同步辐射成像技术应用于HCCLM3细胞裸鼠肝脏移植瘤新生血管形态学研究的初步实验

目的 应用同步辐射微血管造影技术进行裸鼠离体肝细胞癌肿瘤新生血管的形态学研究. 方法 建立高转移人肝癌细胞HCCLM3裸鼠肝脏移植瘤模型.肝脏移植瘤模型建立第28天,取模型鼠6只,随机分为2组(每组3只).第1组裸鼠经腹腔内注射戊巴比妥钠麻醉后开腹,经下腔静脉留置管,手动推注硫酸钡悬浮液,直至肝脏及肝肿瘤表面血管呈白色,结扎肝脏的血管和胆管后切除肝脏,浸泡在甲醛溶液里,准备成像.离体裸鼠肝癌新生血管成像在上海光源(SSRF)X射线成像与生物医学应用光束线站(BL13W)进行.第2组裸鼠腹腔内注射戊巴比妥钠麻醉后,开腹取肝肿瘤标本,行病理学检查,包括HE染色及免疫组织化学CD31、CD34和F8染色. 结果 同步辐射微血管造影结合显微CT获得了高质量的肿瘤新生血管图像,图像显示正常肝血管结构被迅速生长的肿瘤组织取代,可以清晰观察到肿瘤新生血管的形态特征及生长状况,肿瘤周围血管丰富、扭曲,瘤内血管稀疏,与免疫组织化光学显微图像所示肿瘤新生血管分布特征相似.同步辐射成像技术能分辨肿瘤内部最细的血管直径约20μm. 结论 采用硫酸钡作为造影剂,利用同步辐射微血管造影技术显示裸鼠肝肿瘤新生血管的方法可行.     

当归补血汤及其拆方影响肝脏血管新生的药效特点及作用机制

目的观察当归补血汤及其拆方影响肝脏血管新生的抗肝纤维化的药效特点。方法 48只Wistar大鼠随机分为正常组、模型组、当归补血汤组、黄芪组、当归组及索拉非尼对照组。以四氯化碳(CCl4)与高脂低蛋白饮食复合因素诱导肝纤维化模型。通过病理对肝组织形态学进行观察,试剂盒测定血清肝功能、肝组织丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)、一氧化氮合酶(NOS);盐酸水解法测定肝组织羟脯氨酸(Hyp);电镜观察肝窦内皮窗孔结构;同步辐射X线二维成像观察微血管。组间比较使用单因素方差分析,方差齐时用LSD进行两两比较,方差不齐时用Tamhane's T2。结果当归补血汤及其拆方组白蛋白(Alb)显著提高(P0.05)、AST显著降低(P0.05);当归补血汤及黄芪组ALT显著降低(P0.05);各用药组肝组织Hyp含量显著降低。各用药组血管纹理有不同程度的减少;窗孔数量增加。当归补血汤及其拆方组SOD活性显著升高(P0.05),全方及拆方组NOS显著降低(P0.05),黄芪组MDA显著降低(P0.05),全方组及黄芪组NO显著降低(P0.05)。结论当归补血汤及其拆方具有抗肝纤维化及抗血管新生的作用。其机制可能与保护肝窦内皮细胞损伤、抗脂质过氧化有关,黄芪改善炎症、抗脂质过氧化及NO释放作用较为突出。     

肝纤维化小鼠肝组织血管新生特点及其形成机制

目的 探讨肝纤维化小鼠肝组织血管新生特点及其形成机制.方法 C57BL/6小鼠随机分为正常对照组与模型18 h、4周、8周组,共4组.采用CCl4诱导小鼠肝纤维化模型.天狼猩红染色观察肝组织胶原沉积;免疫荧光检测肝组织vWF蛋白表达,分析微血管密度;扫描电镜及透射电镜观察肝窦内皮结构;Western blot法检测肝组...     

