注意缺陷多动障碍患儿血清25（OH）D及微量元素表达水平及临床意义

目的 探究注意缺陷多动障碍(ADHD)患儿血清25羟基维生素D[25(OH)D]、微量元素表达水平及临床意义。方法 选取2019年4月至2020年11月本院诊治的84例ADHD患儿进行研究(ADHD组),依据ADHD分型标准将患儿分为注意缺陷为主型组(28例)、多动为主型组(33例)、混合型组(23例),并选取同期84例体检健康儿童进行对照研究(对照组)。采用高效液相色谱-串联质谱法检测所有受试儿童血清25(OH)D水平；检测血清铁(Fe)、磷(P)、镁(Mg)、钙(Ca)、铜(Cu)、锌(Zn)、铅(Pb)水平；Pearson法分析ADHD患儿血清25(OH)D水平与Cu、Zn、Pb水平的相关性；Logistic回归分析ADHD发生的影响因素；受试者工作特征(ROC)曲线分析血清25(OH)D、Zn、Pb水平对ADHD的诊断价值。结果 ADHD组血清25(OH)D、Cu、Zn水平均显著低于对照组(P<0.05),Pb水平显著高于对照组(P<0.05)；注意缺陷为主型组、多动为主型组、混合型组患儿血清25(OH)D、Fe、P、Mg、Ca、Cu、Zn、Pb水平比较,差异无统计学意义(P>0.05)；ADHD患儿血清25(OH)D水平与Cu、Zn水平均呈正相关(P<0.05),与Pb水平呈负相关(P<0.05)；25(OH)D、Zn是影响ADHD发生的保护因素(P＜0.05),Pb是影响ADHD发生的危险因素(P＜0.05)；血清25(OH)D、Zn、Pb水平诊断ADHD的曲线下面积(AUC)分别为0.773、0.770、0.772,截断值分别为21.01 ng/mL、16.05 μmol/L、50.69 μg/L,相应灵敏度分别为82.1%、77.4%、63.1%,特异度分别为67.9%、71.4%、88.1%；三者联合诊断ADHD的AUC为0.883,其灵敏度、特异度分别为81.0%、81.0%。结论 ADHD患儿血清25(OH)D、Cu、Zn水平降低,Pb水平升高,25(OH)D、微量元素水平与ADHD患儿类型无关,25(OH)D、Zn、Pb联合有助于临床筛查ADHD患儿。     

Comparison of P25 and nanobelts on Kruppel-like factor-mediated nitric oxide pathways in human umbilical vein endothelial cells

Recently, we reported that titanium dioxide (TiO₂) materials activated endothelial cells via Kruppel-like factor (KLF)-mediated nitric oxide (NO) dysfunction, but the roles of physical properties of materials are not clear. In this study, we prepared nanobelts from P25 particles and compared their adverse effects to human umbilical vein endothelial cells (HUVECs). TiO₂ nanobelts had belt-like morphology but comparable surface areas as P25 particles. When applied to HUVECs, P25 particles or nanobelts did not induce cytotoxicity, although nanobelts were much more effective to increase intracellular Ti element concentrations compared the same amounts of P25 particles. Only nanobelts significantly induced THP-1 adhesion onto HUVECs. Consistently, nanobelts were more significant to induce the expression of intracellular adhesion molecule-1 (ICAM1) and the release of soluble ICAM-1 (sICAM-1), indicating that nanobelts were more potent to induce endothelial activation in vitro. As the mechanisms for endothelial activation, both P25 and nanobelts reduced the generation of intracellular NO as well as the expression of NO regulators KLF2 and KLF4. Combined, the results from this study indicated that the different morphologies of P25 particles and nanobelts only changed their internalization into HUVECs but showed minimal impact on KLF-mediated NO signaling pathways.     

Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C

1. Download : Download high-res image (137KB)
2. Download : Download full-size image

     

女性致密性骨炎血清骨转换生化标志物水平变化研究

背景 致密性骨炎（OCI）和其他疾病有时难以鉴别，探讨血清骨转换生化标志物可为OCI的鉴别诊断提供依据。 目的 探索女性OCI患者的血清骨转换生化标志物的水平变化及临床意义。 方法 回顾性选取2013年6月至2022年2月在北京积水潭医院门诊及住院诊断为OCI的61例女性患者作为观察组，年龄15~50岁，平均（33.8±6.6）岁，病程2周~15年。选择同期61例女性体检健康者作为对照组，年龄15~48岁，平均（35.6±7.6）岁。比较两组一般临床资料和血清骨转换生化标志物水平，并对血清骨转换生化标志物与病情相关指标进行相关性分析。 结果 观察组血清白蛋白（45.4±2.9）g/L低于对照组（46.5±2.8）g/L（t=2.190，P<0.05）。血清骨转换生化标志物比较结果显示，观察组血清1型胶原羧基末端肽β特殊序列（β-CTX）〔0.28（0.23，0.37）μg/L〕、N-端骨钙素（OC）〔13.1（11.2，16.2）μg/L〕、25-羟维生素D3〔25-（OH）VD3〕〔（14.1±5.1）μg/L〕低于对照组〔0.36（0.29，0.48）μg/L，15.6（13.7，17.3）μg/L，（17.5±6.6）μg/L〕（Z=-2.983、-3.255，t=3.081，P<0.05）。长病程亚组OC水平〔14.6（12.4，18.5）μg/L〕高于短病程亚组〔11.7（10.2，14.0）μg/L〕（Z=-2.407，P<0.05）。多孕亚组β-CTX〔0.25（0.22，0.32）μg/L〕、OC水平〔12.2（10.3，15.0）μg/L〕低于非多孕亚组〔0.33（0.26，0.44）μg/L、13.4（12.0，18.8）μg/L〕（Z=-2.486、-1.897，P<0.05）。相关性分析显示，观察组血清1型前胶原氨基端延长肽（tP1NP）与妊娠次数、生产次数均呈负相关（rs=-0.276、-0.298，P<0.05），OC与体质指数（BMI）、视觉模拟评分法（VAS）评分、妊娠次数均呈负相关（rs=-0.284、-0.374、-0.360，P<0.05），25-（OH）VD3水平与BMI呈正相关（rs=0.275，P<0.05）。 结论 女性OCI患者血清OC、β-CTX水平明显降低，可为鉴别其他疾病提供依据；血清OC水平可以反映OCI患者的严重程度，同时OC水平与患者妊娠次数相关；tP1NP与妊娠次数、生产次数相关。     

洛克米兰醇对肝癌HepG2细胞的抗增殖作用及其机制研究

目的研究传统中药米仔兰Aglaiaodorata中洛克米兰醇对肝癌细胞HepG2增殖的影响及抗肿瘤作用机制。方法 MTT、细胞克隆形成、EdU染色和CFDA染色方法考察洛克米兰醇对HepG2细胞的抗增殖效果;流式细胞仪检测洛克米兰醇对HepG2细胞细胞周期和细胞凋亡的变化;Western blotting检测洛克米兰醇对细胞周期调控蛋白和丝裂原活化蛋白激酶(MAPK)信号通路相关蛋白表达的影响。结果洛克米兰醇可以时间和浓度依赖性抑制HepG2细胞增殖。同等浓度下洛克米兰醇抗HepG2细胞增殖的效果好于阿霉素,而对正常肝细胞(L02)的毒性弱于阿霉素。流式细胞技术检测发现洛克米兰醇给药48 h能够诱导HepG2细胞G_2/M期细胞周期阻滞,但不诱导细胞凋亡。Western blotting研究发现该化合物抑制调控G_2/M周期相关蛋白cdc25C、cdc2和cyclin B1的表达并且激活细胞外调节蛋白激酶(ERK)和c-Jun氨基末端激酶(JNK)。对其机制深入研究发现,ERK抑制剂(U0126)可以部分逆转洛克米兰醇对HepG2的抗增殖和G_2/M周期阻滞及其抑制蛋白cdc25C和cdc2表达的效果。结论洛克米兰醇在抑制肝癌细胞增殖的效果和对正常肝细胞的选择性方面优于阿霉素。洛克米兰醇能够通过过度活化ERK,从而引起HepG2细胞G_2/M周期阻滞而达到抗增殖效果。     

