YAP1靶向抑制剂CA3对人子宫内膜癌细胞增殖和凋亡的影响及分子机制

目的 探讨YAP1靶向抑制剂CA3对人子宫内膜癌Ishikawa和RL95-2细胞增殖和凋亡的影响及分子机制。方法 采用不同浓度CA3处理Ishikawa和RL95-2细胞,利用CCK-8和克隆形成试验检测细胞增殖能力,微板检测系统检测细胞内ROS水平,流式细胞术检测细胞凋亡,Western blotting检测YAP1、MCM5、Bax和Bcl-2蛋白表达水平。结果 与对照组相比,CA3处理组能够明显降低细胞生存率、减少克隆形成数目、增强细胞内ROS水平和诱导细胞凋亡,下调YAP1、MCM5和Bcl-2蛋白表达水平,但对Bax蛋白表达水平没有影响。结论 CA3靶向沉默YAP1抑制细胞增殖和诱导细胞凋亡,起到明显的抗肿瘤作用,有望成为临床干预和治疗子宫内膜癌的潜在药物。     

参附注射液对家兔心脏骤停-心肺复苏模型循环恢复的影响

目的观察参附注射液对家兔缺氧型心脏骤停-心肺复苏 (CA- CPR)模型循环恢复的影响.方法 30只家兔随机分为三组,每组 10只;夹闭气管复制缺氧型 CA- CPR模型.预防组 (A组 )夹管前 10min、自主循环恢复后 8、 15min分别静注参附注射液,治疗组 (B组 )自主循环恢复后 8、 15、 22min静注参附注射液,对照组 (C组 )静注生理盐水,时间同 A组;监测夹管前后家兔的心电图、平均动脉压 (PAP)的变化,并记录开始 CPR至自主循环恢复时间和自主呼吸恢复时间、肾上腺素用量、撤呼吸机时间;自主循环维持 4h,并计算 4h存活率.结果三组 CPR成功率、 4h存活率相近;在自主循环恢复时间方面 A组明显快于 C组,在自主呼吸维持时间、肾上腺素用量、撤呼吸机时间方面则两组相近.结论参附注射液可明显缩短家兔缺氧型 CA- CPR模型的自主循环恢复时间,对促进 CA的循环恢复具有积极意义.     

乙型肝炎病毒感染者血清CA19-9水平与肝功能指标的临床分析

目的探讨乙肝病毒感染者血清糖类抗原19-9(CA19-9)、血清丙氨酸氨基转移酶(ALT)、天门冬氨酸转移酶(AST)、乙肝病毒脱氧核糖核酸(HBV-DNA)水平变化的临床意义。方法检测乙肝表面抗原阳性的不同病程的慢性乙肝、肝硬化、肝癌患者血清CA19-9、ALT、AST、HBV-DNA水平并进行统计学分析。结果乙肝病毒感染者血清CA19-9水平随乙肝病程进展而升高,与慢性乙肝轻、中、重度感染者的ALT、AST呈正相关,与HBV-DNA无相关性,肝硬化与肝癌两组间CA19-9水平变化无统计学意义。结论血清CA19-9可作为肝损伤程度的动态观察的指标之一,可辅助鉴别诊断肝癌。     

血清CA125测定在卵巢上皮癌中的应用价值

目的：探讨卵巢上皮性癌血清CA125的动态变化，在预测术前病人临床分期，估计预后，早期发现复发中的价值，以指导临床治疗。方法：采用放射免疫方法对52例卵巢上皮性癌患血清CA125进行连续监测。术前测定一次，术后每月测定一次，连续两年以上。结果：52例卵巢上皮性癌患术前有47例血清CA125＞35ku/L，诊断敏感性为91％，血清CA125水平与监床期别有关，临床期别愈晚，阳性率愈高，血清CA125值也愈高；各期术后1个月血清CA125值均较术前明显下降，P＜0．01；有25人两年内复发，其中23人复发前平均3．7个月血清CA125升高，术后4个月未控的5人中，4人术后血清CA125一直无明显下降，1人术后2个月降至正常，第3个月又上升。结论：血清CA125水平与临床期别有关。监测血清CA125对卵巢上皮性癌的诊断，指导治疗，预测得发，评价疗效有重要意义。     

Analysis of potential shifts associated with recurrent spreading depression and prolonged unstable spreading depression induced by microdialysis of elevated K in hippocampus of anesthetized rats

