氨磷汀减轻顺铂致大鼠肾损伤的超微结构研究

应用光学显微镜和透射电镜观察顺铂诱发的肾小管专性损伤及氨磷汀对其的保护作用。结果显示：单纯给大鼠腹腔内注射顺铂6mg／kg。可致肾近端小管直段上皮细胞严重坏死和凋亡,但在注射顺铂前,先用200mg／kg氨磷汀腹腔内注射后。可明显减轻由顺铂诱发的肾毒性损伤作用。结果表明：氨磷汀对顺铂所致的肾毒性损伤可起有效的保护作用。     

牛磺酸对顺铂导致培养的原代兔肾小管细胞损伤的保护作用

目的：研究牛磺酸对顺铂导致培养的原代兔肾近端小管细胞(PTC)损伤的保护作用。方法：在体外建立原代兔肾近端小管细胞培养。采用溴乙锭荧光法测量DNA链间交联和Fur-2／AM测量细胞内游离钙离子浓度。首先将牛磺酸(0．1，1，10g．L^-1)与PTC保温24小时,然后，加入顺铂使其终浓度达到26μmol.L^-1,再继续保温24小时。顺铂损伤组同样培养48小时。前24小时不加入牛磺酸和顺铂,后24小时加入顺铂使其终浓度为26μmol.L^-1。对照组不加入牛磺酸和顺铂，同样培养48小时。结果：顺铂导致损伤组形成DNA链间交联和细胞内游离钙离子浓度升高．牛磺酸1．10g．L^-1可明显降低DNA链间交联和细胞内游离钙离子浓度。结论：牛磺酸可保护顺铂对PTC的损伤。     

大鼠肝细胞癌微血管超微结构的透射电镜观察

二乙基亚硝胺(DEN)在自然界比较广泛地存在于食物中,可诱发多种动物肿瘤,在大鼠所诱发的肿瘤中主要为肝细胞癌(Hepatocellular carcinoma,HCC)。对其诱发动物大鼠肝癌的形态学研究,国内外已有一些报道,但对肿瘤组织中血管形成状况及超微结构特性报道较少。本实验旨在使用适当剂     

CO_2激光气化大鼠移植性肝癌的研究

我们从1978年10月起进行化学诱发大鼠肝癌的二氧化碳激光气化治疗实验,观察到连续波 CO_2激光能有效地气化大鼠肝癌结节,但化学诱发对照困难。为此,1979年起采用中国科学院上海细胞生物研究所建株的 BERH-2肝细胞性肝癌瘤株,手术移植于大鼠肝脏,制成肝内生长的 BERH-2肝细胞性肝癌模型,进一步研究激光对实验性肝癌的疗效并与肝叶     

实验性肝硬变假小叶内细胞超微形态观察

四氯化碳(CCl_4)具有原浆毒性,肝细胞对此尤为敏感,对其他肝小叶内细胞也有毒性作用,我们采用综合方法诱发大鼠肝硬变,在实验的不同时期处死动物,主要用电镜对肝硬变时假小叶内细胞超微形态进行了较为细致的观察,目的在于进一步了解肝硬变时肝内各种细胞的超微形态改变,希望能从而获得有助于阐明肝硬变形态发生的某些线索。     

大鼠肾缺血损伤后肾小管上皮细胞改变的研究

缺血可导致细胞损伤及死亡，缺血的程度不同，导致的后果也不同。本实验用大鼠贤缺血作为模型，观察肾小管上皮细胞结构改变情况，并对有关细胞死亡问题进行探讨。     

钚—239对大鼠肝细胞超微结构的影响

钚—239是毒性很强的放射性核素,经各种途径进入机体的钚,主要沉积于肝脏和骨骼。本文目的是观察钚对大鼠肝细胞超微结构的影响,探讨其损伤特点,为辐射防护提供参考资料。实验用Wistar大鼠,经腹腔一次注入硝酸钚溶液(PH_2),剂量为5uci/kg体重,对照组注入等量硝酸溶液     

肝细胞损伤对钙离子分布的影响

肝细胞损伤是临床常见现象。重金属中毒、药物代谢、制备再灌注等可导致氧自由基大量产生，使机体氧化与抗氧化机制失衡导致肝细胞急性损伤，同时H2O2可诱导细胞凋亡的发生。钙离子超负荷，可能与肝细胞损伤密切有关。研究肝细胞损伤时，细胞钙离子的分布特点具有重要临床意义。     

