“临床早期接触”对医学生关怀能力养成的效果分析——以汕头大学医学院“医者之心（HEART）”课程为例

目的探讨医者之心（HEART）课程中“临床早期接触社会实践环节”对关怀能力养成的效果，对该课程纳入“临床早期接触”的教学设计做小结。方法编纂临床早期接触中的“隐性课程”体验问卷，对参加医者之心（HEART）课程的临床早期接触社会实践环节的学生进行事后访问及问卷调查，以此评估“隐形课程”对医学生关怀能力养成的初步情况。 结果医学实习生对各种具有隐性课程内涵举措的各个维度对其关怀能力培育的帮助，均呈偏正向的态度。“带教教师教学示范”“关怀展现”“专业胜任能力对学生关怀能力影响”这3个构面的强弱程度，会因“学生临床早期接触时长”“带教教师年资”“临床早期接触过程满意程度”的不同而呈现显著差异。结论“临床早期接触各类组织形式”对第一次进入临床体验的医学生关怀能力认知有重要影响，典范学习及同伴影响对医学生关怀能力认知有正向影响。     

Polysialic acid enters the cell nucleus attached to a fragment of the neural cell adhesion molecule NCAM to regulate the circadian rhythm in mouse brain

In the mammalian nervous system, the neural cell adhesion molecule NCAM is the major carrier of the glycan polymer polysialic acid (PSA) which confers important functions to NCAM's protein backbone. PSA attached to NCAM contributes not only to cell migration, neuritogenesis, synaptic plasticity, and behavior, but also to regulation of the circadian rhythm by yet unknown molecular mechanisms. Here, we show that a PSA-carrying transmembrane NCAM fragment enters the nucleus after stimulation of cultured neurons with surrogate NCAM ligands, a phenomenon that depends on the circadian rhythm. Enhanced nuclear import of the PSA-carrying NCAM fragment is associated with altered expression of clock-related genes, as shown by analysis of cultured neuronal cells deprived of PSA by specific enzymatic removal. In vivo, levels of nuclear PSA in different mouse brain regions depend on the circadian rhythm and clock-related gene expression in suprachiasmatic nucleus and cerebellum is affected by the presence of PSA-carrying NCAM in the cell nucleus. Our conceptually novel observations reveal that PSA attached to a transmembrane proteolytic NCAM fragment containing part of the extracellular domain enters the cell nucleus, where PSA-carrying NCAM contributes to the regulation of clock-related gene expression and of the circadian rhythm.     

Cassane-type diterpenes from Caesalpinia minax induce apoptosis in pituitary adenoma: structure–activity relationship,ER stress and Wnt/β-catenin pathways

Plant-derived natural products have been the highly significant sources of novel antitumor agents. The cassane-type diterpenes of genus Caesalpinia have been reported to bear antiproliferative activities toward different types of cancer cells. In this study, we evaluated the antineoplasmic activities of 16 natural origin cassane-type diterpenes isolated from the CHCl₃ extract of the seeds of C. minax in pituitary adenomas cells and identified caesalpin G (CAG) showed the strongest cytotoxicity. Moreover, we further investigated the structure–activity relationship and molecular mechanism of these derivatives systematically. The results confirmed the unsaturated lactone-type ring, hydroxyl at C-7, and alkenyl at C-11 or C-14 functionality as critical for anticancer activity in this family of natural products. In addition, the mechanism experiments also demonstrated unfolded protein response and ER stress and Wnt/β-catenin pathway were involved in the CAG-induced apoptosis.     

核受体PXR在宫颈鳞癌组织及SiHa细胞中的表达及临床意义

目的:探讨核受体孕烷X受体(PXR)在宫颈鳞癌组织的表达及与宫颈鳞癌发生的关系。方法:采用免疫组织化学及细胞免疫化学检测核受体PXR在41例宫颈癌组织及宫颈鳞癌细胞株SiHa中的表达。结果:PXR在宫颈鳞癌细胞株SiHa中有表达;正常宫颈组织有PXR表达,41例宫颈鳞癌组织中PXR的阳性率为59.5%,且宫颈癌组织中明显低表达。结论:PXR的表达水平与宫颈癌的发生有一定的相关性,可能成为今后判断宫颈癌预后有价值的标志物。     

