肠癌组织中的表达及其临床意义

目的：探讨microRNA-451（miR-451）在结直肠癌组织中的表达及其临床意义。方法：采用实时荧光定量聚合酶链反应（real-time qPCR）的方法在40例结直肠癌患者癌组织与切缘正常黏膜标本,以及8种结肠癌细胞株中检测miR-451的表达水平,并分析其与临床病理资料之间的关系。结果：与结直肠正常黏膜组织比较,miR-451在结直肠癌组织及各种结直肠癌细胞株中均呈明显的低表达（均P<0.05）;按结直肠癌患者的不同临床病理特征分组比较发现,miR-451的表达差异与组织学类型和分化程度有关,在黏液性腺癌与低分化腺癌中表达水平最低（均P<0.05）。结论：miR-451在结直肠癌组织中呈低表达,且降低程度与结直肠癌分化程度及组织学类型相关。

     

理想小鼠结直肠癌肝转移模型的建立及研究进展

结直肠癌是世界上第三大常见的恶性肿瘤,尽管对结直肠癌的发病机制、病理、预防和治疗方面的认识有了许多进展,但患者仍有较高的病死率,其病死率与肝脏转移密切相关,因此研究结直肠癌肝转移的机制和控制疾病进展是改善这些患者生存期的重要措施。近年来小鼠结直肠癌肝转移模型已广泛应用于转移研究,笔者就目前应用于结直肠癌肝转移的小鼠模型及其特点进行综述并分析它们的优缺点。以期为研究者在选择小鼠结直肠癌肝转移模型时提供参考,并为开发更为理想的小鼠结直肠癌肝转移模型指明方向,并为结直肠癌肝转移机制研究提供线索。     

阿司匹林对结直肠癌细胞株细胞凋亡的影响

目的：通过检测阿司匹林对结直肠癌细胞株的影响，以探讨其对结直肠癌化学预防的机制。方法：培养结肠癌细胞株Caco-2，用不同浓度阿司匹林进行干预，并观察、检测其对细胞生长、增殖周期、凋亡及细胞形态的影响。结果：高浓度阿司匹林组细胞大量死亡；低浓度阿司匹林促进细胞凋亡，但不影响细胞增殖周期；随浓度增高，凋亡比率增大。阿司匹林能改变细胞形态及细胞的骨架结构。结论：阿司匹林能抑制结肠癌细胞增殖，促进其凋亡，并改变其骨架结构。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Immunomodulation in Transplantation with Photopheresis

Abstract: Photopheresis is a technique in which peripheral blood mononuclear cells, in the presence of a photoacti-vatable compound, are exposed extracorporeally to ultraviolet A light and reinfused, inducing a host autoregula-tory immune response. Experimental work and ongoing clinical studies are helping to define the role of this novel, safe, and non-toxic immunomodulating technology in the field of transplantation.