白细胞介素-6在酒精性肝病中的作用

酒精性肝病（alcoholic liver disease,ALD）是由于长期过量饮酒导致肝的内部组织发生炎症损伤的慢性肝病。乙醇及其衍生物在代谢过程中直接或间接诱导引起的肝炎症反应可能是ALD发病的重要机制。然而,该过程内在的细胞分子机制尚不明确。最新研究发现,白细胞介素-6（interleukin-6,IL-6）对乙醇介导的肝细胞炎症反应具有双重作用,既参与了酒精损伤的炎症驱动过程,激活细胞凋亡的信号通路来刺激巨噬细胞和淋巴细胞合成急性反应蛋白加剧炎症反应,又能引起肝细胞再生,上调抗炎性细胞因子水平,发挥抗炎症功能来改善肝损伤程度。而运动应激可造成肌源性IL-6暂时性显著增加,改变肝的氧化-炎症状态,将机体保持在长期抗炎症的适应性状态中,并防治肝细胞炎症损伤。本文在加深对酒精性肝病炎症病理机制理解的同时,综述有关酒精性肝细胞炎症相关因子变化及IL-6调控途径。考虑临床利用IL-6联合炎性因子途径的靶向治疗,将有望成为一种可行性新颖的疗法,有利于实验室筛选炎症相关酒精性肝病干预药物,为酒精性肝疾病的预防与治疗提供新的靶点与思路。     

免疫检查点程序性细胞死亡蛋白配体-1翻译后修饰及其在免疫治疗中的应用前景

免疫检查点程序性细胞死亡蛋白配体-1（programmed cell death 1 ligand 1,PD-L1）是一种主要表达于肿瘤细胞表面的免疫抑制性分子,其可与T淋巴细胞表面的程序性细胞死亡蛋白-1（programmed cell death protein 1,PD-1）结合,抑制T淋巴细胞的激活,发挥免疫抑制性功能。基于这一原理所开发的PD-1/PD-L1免疫阻断疗法,已在临床广泛应用于多种实体瘤的治疗,使诸多病人受益。与此同时,随着对PD-L1调控机制研究的深入,PD-L1的多种翻译后修饰形式陆续得到了鉴定,包括糖基化、磷酸化、泛素化和棕榈酰化等。研究表明,这些翻译后修饰过程可影响PD-L1的蛋白质稳定性与生理功能。因此,翻译后修饰成了PD-L1研究新的切入点。目前,PD-L1翻译后修饰靶向药物已在免疫治疗中展现出良好的应用前景。通过靶向PD-L1翻译后修饰过程,进而调控由PD-L1介导的肿瘤免疫逃逸,成了提高免疫治疗应答率的新思路和新策略。本文将对PD-L1翻译后修饰的研究进行系统总结,并陈述其在免疫治疗领域中的应用前景,希望为未来针对PD-L1翻译后修饰的研究提供理论支持。     

阿尔茨海默病中β淀粉样蛋白的生成及清除的调节

阿尔茨海默病（Alzheimer’s disease, AD）是一种慢性退行性神经系统疾病,临床主要表现为进行性认知能力下降、记忆力衰退、人格改变等。AD的标志性病理特征包括脑细胞外β淀粉样蛋白（β-amyloid protein,Aβ）沉积形成老年斑、细胞内神经纤维缠结(neurofibrillary tangles,NFT)、神经炎症增加以及神经元凋亡。β淀粉样蛋白主要在神经元产生,是淀粉样前体蛋白经过一系列酶解反应生成的由39～42个氨基酸组成的多肽,调节Aβ的生成和清除能够有效延缓甚至逆转阿尔茨海默病的进程,因而具有重大的研究价值。β-分泌酶（β-site APP cleaving enzyme 1,BACE1）为Aβ产生过程中的关键酶,其含量及活性的改变均能影响Aβ产生,在阿尔茨海默病的发生发展中发挥至关重要的作用;老年斑周围炎性细胞的聚集提示,AD与神经炎症高度相关,神经炎症相关细胞能够参与Aβ的清除,多种炎性因子也能调节Aβ的生成;非编码RNA虽很少直接参与Aβ的产生、沉积和清除,但其可以通过多种途径调节Aβ的产生。本文从β淀粉样蛋白生成及清除的机制着手,重点阐述了BACE1、神经炎症、非编码RNA对Aβ调控的重要作用,以期为AD发病机制的进一步研究提供思路,并对阿尔茨海默病早期干预及治疗提供理论参考。     

