Resting-state network complexity and magnitude changes in neonates with severe hypoxic ischemic encephalopathy

Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases remain poorly understood. In this study, we recruited 14 termborn infants with mild hypoxic ischemic encephalopathy and 14 term-born infants with severe hypoxic ischemic encephalopathy from Changzhou Children's Hospital, China. Resting-state functional magnetic resonance imaging data showed efficient small-world organization in whole-brain networks in both the mild and severe hypoxic ischemic encephalopathy groups. However, compared with the mild hypoxic ischemic encephalopathy group, the severe hypoxic ischemic encephalopathy group exhibited decreased local efficiency and a low clustering coefficient. The distribution of hub regions in the functional networks had fewer nodes in the severe hypoxic ischemic encephalopathy group compared with the mild hypoxic ischemic encephalopathy group. Moreover, nodal efficiency was reduced in the left rolandic operculum, left supramarginal gyrus, bilateral superior temporal gyrus, and right middle temporal gyrus. These results suggest that the topological structure of the resting state functional network in children with severe hypoxic ischemic encephalopathy is clearly distinct from that in children with mild hypoxic ischemic encephalopathy, and may be associated with impaired language, motion, and cognition. These data indicate that it may be possible to make early predictions regarding brain development in children with severe hypoxic ischemic encephalopathy, enabling early interventions targeting brain function. This study was approved by the Regional Ethics Review Boards of the Changzhou Children's Hospital(approval No. 2013-001) on January 31, 2013. Informed consent was obtained from the family members of the children. The trial was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR1800016409) and the protocol version is 1.0.

Hyperbaric oxygen treatment promotes neural stem cell proliferation in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage

Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats （7 days old） subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2＇-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2＇- deoxyuddine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.

Effect of erythropoietin combined with hypothermia on serum tau protein levels and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy

Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy,many neonatal patients die or suffer from severe neurological dysfunction.Erythropoietin is considered one of the most promising neuroprotective agents.We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment.In this study,41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group（hypothermia alone for 72 hours,n = 20） and erythropoietin group（hypothermia ＋ erythropoietin 200 IU/kg for 10 days,n = 21）.Our results show that compared with the control group,serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the erythropoietin group at 8 and 12 days.However,neurodevelopmental outcome was similar between the two groups at 9 months of age.These findings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neurology outcome but does not affect long-term neurodevelopmental outcome.

Applications of advanced signal processing and machine learning in the neonatal hypoxic-ischemic electroencephalography

Perinatal hypoxic-ischemic-encephalopathy significantly contributes to neonatal death and life-long disability such as cerebral palsy. Advances in signal processing and machine learning have provided the research community with an opportunity to develop automated real-time identification techniques to detect the signs of hypoxic-ischemic-encephalopathy in larger electroencephalography/amplitude-integrated electroencephalography data sets more easily. This review details the recent achievements, performed by a number of prominent research groups across the world, in the automatic identification and classification of hypoxic-ischemic epileptiform neonatal seizures using advanced signal processing and machine learning techniques. This review also addresses the clinical challenges that current automated techniques face in order to be fully utilized by clinicians, and highlights the importance of upgrading the current clinical bedside sampling frequencies to higher sampling rates in order to provide better hypoxic-ischemic biomarker detection frameworks. Additionally, the article highlights that current clinical automated epileptiform detection strategies for human neonates have been only concerned with seizure detection after the therapeutic latent phase of injury. Whereas recent animal studies have demonstrated that the latent phase of opportunity is critically important for early diagnosis of hypoxic-ischemic-encephalopathy electroencephalography biomarkers and although difficult, detection strategies could utilize biomarkers in the latent phase to also predict the onset of future seizures.

