肿瘤坏死因子相关诱导凋亡配体与放化疗联用对喉癌细胞的协同杀伤效应及机制

Objective To determine the sensitivity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced apoptosis in Hep-2 cells by means of systematically evaluating the cytotoxicity of TRAIL alone and TRAIL in combination with chemotherapeutic agents (cisplatin, paclitaxel) or radiation in Hep-2 cells in vitro, and whether the synergistic killing effects correlated with the expression level of TRAIL receptors and the activity of caspnse-8 or caspase-9. Methods The cytotoxicities of TRAIL, cisplatin and paclitaxel were investigated by cell counting kit-8 (CCK-8) assay. The expression levels of four TRAIL receptors in Hep-2 cells after treated by TRAIL, chemotherapeutic agents or radiation alone and by combined treatments were measured by flow eytometry and Western blotting respectively. The growth inhibition effects of caspase-8 or caspase-9 inhibitor on Hep-2 cells were determined by CCK-8 assay, and the activities of caspase-8, caspase-9 and caspase-3 were measured by Western blotting. Results The half maximal inhibitory concentration(IC50) of TRAIL to Hep-2 ceils on 24 h was 596. 92 μg/L Cisplatin, paclitaxel and radiation had synergistic inhibitory effects with TRAIL on the growth of Hep-2 cell line. After the activity of caspase-9 was inhibited by Z-LETD-FMK, the inhibition effects of TRAIL, cisplatin and paclitaxel on Hep-2 cells decreased significantly (all P < 0. 05). The expressions of caspase-8, caspase-9 and the death receptors (DR4 and DR5) increased significantly (all P < 0. 05) after combined administration. Conclusions Hep-2 cells are resistant to the apoptosis induced by TRAIL and TRAIL can induce the apoptosis of Hep-2 cells through the endogenous apeptotic pathway. The increase of death receptors expression by chemotherapeutic agents or radiation could enhance the sensitivity of Hep-2 cells to TRAIL and the synergistic killing effects.     

药品行政保护品种介绍:神经系统与精神药物(五)(续完)

神经妥乐平片剂通用名:牛痘免疫病毒疫苗接种家兔炎症皮肤组织提取物片剂.商品名:神经妥乐平(Neurotropin)片剂.     

流式细胞术用于药物抗真菌效应的检测

目的尝试建立用流式细胞术检测药物抗真菌效应的新方法。方法以碘化丙锭为荧光染料,用流式细胞术检测标准菌株近平滑念珠菌ATCC22019在不同浓度氟康唑（FCZ）作用下各管平均荧光强度,探讨最佳实验条件。结果真菌MFI值随着FCZ浓度的增加而增强,其变化具有浓度依赖性,较好地反映了药物的抗真菌效应。结论成功建立用流式细胞术检测药物抗真菌效应的新方法,流式细胞术在该领域的应用值得进一步研究。     

A First-Principles Study on the Hydration Behavior of (MgO)n Clusters and the Effect Mechanism of Anti-Hydration Agents

Magnesia-based refractory is widely used in high-temperature industries; its easy hydration is, however, a key concern in refractory processing. Understanding the hydration mechanism of MgO will help in solving its hydration problem. Herein, the hydration behavior of (MgO)_n (n = 1–6) at the molecular level and the effect mechanisms of several anti-hydration agents on the hydration of (MgO)₄ were investigated with first-principles calculations. The results indicated that the following: (1) The smaller the (MgO)_n cluster size, the more favorable the hydration of MgO and the tendency to convert into Mg(OH)₂ crystal; (2) Anti-hydration agents can coordinate with the unsaturated Mg atom of (MgO)₄ to form a bond, increasing the coordination number of Mg, thus reducing its activity when reacting with H₂O; (3) The greater the number of −COOH groups and the longer the chain length in the anti-hydration agents, the better its effect of inhibiting the hydration of MgO. These findings could enhance the understanding of the mechanism of hydration of MgO and provide theoretical guidance for the design of novel anti-hydration agents.     

Impact of Freeze–Thaw Cycles on the Long-Term Performance of Concrete Pavement and Related Improvement Measures: A Review

Freeze–thaw damage is one of the most severe threats to the long-term performance of concrete pavement in cold regions. Currently, the freeze–thaw deterioration mechanism of concrete pavement has not been fully understood. This study summarizes the significant findings of concrete pavement freeze–thaw durability performance, identifies existing knowledge gaps, and proposes future research needs. The concrete material deterioration mechanism under freeze–thaw cycles is first critically reviewed. Current deterioration theories mainly include the hydrostatic pressure hypothesis, osmolarity, and salt crystallization pressure hypothesis. The critical saturation degree has been proposed to depict the influence of internal saturation on freeze–thaw damage development. Meanwhile, the influence of pore solution salinity on freeze–thaw damage level has not been widely investigated. Additionally, the deterioration mechanism of the typical D-cracking that occurs in concrete pavement has not been fully understood. Following this, we investigate the coupling effect between freeze–thaw and other loading or environmental factors. It is found that external loading can accelerate the development of freeze–thaw damage, and the acceleration becomes more evident under higher stress levels. Further, deicing salts can interact with concrete during freeze–thaw cycles, generating internal pores or leading to crystalline expansion pressure. Specifically, freeze–thaw development can be mitigated under relatively low ion concentration due to increased frozen points. The interactive mechanism between external loading, environmental ions, and freeze–thaw cycles has not been fully understood. Finally, the mitigation protocols to enhance frost resistance of concrete pavement are reviewed. Besides the widely used air-entraining process, the freeze–thaw durability of concrete can also be enhanced by using fiber reinforcement, pozzolanic materials, surface strengthening, Super Absorbent Polymers (SAPs), and Phase Change Materials. This study serves as a solid base of information to understand how to enhance the freeze–thaw durability of concrete pavement.     