白细胞介素37对Toll样受体4激活人冠状动脉内皮细胞核因子κB和细胞间黏附分子1表达的影响

目的探讨抗炎症因子白细胞介素37(IL-37)对人冠状动脉内皮细胞(HCAEC)中Toll样受体4(TLR4)激活后下游信号核因子κB(NF-κB)及细胞间黏附分子1(ICAM-1)表达的影响及机制。方法将HCAEC培养3~5代后进行实验,分为3组:对照组、IL-37干扰组、IL-37过表达组。利用脂质体转染将IL-37干扰序列加入IL-37干扰组,IL-37 DNA过表达质粒加入IL-37过表达组;孵育24 h后,用实时荧光定量PCR检测基因转染效率以确定转染成功。各组给予TLR4激活剂脂多糖(200μg/L)进行干预。Western blot检测干预24 h后ICAM-1蛋白的表达及干预30、60、120 min时磷酸化NF-κB蛋白的表达。结果对照组在TLR4激活后ICAM-1蛋白表达升高,与之相比,IL-37干扰组在TLR4激活后ICAM-1蛋白明显升高(P0.05),但在IL-37过表达组中没有升高(P0.05)。与对照组相比,IL-37干扰组TLR4激活后30、60、120 min各时间点磷酸化NF-κB的蛋白表达明显升高(P0.05),而IL-37过表达组磷酸化NF-κB蛋白表达并没有明显升高(P0.05)。结论 IL-37可以抑制TLR4激活HCAEC中炎症因子ICAM-1的升高,其机制可能是通过抑制NF-κB磷酸化的程度。IL-37的抗炎作用可以防治动脉粥样硬化。     

一个家族性高胆固醇血症家系的基因突变筛查与评估

目的：对一个临床诊断的家族性高胆固醇血症（FH）家系进行全基因组外显子测序，以寻找该家系的致病基因。方法：采集该家系成员外周静脉血样本，检测血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）这四项指标，并提取白细胞DNA进行全基因组外显子测序，筛选出4个FH相关基因LDLR、APOB、PCSK9、LDLRAP1的单核苷酸多态性（SNP）位点情况并进行生物信息学分析，采用Polyphen-2和SIFT软件对SNP位点进行致病性分析。结果：该家系APOB基因的SNP位点rs676210、rs679899、c.10094A > T和c.9937C > G均可能与血脂增高有关，但这些位点均不与疾病表型共分离。经Polyphen-2和SIFT软件预测未发现LDLR，PCSK9和LDLRAP1基因的致病性变异。结论：该FH家系存在可能与血脂增高相关的APOB基因SNP位点，其功能尚需进一步的实验验证。     

Inhibition of curcumin on influenza A virus infection and influenzal pneumonia via oxidative stress,TLR2/4, p38/JNK MAPK and NF-κB pathways

Oxidative stress, Nrf2-HO-1 and TLR-MAPK/NF-κB signaling pathways have been proved to be involved in influenza A virus (IAV) replication and influenzal pneumonia. In the previous studies, we have performed several high-throughput drug screenings based on the TLR pathways. In the present study, through plaque inhibition test, luciferase reporter assay, TCID₅₀, qRT-PCR, western blotting, ELISA and siRNA assays, we investigated the effect and mechanism of action of curcumin against IAV infection in vitro and in vivo. The results showed that curcumin could directly inactivate IAV, blocked IAV adsorption and inhibited IAV proliferation. As for the underlying mechanisms, we found that curcumin could significantly inhibit IAV-induced oxidative stress, increased Nrf2, HO-1, NQO1, GSTA3 and IFN-β production, and suppressed IAV-induced activation of TLR2/4/7, Akt, p38/JNK MAPK and NF-κB pathways. Suppression of Nrf2 via siRNA significantly abolished the stimulatory effect of curcumin on HO-1, NQO1, GSTA3 and IFN-β production and meanwhile blocked the inhibitory effect of curcumin on IAV M2 production. Oxidant H₂O₂ and TLR2/4, p38/JNK and NF-κB agonists could significantly antagonize the anti-IAV activity of curcumin in vitro. Additionally, curcumin significantly increased the survival rate of mice, reduced lung index, inflammatory cytokines and lung IAV titer, and finally improved pulmonary histopathological changes after IAV infection. In conclusion, curcumin can directly inactivate IAV, inhibits IAV adsorption and replication; and its inhibition on IAV replication may be via activating Nrf2 signal and inhibiting IAV-induced activation of TLR2/4, p38/JNK MAPK and NF-κB pathways.     

2012-2016年深圳市南山区某医院儿童伤害住院监测分析

目的 了解广东省深圳市南山区某伤害监测哨点医院因伤害住院儿童的情况,为儿童伤害预防工作提供参考依据。方法 利用Excel 2010和SPSS 21.0软件进行统计学分析,采用描述性研究方法对因伤害住院的儿童病历资料进行分析。结果 2012-2016年深圳市南山区某医院共监测因伤害住院儿童病例1 052人次,占所有因伤害住院人数的7.27%,男女性别比为2.31:1,因伤害住院儿童病例数所占比例逐年下降。17、1和2岁儿童因伤害住院人数较多,10、9和11岁较少,10岁儿童人次逐年上升。伤害原因前4位依次为接触热和烫的物质（32.09%）、跌倒（23.07%）、暴露于无生命机械力量下（16.55%）和交通事故（14.04%）;伤害造成后果前4位依次为烧伤和腐蚀伤（31.78%）、上肢损伤（21.52%）、头部损伤（15.00%）和下肢损伤（14.86%）。人次日均住院费用逐年增高,住院总费用与住院时长呈正相关（r=0.660）,年龄与人次日均住院费用和住院时长呈正相关（r=0.392、0.142）。结论 深圳市南山区某医院不同年龄组儿童伤害的发生特点不同,伤害的发生与年龄呈正相关,男童多于女童,可针对高危人群采取预防和控制措施。