垂体腺苷酸环化酶激活肽对内皮细胞表面低密度脂蛋白受体分布的影响

为研究垂体腺苷酸环化酶激活肽对内皮细胞表面低密度脂蛋白受体分布的影响，以胶体金─低密度脂蛋白为示踪物，结合透射电镜技术观察垂体腺苷酸环化酶激活肽作用于体外培养的内皮细胞后，其表面低密度脂蛋白受体分布变化情况。结果表明，垂体腺苷酸环化酶激活肽作用于内皮细胞后，内皮细胞光镜及电镜下的形态与对照组无明显差异，但内皮细胞表面低密度脂蛋白受体分布发生了变化，胶体金─低密度脂蛋白颗粒单独出现率升高（P＜0．05），内皮细胞内吞胶体金─低密度脂蛋白减少。提示垂体腺苷酸环化酶激活肽可能通过影响内皮细胞表面低密度脂蛋白受体的分布状态而减少低密度脂蛋白入胞代谢，进而减少低密度脂蛋白通过内皮细胞进入内膜下的机会，从而在抗动脉粥样硬化方面发挥作用。     

高钾摄入对家兔血管内皮损伤后的抗增生作用

目的：观察高钾摄入对血管内皮损伤后的抗增生功能，探讨其对再狭窄的预防作用。方法：高脂饲养家兔分为钾剂治疗组（3％KCl100ml/d）和对照组，经髂动脉球囊扩张术建立血管内皮损伤模型，另设正常饮食和非髂动脉球囊扩张术的空白对照组，观察术后脂质过氧状况、血小板聚集功能、血管条3H-TdR掺入量和血管病理形态学改变。结果：（1）对照组MDA和PRMA均较空白组和治疗组显著升高（术后7天P＜0．05，术后30天P＜0.01），而空白组与治疗组之间无明显差异（P＞0．05）；对照组和治疗组SOD在术后30天均较空白组下降（P＜0．05）。（2）对照组3H－TdR掺入量较空白组明显升高（术后7天P＜0．01，术后30天P＜0．05），治疗组3H．TdR掺入量则较对照组明显下降（术后7天P＜0．01，术后30天P＜0．05）。（3）对照组管腔面积较治疗组明显减小（术后30天P＜0．01），而新生内膜面积、新生内膜面积／中膜面积治疗组显著低于对照组（术后7天P＜0.05），术后30天（P＜0．01）。结论：钾具有抗内膜增殖、抗氧化、抗血小板聚集等作用，可有效地抑制血管内皮损伤后再狭窄的发生。     

玉米苞叶对动脉粥样硬化家兔平滑肌细胞凋亡及p53和Fas蛋白表达的影响

目的：探讨玉米苞叶防治动脉粥样硬化（AS）的机制。方法：选用大耳白家兔，复制家兔AS模型，随机分为动脉粥样硬化模型组，玉米苞叶组和正常对照组，成模后给予玉米苞叶煎剂治疗，8w后处死家兔，采用流氏细胞术检测平滑肌细胞的凋亡率以及凋亡相关基因p53和Fas蛋白表达。结果：模型组血管平滑肌细胞的凋亡率明显高于对照组（P＜0．05），p53和Fas蛋白的表达增强（P＜0．05），主动脉壁肉眼观测出现典型斑块。玉米苞叶组平滑肌细胞的凋亡率明显低于模型组（P＜0．05），p53和Fas蛋白表达下调（P＜0．05）；主动脉斑块面积较模型组明显减小，结论：玉米苞叶通过调节p53和Fas蛋白表达而调节AS家兔平滑肌细胞凋亡。     

无症状性基底动脉粥样硬化患者动脉重塑临床研究

目的探究无症状性基底动脉粥样硬化的动脉重塑特征。方法回顾性分析北京协和医院2014年8月至2016年12月前瞻性建立的高分辨磁共振数据库,将基底动脉存在无症状性动脉粥样硬化性斑块的人群和基底动脉正常且未发生供血区缺血性卒中者进行对照研究。采用3D CUBE T1WI成像方法,测量并比较分析两组人群的斑块和管壁特征,包括管周面积、管腔面积、最大管壁厚度和基底动脉直径。结果研究共纳入无症状性基底动脉病变组46例和对照组55例。缩窄性重塑是无症状性基底动脉粥样硬化斑块的主要形式,占55.1%。1例患者的基底动脉可见缩窄性重塑斑块和扩张性重塑斑块共存。与扩张性重塑斑块相比,缩窄性重塑斑块的狭窄率更大(P0.01),重塑指数、管周面积、管腔面积、管壁面积和基底动脉直径更小(P均0.01)。与对照组相比,无症状性基底动脉病变组的基底动脉管周面积和直径差异均无统计学意义(P=0.246,P=0.137),而管壁面积(P0.01)和最大管壁厚度(P0.01)更大,管腔面积更小(P0.01)。结论无症状性基底动脉粥样硬化存在以缩窄性重塑为主的局灶性重塑,但不存在累及血管走行全程的普遍性重塑。     