肝硬化门静脉高压CT和磁共振成像的表现及研究进展

门静脉高压是肝硬化最常见的并发症。无创的影像学在肝硬化肝实质评估、侧枝循环评价及食管胃底静脉曲张破裂出血评价方面具有重要价值。CT和磁共振成像(MRI)均可反映肝脏形态学、肝实质密度和信号以及血流动力学的变化,对疾病诊断和预后评估有重要的补充价值。CT和磁共振(MR)功能成像如灌注加权成像、MR弹性成像、MR弥散加权成像等,可提供量化的信息,对肝纤维化及早期肝硬化的诊断有潜在的临床应用价值。CT血管成像和MR血管成像,特别是非增强MR血管成像,可显示门静脉分支情况,有助于评估食管胃底静脉曲张破裂风险,发现早期预警指标。综合运用CT及MRI技术,深入研究其临床应用潜力,可以更好的发挥影像学在肝硬化门静脉高压诊断、病情评估及预后判断中的作用。     

磁共振T2WI肝脏信号强度指标评估慢性乙型肝炎肝纤维化的应用价值

目的探讨磁共振T2WI序列肝脏信号强度指标(SII值)对慢性乙型肝炎肝纤维化的诊断价值。方法选取2016年1月至2017年12月在我院接受治疗的118例慢性乙型肝炎患者作为肝纤维化组,同时选取20名健康人作为对照组。对入组者行肝脏MR平扫及动态增强扫描,并在MR检查后两天内行肝脏穿刺活检,根据病理结果依肝纤维化程度(S),将肝纤维化组分为S1级、S2级、S3级、S4级,在脂肪抑制T2加权成像序列(T2WI)测量肝脏信号强度与右侧竖脊肌信号强度的比值(SII),并进行统计学分析。结果肝纤维化组与对照组、S1与S4、S2与S4、S3与S4级间SII值差异有统计学意义(P0.05);S1与S2、S1与S3、S2与S3级间SII值差异无统计学意义(P0.05),绘制受试者工作特征曲线(ROC),SII值诊断S2及S3级以上肝纤维化程度的曲线下面积AUC=0.646、0.754,敏感度为74.5%、92.1%,特异度为68.2%、79.5%。结论 SII值能定量评估慢性乙型肝炎肝纤维化程度。     

超声弹性成像技术诊断非酒精性脂肪性肝炎肝纤维化的临床应用

目的探讨超声弹性成像技术评价非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)肝纤维化的诊断价值。方法用超声二维弹性成像技术观察65例NASH患者的肝弹性数值,二维彩超观察肝脾结构和门脾静脉内径和血流速度,以及血清肝纤维化指标,随机选取37例患者做肝CT平扫加增强扫描,4例行肝组织学检查,20例健康人做对照。结果 65例NASH患者的弹性数值水平明显高于正常对照组,其中19例弹性数值水平高于35的患者伴有肝纤维化指标活动性改变、CT和超声脾大及门脉直径轻度增宽等肝纤维化改变,肝纤维化程度越严重,弹性数值越大,弹性数值大于35提示NASH合并肝纤维化。结论超声弹性成像技术测定肝脏组织弹性数值,可动态评估NASH肝纤维化程度,为临床诊断NASH肝纤维化提供了一种无创、经济、客观和可动态观察的新的检测手段。     

不同程度肝纤维化的肝脏多层螺旋CT灌注成像初步研究

目的 探讨多层螺旋CT灌注成像在肝纤维化早期诊断中的应用价值.方法 33例受检者接受多层螺旋CT肝脏灌注成像检查,其中11例为无明显肝脏疾病的志愿者(对照组),22例经肝脏穿刺活检证实为肝纤维化患者,根据Ishak评分系统再分为轻度肝纤维化组(10例)和显著肝纤维化组(12例).计算各组的各项灌注指标并进行组间比较.结果 对照组、轻度肝纤维化组和显著肝纤维化组的肝动脉分数(HAF)晕升高趋势,均值分别为(18.49±9.69)%、(19.92±6.01)%、(21.31±7.47)%;平均通过时间(MTT)则呈降低趋势.三组的均值分别为(13.80±2.60)s、(12.35±1.31)s和(12.19±3.33)s.对照组、轻度肝纤维化组和显著肝纤维化组的平均血流量(BF)值分为(107.77±37.80)ml·100 g-1·min-1、(114.54±25.81)ml·100 g-1·min-1和(111.98±19.81)ml·100 g-1·min-1;平均血容量(BV)值分别为(16.61±5.78)ml·100 g-1、(17.07±2.94)ml·100 g-1和(16.42±5.53)ml·100 g-1.统计结果显示各组平均HAF、MTT、BF及BV值的差异无统计学意义(P>0.05).结论 CT肝脏灌注可定量测量各项肝脏血流灌注参数,一些灌注值的变化对肝纤维化分期具有一定程度的参考价值,但尚不能有效地进行肝纤维化的早期诊断.     