Estrogen inhibits lipid peroxidation after hypoxic-ischemic brain damage in neonatal rats

Sprague-Dawley neonatal rats within 7 days after birth were used in this study. The left common carotid artery was occluded and rats were housed in an 8% O2 environment for 2 hours to establish a hypoxic-ischemic brain damage model. 17β-estradiol （1 × 10-5 M） was injected into the rat abdominal cavity after the model was successfully established. The left hemisphere was obtained at 12, 24, 48, 72 hours after operation. Results showed that malondialdehyde content in the left brain of neonatal rats gradually increased as modeling time prolonged, while malondialdehyde content of 17β-estrodial-treated rats significantly declined by 24 hours, reached lowest levels at 48 hours, and then peaked at 72 hours after injury. Nicotinamide-adenine dinucleotide phosphate histochemical staining showed the nitric oxide synthase-positive cells and fibers dyed blue/violet and were mainly distributed in the cortex, hippocampus and medial septal nuclei. The number of nitric oxide synthase-positive cells peaked at 48 hours and significantly decreased after 17β-estrodial treatment. Our experimental findings indicate that estrogen plays a protective role following hypoxic-ischemic brain damage by alleviating lipid peroxidation through reducing the expression of nitric oxide synthase and the content of malondialdehyde.

Effects of mild hypothermia combined EPO therapy on cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy

Objective:To explore the effects of mild hypothermia combined EPO therapy on cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy. Methods: A total of 72 children with HIE who were diagnosed and treated in the hospital between December 2015 and June 2017 were chosen as the study subjects and divided into control group (n=36) and EPO group (n=36) by random number table method. Control group received mild hypothermia therapy on the basis of conventional therapy, and EPO group received EPO therapy on the basis of the therapy for control group. The differences in serum levels of cerebral injury indexes, myocardial injury indexes and oxidative stress indexes were compared between the two groups before and after treatment.Results: The differences in serum levels of cerebral injury indexes, myocardial injury indexes and oxidative stress indexes were not statistically significant between the two groups before treatment. After the treatment ended, serum cerebral injury indexes VILIP-1, NPY and NSE levels of EPO group were lower than those of control group whereas IGF-1 level was higher than that of control group;myocardial injury indexes CT-1, Myo and cTnⅠ levels were lower than those of control group;oxidative stress indexes GSH-Px and SOD levels were higher than those of control group whereas AOPP and ROS levels were lower than those of control group.Conclusion: Mild hypothermia combined with EPO therapy can improve the cerebral injury, myocardial injury and oxidative stress of neonatal hypoxic ischemic encephalopathy.

The evaluation value of the quantitative electroencephalogram for the prognosis of neonatal hypoxic ischemic encephalopathy and its relationship with serological indicators

Objective:To study the evaluation value of the quantitative electroencephalogram (qEEG) for the prognosis of neonatal hypoxic ischemic encephalopathy (HIE) and its relationship with serological indicators.Methods: 76 children with HIE who were born and treated in our hospital between April 2013 and February 2017 were collected as observation group, and 50 healthy newborns who were born in our hospital during the same period were collected as normal control group. qEEG parameter values of two groups of children were determined, serum levels of nerve injury indexes, nerve apoptosis indexes and oxidative stress indexes were compared between the two groups, and Pearson test was used to evaluate the inner link between qEEG parameter values and disease severity in children with HIE.Results: qEEG Fp1, Fp2, C3, C4, T3, T4, O1 and O2 loci power spectrum values of observation group were significantly lower than those of normal control group. Serum NSE, NPY, S-100B and MBP contents in observation group were higher than those in normal control group;nerve apoptosis indexes sFas, sFasL and Caspase-3 contents were higher than those in normal control group while Bcl-2 content was lower than that in normal control group;serum oxidative stress indexes AOPP and MDA contents were higher than those in normal control group while SOD content was lower than that in normal control group. Pearson test showed that qEEG Fp1, Fp2, C3, C4, T3, T4, O1 and O2 loci power spectrum values in children with HIE were directly correlated with the contents of nerve injury indexes, nerve apoptosis indexes and oxidative stress indexes. Conclusion: The qEEG parameter values in children with HIE are lower than those in normal children, and the specific values are closely related to the severity of the disease.