Use of ginger to control nausea and vomiting caused by chemotherapy in patients with cervical cancer undergoing treatment: An experiment

Introduction:Uterine cervix tumors have an invasive nature, with the capacity to proliferate to surrounding organs such as the vagina, bladder, and rectum, as well as the capacity for dissemination and involvement of structures distant from its place of origin. According to the International Federation of Gynecology and Obstetrics, patients with stages IB I, IB I microscopic (small dimension <4 cm) are indicated for radiotherapy or adjuvant chemoradiotherapy with cisplatin (40 mg/m²). However, cisplatin has side effects such as hematological implications (anemia, neutropenia, and thrombocytopenia), gastrointestinal disorders (nausea, vomiting, diarrhea, constipation), and fatigue. Zingiber officinale contains bioactive compounds that act on pregnancy and postoperative nausea, chemotherapy-induced nausea and vomiting, and also in the management of fatigue, myalgia, and insomnia. This study aimed to evaluate the effects of ginger on chemotherapy-induced nausea and vomiting in patients with cervical cancer undergoing treatment with cisplatin and radiotherapy.Methods and analyses:A randomized intervention clinical and controlled trial with a triple-blind design is described, comparing the effects of institutional antiemetic therapy alone, as well as in combination with 2 different ginger concentrations.Ethics and dissemination:Due to the nature of the study, we obtained approval from the Division Ethics Committee of Liga Contra o Câncer. All participants signed an informed consent form prior to randomization. The results of this study will be published in peer-reviewed journals. The data collected will also be available in a public repository of data.Trial registration number:This study is registered in the Brazilian Registry of Clinical Trials under number RBR-47yx6p9. This study was approved by the Division Ethics Committee of Liga Contra o Câncer under CAAE 40602320.0.0000.5293.     

两种指标计算住院病人抗菌药物使用强度的适用性比较

目的：比较采用实际占用总床日数和收治病人人数天数计算住院病人抗菌药物使用强度（antibacterial use density, AUD）的准确性,以确定一个适用性更高的AUD计算方法。方法：分别使用实际占用总床日数和收治病人人数天数（即抽样时间段内出院人数×平均住院天数）计算上海市公共卫生临床中心2009-2011年每年,以及2012年1-3月每月住院病人的AUD,记为AUD1和AUD2,比较月度AUD1和AUD2、年度AUD1和AUD2的离散度。结果：月度AUD1的离散度显著小于月度AUD2离散度,年度AUD1和年度AUD2的离散度相差不大。结论：与收治病人人数天数相比,使用实际占用总床日数计算AUD适用性更佳,更能真实反映住院病人抗菌药物使用水平。     

DNA拓扑异构酶Ⅰ抑制剂诱导鼻咽癌上皮细胞凋亡的实验研究

拟从细胞凋亡角度出发，探讨能够诱导鼻咽癌上皮细胞凋亡的因素，为有效地防治该恶性肿瘤提供新的思路。方法：光镜下观察细胞的形态变化；流式细胞仪检测细胞周期变化及亚二倍体比例；ＤＮＡ凝胶电泳及二苯胺法测定ＤＮＡ片段化程度。结果：一定浓度的拓朴异构酶Ⅰ（Ｔｏｐｏｉｓｏ－ｍｅｒａｓｅⅠ，ＴＯＰＯⅠ）抑制剂喜树碱（Ｃａｍｐｔｏｔｈｅｃｉｎ，ＣＰＴ）体外作用于人低分化鼻咽癌上皮细胞系ＣＮＥ－２Ｚ细胞一定时间后，镜下可见细胞体积缩小，染色质凝聚，胞膜突起及凋亡小体形成等形态变化。２～１０μｍｏｌ／Ｌ的ＣＰＴ分别作用１２小时后作流式细胞仪检测，亚二倍体比例均为３０％左右；各浓度分别作用２４小时，亚二倍体比例均为５０％左右；同时细胞周期有明显的变化，主要表现为Ｇ２／Ｍ期细胞减少。ＤＮＡ琼脂糖凝胶电泳呈典型的梯形带。结论：拓朴异构酶Ⅰ抑制剂ＣＰＴ对人低分化鼻咽癌上皮细胞具有明显的凋亡诱导作用。     

变应性鼻炎的长期抗炎治疗

已经证实许多没有症状的变应性鼻炎(AR)患者存在亚临床的炎症状态,接触阈值以下的变应原剂量能够引起鼻黏膜炎性细胞的浸润,包括细胞黏附分子、鼻腔和结膜嗜酸性粒细胞以及其他炎性标记物的表达显著增加,这些都不会导致明显的过敏症状。虽然治疗AR通常以缓解症状为主,减轻无症状时期的炎性反应可能会对AR发病、进展以及严重程度有积极的影响。因此制定治疗方案时应该充分考虑到对于症状缓解后仍存在的潜在炎性反应。目前主要有三类治疗AR的药物,包括抗组胺药、抗白三烯药和鼻内糖皮质激素,鼻内糖皮质激素对AR患者持续炎症的长期抑制可能是最合理的治疗选择。