胃癌组织碱性成纤维细胞生长因子表达及对血管新生和肿瘤进展的影响

目的　探讨碱性成纤维细胞生长因子 (bFGF)在胃癌组织中表达及其对血管新生和肿瘤生物学行为的影响。方法　应用免疫组化SP法检测 74例胃癌 ,17例癌旁组织bFGF表达及间质微血管密度 (MVD)。结果　胃癌组织中肿瘤细胞、间质新生血管高度表达bFGF。癌组织bFGF表达(77.0 3% )明显高于癌旁组织 (2 9.4 1% ,P <0 .0 1)。癌旁胃黏膜及伴有肠上皮化生的胃黏膜表达bFGF较弱。bFGF高表达组的平均MVD值 (79.3± 11.2 )明显高于bFGF低表达组 (71.2± 11.9,P <0 .0 5 )。此外bFGF表达程度与胃癌淋巴结转移和癌浸润深度密切相关。结论　bFGF可促进肿瘤间质微血管生成 ,加速肿瘤浸润和转移。     

Ezrin蛋白表达对胃癌组织MVD的影响

采用免疫组化SP法检测正常胃黏膜、不典型增生胃黏膜及胃癌组织Ezrin蛋白的表达及微血管密度（MVD）。结果正常胃黏膜、不典型增生胃黏膜及胃癌组织中Ezrin蛋白阳性表达率及MVD值两两比较均有统计学差异（P〈0.05）。胃癌组织Ezrin蛋白的表达与肿瘤浸润深度和淋巴结转移密切相关（P〈0.01）;胃癌组织MVD值与其分化程度、浸润深度和淋巴结转移密切相关（P〈0.01）;Ezrin蛋白阴性的胃癌患者低于Ezrin蛋白阳性（P〈0.01）。提示Ezrin蛋白在胃癌组织中的高表达可促进胃癌组织的微血管生成,进而促进胃癌的侵袭与转移。     

胃癌组织Bmi-1蛋白、MMP-9蛋白、血管内皮生长因子表达情况和微血管密度变化及其临床意义

目的观察胃癌组织Bmi-1蛋白、MMP-9蛋白、血管内皮生长因子(VEGF)表达情况及和微血管密度(MVD)变化,探讨其临床意义。方法选取2010—2013年在邯郸市中心医院行胃癌切除术患者56例,收集其胃癌组织标本56份和残端正常胃黏膜组织标本40份。采用EliVisionTM免疫组织化学法检测Bmi-1蛋白、MMP-9蛋白、VEGF表达情况和MVD(CD34标记)。结果正常胃黏膜组织Bmi-1蛋白、MMP-9蛋白、VEGF阳性表达率分别为27.5%、35.0%、12.5%,低于胃癌组织中的76.8%、83.9%、89.3%(P0.05)。不同性别、年龄、肿瘤大小患者胃癌组织Bmi-1蛋白、MMP-9蛋白、VEGF阳性表达率比较,差异无统计学意义(P0.05);不同肿瘤分化程度、TNM分期及有无淋巴结转移患者胃癌组织Bmi-1蛋白、MMP-9蛋白、VEGF阳性表达率比较,差异有统计学意义(P0.05)。Bmi-1蛋白、MMP-9蛋白、VEGF阳性表达者MVD高于阴性表达者(P0.05)。胃癌组织中Bmi-1蛋白表达与MMP-9蛋白表达(r=0.450)、VEGF表达(r=0.493)呈正相关(P0.05)。结论 Bmi-1蛋白、MMP-9蛋白和VEGF在胃癌组织中均呈高表达,且肿瘤分化程度较低、TNM分期较晚和有淋巴结转移患者胃癌组织Bmi-1蛋白、MMP-9蛋白和VEGF阳性表达率明显升高,且与MVD密切相关。     