Single-nucleotide polymorphism screening and RNA sequencing of key messenger RNAs associated with neonatal hypoxic-ischemia brain damage

A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neonatal hypoxic-ischemic brain damage remain elusive.Seven-day-old rats were used to establish a hypoxic ischemic encephalopathy model.SNPs and expression profiles of mRNAs were analyzed in hypoxic ischemic encephalopathy model rats using RNA sequencing.Genes exhibiting SNPs associated with hypoxic ischemic encephalopathy were identified and studied by gene ontology and pathway analysis to identify their possible involvement in the disease mechanism.We identified 89 up-regulated genes containing SNPs that were mainly located on chromosome 1 and 2.Gene ontology analysis indicated that the up-regulated genes containing SNPs are mainly involved in angiogenesis,wound healing and glutamatergic synapse and biological processing of calcium-activated chloride channels.Signaling pathway analysis indicated that the differentially expressed genes play a role in glutamatergic synapses,long-term depression and oxytocin signaling.Moreover,intersection analysis of high throughput screening following PubMed retrieval and RNA sequencing for SNPs showed that CSRNP1,DUSP5 and LRRC25 were most relevant to hypoxic ischemic encephalopathy.Significant up-regulation of genes was confirmed by quantitative real-time polymerase chain reaction analysis of oxygen-glucose-deprived human fetal cortical neurons.Our results indicate that CSRNP1,DUSP5 and LRRC25,containing SNPs,may be involved in the pathogenesis of hypoxic ischemic encephalopathy.These findings indicate a novel direction for further hypoxic ischemic encephalopathy research.This animal study was approved on February 5,2017 by the Animal Care and Use Committee of Kunming Medical University,Yunnan Province,China(approval No.kmmu2019038).Cerebral tissue collection from a human fetus was approved on September 30,2015 by the Ethics Committee of Kunming Medical University,China(approval No.2015-9).

Brainstem tegmental lesions in neonates with hypoxicischemic encephalopathy: Magnetic resonance diagnosis and clinical outcome

Lesions of the brainstem have been reported in the clinical scenarios of hypoxic-ischemic encephalopathy(HIE), although the prevalence of these lesions is probably underestimated. Neuropathologic studies have demonstrated brainstem involvement in severely asphyxiated infants as an indicator of poor outcome. Among survivors to HIE, the most frequent clinical complaints that may be predicted by brainstem lesions include feeding problems, speech, language and communication problems and visual impairments. Clinical series, including vascular and metabolic etiologies, have found selective involvement of the brainstem with the demonstration of symmetric bilateral columnar lesions of the tegmentum. The role of brainstem lesions in HIE is currently a matter of debate, especially when tegmental lesions are present in the absence of supratentorial lesions. Differential diagnosis of tegmental lesions in neonates and infants include congenital metabolic syndromes and drug-related processes. Brainstem injury with the presence of supratentorial lesions is a predictor of poor outcome and high rates of mortality and morbidity. Further investigation will be conducted to identify specific sites of the brainstem that are vulnerable to hypoxic-ischemic and toxic-metabolic insults.

Electroencephalography studies of hypoxic ischemia in fetal and neonatal animal models

Alongside clinical achievements,experiments conducted on animal models (including primate or non-primate) have been effective in the understanding of various pathophysiological aspects of perinatal hypoxic/ ischemic encephalopathy (HIE).Due to the reasonably fair degree of flexibility with experiments,most of the research around HIE in the literature has been largely concerned with the neurodevelopmental outcome or how the frequency and duration of HI seizures could relate to the severity of perinatal brain injury,following HI insult.This survey concentrates on how EEG experimental studies using asphyxiated animal models (in rodents,piglets,sheep and non-human primate monkeys) provide a unique opportunity to examine from the exact time of HI event to help gain insights into HIE where human studies become difficult.

Research progress of relationship between hyptoxic ischemic encephalopathy and interleukin in neonates

Hypoxic ischemic encephalopathy (HIE) refers to brain lesions caused by hypoxia in perinatal neonates, usually combined with damage or dysfunction of other organs. The pathogenesis of HIE is very complex, which is still unclear, and it is one of the important subjects of perinatal medicine research. In recent years, the role of immune system in the pathogenesis of HIE has attracted more and more attention, especially interleukin (IL), which plays an important role in the pathogenesis of HIE. Therefore, further study on the immune mechanism of neonatal HIE, to realize early diagnosis and early intervention is of great significance for preventing HIE complications.