温阳补肾法对高原类风湿关节炎患者血清25羟维生素D3水平的影响

目的:观察温阳补肾法对高原类风湿关节炎患者血清25羟维生素D3水平的影响。方法:选取2015年7月至2017年8月青海省中医院收治的高原类风湿关节炎患者132例作为研究对象,随机分为对照组和观察组,每组66例。对照组应用常规西医治疗,观察组在对照组治疗基础上应用温阳补肾法治疗,2组均连续治疗3个月。比较2组治疗后临床疗效,统计2组治疗前后主要临床症状与体征、健康状况评定量表(HAQ)评分和DAS28评分,检测2组治疗前后实验室检查指标、血清25羟维生素D3以及血液流变学指标水平。结果:治疗后,观察组临床治疗总有效率显著高于对照组(P 0. 05); 2组关节肿胀指数、关节疼痛指数、关节压痛指数、晨僵时间、关节功能分级和20 m步行时间均较治疗前显著降低(P 0. 05),且观察组均显著低于对照组(P 0. 05); 2组HAQ评分、DAS28评分、类风湿因子(RF)、C反应蛋白(CRP)和红细胞沉降率(ESR)水平均较治疗前显著降低(P 0. 05),且观察组均显著低于对照组(P 0. 05); 2组血清25羟维生素D3水平均较治疗前显著升高(P 0. 05),且观察组显著高于对照组(P 0. 05); 2组红细胞电泳指数、红细胞压积、血浆黏度、全血低切黏度、全血高切黏度水平均较治疗前显著降低(P 0. 05),且观察组均显著低于对照组(P 0. 05)。结论:温阳补肾法治疗高原类风湿关节炎,疗效满意,同时能明显增加血清25羟维生素D3水平。     

维生素D联合糠酸莫米松乳膏治疗婴幼儿中重度湿疹的临床分析

目的:分析维生素D联合糠酸莫米松乳膏治疗婴幼儿中重度湿疹的临床疗效并探究维生素D对患儿免疫功能的影响。方法:104例中重度湿疹婴幼儿随机分为对照组和治疗组各52例,对照组用0.1%糠酸莫米松乳膏治疗,治疗组在对照组基础上予维生素D制剂阿法骨化醇滴剂治疗。分析治疗后2组患儿治疗总有效率,同时检测患儿治疗前及治疗4周后血清25-(OH)D3、干扰素-γ(IFN-γ)、白细胞介素(IL-2)、IL-4、IL-13水平。结果:治疗组总有效率为92.31%,优于对照组(76.92%),差异有统计学意义(P<0.05)。治疗组治疗后血清IFN-γ、IL-2水平较治疗前上升,并明显高于对照组,血清IL-4、IL-13水平较治疗前下降,并明显低于对照组(P<0.05)。结论:维生素D能调节中重度湿疹婴幼儿免疫功能,因此维生素D联合糠酸莫米松乳膏能提高中重度湿疹婴幼儿治疗疗效,值得在临床上应用。     

CDC25B and CDC25C overexpression in nonmelanoma skin cancer suppresses cell death

Non‐melanoma skin cancer frequently results from chronic exposure to ultraviolet (UV) irradiation. UV‐induced DNA damage activates cell cycle arrest checkpoints through degradation of the cyclin‐dependent kinase activators, the cell division cycle 25 (CDC25) phosphatases. We previously reported increased CDC25A in nonmelanoma skin cancer, but CDC25B and CDC25C had not been previously examined. Consequently, we hypothesized that increased expression of CDC25B and CDC25C increases tumor cell proliferation and skin tumor growth. We found that CDC25B and CDC25C were increased in mouse and human skin cancers. CDC25B was primarily cytoplasmic in skin and skin tumors and was significantly increased in the squamous cell carcinoma (SCC), while CDC25C was mostly nuclear in the skin, with an increased cytoplasmic signal in the premalignant and malignant tumors. Surprisingly, forced expression of CDC25B or CDC25C in cultured SCC cells did not affect proliferation, but instead suppressed apoptosis, while CDC25C silencing increased apoptosis without impacting proliferation. Targeting CDC25C to the nucleus via mutation of its nuclear export sequence, however, increased proliferation in SCC cells. Overexpression of CDC25C in the nuclear compartment did not hinder the ability of CDC25C to suppress apoptosis, neither did mutation of sites necessary for its interaction with 14‐3‐3 proteins. Analysis of apoptotic signaling pathways revealed that CDC25C increased activating phosphorylation of Akt on Ser⁴⁷³, increased inhibitory phosphorylation of proapoptotic BAD on Ser¹³⁶, and increased the survival protein Survivin. Silencing of CDC25C significantly reduced Survivin levels. Taken together, these data suggest that increased expression of CDC25B or CDC25C are mechanisms by which skin cancers evade apoptotic cell death.