实时剪切波弹性成像检测肝脏硬度与血清肝纤维化指标及其与肝脏病理的相关性

目的:探讨实时剪切波弹性成像(supersonic shear imaging,SSI)测得肝脏硬度与血清肝纤维化指标及肝脏病理的相关性.方法:选取郑州大学第一附属医院2011-05/2012-07诊断为"自身免疫性肝病"患者70例,均进行血清肝纤维化指标检测,肝脏活检和SSI检测.分析肝脏硬度与血清肝纤维化指标及肝脏病理的相关性.结果:(1)肝脏硬度与肝组织炎症分级及纤维化分期有显著相关性(45.45,20.18,21.21,13.60vs15.18;19.33,37.29vs14.49;均P<0.05),相关系数为0.584和0.541;(2)肝脏硬度与Ⅲ型前胶原、Ⅳ型胶原、层粘蛋白、透明质酸均有显著相关性(12.02±8.55vs6.96±2.27;97.96±27.89vs78.67±25.57;306.78±208.48vs46.14±41.23;257.42±124.51vs88.05±15.08;P<0.05),相关系数为0.339,0.365,0.409和0.450;(3)肝组织炎症分级与纤维化分期有显著相关性(r=0.616,P<0.01).结论:SSI测得肝脏硬度与血清肝纤维化指标及肝脏病理有较好的相关性,SSI可动态监测肝纤维化进展,评估肝纤维化程度.     

强肝胶囊治疗非酒精性脂肪性肝纤维化的临床研究

目的：观察强肝胶囊治疗非酒精性脂肪性肝纤维化的疗效。方法：将104例非酒精性脂肪性肝纤维化患者随机分为两组。对照组40例进行基础护肝治疗,治疗组64例在此基础上加用强肝胶囊治疗,疗程均为6个月,观察治疗前后的临床症状、肝功能、肝纤维化谱、肝脏B超、肝脏MR扩散加权成像及肝脏病理情况。结果：治疗组患者治疗前后比较,其临床症状缓解,肝功能恢复,肝纤维化谱、肝脏B超、肝脏MR扩散加权成像及肝脏病理均显示出肝脏纤维化程度明显减轻,差异有显著性意义（P〈0.05）。治疗组与对照组治疗后比较肝纤维化程度明显改善,差异有显著性意义（P〈0.05）。结论：强肝胶囊不仅改善患者临床症状及肝功能,而且具有明显的改善肝脏纤维化程度的作用,是治疗非酒精性脂肪性肝纤维化的有效药物之一。     

瞬时弹性成像与实时组织弹性成像评估肝纤维化的比较

目的 对比分析瞬时弹性成像和实时组织弹性成像评估慢性肝病肝纤维化的价值.方法 对92例行肝组织学检查的慢性肝病患者同时行瞬时弹性成像和实时组织弹性成像检查,以肝组织病理学检查结果为金标准,比较瞬时弹性成像和实时组织弹性成像与肝纤维化病理分期的相关系数、诊断肝纤维化的受试者工作特征曲线下面积. 结果 瞬时弹性成像与肝纤维化病理分期的相关系数(r=0.755,95％ CI0.651 ～ 0.831,P=0.000)高于实时组织弹性成像(r=0.481,95％CI0.306 ～ 0.624,P=0.000),Z=3.07,P=0.002.瞬时弹性成像和实时组织弹性成像诊断肝纤维化(S≥2)、肝硬化(S=4)的受试者工作特征曲线下面积分别为0.903和0.740、0.915和0.786,瞬时弹性成像高于实时组织弹性成像(P值分别为0.003和0.020). 结论 瞬时弹性成像诊断慢性肝病肝纤维化效能优于实时组织弹性成像,但后者与二维超声图像融合,具有广泛的应用前景.     

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.