D2-40阳性微淋巴管密度与直肠癌进展的关系

目的探讨直肠癌中微淋巴管密度（MI．VD）、微血管密度（MVD）与淋巴结转移及其生物学行为之间的关系。方法应用免疫组化法检测76例直肠癌和瘤周、远端切缘黏膜中D2-40和CD34阳性标记的微淋巴管和微血管数，并应用Western blot法检测7例直肠癌组织中D2-40蛋白含量。结果直肠癌总MLVD（15．66±4．82）、前缘区MLVD（18．26±2．36）显著高于瘤周、远端切缘黏膜MLVD（5．70±2．95、6．00±3．12，P〈0．05），与Dukes’s分期、淋巴结转移、淋巴管受累呈正相关关系（P〈0．05）。直肠癌总MVD、前缘区MVD与Duke’S分期相关（P〈0．01）。结论微淋巴管密度，尤其在前缘区．与直肠癌的淋巴结转移及侵袭性生长有密切相关。干预直肠癌生长转移需要抑制血管生成的同时也要抑制淋巴管生成。     

非小细胞肺癌中血管内皮生长因子C表达与淋巴结转移关系的研究

目的探讨血管内皮生长因子C（VEGF—C）与非小细胞肺癌（NSCLC）淋巴管生成和淋巴结转移的关系。方法52例NSCLC患者分为淋巴结转移阳性组（25例）和淋巴结转移阴性组（27例）,采用半定量反转录PCR及免疫组织化学方法检测2组患者手术切除癌组织及196枚淋巴结组织（2组各98枚,淋巴结转移阳性组98枚中病理阳性淋巴结72枚,阴性26枚）中VEGF．CmRNA及蛋白的表达。结果淋巴结转移阳性组患者癌组织VEGF-CmRNA表达水平（0．273±0．179）明显高于淋巴结转移阴性组（0．089±0．087,P〈O．01）;阳性淋巴结组织VEGF—CmRNA表达水平（0．207±0．174）明显高于淋巴结转移阴性组的淋巴结组织（011±0．107,P〈0.01）。在淋巴结转移阳性组中,阳性与阴性淋巴结组织VEGF—CmRNA表达水平分别为0．207±0．174、0．196±0．186,差异无统计学意义（p〉O．05）。淋巴结转移阳性组15例患者中14例（93．3％）肺癌组织VEGF—C蛋白表达阳性,46枚阳性淋巴结组织中37枚（8014％）VEGF—C蛋白表达阳性;而淋巴结转移阴性组15例患者中仅1例（6．7％）肺癌组织VEGF-C蛋白表达阳性,52枚淋巴结组织VEGF-C蛋白表达均为阴性,组间差异均有统计学意义（均JD〈O．01）。结论VEGF—CmRNA与蛋白的表达水平与NSCLC淋巴结转移关系密切,在淋巴结转移的早期诊断中有潜在的应用价值。     

CD24蛋白与胃癌MVD表达及预后的关系

采用免疫组化SP法检测68例胃癌组织中的CD24蛋白及CD34,根据CD34的表达判断微血管密度（MVD）。结果显示,胃癌组织中CD24表达为-、＋、＋＋、＋＋＋者分别为7、15、20、26例,其MVD分别为（32.43±5.03）、（38.47±6.64）、（45.30±6.40）、（52.19±6.72）条/HP,CD24的表达与MVD呈正相关（r=0.72,P〈0.01）;随访死亡的51例胃癌中,CD24表达为-、＋、＋＋、＋＋＋者分别为5、11、15、20例,不同CD24表达者的病死率相比,P〈0.01。认为CD24蛋白高表达与胃癌血管生成及预后有关,可作为判断胃癌预后的指标之一。     

DC活化的特异性CTL对裸鼠胃癌移植瘤的杀伤效应

用人胃癌细胞抗原致敏成熟树突状细胞（DC）。将DC活化的特异性细胞毒性T细胞（CTL）注射到胃癌裸鼠体内。用流式细胞术（FCM）检测移植瘤细胞C0／G1、S、G2／M期细胞凋亡情况。结果DC活化的特异性CTL作用于裸鼠皮下移植瘤，可显著抑制其生长，瘤细胞出现不同程度的坏死、变性。特异性CTL作用后，裸鼠皮下移植瘤细胞的增殖指数（PI）为（24.39±2.46）％，显著低于非抗原特异CTL作用后组的（31.24±3.85）％和对照组的（32.78±4.17）％；凋亡细胞比率为（15.83±2.77）％，显著高于非抗原特异CTL组的（7.28±2.26）％和对照组的（9.15±1.33）％，P均〈0.05。认为胃癌细胞抗原致敏DCs活化的CTL在体内可特异性的抑制裸鼠移植瘤细胞生长、增殖，促进瘤细胞凋亡，有效预防裸鼠移植瘤的发生。     

