吉非罗齐对高脂血症兔心肌缺血再灌注损伤的影响及机制

目的探讨吉非罗齐对高脂血症兔心肌缺血再灌注损伤的影响。方法24只新西兰大白兔随机分成缺血再灌注组、吉非罗齐 缺血再灌注组(简称吉非罗齐组)和假手术组,所有动物给以高脂饮食9周以建立高脂血症兔模型,吉非罗齐组在喂养8周后同时给予吉非罗齐200mg(kg·d)口服1周。冠状动脉左前降支结扎法复制心肌缺血再灌注损伤模型。9周后观察各组血脂水平的变化及心肌细胞超微结构改变,并测定心肌梗死面积。逆转录聚合酶链反应测定心肌过氧化体增殖物激活型受体α和脂肪酸转位酶CD36 mRNA的表达。结果喂饲高脂饮食后,兔血清总胆固醇、低密度脂蛋白胆固醇水平明显升高(P<0.01),吉非罗齐干预1周未对血脂水平产生影响。吉非罗齐组心肌梗死面积较缺血再灌注组明显减少(P<0.05);且心肌细胞超微结构损伤明显低于缺血再灌注组。缺血再灌注组心肌过氧化体增殖物激活型受体α和CD36 mRNA的表达低于假手术组(P<0.05),而吉非罗齐组与假手术组过氧化体增殖物激活型受体α和CD36 mRNA的表达无明显差异(P>0.05)。结论吉非罗齐短期干预可减少高脂血症兔缺血再灌注后心肌梗死面积,并上调心肌过氧化体增殖物激活型受体α和CD36 mRNA的表达。     

肝脏卵圆细胞分选与向胰岛β细胞分化研究现状

肝脏卵圆细胞是具有多向分化潜能的干细胞,可转化为胰岛β细胞,为糖尿病的治疗带来了新的希望.目前对于肝脏卵圆细胞的分选主要有Percoll密度梯度离心法、流式细胞技术结合免疫荧光标记单克隆技术(FACS)、免疫磁珠分选技术(MACS)等.分选得到的肝脏卵圆细胞通过一系列转录因子的介导作用可转化为胰岛β细胞,主要的转录因子包括胰腺十二指肠同源盒基因-1(Pdx1)、神经元素3(Ngn3)、神经元分化因子(NeuroD)等,本文从肝脏卵圆细胞的分选和分化等方面对肝脏卵圆细胞向胰岛β细胞分化的研究现状作一综述.     

间充质干细胞成骨和成脂分化调控机制研究

间充质干细胞（MSCs）是人体内参与免疫平衡、维持组织器官的稳态和功能以及组织损伤修复的一类重要成体干细胞。MSCs具有自我更新能力和多向分化潜能,国际干细胞协会将MSCs向脂肪、成骨等细胞分化的能力作为其重要的检测标准。作为骨细胞和脂肪细胞的共同来源,MSCs在成骨和成脂分化之间相互协调和相互竞争,并在多种调控因素作用下保持着微妙的平衡。对MSCs成骨、成脂分化的信号通路、调控因素进行分析,并对其分化诱导方法以及鉴定方法进行总结,以期为MSCs基础研究及临床应用提供参考依据。     

Krüppel 样因子4 在神经母细胞瘤中的表达及其与细胞 增殖和侵袭的关系

目的观察Krüppel样因子4(KLF4)在神经母细胞瘤中的表达及其对神经母细胞瘤细胞增殖和侵袭的影响。方法RT-PCR和免疫组织化学法检测神经母细胞瘤组织及癌旁组织中KLF4的表达。采用电穿孔转染法将KLF4 siRNA转入神经母细胞瘤SK-N-MC细胞中,MTT检测KLF4对神经母细胞瘤SK-N-MC细胞增殖的影响,Boyden小室检测KLF4对神经母细胞瘤SK-N-MC细胞侵袭的影响。结果与癌旁组织相比,神经母细胞瘤组织中KLF4表达水平显著降低,并随病理分期的升高而降低(P<0.05)。转染KLF4 siRNA可显著下调神经母细胞瘤SK-N-MC细胞中KLF4的表达,而KLF4表达下调可显著促进SK-N-MC细胞的增殖和迁移(P<0.01)。结论KLF4可抑制神经母细胞瘤细胞的增殖和侵袭,KLF4低表达可能与神经母细胞瘤的发生和发展密切相关。     