The potential shifts (ΔV_o) associated with spreading depression (SD) were analysed with the help of multiple extracellular recording and ion-selective microelectrodes in the CA1 region of the dorsal hippocampus of anesthetized rats. Recurrent waves of SD were induced by perfusing high K⁺ solution through microdialysis probes. SD-related ΔV_o had a composite wave shape, consisting of an early, rapidly shifting part (phase I) followed by a slower shift to a second negative maximum (phase II). ΔV_o shifts in stratum radiatum usually started earlier, always lasted longer and had lartger amplitude than those recorded in stratum pyramidale. The ΔV_o responses in stratum radiatum had an inverted saddle shape created by a transient relatively positive “hump” interposed between phases I and II. During this “hump”, the potentials in the two layers transiently approached one another. During continuous high K⁺ dialysis, successive ΔV_o waves episodes evolved according to a consistent pattern: while phase I remained unchanged, phase II increased in amplitude and duration with each episode. Eventually, a depressed state developed which lasted for many minutes, termed here prolonged unstable spreading depression. During phase I, ΔV_o and extracellular K ([K⁺]_o) changes were correlated. During phase II, [K⁺]_o decreased even as ΔV_o continued to increase. During SD, [Ca²⁺]_o decreased to <0.01 mM. During phases I and II, both [Ca²⁺]_o and [Na⁺]_o remained low. the recoverries of [Ca²⁺]_o and [Na⁺]_o had an initial fast and a later much slower phase and took several minutes longer than the recoveries of [K⁺]_o and ΔV_o. Depth profiles of ΔV_o and Δ[K⁺]_o revealed strikingly steep gradients early and late during a wave; but voltage and ion gradients were not precisely correlated either in time or in space. We conclude that ΔV_o of phases I and II are generated by different processes. Membrane ion currents cannot fully explain the ΔV_o responses. The possible contributions by ion diffusion and by active ion transport are discussed. The extremely low level to which [Ca²⁺]_o sinks during SD, and its two-phase recovery, indicate intracellular sequestration or binding of substantial amounts of Ca²⁺ ions. The residual deficit of [Ca²⁺_o following recovery of SP shifts may account for the persistent depression of synaptic transmission after repolarization of neurons.     

Topographically specific hippocampal projections target functionally distinct prefrontal areas in the rhesus monkey

The sources of ipsilateral projections from the hippocampal formation, the presubiculum, area 29a-c, and parasubiculum to medial, orbital, and lateral prefrontal cortices were studied with retrograde tracers in 27 rhesus monkeys. Labeled neurons within the hippocampal formation (CA1, CA1′, prosubiculum, and subiculum) were found rostrally, although some were noted throughout the entire rostrocaudal extent of the hippocampal formation. Most labeled neurons in the hippocampal formation projected to medial prefrontal cortices, followed by orbital areas. In addition, there were differences in the topography of afferent neurons projecting to medial when compared with orbital cortices. Labeled neurons innervating medial cortices were found mainly in the CA1′ and CA1 fields rostrally, but originated in the subicular fields caudally. In contrast, labeled neurons which innervated orbital cortices were considerably more focal, emanating from the same relative position within a field throughout the rostrocaudal extent of the hippocampal formation. In marked contrast to the pattern of projection to medial and orbital prefrontal cortices, lateral prefrontal areas received projections from only a few labeled neurons found mostly in the subicular fields. Lateral prefrontal cortices, lateral prefrontal cortices received the most robust projections from the presubiculum and the supracallosal area 29a-c. Orbital, and to a lesser extent medial, prefrontal areas received projections from a smaller but significant number of neurons from the presubiculum and area 29a-c. Only a few labeled neurons were found in the parasubiculum, and most projected to medial prefrontal areas. The results suggest that functionally distinct prefrontal cortices receive projections from different components of the hippocampal region. Medial and orbital prefrontal cortices may have a role in long-term mnemonic process similar to those associated with the hippocampal formation with which they are linked. Moreover, the preponderance of projection neurons from the hippocampal formation innervating medial when compared with orbital prefrontal areas followed the opposite trend from what we had observed previously for the amygdala (Barbas and De Olmos [1990]) (J Comp Neurol 301:1–23). Thus, the hippocampal formation, associated with mnemonic processes, targets predominantly medial prefrontal cortices, whereas the amygdala, associated with emotional aspects of memory, issues robust projections to orbital limbic cortices. Lateral prefrontal cortices receive robust projections from the presubiculum and area 29a-c and sparse projections from the hippocampal formation. These findings are consistent with the idea that the role of lateral prefrontal cortices in memory is distinct from that of either medial or orbital cortices. The results suggest that signals from functionally distinct limbic structures to some extent follow parallel pathways to functionally distinct prefrontal cortices. © 1995 Wiley-Liss, Inc.     