食管癌组织中WISP3的表达变化及意义

目的探讨人食管癌组织中WISP3的表达变化及其与食管癌临床病理参数的关系。方法采用荧光实时定量RT-PCR和免疫组化法对186例食管癌患者的癌组织和癌旁正常组织中的WISP3进行检测。结果食管癌组织中WISP3 mRNA的ΔCt值为6.31±3.77、WISP3蛋白的阳性表达率为25.63%±7.81%,癌旁正常组织分别为8.93±3.83、7.50%±2.38%,两者相比,P均〈0.01;WISP3 mRNA的表达与食管癌淋巴结转移及肿瘤浸润深度及大小、分期有关（P均〈0.05）;WISP3蛋白表达与食管癌淋巴结转移、肿瘤浸润深度、分期相关（P均〈0.05）,WISP3蛋白是对食管癌患者生存率有影响的因素之一（相对危险度为2.287）。结论WISP3在食管癌中的表达增加,可作为食管癌临床分期、转移潜能及预后的评估指标。     

胃癌淋巴结转移与VEGF—D、VEGFR-3、LVD的关系

目的探讨胃癌淋巴结转移与血管内皮生长因子D（VEGF—D）、血管内皮生长因子受体3（VEGFR-3）、淋巴管密度（LVD）表达间的关系。方法对59例胃癌术后标本采用免疫组织化学sP法检测VEGF—D表达,用VEGFR-3抗体免疫组织化学sP法标记淋巴管,检测肿瘤组织及正常组织LVD。结果VEGF—D、VEGFR-3在癌组织中表达率分别为59．32％、67．80％,明显高于癌旁不典型增生组织及正常胃黏膜组织（P〈0．05）。癌周组织的LVD表达为（21．29±8．21）,明显高于周边正常组织（P〈0．05）。VEGF—D表达阳性组35例与阴性组24例的LVD分别为（23．15±7．58）和（11．93±5．31）,其差异具有统计学意义（P〈0．05）。VEGF—D、LVD在癌组织中的表达与淋巴结直径、淋巴结分期、浸润深度、TNM分期及分化程度有关（P〈0．05）。结论VEGF．D在胃癌组织中高表达,并与肿瘤的淋巴管形成及淋巴结转移密切相关。     

SELDI-TOF-MS技术在HD患儿血清蛋白质标记物检测中的应用

目的从先天性巨结肠（HD）患儿血清蛋白质中筛选特异的蛋白质标记物,构建诊断HD的血清蛋白质指纹图谱模型。方法采用表面增强激光解吸电离—飞行时间质谱（SELDI-TOF-MS）技术检测132例份血清标本（来自HD术前患儿64例份,术后40例份,术后复发5例份,对照组23例份）的蛋白质质谱,用支持向量机分析数据。结果筛选出质荷比（m/z）为3221.7、5639.2、6884.2的三个蛋白质标记物,其在HD术前组低表达（分别为2.96±1.17、15.57±8.87、4.09±1.78）,在对照组高表达（分别为4.95±0.99、30.31±6.18、8.31±3.07）,两组相比,P均〈0.01;在HD术后组高表达（分别为3.76±2.15、27.98±7.22、9.06±2.14）,与术前组相比,P均〈0.01,与对照组相比,P均〉0.05;5例术后复发者三种蛋白质标记物表达强度（分别为3.18±0.951、3.86±10.69、3.95±1.83）,与术前组相比,P均〉0.05。结论采用SELDI-TOF-MS结合支持向量机构建的血清蛋白质指纹图谱模型可用于HD的诊断及判断其是否完全根治。     