2021-09期目录

Objective To investigate the predictive effect of thyroglobulin antibody (TgAb) level after operation and the trend of TgAb change after 131I treatment on the curative effect of 131I treatment in patients with differentiated thyroid carcinoma (DTC). Methods A total of 95 patients with DTC who were positive for TgAb and who underwent total thyroidectomy and 131I treatment in the Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from December 2016 to May 2018 were retrospectively analyzed. The patients included 16 males and 79 females, aged 11?63 (37.74±11.27) years old. 131I treatment was administered 2–6 months after surgery. Based on the response to therapy assessment system of DTC in the American Thyroid Association Management Guidelines and according to the images, the curative effect was divided into three groups, namely, structural excellent response group (A group, 54 cases), structural incomplete response group (B group, 19 cases), and structural indeterminate response group (C group, 22 cases). The following parameters were observed among the three groups: TgAb level before 131I treatment; percentage change at 1.5 months, 3–6 months, and 6–12 months; and rate of change of TgAb. The factors that might affect the curative effect were analyzed. Receiver operating characteristic (ROC) curves were drawn with the following: the TgAb level before 131I treatment; percentage change of TgAb at 1.5 months after treatment; and percentage change of TgAb at 3–6 months after treatment. The best critical value for predicting therapeutic effect was determined, and the diagnostic efficiency was calculated. The measurement data were compared through variance analysis or Kruskal-Wallis rank sum test. Chi-square test or Fisher's exact text were used to compare the count data among the groups. The multivariate Logistic regression analysis was used to analyze the factors that may affect the curative effect. Results The univariate regression analysis results showed that the mean age (F=3.48, P=0.03), lymph node metastasis rate (χ2=10.28, P<0.01), TgAb level before 131I treatment (χ2=16.03, P<0.01), 131I dose (Fisher's exact text, P=0.002), percentage changeand and rate of change of TgAb (except percentage change at 6?12 months) at 1.5 months, 3?6 months, and 6?12 months were significantly different among the three groups (χ2=8.55–22.79, all P<0.05). The multivariate Logistic regression analysis result showed that TgAb levels before 131I treatment were significantly different among the three groups (β=?0.006, OR=0.994; P<0.01), percentage change of TgAb at 1.5 months (β=0.327, OR=1.387; P=0.046), and percentage change of TgAb at 3?6 months (β=2.521, OR=12.439; P=0.041) had statistical significance. The optimal cut-off value of TgAb level on ROC curve was 201.4 U/mL with a sensitivity of 74.1% and specificity of 68.3%. The area under ROC curve (AUC) was 0.740. The optimal cut-off values of the percentage change of TgAb in 1.5 months and for 3–6 months after treatment were 9.7% and 19.2%; the sensitivities were 72.2% and 61.0%; the specificities were 87.0% and 58.5%; and the AUCs were 0.660 and 0.752, respectively. Conclusions Postoperative TgAb level enabled the prediction of the therapeutic effect of 131I. Patients with lower TgAb level showed better therapeutic effect. The decrease of TgAb after treatment was more significant than before treatment, suggesting that the 131I therapeutic effect was satisfactory.     

131I治疗分化型甲状腺癌指南(2021版)

近几年有关分化型甲状腺癌(differentiated thyroid cancer,DTC)术后¹³¹I治疗理念、治疗手段、随访监测及评估体系不断更新,针对我国DTC的发病及诊治现状,中华医学会核医学分会组织专家委员会对《¹³¹I治疗分化型甲状腺癌指南(2014版)》进行了修订,制定了《¹³¹I治疗分化型甲状腺癌指南(2021版)》,以期进一步规范和指导我国¹³¹I治疗DTC的临床诊治行为。本指南的推荐级别见表1,证据强度分级见表2.     

小鼠角膜的发生与细胞凋亡

目的 通过观察小鼠角膜的发生过程,探讨角膜细胞的增殖与凋亡对角膜结构修复与塑形的作用。方法 各日龄共计120只小鼠,用HE染色或4’,6-二脒基-2-苯基吲哚（DAPI）染色对小鼠角膜的一般结构进行观察;用5′-溴脱氧尿嘧啶核苷（BrdU）技术标记角膜增殖细胞和免疫荧光法标记干细胞和凋亡细胞。结果 胚胎发育及出生后早期,角膜以实质层的发育为主。出生14d（P14）左右,角膜上皮细胞层开始增殖分化为两层细胞,同时内皮细胞也开始分化。至P30时,我们可以辨别出角膜的6层结构。BrdU阳性细胞主要存在实质层中的成纤维细胞,出生以后也可见于角膜上皮细胞层和内皮细胞层。随着角膜发育,P10左右,其他层的BrdU阳性细胞都消失,仅存在于角膜上皮细胞层。增殖细胞核抗原（PCNA）阳性细胞在发育早期散在分布于角膜的各层,P14以后PCNA阳性细胞均匀的分布于角膜上皮细胞的基底层,并维持在稳定状态。在角膜发育早期,在各层可见许多细胞凋亡。结论 角膜的发育与其感光功能形成的过程相一致,角膜干细胞的增殖与其修复有关;有大量的凋亡细胞参与角膜结构的塑形。     