Current Source Density Profiles of Optical Recording Maps: a New Approach to the Analysis of Spatio-temporal Neural Activity Patterns

Spatio-temporal spreading of activity in the CA1 region of the rat hippocampal slice was studied by two experimental approaches. At identical locations in the tissue we measured both the extracellular field potential distribution with microelectrode recordings and the intracellular potential distribution by optical recording, using voltage-sensitive fluorescent dyes. Current source density analysis (CSD) was applied to the extracellular field potential distributions (eCSD) to enhance the spatial resolution. In order to obtain an analogous improvement for the optical recordings, we developed a new CSD transformation, which calculates the locations of the transmembrane current generators from the intracellular potential distributions (iCSD). Compared to the underlying fluorescence maps, the new iCSD profiles exhibit a considerable improvement in spatial resolution. Results can be directly interpreted in terms of physiological membrane processes, such as postsynaptic potentials and action potentials. The iCSD profiles show a surprisingly good correspondence with the classical eCSD profiles both qualitatively and quantitatively, the only difference being that cell body activity is reduced in amplitude. Thus, this new optical CSD analysis paves the way for a quantitative interpretation, rather than the hitherto predominantly qualitative interpretation of spatio-temporal activity profiles from optical recording measurements.     

赛拉嗪对麻醉大鼠海马CA1区乙酰胆碱含量的影响

应用乙酰胆碱选择性微电极技术,观察到小剂量赛拉嗪(2.0和6.0mg·kg^-1)可显著增加大鼠海马CA1区ACh的含量,而大剂量赛拉嗪(10.0mg·kg^-1)及咪唑克生(0.6mg·kg^-1)则作用相反。咪唑克生虽可明显拮抗赛拉嗪的作用,但海马CA₁区ACh的含量仍显著低于正常水平。在去兰斑核的大鼠上,赛拉嗪(2.0和6.0mg·kg^-1)及咪唑克生(0.6mg·kg^-1)分别对海马CA₁区ACh的含量具有减少和增加作用,且咪唑克生拮抗赛拉嗪的作用后,海马CA₁区ACh的含量基本恢复至正常水平。结果提示,赛拉嗪对麻醉大鼠海马CA₁区ACh含量呈双相性影响,咪唑可生虽能显著拮抗赛拉嗪的作用,但海马CA₁区ACh的含量仍明显低于正常水平,可能分别与赛拉嗪和咪唑克生降低或提高中枢NE能系统的功能有关。     

Effects of discrete kainic acid-induced hippocampal lesions on spatial and contextual learning and memory in rats

Substantial information is available concerning the influence of global hippocampal lesions on spatial learning and memory, however the contributions of discrete subregions within the hippocampus to these functions is less well understood. The present investigation utilized kainic acid to bilaterally lesion specific areas of the rat hippocampus. These animals were subsequently tested on a spatial orientation task using a circular water maze, and on an associative/contextual task using passive avoidance conditioning. The results indicate that both the dorsal CA1 and the ventral CA3 subregions play important roles in learning. Specifically, CA1 lesions produced a deficit in the acquisition of the water maze task and a significant memory impairment on the passive avoidance task. CA3 lesions also caused learning deficits in the acquisition of the water maze task, and produced even greater impairments in performance on the passive avoidance task. We conclude that CA1 and CA3 hippocampal subregions each play significant roles in the overall integration of information concerning spatial and associative learning.     

卵巢纤维卵泡膜细胞瘤合并血清CA125异常临床观察

目的探讨卵巢纤维卵泡膜细胞瘤合并血清CA125升高病例的临床特征和血清CA125升高的原因。方法回顾性分析8例卵巢纤维卵泡膜细胞瘤合并血清CA125升高患者的临床和病理资料,用免疫组化EnvisinTM法检测CA125和VEGF蛋白在肿瘤以及大网膜组织中的表达情况。结果8例卵巢纤维卵泡膜细胞瘤临床特征为单侧附件实质性包块,质地硬,与周围组织无黏连;影像学检查显示肿块内部血流缺乏或血流稀疏,无腹腔内转移病灶征象。其血清CA125中位值158IU/ml。免疫组化提示肿瘤和大网膜的CA125蛋白表达均为阴性,而VEGF均为强阳性。结论卵巢纤维卵泡膜细胞瘤合并血清CA125升高者术前经常误诊为卵巢癌。肿瘤细胞自身不分泌CA125,其血清CA125升高的机制有待进一步研究。