亚低温对新生儿缺氧缺血性脑病患儿血清泛素羧基末端水解酶-L1、低氧诱导因子-1α表达水平及神经发育结局的影响

目的探讨亚低温对新生儿缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)患儿血清泛素羧基末端水解酶-L1(ubiquitin carboxy-terminal hydrolase-L1,UCH-L1)、低氧诱导因子-1a(hypoxiainducible factor-1α,HIF-1α)表达水平及预后的影响。方法选取2015年8月至2022年8月邯郸市妇幼保健院新生儿重症监护病房(neonatal intensive care unit,NICU)收治的110例中重度HIE患儿作为研究对象。根据家属是否同意患儿接受亚低温治疗,将患儿分为亚低温治疗组(n=70)和传统治疗组(n=40);亚低温治疗组患儿除常规治疗外,于出生后0~6 h实施选择性头部亚低温治疗。传统治疗组患儿给予常规治疗;治疗前和治疗后第3天,采用酶联免疫吸附实验双抗夹心法检测UCH-L1、HIF-1α表达水平。随访患儿出生后12~15个月神经发育结局。统计学方法采用独立样本t检验、配对t检验、χ^(2)检验或Fisher确切概率法。结果亚低温治疗组与传统治疗组治疗后血清UCH-L1[(1.9±0.4)与(3.1±0.3)μg/L,t=16.495,P<0.001]、HIF-1α表达水平[(1.40±0.22)与(2.75±0.19)μg/L,t=32.486,P<0.001]比较,亚低温治疗组明显低于传统治疗组;亚低温治疗组患儿治疗后血清UCH-L1表达水平低于治疗前[(1.9±0.4)与(3.3±0.5)μg/L,t'=18.293,P<0.01]。亚低温治疗组和传统治疗组在治疗3 d后,虽然两组血清中HIF-1α表达水平均出现高于治疗前[(1.40±0.22)与(1.23±0.29)μg/L,t'=3.907,P<0.001;(2.75±0.19)与(1.27±0.35)μg/L,t'=23.504,P<0.001],但是,亚低温抑制血清HIF-1α表达水平升高的效果明显优于传统治疗组。随访结果显示,亚低温治疗组患儿神经发育正常的比例高于传统治疗组[68.6%(48/70)与32.5%(13/40),χ^(2)=13.408,P<0.001];亚低温治疗组神经发育迟缓的比例低于传统治疗组[11.4%(8/70)与37.5%(15/40),χ^(2)=10.462,P<0.001]。结论亚低温治疗可以明显降低中重度HIE患儿血清UCHL1表达水平,抑制血清HIF-1a表达水平升高的作用明显优于传统治疗,这可能是低温治疗的神经保护机制之一。

血清S-100B蛋白、可溶性凝集素样氧化低密度脂蛋白受体-1、胶质纤维酸性蛋白检测在新生儿缺血缺氧性脑病病情严重程度中的诊断价值

目的:探讨血清S-100B蛋白、可溶性凝集素样氧化低密度脂蛋白受体-1(sLOX-1)、胶质纤维酸性蛋白(GFAP)与新生儿缺血缺氧性脑病(HIE)病情严重程度的关系。方法:选择80例HIE患儿作为观察组,另选择90例健康新生儿作为对照组,收集所有患儿一般资料,并检测两组患儿血清S-100B蛋白、sLOX-1、GFAP水平,分析HIE患儿血清S-100B蛋白、sLOX-1、GFAP与病情严重程度的相关性及预后不良的影响因素。结果:对照组血清S-100B蛋白、sLOX-1、GFAP水平低于观察组(均P<0.05)。重度组血清S-100B蛋白、sLOX-1、GFAP水平高于中度组、轻度组和对照组(均P<0.05)。Pearson相关分析显示,疾病严重程度与HIE患儿血清S-100B蛋白、sLOX-1、GFAP水平呈正相关(均P<0.001)。随访预后良好患儿59例,预后不良21例,经多因素Logistic回归分析显示,产程异常、病情重度、S-100B蛋白、sLOX-1、GFAP为影响HIE患儿预后的危险因素(均P<0.05)。结论:HIE患儿病情严重程度和预后与血清S-100B蛋白、sLOX-1、GFAP水平有关,监测其水平变化有利于临床早期完善干预方案改善预后。