VEGF和MVD可作为判断胃癌患者预后和上消化道出血风险的指标

背景:血管内皮生长因子(VEGF)是主要血管生成调控因子之一,与肿瘤血管发生密切相关,微血管密度(MVD)是评价肿瘤血管发生的重要指标。有研究发现VEGF表达和MVD与胃癌患者的上消化道出血(UGIB)风险相关。目的:探讨VEGF和MVD与胃癌患者临床病理特征、预后和UGIB风险的关系。方法:收集60例伴或不伴UGIB胃癌患者的胃癌手术标本石蜡包埋组织,以免疫组化方法检测VEGF表达和MVD(计数CD34阳性血管内皮细胞)。结果:胃癌组织VEGF阳性表达率为51.7%(31/60),MVD均值为35.18±19.72。伴UGIB的胃癌患者VEGF阳性表达率和MVD均值显著高于不伴UGIB者(VEGF:64.5%对37.9%,P<0.05;MVD:42.70±15.50对27.13±20.80,P<0.01)。VEGF表达和MVD均与胃癌T分期和pTNM分期呈正相关(P<0.01),VEGF表达与肿瘤组织分化呈负相关(P<0.05),MVD与N分期呈正相关(P<0.001)。COX多元回归分析显示MVD是影响胃癌患者术后生存时间的危险因素,而VEGF与术后生存时间无关。结论:VEGF表达和MVD与胃癌患者的临床病理进展和UGIB风险相关,MVD为胃癌患者术后生存时间的重要影响因素,两者可共同作为判断胃癌患者预后和UGIB风险的有效指标。     

TLR4蛋白在胃癌组织中的表达及其与微血管密度的关系

目的探讨Toll样受体4(TLR4)蛋白在胃癌发生、发展中的作用及机制。方法采用免疫组化法检测52份胃癌组织及30份正常胃组织标本中TLR4蛋白表达;采用CD34抗体标记微血管内皮细胞,计算微血管密度(MVD)。分析TLR4蛋白表达、MVD与胃癌主要临床病理参数的关系。结果胃癌组织TLR4蛋白阳性率和MVD分别为76.9%和32.5±8.3,均显著高于正常胃黏膜(P<0.01);有淋巴结转移者TLR4阳性率显著高于无淋巴结转移者(P<0.05);TNM分期为Ⅲ+Ⅳ期者TLR4蛋白表达率明显高于Ⅰ+Ⅱ期者(P<0.05)。MVD与肿瘤TNM分期、淋巴结转移及分化程度密切相关(P<0.01,P<0.05)。Spearman等级相关分析表明,TLR4蛋白表达与MVD呈显著正相关(P<0.01)。结论 TLR4蛋白表达与胃癌的发生发展密切相关,其机制可能为促进肿瘤血管生成。     

一氧化氮合酶和微血管生成与胃癌发展的关系

目的　研究诱导型一氧化氮合酶 (iNOS)在人胃癌组织中的表达及其与胃癌微血管形成、淋巴结转移及临床分期的关系。方法　采用免疫组化S P法检测 50例原发性胃癌组织、癌周组织及 2 0例正常胃黏膜组织中iNOS的表达 ,同时检测微血管密度 (MVD) ,以抗CD3 4标记血管内皮细胞 ,并分析其与肿瘤行为之间的关系。结果　 50例胃癌组织中iNOS阳性表达率为 70 .0 % ,MVD均值为 2 2 .0± 9 .8,显著高于癌周组织 (16.2 % ,6.1± 3 .4)和正常胃组织 (15.0 % ,5.5± 2 .6;P <0 .0 1)。按TNM分期 ,Ⅳ期胃癌组织iNOS阳性表达率为 93 .8% ,MVD为 42 .3± 3 .7,两者显著高于Ⅰ、Ⅱ、Ⅲ期 ,差异有显著性 (P <0 .0 1)。有淋巴结转移组iNOS的阳性表达率为 84.6% ,MVD均值为 2 7.4± 6.5;无淋巴结转移组iNOS阳性表达率为 54.2 % ,MVD均值为 15.3± 4.7,两组差异有显著性 (P <0 .0 5)。iNOS阳性表达组及高MVD值 (≥ 2 2 .0 )组的 3年生存率均显著低于iNOS阴性表达组及低MVD值 (<2 2 .0 )组 ,差异有显著性 (P <0 .0 5)。结论　胃癌组织中iNOS高阳性表达 ,随着iNOS阳性表达的增强 ,MVD值也增加 ,两者呈正相关。iNOS的表达及MVD与胃癌TNM分期、淋巴结转移及预后有密切关系。iNOS的表达及MVD值可作为判断胃癌预后的重要指标     

胃癌中血管生成素-2的表达及意义

应用免疫组织化学方法检测55例胃癌组织、12例癌旁胃组织和正常胃组织中的血管生成素-2(Ang-2)蛋白的表达及微血管密度(MVD).发现Ang-2蛋白表达及MVD在胃癌组织中均显著高于癌旁正常组织及正常胃黏膜组织;胃癌中Ang-2表达与浸润深度、淋巴结转移、病理分期、肿瘤分化程度密切相关.认为Ang-2可能在胃癌的发生、发展中起重要作用,有望作为胃癌抗血管治疗的靶点.     

