丙戊酸增强人卵巢癌耐药细胞株COC1/DDP对顺铂敏感性的研究

探讨丙戊酸是否增强COC1/DDP对顺铂的敏感性并初步探讨其机制.采用WST-1、流式细胞术、免疫细胞化学法.结果丙戊酸与顺铂联合对细胞生长抑制和凋亡诱导明显强于顺铂组;NF-κB P65的表达量顺铂组高于对照组,联合组明显低于顺铂组.因此,丙戊酸增强COC1/DDP对顺铂的敏感性,且与NF-κB有关.     

丙戊酸增强人卵巢癌耐药细胞株COC1/DDP对顺铂敏感性的研究

探讨丙戊酸是否增强COC1/DDP对顺铂的敏感性并初步探讨其机制。采用WST-1、流式细胞术、免疫细胞化学法。结果丙戊酸与顺铂联合对细胞生长抑制和凋亡诱导明显强于顺铂组;NF-κBP65的表达量顺铂组高于对照组,联合组明显低于顺铂组。因此,丙戊酸增强COC1/DDP对顺铂的敏感性,且与NF-κB有关。     

NF-κB圈套寡脱氧核苷酸联合紫杉醇对肺癌细胞增殖凋亡的影响

探讨NF-κB圈套寡脱氧核苷酸(NF-κB decoy ODN)联合紫杉醇对肺癌细胞增殖凋亡的影响。培养人肺癌细胞A549:(1)脂质体瞬时转染细胞;(2)MTT试验观察细胞生长曲线;(3)流式细胞术检测细胞凋亡率。NF-κB decoyODN使细胞生长受到抑制,NF-κBdecoy ODN联合紫杉醇使细胞凋亡增加。NF-κB decoy ODN联合紫杉醇可增强对肺癌细胞增殖的抑制及凋亡的诱导。     

NF-κB圈套寡脱氧核苷酸联合紫杉醇对肺癌细胞增殖凋亡的影响

探讨NF-κB圈套寡脱氧核苷酸(NF-κB decoy ODN)联合紫杉醇对肺癌细胞增殖凋亡的影响.培养人肺癌细胞A549:(1)脂质体瞬时转染细胞;(2)MTT试验观察细胞生长曲线;(3)流式细胞术检测细胞凋亡率.NF-κB decoy ODN使细胞生长受到抑制,NF-κB decoy ODN联合紫杉醇使细胞凋亡增加.NF-κB decoy ODN联合紫杉醇可增强对肺癌细胞增殖的抑制及凋亡的诱导.     

盐酸戊乙奎醚对心脏瓣膜置换术患者NF-κB表达的影响

为研究盐酸戊乙奎醚对心脏瓣膜置换术患者心肌NF-κB转录活性的影响,选取择期瓣膜置换术患者60例,随机分为对照组（C）、盐酸戊乙奎醚组1（P1）、盐酸戊乙奎醚组2（P2）,每组20例。结果心肌缺血再灌注后,P1、P2组NF-κB的转录活性明显下降,可见盐酸戊乙奎醚可以抑制心肌NF-κB的激活,在一定程度上具有心肌保护作用。     

盐酸戊乙奎醚对心脏瓣膜置换术患者NF-κB表达的影响

为研究盐酸戊乙奎醚对心脏瓣膜置换术患者心肌NF-κB转录活性的影响,选取择期瓣膜置换术患者60例,随机分为对照组(C)、盐酸戊乙奎醚组1(P1)、盐酸戊乙奎醚组2(P2),每组20例.结果心肌缺血再灌注后,P1、P2组NF-κB的转录活性明显下降,可见盐酸戊乙奎醚可以抑制心肌NF-κB的激活,在一定程度上具有心肌保护作用.     

慢性肺心病并发多器官衰竭（MOF）患者NF-κB活性的变化及其临床意义

为观察慢性肺心病并发多器官衰竭(MOF)患者外周血单核细胞(PBMC)中核因子κB(NF-κB)活性的变化及其在慢性肺心病并发MOF的作用,将30例慢性肺心病并发MOF患者作为观察组,同时选择30例无MOF的慢性肺心病患者作为对照组结论显示慢性肺心病并发MOF患者PBMC中NF-κB的活性显著增高,NF-κB活化后上调TNF-α、IL-6等的表达在MOF的发生、发展过程中起着重要作用。     

慢性肺心病并发多器官衰竭(MOF)患者NF-κB活性的变化及其临床意义

为观察慢性肺心病并发多器官衰竭(MOF)患者外周血单核细胞(PBMC)中核因子κB(NF-κB)活性的变化及其在慢性肺心病并发MOF的作用,将30例慢性肺心病并发MOF患者作为观察组,同时选择30例无MOF的慢性肺心病患者作为对照组结论显示慢性肺心病并发MOF患者PBMC中NF-κB的活性显著增高,NF-κB活化后上调TNF-α、IL-6等的表达在MOF的发生、发展过程中起着重要作用.     