实验性急性出血坏死性胰腺炎时肝脏的病理形态学观察及肝细胞的凋亡

目的：从实验性急性出血坏死性胰腺炎(AHNP)早期开始动态观察大鼠肝组织的病理形态学变化,研究肝细胞凋亡的发生情况。方法：胰胆管内逆行注射5％的牛磺胆酸钠,建立大鼠急性出血坏死性胰腺炎模型,通过光镜及电镜观察肝组织的病理形态学变化,用原位末端标记法(TUNEL法)测定大鼠肝细胞发生凋亡的情况。结果：诱导AHNP3h后大鼠肝细胞出现气球样变性,随着疾病的发展损伤加重,肝细胞发生坏死,炎性细胞浸润,并有血栓形成;肝细胞在诱导3h后出现凋亡,且随时间延长,凋亡的数目也增多,肝细胞出现凋亡和坏死并存的现象。     

碲锌镉晶片的机械化学磨抛分析

对<111>方向的三块碲锌镉晶片进行了不同的机械磨抛、化学机械抛光、化学抛光,在相同的测量条件下用三维形貌干涉仪进行表面监测.比较了碲锌镉晶片不同的磨抛方法对碲锌镉晶片表面机械损伤的情况,开展了碲锌镉晶片不同的磨抛方法对损伤的去除程度的对比实验,进行了碲锌镉晶片表面粗糙度及平整度实现的研究.     

形态计量学在肝窦细胞超微结构研究中的应用

本文尝试以形状计量学方法用于常规超微病理诊断中。通过对肝窦内皮细胞及隐窝细胞多项参数的测定,初步提出了二种细胞在不同病理状态下的定量指标,为准确及可重复性的分析提供了数据,并为进一步过渡为三维体视学分析打下良好的基础。     

Transformable Nanoparticle‐Enabled Synergistic Elicitation and Promotion of Immunogenic Cell Death for Triple‐Negative Breast Cancer Immunotherapy

Although cisplatin‐based neoadjuvant chemotherapy is an efficient therapy approach for triple‐negative breast cancer (TNBC), it has dismal prognosis and modestly improved survival benefit. Here, a synergistic immunotherapy of TNBC premised on the elicitation and promotion of immunogenic cell death (ICD) response, through a transformable nanoparticle‐enabled approach for contemporaneous delivery of cisplatin, adjudin, and WKYMVm is reported. The nanoparticles can sequentially respond to matrix metalloproteinases‐2, pH, and glutathione to achieve structural transformation with the advantages of optimal size change, efficient drug delivery, and well‐controlled release. Cisplatin and adjudin can synergistically amplify reactive oxygen species (ROS) cascade and eventually increase the formation of hydrogen peroxide and downstream highly toxic ROS like ?OH, which can elicit ICD response by mechanisms of endoplasmic reticulum stress, apoptotic cell death, and autophagy. WKYMVm can further promote anti‐TNBC immunity by activation of formyl peptide receptor 1 to build stable interactions between dendritic cells and dying cancer cells. Thus, the nanoparticles achieve significant primary tumor regression and pulmonary metastasis inhibition as well as a remarkable survival benefit, with boosting of the innate and adaptive anti‐TNBC immunity.     

体外冲击波对肝细胞及其质膜Na^＋—K^—ATP酶活性的影响

体外冲击波碎石术对胆石症病人进行治疗的过程中对肝细胞的超微结构和功能有无不可逆的损伤是值得探讨的。用电镜酶细胞化学方法结合电镜Ｘ射线显微分析法对冲击波作用后肝细胞质膜Ｎａ＾＋－Ｋ＋－ＡＴＰ酶活进行检测，结果显示：施冲击波１５分钟后，肝细胞质膜Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶的活性见下降，４５分钟降至最低，随后逐渐恢复，２个月时已完全恢复接近正常对照，与相同时程肝细胞微结构变化对比，酶活性受损较早，恢复亦     

In Situ Supramolecular Self-Assembly of Pt(IV) Prodrug to Conquer Cisplatin Resistance

Drug resistance has always been a huge challenge that should be urgently conquered to improve the efficacy of anticancer drugs. Herein, a synergistic Pt(IV) prodrug, Npx-p_p-Pt(IV), is proposed, combining dual responsive behavior with dual drug resistance-related pathways deactivation. First, Npx-p_p-Pt(IV) can in situ form a supramolecular self-assembly with a nanofiber structure on the cancer cell surface triggered by phosphatase, which confines the drug in the tumor and effectively enhances the cellular uptake of cisplatin, resulting in a high cancer cell selectivity and an extremely low non-targeted cytotoxicity. After being endocytosed, the self-assembly shows glutathione-responsive cisplatin release and reverses the IC₅₀ of cisplatin-resistant cancer cells to that of sensitive ones. Second, the obtained Pt(IV) prodrug can significantly damage cisplatin-resistance cancer cells through cyclooxygenase-2 and nuclear factor-kappa B-mediated apoptosis pathways, which benefit from the integration of naproxen into the prodrug. The in vivo experiment demonstrates a tumor inhibition rate of 80%. Therefore, Npx-p_p-Pt(IV) is a multispecific cisplatin derivative, and in situ self-assembly is believed to be a new strategy to conquer drug resistance for clinical care.     