无症状性基底动脉粥样硬化患者动脉重塑临床研究北大核心CSCD

目的探究无症状性基底动脉粥样硬化的动脉重塑特征。方法回顾性分析北京协和医院2014年8月至2016年12月前瞻性建立的高分辨磁共振数据库,将基底动脉存在无症状性动脉粥样硬化性斑块的人群和基底动脉正常且未发生供血区缺血性卒中者进行对照研究。采用3D CUBE T1WI成像方法,测量并比较分析两组人群的斑块和管壁特征,包括管周面积、管腔面积、最大管壁厚度和基底动脉直径。结果研究共纳入无症状性基底动脉病变组46例和对照组55例。缩窄性重塑是无症状性基底动脉粥样硬化斑块的主要形式,占55.1%。1例患者的基底动脉可见缩窄性重塑斑块和扩张性重塑斑块共存。与扩张性重塑斑块相比,缩窄性重塑斑块的狭窄率更大(P<0.01),重塑指数、管周面积、管腔面积、管壁面积和基底动脉直径更小(P均<0.01)。与对照组相比,无症状性基底动脉病变组的基底动脉管周面积和直径差异均无统计学意义(P=0.246,P=0.137),而管壁面积(P<0.01)和最大管壁厚度(P<0.01)更大,管腔面积更小(P<0.01)。结论无症状性基底动脉粥样硬化存在以缩窄性重塑为主的局灶性重塑,但不存在累及血管走行全程的普遍性重塑。     

老龄ApoE基因敲除小鼠动脉粥样硬化斑块的病理观察

目的：观察西方饮食喂养的老龄（≥48周）ApoE基因敲除小鼠血管动脉粥样硬化斑块的病理组织学状况。方法：选取6周龄雄性纯合子ApoE基因敲除小鼠30只，均予以西方饮食喂养，分别在喂养42周（48周龄）、54周（60周龄）、66周（72周龄）时，随机各取10只，取无名动脉做病理检测。酶法检测血脂情况，冰冻切片光镜下观察无名动脉粥样硬化斑块病理情况，图像分析管腔及斑块面积，免疫组化染色观察斑块中骨桥蛋白、α肌动蛋白的表达。von Kossa染色观察斑块钙化情况。结果：西方饮食喂养48周龄后，ApoE基因敲除小鼠主动脉弓内形成广泛而且典型的动脉粥样硬化成熟斑块，60周龄时，无名动脉内斑块面积、其与血管面积比率和自发破裂率最高，不稳定斑块比例最大（P〈0．05～〈0．01）。结论：长期西方饮食喂养ApoE基因敲除小鼠，是研究动脉粥样硬化成熟斑块很好的动物模型。     

低强度氦氖激光血管内照射对家兔血栓素、前列环素及脂质过氧化物的影响

通过观察低强度氦氖激光血管内照射（ILLLI）对饲脂家兔血浆中血栓素B2（TxB2）、6-酮-前列腺素F1α（6－keto－PGF1α）、脂质过氧化物（LPO）、TxB2／6-keto－PGF1α及主动脉和冠状动脉病理学改变，探讨ILLLI预防动脉粥样硬化（AS）的机制。结果表明：ILLLI可显著降低TxB2、LPO及TxB2／6－keto－PGF1α（P＜0.01），而对6-keto-PGF1α无升高作用（P＞0．05）。主动脉粥样斑块面积百分比与TxB2、LPO呈显著正相关（r=0．8641，P＜0．01），与6-keto－PGF1α是显著负相关（r=-0.7432，P＜.05）。光镜观察，ILLLI治疗后主动脉及冠状动脉粥样斑块病变程度明显减轻。提示：ILLLI具有预防AS的作用。     

冠脉造影无明显狭窄患者斑块面积大小对血管重构的影响

目的 用血管内超声（IVUS）探讨冠脉造影无明显狭窄患者的冠状动脉斑块面积大小对血管重构的影响。方法 临床拟诊冠心病（CAD）者,经冠脉造影（CAG）发现无明显狭窄（直径狭窄率〈50％）者22例行IVUS检查,根据CAG结果对罪犯血管行IVUS检查。分别分析血管面积与斑块面积之间、管腔面积与斑块面积之间的相关性。结果 （1）血管面积随斑块面积的增加而增加,成线性相关;（2）当斑块面积〈50％时,管腔面积与斑块面积成线性正相关（r=0．47,P〈0．01）。当斑块面积1≥50％时,管腔面积与斑块大小不相关（r=0．43,P〈0．05）。结论 冠脉造影无明显狭窄患者,冠状动脉血管面积、管腔面积与斑块面积存在一定相关性。斑块面积大小对血管重构具有一定的影响。     