新生儿缺氧缺血性脑病血清miR-124与miR-126的表达及临床意义

目的探讨新生儿缺氧缺血性脑病(HIE)血清微小核糖核酸(miR)-124、miR-126的表达及临床意义。方法选取2019-01—2023-02湘南学院附属医院收治的92例HIE患儿为HIE组,根据病情严重程度分为轻度组44例,中度组27例,重度组21例,另选取同期31名健康新生儿为对照组。采用Spearman相关性分析HIE患儿血清miR-124、miR-126表达与S100B、NSE水平的相关性,采用受试者工作特征(ROC)曲线分析血清miR-124、miR-126水平对新生儿HIE的诊断价值。结果与对照组比较,HIE组血清miR-124、miR-126表达降低,S100钙结合蛋白B(S100B)、神经元特异性烯醇化酶(NSE)水平升高(P<0.05)。轻度组、中度组、重度组血清miR-124、miR-126表达依次降低,S100B、NSE水平依次升高(P<0.05)。Spearman相关性分析显示,HIE患儿血清miR-124、miR-126表达与S100B、NSE水平呈负相关(rs=—0.757、—0.781、—0.800、—0.785,P<0.001)。ROC曲线分析显示,血清miR-124、miR-126表达单独和联合诊断新生儿HIE的曲线下面积分别为0.872、0.882、0.946。结论新生儿HIE血清miR-124、miR-126低表达,可能通过神经细胞损伤参与新生儿HIE过程,血清miR-124、miR-126表达联合诊断新生儿HIE的价值较高。

Challenges in developing therapeutic strategies for mild neonatal encephalopathy

There is increasing evidence that infants with mild neonatal encephalopathy(NE) have significant risks of mortality, brain injury and adverse neurodevelopmental outcomes. In the era of therapeutic hypothermia, infants need to be diagnosed within 6 hours of birth, corresponding with the window of opportunity for treatment of moderate to severe NE, compared to the retrospective grading over 2 to 3 days, typically with imaging and formal electroencephalographic assessment in the pre-hypothermia era. This shift in diagnosis may have increased the apparent prevalence of brain damage and poor neurological outcomes seen in infants with mild NE in the era of hypothermia. Abnormal short term outcomes observed in infants with mild NE include seizures, abnormal neurologic examination at discharge, abnormal brain magnetic resonance imaging and difficulty feeding. At 2 to 3 years of age, mild NE has been associated with an increased risk of autism, language and cognitive deficits. There are no approved treatment strategies for these infants as they were not included in the initial randomized controlled trials for therapeutic hypothermia. However, there is already therapeutic creep, with many centers treating infants with mild NE despite the limited evidence for its safety and efficacy. The optimal duration of treatment and therapeutic window of opportunity for effective treatment need to be specifically established for mild NE as the evolution of injury is likely to be slower, based on preclinical data. Randomized controlled trials of therapeutic hypothermia for infants with mild NE are urgently required to establish the safety and efficacy of treatment. This review will examine the evidence for adverse outcomes after mild NE and dissect some of the challenges in developing therapeutic strategies for mild NE, before analyzing the evidence for therapeutic hypothermia and other strategies for treatment of these infants.

基于MRI研究血清GH、8-OHdG、HMGB1与新生儿缺氧缺血性脑病临床分度的相关性

目的 研究血清生长素(GH)、8-羟基脱氧鸟苷(8-OHdG)、高迁移率族蛋白(HMG)B1与新生儿缺氧缺血性脑病(HIE)临床分度的相关性。方法 选取2019年1月至2022年12月在秦皇岛市第一医院进行诊断并治疗的120例HIE患儿作为研究组,另选取同期健康新生儿120例作为对照组,比较研究组及对照组、不同临床分度及不同磁共振成像(MRI)评分的血清GH、8-OHdG、HMGB1的差异。采用Spearman相关性分析研究对象临床分度、MRI评分与血清GH、8-OHdG、HMGB1水平的相关性。结果 研究组血清GH低于对照组,8-OHdG、HMGB1高于对照组,差异有统计学意义(t值分别为22.828、48.563、98.440,P<0.05);不同病情患儿的血清GH、8-OHdG、HMGB1水平及MRI评分差异存在统计学意义,进一步两两比较,患儿的血清GH、HMGB1水平从高到低依次为轻度组、中度组及重度组,8-OHdG及MRI评分从高到低依次为重度组、中度组及轻度组(F值分别为13.055、13.150、12.710、14.205,P<0.05);不同MRI评分患儿血清GH、8-OHdG、HMGB1水平差异存在统计学意义,进一步两两比较,患儿的血清GH、HMGB1水平从高到低依次为0~3分组、4~7分及8~10分组,8-OHdG从高到低依次为8~10分组、4~7分组及0~3分组(F值分别为15.432、13.674、19.076,P<0.05);相关性分析结果显示,患儿的临床分度、MRI评分与GH、HMGB1呈负相关性(r值分别为-0.738、-0.666,-0.579、-0.671,P<0.05),与8-OHdG呈正相关性(r值分别为0.617、0.690,P<0.05)。结论 血清GH、8-OHdG、HMGB1与新生儿缺氧缺血性脑病临床分度呈现显著相关性,可作为临床诊断的重要依据。