The visualization of hepatic vasculature by X-ray micro-computed tomography

In this study, X-ray micro-computed tomography (CT) was used to reconstruct the fine structure macro- and microvasculature in three dimensions in contrast-enhanced rat liver samples. The subsequent application in the experimental CC531s colorectal cancer model was concurrent with results obtained from confocal microscopy in earlier studies. The en bloc stains osmium tetroxide in combination with uranyl acetate provided an excellent contrasting result for hepatic tissue after a trial of several contrasting agents. X-ray micro-CT allowed us to image the large blood vessels together with the branching sinusoids of hepatic tissue in three dimensions. Furthermore, interruption of the microvasculature was noted when rats were injected with CC531s colorectal cancer cells indicating the presence of hepatic metastases.     

Enhancing Chemotherapy of p53‐Mutated Cancer through Ubiquitination‐Dependent Proteasomal Degradation of Mutant p53 Proteins by Engineered ZnFe‐4 Nanoparticles

A significant percentage of human cancers harbor missense mutations in the TP53 gene and express highly stabilized mutant p53 protein (mutp53) with tumor‐promoting gain‐of‐function (GOF) properties. Inducing mutp53 degradation is a viable precision anti‐tumor therapeutic strategy. Based on the previously reported finding that a zinc‐curcumin compound induced mutp53 degradation, a series of ZnFe nanoparticles (ZnFe NPs) are synthesized and it is found that ZnFe‐4, with an Zn:Fe ratio of 1:2, exhibits outstanding mutp53‐degrading capability. ZnFe‐4 induced ubiquitination‐mediated proteasomal degradation of several different mutp53 species, but not the wild‐type p53 protein. Cellular internalization, intracellular Zn++ elevation and increased ROS are all necessary for ZnFe‐4‐induced mutp53 degradation. Degradation of mutp53 by ZnFe‐4, abrogated mutp53‐manifested GOF, leading to increased p21 expression, cell cycle arrest, reduced cell proliferation and cell migration, and cell demise. ZnFe‐4 also sensitized to cisplatin‐elicited killing in p53 S241F ES‐2 ovarian cancer cells, and dramatically improved the therapeutic efficacy of cisplatin in a subcutaneous ES‐2 tumor model. The potential clinical utility of ZnFe‐4 is further demonstrated in an orthotopically‐implanted p53 Y220C patient‐derived xenograft (PDX) breast cancer model. ZnFe‐4 is the first reported mutp53‐degrading nanomaterial, and further materials engineering may lead to the development of zinc‐based nanoparticles with minimal toxicity and maximized mutp53‐degrading capability.     

Effect of concentration of cadmium sulfate solution on structural,optical and electric properties of Cd1-xZnxS thin films

Cd1-xZnxS thin films were deposited by chemical bath deposition(CBD)on the glass substrate to study the influence of cadmium sulfate concentration on the structural characteristics of the thin film.The SEM results show that the thin film sur-faces under the cadmium sulfate concentration of 0.005 M exhibit better compactness and uniformity.The distribution dia-grams of thin film elements illustrate the film growth rate changes on the trend of the increase,decrease,and increase with the increase of cadmium sulfate concentration.XRD studies exhibit the crystal structure of the film is the hexagonal phase,and there are obvious diffraction peaks and better crystallinity when the concentration is 0.005 M.Spectrophotometer test results demonstrate that the relationship between zinc content x and optical band gap value Eg can be expressed by the equation Eg(x)=0.59x2+0.69x+2.43.Increasing the zinc content can increase the optical band gap,and the absorbance of the thin film can be improved by decreasing the cadmium sulfate concentration,however,all of them have good transmittance.At a concen-tration of 0.005 M,the thin film has good absorbance in the 300-800 nm range,80％transmittance,and band gap value of 3.24 eV,which is suitable for use as a buffer layer for solar cells.     

多肽胰岛素正常转运经淋巴而非门脉途径IGMEI胰组织注射SEM观察

探讨胰岛素等多肽激素在细胞外的正常转运途径或规律,对免疫金标记外源性胰岛素（IGMEI）注射的大鼠胰组织冷冻切片,进行了二次电子和背散射电子图像（SEI／BEI）的扫描电镜（SEM）示踪性观察,SEM观察SEI显示胰腺小叶和小叶间结缔组织,血管和淋巴管,胰腺导管和胰岛的结构特点清晰可见,根据管腔内是否存在红细胞和内皮细胞的结构特点,可以区别血管或淋巴管。SEM观察BEI表明,较强的背散射电子出现在胰结缔组织间隙,淋巴管或毛细淋巴管内;然而,胰的血管或毛细血管内,无标记金颗粒的背散射电子或BEI微弱,结果提示,注射或释放入胰组织液中的胰岛素等多肽激素或分泌颗粒,其正常转运途径或规律,可能通过淋巴而非肝门静脉途径转运进入血液。