食管癌中抑癌基因PTEN表达及其对血管新生的影响

目的　探讨食管癌中抑癌基因PTEN(第 10号染色体同源丢失性磷酸酶—张力蛋白基因 )蛋白表达及其对血管新生和肿瘤生物学行为的影响。方法　应用免疫组化SABC法检测 60例食管鳞癌及其相应的癌旁正常组织中PTEN蛋白表达 ,用CD3 4 作为检测间质微血管密度 (MVD)标志物。结果　 60例癌旁正常组织PTEN蛋白全部阳性表达 ,食管癌组织中PTEN蛋白阳性表达率为 66.7% (P <0 .0 1)。PTEN蛋白表达与组织分化程度、淋巴结转移和浆膜浸润有明显相关性 (P <0 .0 5 )。PTEN蛋白表达强度与MVD呈负相关。PTEN蛋白阳性表达组的平均MVD值 ( 76.97± 4.98)明显低于阴性表达组 ( 89.5 0± 5 .67) ,P <0 .0 1。结论　PTEN有可能作为食管癌进展的肿瘤标志物 ,PTEN基因的丢失或突变可以促进肿瘤间质微血管生成 ,加速肿瘤浸润转移。     

三叶因子1表达与胃黏膜损伤及胃癌的关系

目的　测定三叶因子 1(TFF1)在正常及病理条件下胃黏膜中的表达情况 ,探讨TFF1在胃黏膜损伤修复及胃癌抑制中的作用及意义。方法　应用免疫组化方法测定正常及不同病理条件下胃黏膜中TFF1的表达情况 ,通过图像分析软件分析阳性信号平均吸光度值以了解其表达情况。结果　胃炎、胃溃疡及十二指肠球部溃疡患者TFF1表达明显高于正常胃黏膜 (0 .5 1± 0 .0 5 ,0 .5 1± 0 .0 6 ,0 .5 0± 0 .0 6比 0 .4 4± 0 .0 6 ;P值均 <0 .0 1)。胃腺癌患者癌旁组织表达 (0 .5 1± 0 .0 7)明显高于正常胃黏膜 ,而腺癌组织的表达强度则与癌组织的分化程度呈正比 ,分化程度愈低 ,表达愈弱 ,低分化腺癌无阳性表达 ,中、高分化腺癌表达 (0 .4 1± 0 .0 7)略低于正常黏膜 ,但差异无显著性 (P >0 .0 5 )。结论　TFF1表达随黏膜损伤程度的加重而表达增强 ,提示其在胃黏膜保护及促进上皮重建机制中具有一定的作用。TFF1在癌旁组织中表达增强提示其可能与肿瘤抑制及分化机制有关 ,而在癌组织中表达减弱可能与其分泌减少有关。     

胃癌组织中COX-2、VEGF的表达及临床意义

目的探讨COX-2和VEGF在人胃癌组织中的表达及临床意义。方法应用免疫组化SABC法检测45例人胃癌组织中COX-2、VEGF的表达,并以30例正常胃黏膜组织作为对照。对COX-2、VEGF的表达采用平均光密度测定,并对临床相关资料进行统计学分析。结果胃癌组织中COX-2、VEGF的平均光密度值(OD)为19.85±7.34,134.67±13.11,显著高于正常胃黏膜组织的表达(12.49±4.87,83.89±8.74,P<0.01),癌组织中COX-2、VEGF的表达与性别、年龄、部位、组织类型、分化程度无相关性,而与肿瘤直径、TNM分期、淋巴转移、远处转移(P<0.05)相关;同时,胃癌组织中COX-2与VEGF表达有显著相关性(r=0.473,P=0.005)。结论COX-2可能诱导VEGF的表达而促进肿瘤血管的生成和侵袭转移。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Language of CTO interventions – Focus on hardware

The knowledge of variety of chronic total occlusion (CTO) hardware and the ability to use them represents the key to success of any CTO interventions. However, the multiplicity of CTO hardware and their physical character and the terminology used by experts create confusion in the mind of an average interventional cardiologist, particularly a beginner in this field. This knowledge is available but is scattered. We aim to classify and compare the currently used devices based on their properties focusing on how physical character of each device can be utilized in a specific situation, thus clarifying and simplifying the technical discourse.