左卡尼汀联合胞二磷胆碱对新生儿缺氧缺血性脑病的疗效及血清NO、ET-1的影响

目的 探讨左卡尼汀联合胞二磷胆碱对新生儿缺氧缺血性脑病(NHIE)的疗效及血清一氧化氮(NO)、内皮素-1(ET-1)的影响。方法 选取2020年4月至2023年1月该院收治的95例NHIE患儿,采用随机数字表法将其分为观察组(47例)和对照组(48例)。对照组给予胞二磷胆碱治疗,观察组给予胞二磷胆碱联合左卡尼汀治疗。治疗14 d后评估患儿疗效,统计患儿原始反射、肌张力及意识的恢复时间。检测患儿治疗前、治疗14 d后的氧化应激指标[丙二醛(MDA)、超氧化物歧化酶(SOD)]及血管内皮功能指标(NO、ET-1)水平,采用新生儿神经行为评分(NBNA)评估患儿神经功能水平,并观察治疗方案的安全性,采用Pearson相关性分析NBNA与血管内皮功能指标的相关性。结果 观察组治疗总有效率为91.49%,高于对照组的72.92%(P<0.05);观察组原始反射恢复时间、肌张力恢复时间及意识恢复时间较对照组均缩短(P<0.05);治疗前两组NBNA得分差异无统计学意义(t=1.225,P=0.224),治疗后观察组NBNA得分高于对照组(t=6.223,P<0.001);治疗后,两组MDA水平降低,SOD水平升高(P<0.05),观察组治疗后MDA水平低于对照组,SOD水平高于对照组(P<0.05);治疗后,两组NO、ET-1水平均降低(P<0.05),观察组治疗后NO、ET-1水平低于对照组(P<0.05);观察组、对照组药物不良反应率分别为17.02%、8.33%,两组比较差异无统计学意义(P>0.05);Pearson相关性分析显示,NHIE患儿血清NO、ET-1与NBNA得分均呈负相关(r=-0.546、-0.608,P<0.05)。结论 左卡尼汀联合胞二磷胆碱能够提高NHIE的疗效,缩短临床表现恢复时间,改善神经功能、氧化应激反应、血管内皮功能,不会增加药物不良反应,且血管内皮功能指标与NBNA得分均呈负相关,可作为判断NHIE病情的辅助参考指标。

振幅整合脑电图联合血清HIF-1α、NFP在新生儿脑损伤中的诊断价值

目的:探讨振幅整合脑电图联合血清缺氧诱导因子–1α(HIF–1α)、神经丝蛋白(NFP)在新生儿脑损伤中的诊断价值。方法:选择2020年1月至2023年1月灵宝市第一人民医院收治的76例足月新生儿缺氧缺血性脑病(HIE)患儿作为观察组,根据脑损伤程度将其分为轻度损伤组(19例)、中度损伤组(37例)、重度损伤组(20例),行振幅整合脑电图(aEEG)监测,并检测血清HIF–1α、NFP水平。并选择同期50例健康新生儿作为对照组。采用受试者工作特征(ROC)曲线评估aEEG、HIF–1α、NFP及联合诊断新生儿脑损伤的价值。结果:观察组患儿血清HIF–1α、NFP水平明显高于对照组(P<0.05)。随着脑损伤程度加重,血清HIF–1α、NFP水平随之升高(P<0.05)。经ROC曲线分析,血清HIF–1α诊断新生儿HIE的曲线下面积(AUC)为0.683(95%CI:0.327~0.973),截断值为764.09 pg·mL-1。血清NFP诊断新生儿HIE的AUC为0.771(95%CI:0.506~0.879),截断值为19.29 ng·mL-1,aEEG、血清HIF–1α和NFP联合诊断新生儿HIE的AUC为0.889(95%CI:0.627~0.995)。结论:联合aEEG和血清HIF–1α、NFP在诊断新生儿HIE上具有较高的潜能。