bFGF Promotes the Proliferation of Rat Peripheral Blood Mesenchymal Stem Cells Through β-Catenin Signaling

bFGF (basic fibroblast growth factor, bFGF) could promote the proliferation of bone marrow and cord blood mesenchymal stem cells. However, the effect of bFGF on the proliferation of peripheral blood mesenchymal stem cells (PBMSCs) needs further research. This study aimed to investigate the role of bFGF on the culture and expansion of PBMSCs in vitro. Firstly, arterial blood was collected from rats abdominal aorta. After mononuclear cells (MNCs) were separated with Ficoll separation fluid, MNCs were cultured in the DMEM medium without bFGF (served as control group) or with bFGF (10, 20 ng/mL, served as 10 or 20 ng/mL bFGF group). PBMSCs were obtained by adherent culture method. The third passage of PBMSCs was detected for the MSC surface markers and the effect of bFGF on the cell cycle of PBMSCs using flow cytometry. The effects of bFGF on colony formation, cell growth, and the expressions of cyclin D1, cyclin E, p21 and β-catenin were evaluated. PBMSCs showed no difference in morphology among the three groups. PBMSC clonies appeared 14 days after cultivation. Compared with the control group, the cell growth confluence of PBMSCs was obviously increased by 40% and 80% in groups treated with 10 ng/mL bFGF or 20 ng/mL bFGF respectively after culture of 21 days (all P<0.05). Compared with the group treated with 10 ng/mL bFGF, the confluence of PBMSCs in 20 ng/mL group was further increased by 28% (P<0.05). Cells of the third passage were positively stained for CD29 and CD90, while were negative for CD45. These results were consistent with the phenotypic characteristics of MSCs. Compared with the control group, the colony number of PBMSCs in the 10 ng/mL and 20 ng/mL bFGF groups was increased by 51% (P<0.05) and 92% (P<0.05), respectively. Compared with the 10 ng/mL group, the colony number of PBMSCs was further increased in 20 ng/mL group by 14% (P<0.05). The growth curve of PBMSCs showed that after 7 days of culture, the number of PBMSCs in 10 ng/mL bFGF group and 20 ng/mL bFGF group was increased by 41% (P<0.05) and 61% (P<0.05), respectively. Moreover, the cell number had a statistically significant difference between these two groups (P<0.05). Results from flow cytometry cell cycle showed that the numbers of PBMSCs in the G1 phase of experimental groups were significantly decreased as the concentration of bFGF increased when compared with the control group (P<0.05), whereas the number of PBMSCs in the S phase was significantly increased (P<0.05). Immunofluorescence experiments showed that, compared with the control group, bFGF significantly promoted the nuclear translocation and expression of β-catenin in PBMSCs. Compared with the 10 ng/mL group, the PBMSCs in 20 ng/mL bFGF group showed stronger nuclear translocation and expression of β-catenin. Western blot experiments showed that the levels of β-catenin and its target proteins cyclinD1 and cyclinE were significantly increased (all P<0.05), whereas expression of p21 was significantly decreased in PBMSCs in the bFGF groups in a concentration dependent pattern when compared with control group (P<0.05). The study firstly confirms that bFGF promotes the proliferation of PBMSCs by regulating the β-catenin signaling pathway, which may facilitate the aquisition of larger number of PBMSCs for stem cell engineering in vitro.     

不同剂量地佐辛用于腹腔镜妇科手术超前镇痛的效果观察

目的：观察不同剂量地佐辛用于腹腔镜妇科手术超前镇痛的效果。方法：将90例ASAI．II级、年龄18~60岁拟行腹腔镜妇科手术的患者随机分成3组,每组30例,A组给予地佐辛0．1mg／kg开皮前15rain静脉注射;B组给予地佐辛0．15mg／kg开皮前15min静脉注射;C组给予地佐辛0．2mg／kg开皮前15min静脉注射,采用VAS评分评估术后镇痛效果并观察术后辅助镇痛药物的使用和不良反应的发生情况。结果：B、c组术后2、4、6、8h的VAS评分明显低于A组（P〈0．05）;C组术后2、4h的Ramsay评分明显高于A、B组（P〈0.05）;A组术后辅助镇痛药的使用率明显高于B组和C组（P／0．05）;3组不良反应的发生率比较均无统计学差异（P〉0．05）。结论：开皮前15rain静注地佐辛0．15mg／kg用于腹腔镜妇科手术镇痛效果好,且不增加不良反应的发生率。     