不同浓度顺铂对肺癌A549细胞凋亡相关蛋白Bcl-2与Bax表达的影响

通过观察不同浓度顺铂作用下肺腺癌A549细胞凋亡相关蛋白Bcl-2和Bax表达及表达比例的变化,探讨Bcl-2和Bax与铂类药物敏感性的关系。研究采用CCK8检测顺铂作用下A549细胞的半数抑制浓度IC50值,确定顺铂用药范围。实时定量PCR、Western blotting法检测不同浓度顺铂作用下肺腺癌A549细胞中抗凋亡因子Bcl-2、促凋亡因子Bax的mRNA及蛋白表达情况,以及两者表达比例的变化。结果随着顺铂浓度的不断升高,Bcl-2及Bax的表达均增加,而抗凋亡因子Bcl-2升高的趋势更为明显,Bcl-2/Bax表达比例增加。提示随着顺铂浓度的提高,抗凋亡蛋白Bcl-2表达比例逐渐增加,可能会部分降低铂类促肿瘤细胞凋亡的作用,从而参与了铂类的耐药过程。     

紫杉醇、顺铂在中晚期宫颈癌同步放化疗中的临床疗效比较

探讨61例中晚期宫颈癌患者分别行紫杉醇、顺铂同步放化疗的疗效和不良反应。两组近期有效率,1年、2年、3年总生存率,无瘤生存率差异无统计学意义（P＞0．05）。紫杉醇同步放化疗组主要表现为白细胞计数下降、神经毒性和心脏毒性;顺铂同步放化疗组主要表现为消化道反应和肝肾功能受损;两组的消化道反应、神经毒性、肝肾功能受损发生率差异有统计学意义（P＜0．05）,紫杉醇组骨髓抑制、心脏毒性发生率均高于顺铂组,但差异无统计学意义（P ＞0．05）。顺铂组肝功能受损发生率稍高于紫杉醇组,但差异无统计学意义（P＞0．05）。同步放化疗中使用紫杉醇治疗中晚期宫颈癌疗效与顺铂相当,不良反应可耐受。     

Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways

Evidence indicates that systemic administration of lipopolysaccharide (LPS) induces brain inflammation, ultimately resulting in cognitive deficits. Ursolic acid (UA), a plant-derived pentacyclic triterpenoid, is well known to possess multiple biological functions, including antioxidant, anti-tumor and anti-inflammatory activities. In the present study, we assessed the protective effect of UA against the LPS-induced cognitive deficits in mice. We found that UA significantly improved cognitive deficits of LPS-treated mice in open field, step-through passive avoidance and Morris water maze tasks. One potential mechanism of this action was attributed to the decreased production of pro-inflammatory markers including COX-2, iNOS, TNF-α, IL-1β, IL-2 and IL-6 in LPS-treated mouse brain. Mechanistically, UA markedly inhibited LPS-induced IκBα phosphorylation and degradation, NF-κB p65 nuclear translocation and p38 activation in mouse brain, but did not affect the activation of TLR4, MyD88, ERK, JNK and Akt. Taken together, these results suggest that UA may be useful for mitigating inflammation-associated brain disorders by inhibiting pro-inflammatory factors production, at least in part, through blocking the p38/NF-κB signaling pathways.     

Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear

Extinction of conditioned fear is an important model both of inhibitory learning and of behavior therapy for human anxiety disorders. Like other forms of learning, extinction learning is long-lasting and depends on regulated gene expression. Epigenetic mechanisms make an important contribution to persistent changes in gene expression; therefore, in these studies, we have investigated whether epigenetic regulation of gene expression contributes to fear extinction. Since brain-derived neurotrophic factor (BDNF) is crucial for synaptic plasticity and for the maintenance of long-term memory, we examined histone modifications around two BDNF gene promoters after extinction of cued fear, as potential targets of learning-induced epigenetic regulation of gene expression. Valproic acid (VPA), used for some time as an anticonvulsant and a mood stabilizer, modulates the expression of BDNF, and is a histone deacetylase (HDAC) inhibitor. Here, we report that extinction of conditioned fear is accompanied by a significant increase in histone H4 acetylation around the BDNF P4 gene promoter and increases in BDNF exon I and IV mRNA expression in prefrontal cortex, that VPA enhances long-term memory for extinction because of its HDAC inhibitor effects, and that VPA potentiates the effect of weak extinction training on histone H4 acetylation around both the BDNF P1 and P4 gene promoters and on BDNF exon IV mRNA expression. These results suggest a relationship between histone H4 modification, epigenetic regulation of BDNF gene expression, and long-term memory for extinction of conditioned fear. In addition, they suggest that HDAC inhibitors may become a useful pharmacological adjunct to psychotherapy for human anxiety disorders.     

