Electroconvulsive therapy plays an irreplaceable role in treatment of major depressive disorder

Major depressive disorder is a serious and common neuropsychiatric disorder that affects more than 350 million people worldwide. Electroconvulsive therapy is the oldest and most effective treatment available for the treatment of severe major depressive disorder. Electroconvulsive therapy modifies structural network changes in patients with major depressive disorder and schizophrenia. And it can also affect neuroinflammatory responses and may have neuroprotective effects. Electroconvulsive therapy plays an irreplaceable role in the treatment of major depressive disorder.     

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。     

我国弓形虫Chinese 1优势基因型感染对小鼠脑组织铁代谢影响

目的　探讨我国弓形虫Chinese 1优势基因型感染对宿主脑组织铁代谢及脑损伤的影响。方法　将20只C57BL/6（体质量15～17 g）小鼠随机分为对照组和感染组，每组10只。感染组每只小鼠腹腔注射4 000个弓形虫Chinese 1优势基因型TgCtwh3虫株速殖子，对照组小鼠注射等量无菌PBS，饲养6 d后处死小鼠并取其脑组织。采用电感耦合等离子体质谱法（inductively coupled plasma mass spectrometry, ICP⁃MS）检测小鼠脑组织铁元素水平；采用RNA芯片检测两组小鼠脑组织差异基因数目并对功能基因表达情况进行基因本体论（Gene Ontology, GO）功能富集；采用实时荧光定量PCR（fluorescent quantitative real⁃time PCR, qPCR）技术检测小鼠脑组织中弓形虫表面抗原1（Toxoplasma gondii surface antigen 1，TgSAG1）基因及部分锌铁调控蛋白（Zrt⁃ and Irt⁃like protein, ZIP）家族mRNA表达水平；采用光镜和电镜观察小鼠脑组织海马齿轮回（dentate gyrus, DG）超微结构；采用Western blotting检测谷胱甘肽过氧化物酶4（glutathione peroxidase 4, GPx4）蛋白表达水平；采用硫代巴比妥酸（TBA）法检测丙二醛（malondialdehyde, MDA）水平；采用免疫组化检测血管内皮生长因子（vascular endothelial growth factor, VEGF）蛋白表达光密度（optical density, OD）值。结果　光镜下可见感染组小鼠脑组织海马DG区细胞坏死，电镜下见感染组小鼠脑组织海马区出现胞质空泡化、核皱缩坏死、线粒体嵴断裂消融、自噬小体增加等超微结构变化。与对照组相比，感染组小鼠脑组织中铁元素水平上调[（32.92 ± 0.90） µg/g vs.（37.72 ± 1.10） µg/g；t = 3.397, P < 0.01]；RNA芯片检测感染组小鼠脑组织发现721个基因上调、276个基因下调，差异表达基因在金属离子结合能力上有明显富集。与对照组相比，感染组小鼠脑组织金属元素转运体ZIP2 mRNA表达水平上调（t = 8.659，P < 0.05）、GPx4表达下降[（1.046 ± 0.025） vs. （0.720 ± 0.101）；t = 3.129，P < 0.01]）、MDA水平升高[（4.37 ± 0.33） nmol/mgprot vs.（5.93 ± 0.54） nmol/mgprot；t = 2.451，P < 0.05）]、VEGF蛋白平均OD值上调[（0.348 3 ± 0.017 8） vs. （0.490 6 ± 0.010 5）；t = 6.641，P < 0.01]。结论　Chinese 1优势基因型弓形虫感染后，小鼠脑组织中铁元素蓄积、抗氧化能力下调、氧化应激水平升高，提示弓形虫感染可影响宿主脑组织铁代谢而导致脑损伤。     

Metabolism of non-steroidal anti-inflammatory drugs (NSAIDs) by Streptomyces griseolus CYP105A1 and its variants

In the field of drug development, technology for producing human metabolites at a low cost is required. In this study, we explored the possibility of using prokaryotic water-soluble cytochrome P450 (CYP) to produce human metabolites. Streptomyces griseolus CYP105A1 metabolizes various non-steroidal anti-inflammatory drugs (NSAIDs), including diclofenac, mefenamic acid, flufenamic acid, tolfenamic acid, meclofenamic acid, and ibuprofen. CYP105A1 showed 4′-hydroxylation activity towards diclofenac, mefenamic acid, flufenamic acid, tolfenamic acid, and meclofenamic acid. It should be noted that this reaction specificity was similar to that of human CYP2C9. In the case of mefenamic acid, another metabolite, 3′-hydroxymethyl mefenamic acid, was detected as a major metabolite. Substitution of Arg at position 73 with Ala in CYP105A1 dramatically reduced the hydroxylation activity toward diclofenac, flufenamic acid, and ibuprofen, indicating that Arg73 is essential for the hydroxylation of these substrates. In contrast, substitution of Arg84 with Ala remarkably increased the hydroxylation activity towards diclofenac, mefenamic acid, and flufenamic acid. Recombinant Rhodococcus erythrocyte cells expressing the CYP105A1 variant R84A/M239A showed complete conversion of diclofenac into 4′-hydroxydiclofenac. These results suggest the usefulness of recombinant R. erythropolis cells expressing actinomycete CYP, such as CYP105A1, for the production of human drug metabolites.