糖尿病肾病与非糖尿病肾病维持性血液透析患者血钙、血磷及甲状旁腺激素水平的分析

目的：探讨糖尿病肾病（diabtic nephropgthy,DN）与非糖尿病肾病（non-DN）维持性血液透析患者（maintenance hemodialysis,MHD）血钙、血磷、甲状旁腺激素（intact parathyroid hormone,iPTH）水平的差异;分析其血钙、血磷、iPTH和糖化血红蛋白（glycosylated hemoglobin,HbA1c）水平的相关性。方法：选择沈阳军区总医院血液透析中心收治的148例MHD患者,分为糖尿病组（58例）和非糖尿病组（90例）,比较两组间血钙、血磷、甲状旁腺激素水平的差异,并分析其血钙、血磷、iPTH、HbA1c水平的相关性。结果：糖尿病组iPTH、血磷水平均明显低于非糖尿病组（P〈0.05）,两组血钙水平比较无明显差异。在非DN组中,iPTH与血钙水平呈显著负相关（r=-0.320,P=0.036）,iPTH与血磷水平呈明显正相关（r=0.426,P=0.005）。在DN组中,iPTH与血钙、血磷无显著相关性,而iPTH与HbA1C水平呈显著负相关（r=-0.732,P=0.007）。结论：糖尿病肾病血液透析患者的iPTH水平和血磷水平明显低于非糖尿病肾病血液透析患者,HbA1c可能抑制iPTH的分泌。     

燕麦雄性不育新种质在遗传改良中的应用

对燕麦CA雄性不育材料的特征与遗传表现的研究表明,该不育性状是由1对隐性核基因控制的。对原CA雄性不育材料进行改造,设计出培育不同类型不育材料的选育程序,并转育出性状独特、不育株分离比例较高的新种质。提出了利用不育新种质改进燕麦杂交技术的方法,采用改进的杂交技术建成具有高千粒重、高蛋白质、低脂肪、丰产、抗病等性状的,遗传基础丰富的后代选择群体供育种应用。     

结直肠癌组织异常表达miRNA的鉴定

目的：筛选结直肠癌组织异常表达的miRNAs。方法：采用Agilem基因芯片（V12．0）分析结直肠癌组织及其配对正常粘膜组织间差异表达的miRNAs,MiRNAs错误发生率（FDR）〈0．05和微矩阵显著性分析（SAM）q值〈0．05为差异显著。结果：鉴定出结直肠癌中32个差异表达的miRNAs,显著上调和下调各16个。实时定量PCR（RT—qPCR）证实基因芯片中4个表达上调的miRNAs在结直肠癌组织中也显著上调。结论：MiRNA基因芯片鉴定出了结直肠癌组织一系列新的差异表达的miRNAs。     

miR396基因家族的进化及功能分析

MicroRNA(miRNA)是由约22个核苷酸组成的内源性非编码小分子RNA,广泛存在于真核细胞中,通过与靶基因的互补配对在转录后水平对基因表达进行调控,导致mRNA的降解或翻译抑制。本文通过对目前miRBase中收录的miR396家族进行生物信息学分析发现,该家族在植物界中高度保守,它们可能起源于较为古老的物种,经历长期复杂的进化过程而保留了下来;靶基因预测结果显示生长调控因子GRF为其主要靶标;启动子分析表明, miR396编码基因的上游存在光、温度、激素、厌氧、干旱及病害等胁迫响应相关的顺式作用元件,它们可与转录因子结合,参与多种胁迫应答反应。本文可为全面深入研究miRNA的作用机制奠定基础。     

某部入伍新兵心理卫生服务状况及需求调查

目的：调查入伍新兵心理卫生服务状况及对心理卫生服务的需求。方法：采用质性研究和量性研究相结合的方法,对42名入伍新兵作半结构性访谈,编制《部队心理卫生服务状况和需求》调查表,采用调查表对1609名新兵进行调查。结果：9．4％的新兵心理健康知识比较了解;接近半数新兵（43．5％）对心理健康知识很感兴趣;新兵获取心理知识的途径依次为网络、心理知识讲座、报刊杂志、广播电视、面对面咨询;新兵最期望获得的心理知识依次为如何调节自己的情绪、如何建立良好的人际关系、如何塑造自己的个性和常见的心理障碍表现;新兵认为最有帮助的心理服务形式依次为一对一心理咨询、心理知识讲座、心理测验和团体心理活动;只有7．7％的新兵接受过心理卫生服务。结论：新兵对心理健康知识感兴趣,但认知度和利用度均较低,应通过网络、心理知识讲座等方式普及新兵需要的心理健康知识。