UNC5H3和DCC在胃癌中的表达与增殖的关系及其预后

目的 探讨UNC5H3和DCC在胃癌组织的表达,与临床病理特征和增殖的关系以及与患者生存和预后的关系。 方法 应用组织芯片和免疫组织化学技术,分析60例胃癌组织中UNC5H3、DCC和Ki-67的表达,并对其表达进行相关分析。利用图像分析软件Image-Pro Plus 6.0测量切片积分吸光度,对结果进行验证。采用Kaplan-Meier限乘法计算生存率。建立Cox回归模型,评价UNC5H3和DCC作为胃癌患者预后的独立影响因素的可行性。结果 在60例胃癌组织中,UNC5H3、DCC和Ki-67的阳性表达率分别为43.3%、53.3%和60.0%。UNC5H3和DCC与淋巴转移和远处转移之间,差异有显著性(P<0.05)。UNC5H3和DCC表达与Ki-67表达相互之间无相关性（P>0.05）。用Kaplan-Meier生存曲线经 Log-rank检验发现,UNC5H3的阳性表达与胃癌患者生存之间存在相关性（P<0.05）。DCC的阳性表达与胃癌患者生存之间无相关性（P>0.05）。经Cox回归分析,UNC5H3和DCC的表达与胃癌患者预后无明显相关性。结论 依赖性受体UNC5H3和DCC共同参与了胃癌的发生进展,检测UNC5H3和DCC可作为反映胃癌临床病理学特点的指标,检测UNC5H3可作为胃癌患者生存期的指标,但UNC5H3和DCC的表达不是判断胃癌患者预后的独立影响因素。     

ZAC基因在奥曲肽抑制胃癌细胞体外增殖通路的作用

目的 探讨ZAC基因在生长抑素类似物奥曲肽（OCT）抑制胃癌细胞增殖通路的作用。方法 分别以不同浓度OCT处理胃癌细胞BGC823和 SGC7901不同时间,MTT法筛选其增殖抑制的有效条件。OCT处理胃癌细胞（有效浓度/不同时间,有效时间/不同浓度）,Western blotting检测
OCT对胃癌细胞ZAC基因的效应。设计3条ZAC基因RNA干扰片段,分别插入pSUPER-EGFP-I载体,构建3个ZAC-shRNA表达载体（pSUPER-EGFP-ZAC/1 pSUPER-EGFP-ZAC/2和pSUPER-EGFP-ZAC/3）。经酶切和序列分析鉴定后,分别转染胃癌细胞BGC823和SGC7901。经G418筛选,RT-PCR鉴定,建立
ZAC基因敲低（knock-down）的胃癌细胞系。以有效条件OCT孵育胃癌细胞（对照组）和ZAC基因敲低胃癌细胞（实验组）,MTT法检测OCT对胃癌 细胞的生长抑制效应。结果 OCT抑制胃癌细胞增殖的有效条件为10nmol/L 孵育24h;OCT以时间和浓度依赖的方式诱导胃癌细胞ZAC基因表达。酶切及序列分析鉴定表明ZAC-shRNA表达载体构建成功。转染shRNA-ZAC/2的胃癌细胞,其ZAC mRNA水平明显降低（P<0.05）,为ZAC基因敲低胃癌 细胞。ZAC基因敲低胃癌细胞的增殖明显高于对应的BGC823细胞和SGC7901细胞（P<0.05）。OCT孵育后,BGC823细胞和SGC7901细胞的增殖明显降低（P<0.05）。然而,ZAC基因敲低胃癌细胞的增殖无明显改变（P>0.05）。结论 OCT以时间和浓度依赖的方式诱导胃癌细胞ZAC基因表达;ZAC 基因在OCT抑制胃癌细胞增殖通路中具有重要作用。