肥厚性心肌病患者合并心房颤动的危险因素分析

目的 探讨肥厚性心肌病合并心房颤动患者的危险因素。方法 纳入2015-01至2018-03间在我院住院的肥厚性心肌病的患者69例（HCM组）及肥厚性心肌病合并房颤患者23例（HCM-AF组）,统计患者临床资料及相关检查结果。以Logistic回归分析肥厚性心肌病患者发生房颤的危险因素。结果 单因素分析结果显示,HCM组与HCM-AF组在NYHA分级（2.33±0.69比3.00±0.85）、病程[1.0（1.0,2.0）年比5.5（1.1,17.5）年]、淋巴细胞计数（1.92±0.73比1.59±0.40）、NLR（2.27±1.20比3.37±2.32）、N末端B型利钠肽原[696.50（243.75,1788.00）pg/mL比1746.50（602.25,7719.75）pg/mL]、总胆固醇（4.28±0.96mmol/L比3.54±0.77mmol/L）、甘油三酯（1.98±1.68mmol/L比1.15±0.53mmol/L）、低密度脂蛋白胆固醇（2.34±0.76mmol/L比1.84±0.65mmol/L）、左心房内经（38.48±6.65mm比46.21±11.03mm）、左室射血分数（57.95±6.70比53.86±7.71）的差异均有统计学意义（P<0.05）。多因素Logistic回归分析发现,NYHA分级（OR=5.15, 95% CI 1.03~25.70,P<0.05）、病程（OR=1.20, 95% CI 1.04~1.39,P<0.05）、NLR（OR=2.03, 95% CI 1.10~3.76,P<0.05）、左心房内经（OR=1.10, 95% CI 1.02~1.19,P<0.05）是肥厚性心肌病患者发生房颤的独立危险因素。结论 NYHA分级差、病程长、NLR高和左心房内经增大是肥厚性心肌病患者发生房颤的独立危险因素。     

子宫内膜异位症患者血清、腹腔液中Ang-2和ENS的表达变化及意义

选择卵巢子宫内膜异位症（EMs）患者30例（研究组）、子宫肌瘤及输卵管绝育术（无子宫内膜病变）30例（对照组）,采用酶联免疫吸附试验检测两组患者血清及腹腔液中的血管生成素-2（Ang-2）及内皮抑素（ENS）。结果显示,研究组血清、腹腔液的Ang-2分别为（98.36±17.92）、（114.74±40.73）ng/ml,对照组分别为（33.91±7.17）、（37.66±6.09）ng/ml,两组相比,P均〈0.05;研究组血清、腹腔液的ENS分别为（7.50±1.91）、（5.31±0.91）pg/ml,对照组分别为（4.14±0.73）、（3.27±0.80）pg/ml,两组相比,P均〈0.05;研究组血清与腹腔液Ang-2含量呈正相关（r=0.75,P〈0.05）,与ENS含量也呈正相关（r=0.63,P〈0.05）。认为Ang-2和ENS参与了EMs的血管生成过程,二者在血清中的高表达有望作为EMs诊断及治疗随访的指标之一,腹腔微环境改变参与调节EMs异位病灶的生长和进展。     

血清pro-GRP、NSE、CEA、ADA检测在肺癌、肺结核鉴别诊断中的意义

目的探讨血清胃泌素释放肽前体（pro—GRP）、神经元特异性烯醇化酶（NSE）、癌胚抗原（CEA）、腺苷脱氨酶（ADA）的检测在肺癌和肺结核鉴别诊断中的临床应用价值。方法采用ELISA法检测120例肺癌患者、55例肺结核患者和50例正常对照者血清中pro—GRP、NSE和CEA的水平,应用全自动生化分析仪检测血清中ADA的水平。结果肺癌患者血清中NSE、pro—GRP、CEA的水平分别为（29．5±13．8）ng／ml、（169．2±79．8）pg／ml、（28．6±11．7）ng／ml,均明显高于肺结核组（P〈0．01）}NSE、pro—GRP在小细胞肺癌中的水平[（39．3±13．7）ng／ml,（291．2±217．5）pg／m1]明显高于腺癌[（16．9±7．2）ng／ml,（79．2±48．1）pg／ml]和鳞癌[（15．2±5．3）ng／ml,（816±62．1）pg／ml]（P〈0．01）;CEA在腺癌中的水平为（47．2±20．5）ng／ml,明显高于鳞癌[（21．5±9．8）ng／ml]和小细胞肺癌[（18．6±7．5）ng／m1]（P〈0．01）。肺结核患者血清中ADA的水平明显高于肺癌患者（P〈0．01）。结论血清pro．GRP、NSE、CEA、ADA对于肺癌和肺结核的鉴别诊断有一定的临床意义。NSE、pro—GRP二者可作为联合检测小细胞肺痛的标志物绢合．     

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.     

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.     

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.