Sym（f（n））上最终无不动点且最终不同的集合

本文研究的是极大的最终无不动点且最终不同的集合（m.e.fd.集合）的基数,并讨论了与此相关的一个连续统常量,证明了以下结果：1.c_e〉W2.存在一个大小为2~w的m.e.f.d.集合。3.ZFC＋MA c_e=2~w4.令M｜=ZFC＋ CH,κ是M中满足条件w1≤κ〈2~w=λ的基数。则存在一个c.c.c.的力迫概念P,使得在模型M~p中有：（i）2~w=λ（ii）存在一个m.e.f.d的集合,其基数为κ。5.令M｜=（ZFC＋CH）。则在M中存在一个基数为W1的m.e.f.d.的集合A,使得对任意一个M上的Cohen力迫概念P,A在M~p中还是m.e.f.d.的集合。     

洛铂与顺铂联合培美曲塞一线治疗晚期肺腺癌的临床观察

观察洛铂与顺铂联合培美曲塞治疗晚期肺腺癌的疗效和不良反应。将64例肺腺癌患者分为PL组（培美曲塞＋洛铂）和PC组（培美曲塞＋顺铂）,每2个周期评价疗效,观察不良反应。结果两组疗效无显著差异。PL组恶心、呕吐、腹泻较轻,口腔黏膜炎反应较重。结论两组疗效相当,但洛铂组不良反应较轻,耐受性好。     

帕罗西汀配合心理干预对术后焦虑情绪的影响

研究帕罗西汀配合心理干预对术后焦虑情绪的影响。90例手术患者随机分为三组:A组术后常规治疗,B组常规治疗+帕罗西汀,C组常规治疗+帕罗西汀+心理干预。1周末B、C两组SAS和HAMA得分显著下降(P0.01),HAMA得分比较差异显著(P0.01),与A组比较差异显著(P0.01);2周末A组HAMA评分显著改善(P0.01)。帕罗西汀配合心理干预对术后焦虑情绪有显著而快速的影响。     

右旋柠烯对幼鼠颞叶癫痫海马星形胶质细胞的影响

探讨右旋柠烯（D-L）对癫痫幼鼠海马星形胶质细胞胶质原纤维酸性蛋白（GFAP）的影响。利用尼氏染色及免疫组化技术观察匹罗卡品致癫痫的幼鼠经药物（左乙拉西坦、丙戊酸钠、D-L）治疗后星形胶质细胞形态学变化和GFAP的表达。尼氏染色显示药物治疗后幼鼠海马胶质神经元脱失较未治疗的幼鼠明显减轻;海马GFAP免疫阳性细胞数在药物治疗后的幼鼠较未治疗幼鼠明显减少（P〈O．05）。幼鼠癫痫发作可能与海马星形胶质细胞增生有关,D-L对发育期大鼠颞叶癫痫星形胶质细胞的增生及GFAP的表达似有抑制作用,推测D-L可能具有抗癫痫作用。     

The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear

Histone modifications contribute to the epigenetic regulation of gene expression, a process now recognized to be important for the consolidation of long-term memory. Valproic acid (VPA), used for many years as an anticonvulsant and a mood stabilizer, has effects on learning and memory and enhances the extinction of conditioned fear through its function as a histone deacetylase inhibitor (HDAC). Here we report that VPA enhances long-term memory for both acquisition and extinction of cued-fear. Interestingly, VPA enhances extinction, but also enhances renewal of the original conditioned fear when tested in a within-subjects design. This effect appears to be related to a reconsolidation-like process since a single CS reminder in the presence of VPA can enhance long-term memory for the original fear in the context in which fear conditioning takes place. We also show that by modifying the intertrial interval during extinction training, VPA can strengthen reconsolidation of the original fear memory or enhance long-term memory for extinction such that it becomes independent of context. These findings have important implications for the use of HDAC inhibitors as adjuncts to behavior therapy in the treatment of phobia and related anxiety disorders.