颈动脉斑块破裂动物模型的建立

目的：建立颈动脉斑块破裂的动物模型。方法36只载脂蛋白E（ ApoE）缺陷小鼠,随机分为未结扎组、单纯结扎组、结扎套管2天组、结扎套管4天组、结扎套管7天组和假手术组各6只,除未结扎组外各组结扎其左侧颈总动脉并饲以普通饮食。假手术组小鼠套管后即刻取下套管。结扎套管2天组、结扎套管4天组、结扎套管7天组于结扎处近段放置套管,分别于套管后第2、4和7天剪取结扎侧颈总动脉。血管切片,行HE、Masson胶原染色,计算病变血管管腔狭窄率、管壁厚度、单位中膜面积细胞数和单位内膜面积胶原含量;应用免疫组化法检测平滑肌α肌动蛋白（αSMC-actin）、血管假性血友病因子（ vWF）表达。结果单纯结扎组结扎动脉管腔内膜增生明显,管腔狭窄,斑块内散在分布大量泡沫细胞,斑块表面可看到明显纤维帽形成。未结扎组、单纯结扎组管腔狭窄率分别为0．10％±0．018％、0．88％±0．033％,中膜厚度分别为（0．44±0．02）、（0．70±0．04）mm,单位中膜面积细胞数分别为（16．5±1．03）、（12．7±1．07）个,两组比较,P均＜0．05。单纯结扎组、结扎套管2天组、结扎套管4天组、结扎套管7天组和假手术组斑块破裂分别为0、5、4、6、0只;单位斑块面积内胶原含量分别为0．47±0．04、0．09±0．03、0．12±0．04、0．16±0．08、0．41±0．07,单纯结扎组与套管各组比较,P均＜0．05。单纯结扎组动脉斑块内部和纤维帽处均可检测到αSMC-actin表达,但纤维帽处表达更明显;斑块破裂后局部仍有表达,但纤维帽处表达减弱。 vWF在部分斑块内表达,在斑块破裂处无表达。结论通过结扎并套管成功制作了小鼠颈动脉斑块破裂模型。     

雌激素抑制去卵巢家兔实验性主动脉粥样硬化的形成

为探讨雌激素对动脉粥样硬化的作用和机制，以不同剂量雌激素或联合应用孕激素来替代治疗去卵巢动脉粥样硬化家兔。分别于实验前、第4和14周末分别测定血清脂质、丙二醛和超氧化物歧化酶，实验第14周末测定血浆氧化型低密度脂蛋白、6－酮基－前列腺素F1α和血栓素B2浓度，并做病理形态学检查。结果发现，与对照组相比，激素替代治疗各组血清总胆固醇、甘油三酯、丙二醛、氧化型低密度脂蛋白及血栓素B2浓度显著降低（P＜0．01，P＜0．05）；而血浆6-酮基-前列腺素F1α浓度显著增高（P＜0．05）；激素替代治疗组主动脉斑块面积百分比平均减少了57．8％（P＜0．01）。孕激素对雌激素的作用无影响。以上提示雌激素能够抑制家兔主动脉粥样硬化形成，其机制可能与改善脂质作用，抑制过氧化形成和调节前列腺素代谢有关。     

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.     

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.     

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.     

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.     

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.     

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.     

High prevalence of distal sensory polyneuropathy in antiretroviral-treated and untreated people with HIV in Tanzania

Objectives To describe the prevalence of distal sensory polyneuropathy (DSP), a complication of both advanced HIV disease and of antiretroviral therapy (ART), amongst Tanzanians with HIV, on and off ART (including stavudine) with CD4 counts above and below 200 cells/μl. Methods We recruited participants attending ART clinic into four groups: >6 months ART exposure and (i) CD4 < 200 cells/μl or (ii) CD4 > 200 cells/μl (ART/CD4 < 200 and ART/CD4 > 200, respectively); ART‐naïve and (iii) CD4 < 200 cells/μl or iv)CD4 > 200 cells/μl (noART/CD4 < 200 and noART/CD4 > 200, respectively). Primary outcome was DSP, as defined by presence of at least one symptom and one sign. Results Of 326 evaluable participants, 81 (32 men, median age 38 years, median CD4 142 cells/μl) were enrolled in the ART/CD4 < 200 group, 78 (17 men, median age 37 years, median CD4 345 cells/μl) in ART/CD4 > 200, 81 (30 men, median age 37 years, median CD4 128 cells/μl) in noART/CD4 < 200 and 86 (22 men, median age 33 years, median CD4 446 cells/μl) in noART/CD4 > 200. Numbness was the most commonly reported symptom. DSP prevalence ranged from 43.2% in ART/CD4 < 200 to 20.9% in noART/CD4 > 200. DSP was more common among men (adjusted odds ratio [aOR] 1.9, 95% confidence interval [CI] 1.2–3.3) and older participants (aOR 2.7, 95% CI 1.1–6.2 for age 40 + vs. <30 years). Conclusion Distal sensory polyneuropathy is common amongst those attending this clinic, even those with no ART exposure and a CD4 count above 200 cells/μl. Stavudine and didanosine expose HIV‐infected patients to an additional avoidable risk of DSP. Access to non‐neurotoxic ART regimes as well as earlier HIV diagnosis and initiation of ART is needed.