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河北医学  2024, Vol. 30 Issue (7): 1114-1120    DOI: 10.3969/j.issn.1006-6233.2024.05.010
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血乳酸 FGF21在儿童线粒体脑肌病诊断与疗效监测中作用及意义
王左华, 王惠萍, 王春霞, 张霞, 聂文莎, 郑宇霞
云南省昆明市儿童医院/昆明医科大学附属儿童医院神经内科, 云南 昆明 650228
The Role and Significance of Blood Lactate and FGF21 in the Diagnosis and Efficacy Monitoring of Mitochondrial Myopathy in Children
WANG Zuohua, WANG Huiping, WANG Chunxia, et al
Kunming Children's Hospital / Affiliated Children's Hospital of Kunming Medical University, Yunnan Kunming 650228, China
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摘要 目的: 分析血乳酸、纤维母细胞生长因子21(FGF21)在儿童线粒体脑肌病(ME)诊断与疗效监测中作用及意义。方法: 按照1∶1∶1选取2020年8月至2023年2月昆明市儿童医院收治的47例儿童ME患儿(ME组)、47例非线粒体病的肌肉病患儿(肌肉病组)及47例健康儿童(对照组)。给予ME患儿饮食和运动指导、左乙拉西坦、艾地苯醌、维生素C、叶酸、辅酶Q10等对症治疗,治疗后3个月评估疗效,根据疗效将ME患儿分为控制与未控制亚组。治疗前、治疗后1个月和3个月留取空腹血标本,以美国YSI 1500 SPORT型血乳酸分析仪及配套试剂盒检测血乳酸水平,以酶联免疫吸附法及酶标仪检测血清FGF21水平。比较3组治疗前血乳酸、FGF21,使用交互作用系数γ与OR值分析血乳酸、FGF21对儿童ME易感性影响的交互作用,受试者工作特征曲线(ROC)分析血乳酸、FGF21诊断儿童ME的价值,并比较ME不同疗效患儿治疗前、治疗后1个月和3个月血乳酸、FGF21、Newcastle线粒体病评分量表(NMDAS)评分变化,Pearson分析治疗后1个月和3个月血乳酸、FGF21降低值与NMDAS评分降低值相关性。结果: 与对照组相比,ME组血乳酸、FGF21升高(t=13.901、38.082,P<0.05);与肌肉病组相比,ME组血乳酸、FGF21升高(t=12.734、35.696,P<0.05);对照组、肌肉病组血乳酸、FGF21相比,无明显差异(t=0.821、1.326,均P>0.05);交互作用分析显示,血乳酸、FGF21共存所致OR值为1350.500,回归系数为7.208,交互作用OR值<两单独因素OR值的乘积,为次相乘模型,γ=1.535>1,血乳酸对FGF21的效应具有正向交互作用;ROC曲线显示,血乳酸+FGF21诊断儿童ME的AUC为0.904,高于血乳酸的0.839及FGF21的0.719,其诊断敏感度为78.72%,特异度为87.23%;病情获得控制患儿治疗后1个月、治疗后3个月血乳酸、FGF21、NMDAS评分低于未控制患儿(P<0.05);相关性分析显示,血乳酸、FGF21治疗后1个月降低值、治疗后3个月降低值与NMDAS评分治疗后1个月降低值、治疗后3个月降低值呈正相关(P<0.05)。结论: ME患儿血乳酸、FGF21升高,两者具有正向交互作用,并与患儿病情、疗效密切相关。
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关键词 血乳酸纤维母细胞生长因子21儿童线粒体脑肌病诊断疗效监测    
AbstractObjective: To analyze the role and significance of blood lactate and fibroblast growth factor 21 (FGF21) in the diagnosis and efficacy monitoring of mitochondrial myopathy (ME) in children. Methods: A total of 141 subjects were enrolled in this study, including 47 children with ME (ME group), 47 children with non-mitochondrial myopathies (muscle disease group), and 47 healthy children (control group), all of whom were admitted to Kunming Children's Hospital from August 2020 to February 2023. The ME group received dietary and exercise guidance, lamotrigine, idebenone, vitamin C, folic acid, and coenzyme Q10 for treatment. The efficacy was evaluated 3 months after treatment, and the ME patients were divided into controlled and uncontrolled subgroups according to the efficacy. Fasting blood samples were collected before treatment, 1 month after treatment, and 3 months after treatment. Blood lactate levels were measured using the American YSI 1500 SPORT blood lactate analyzer and matching reagent kit, and serum FGF21 levels were measured using enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent assay (ELISA). The levels of blood lactate and FGF21 in the three groups before treatment were compared. The interaction coefficient γ and OR values were used to analyze the interaction of blood lactate and FGF21 on the susceptibility of children to ME. The receiver operating characteristic (ROC) curve was used to analyze the value of blood lactate and FGF21 in the diagnosis of ME in children. The changes in blood lactate, FGF21, and Newcastle Mitochondrial Disease Assessment Scale (NMDAS) scores before and after treatment were compared between ME patients with different efficacies. Pearson correlation analysis was used to analyze the correlation between the decrease in blood lactate and FGF21 after 1 month and 3 months of treatment and the decrease in NMDAS score. Results: Compared with the control group, the levels of blood lactate and FGF21 were elevated in the ME group (t=13.901, 38.082, P<0.05); compared with the muscle disease group, the levels of blood lactate and FGF21 were also elevated in the ME group (t=12.734, 35.696, P<0.05); there was no significant difference in blood lactate and FGF21 levels between the control group and the muscle disease group (t=0.821, 1.326, both P>0.05); interaction analysis showed that the OR value caused by the coexistence of blood lactate and FGF21 was 1350.500, the regression coefficient was 7.208, the interaction OR value was less than the product of the OR values of the two single factors, which was a sub-multiplicative model, γ=1.535>1, and the effect of blood lactate on FGF21 had a positive interaction effect; ROC curve showed that the AUC of blood lactate + FGF21 for the diagnosis of ME in children was 0.904, which was higher than that of blood lactate (0.839) and FGF21 (0.719), with a diagnostic sensitivity of 78.72% and a specificity of 87.23%; the levels of blood lactate, FGF21 and NMDAS scores in patients with controlled disease were lower than those in patients with uncontrolled disease after 1 month and 3 months of treatment (P<0.05); correlation analysis showed that the decrease in blood lactate and FGF21 after 1 month and 3 months of treatment was positively correlated with the decrease in NMDAS score after 1 month and 3 months of treatment (P<0.05). Conclusion: The blood lactate and FGF21 levels in children with ME are elevated, and there is a positive interaction between the two, which is closely related to the condition and efficacy of the disease.
Key wordsBlood lactate    FGF21    Children    Mitochondrial encephalomyopathy    Diagnosis    Efficacy monitoring
    
基金资助:昆明市卫生科技人才培养项目-医学科技学科后备人才培养计划,(编号:2023-SW(后备)-73);昆明市卫生科技人才培养项目 医学技术中心建设项目,(编号:2022-SW(技术)-19)
通讯作者: 郑宇霞   
引用本文:   
王左华, 王惠萍, 王春霞, 张霞, 聂文莎, 郑宇霞. 血乳酸 FGF21在儿童线粒体脑肌病诊断与疗效监测中作用及意义[J]. 河北医学, 2024, 30(7): 1114-1120.
WANG Zuohua, WANG Huiping, WANG Chunxia, et al. The Role and Significance of Blood Lactate and FGF21 in the Diagnosis and Efficacy Monitoring of Mitochondrial Myopathy in Children. HeBei Med, 2024, 30(7): 1114-1120.
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