Semi-quantitative Assessment of Brain Maturation by Conventional Magnetic Resonance Imaging in Neonates with Clinically Mild Hypoxic-ischemic Encephalopathy

Background：Mild hypoxic-ischemic encephalopathy （HIE） injury is becoming the major type in neonatal brain diseases.The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score （TMS） based on conventional magnetic resonance imaging （MRI）.Methods：Totally,45 neonates with clinically mild HIE and 45 matched control neonates were enrolled.Gestated age,birth weight,age after birth and postmenstrual age at magnetic resonance （MR） scan were homogenous in the two groups.According to MR findings,mild HIE neonates were divided into three subgroups：Pattern Ⅰ,neonates with normal MR appearance; Pattern Ⅱ,preterm neonates with abnormal MR appearance; Pattern Ⅲ,full-term neonates with abnormal MR appearance.TMS and its parameters,progressive myelination （M）,cortical infolding （C）,involution of germinal matrix tissue （G）,and glial cell migration bands （B）,were employed to assess brain maturation and compare difference between HIE and control groups.Results：The mean of TMS was significantly lower in mild HIE group than it in the control group （mean ± standard deviation [SD] 11.62 ± 1.53 vs.12.36 ± 1.26,P 〈 0.001）.In four parameters of TMS scores,the M and C scores were significantly lower in mild HIE group.Of the three patterns of mild HIE,Pattern Ⅰ （10 cases） showed no significant difference of TMS compared with control neonates,while Pattern Ⅱ （22 cases）,Ⅲ （13 cases） all had significantly decreased TMS than control neonates （mean ± SD 10.56 ± 0.93 vs.11.48 ± 0.55,P 〈 0.05; 12.59 ± 1.28 vs.13.25 ± 1.29,P 〈 0.05）.It was M,C,and GM scores that significantly decreased in Pattern Ⅱ,while for Pattern Ⅲ,only C score significantly decreased.Conclusions：The TMS system,based on conventional MRI,is an effective method to detect delayed brain maturation in clinically mild HIE.The conventional MRI can reveal the different retardations in subtle structures and development processes among the different patterns of mild HIE.

新生儿缺血缺氧性脑病患儿cTnI、CK-MB、IL-6及hs-CRP表达水平及意义

目的探讨新生儿缺血缺氧性脑病(HIE)患儿心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)、白细胞介素-6(IL-6)及超敏C-反应蛋白(hs-CRP)表达水平及意义。方法选取2019年2月—2021年11月本院收治的90例HIE患儿作为病例组,另选取同期健康体检新生儿66例作为对照组,采用酶联免疫吸附法(ELISA)检测两组患者血清cTnI、CK-MB、IL-6及hs-CRP水平,分析cTnI、CK-MB、IL-6、hs-CRP表达差异及其与HIE严重程度和预后的诊断价值。结果重度组患儿血清cTnI、CK-MB、IL-6及hs-CRP水平高于轻度组和中度组(P<0.05);Spearman相关性分析显示,cTnI表达与CK-MB、IL-6及hs-CRP表达呈正相关(P<0.05),CK-MB表达与IL-6、hs-CRP表达呈正相关(P<0.05),IL-6表达与hs-CRP表达呈正相关(P<0.05);预后不良组患儿血清cTnI、CK-MB、IL-6及hs-CRP水平高于预后良好组(P<0.05);ROC曲线分析显示,cTnI、CK-MB、IL-6、hs-CRP联合预测HIE预后的AUC为0.937高于cTnI的0.702、CK-MB的0.831、IL-6的0.774,hs-CRP的0.743(P<0.05)。结论HIE患儿血清cTnI、CK-MB、IL-6及hs-CRP随着病情加剧表达升高,可用于预后诊断。