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.

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.

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.

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.

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.

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.

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.

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).

Observation on the therapeutic effect of aspirin in combined with ozagrel sodium in the treatment of acute cerebral infarction

Objective:To evaluate the changes in serum index levels after monosialoganglioside injection combined with conventional treatment of neonatal hypoxic ischemic encephalopathy. Methods:A total of 70 children with neonatal hypoxic ischemic encephalopathy treated in our hospital between February 2013 and February 2016 were selected and randomly divided into observation group and control group, control group received clinical routine treatment and observation group accepted monosialoganglioside injection combined with conventional treatment. After 1 week of treatment, serum levels of apoptosis factors, nerve function indexes, oxidation/anti-oxidation indexes and disease severity indexes of two groups of patients were detected.Results:Serum PDCD5, sFas, sFasL, NSE, S100-β, MDA, NO, NOS, H-FABP, NPY, caspase-1 and ET-1 levels of observation group were lower than those of control group while BDNF, NGF, SOD, GSH-PX, IGF-1 and GH levels were higher than those of control group.Conclusion: Monosialoganglioside injection can enhance the overall treatment effect and promote the realization of homeostasis in children with HIE.

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.

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.

Neonatal infratentorial subdural hematoma contributing to obstructive hydrocephalus in the setting of therapeutic cooling: A case report

BACKGROUND Symptomatic neonatal subdural hematomas usually result from head trauma incurred during vaginal delivery,most commonly during instrument assistance.Symptomatic subdural hematomas are rare in C-section deliveries that were not preceded by assisted delivery techniques.Although the literature is inconclusive,another possible cause of subdural hematomas is therapeutic hypothermia.CASE SUMMARY We present a case of a term neonate who underwent therapeutic whole-body cooling for hypoxic ischemic encephalopathy following an emergent C-section delivery for prolonged decelerations.Head ultrasound on day of life 3 demonstrated a rounded mass in the posterior fossa.A follow-up brain magnetic resonance imaging confirmed hypoxic ischemic encephalopathy and clarified the subdural hematomas in the posterior fossa causing mass effect and obstructive hydrocephalus.CONCLUSION The aim of this report is to highlight the rarity and importance of mass-like subdural hematomas causing obstructive hydrocephalus,particularly in the setting of hypoxic ischemic encephalopathy and therapeutic whole-body cooling.

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.

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.

袋鼠式护理联合被动康复训练在新生儿缺氧缺血性脑病中的应用

目的:探究袋鼠式护理(Kangaroo mother care,KMC)联合被动康复训练在新生儿缺氧缺血性脑病(Hypoxieischemic encephalopathy,HIE)患儿中的应用效果。方法:选取2020年3月至2021年12月于我院就诊的80例HIE患儿作为研究对象。按随机数字表法分为对照组和观察组,每组各40例。对照组采取常规护理联合被动康复训练,观察组采取KMC联合被动康复训练。分析比较两组的神经行为、神经系统后遗症发生率以及护理满意度。结果:护理后,两组的新生儿神经行为测定量表(Neonatal Behavioral Assessment Scale,NBNA)评分均高于护理前;并且观察组高于对照组(P<0.05)。观察组神经系统后遗症总发生率低于对照组(P<0.05)。观察组患儿家长满意度高于对照组(P<0.05)。结论:KMC联合被动康复训练可改善HIE患儿的神经行为,降低神经系统后遗症发生率,提高患儿家长的满意度。

单唾液酸四己糖神经节苷脂联合重组人促红细胞生成素治疗新生儿缺氧缺血性脑病疗效观察

目的探讨单唾液酸四己糖神经节苷脂(GM1)联合重组人促红细胞生成素(rhEPO)治疗新生儿缺氧缺血性脑病(HIE)临床疗效及其对炎症因子和神经功能的影响。方法选择2017年6月至2020年6月南阳市中心医院新生儿科收治的78例HIE患儿为研究对象,采用随机数字表法将患儿分为对照组(n=39)和观察组(n=39)。所有患儿给予常规治疗,包括吸氧、维持水电解质酸碱平衡、控制惊厥与颅内压等治疗,中重度患儿给予亚低温治疗。对照组患儿在常规治疗基础上给予rhEPO 200 IU·kg^(-1),皮下注射,每周3次;观察组患儿在对照组基础上给予GM120 mg静脉滴注,每日1次。7 d为1个疗程,连续治疗4个疗程,中、重度患儿依据病情再治疗1~3个疗程。比较2组患儿治疗后的总有效率;于治疗前和治疗后14、28 d采用新生儿神经行为评分(NBNA)评估2组患儿的神经功能;治疗前和治疗后14、28 d,采用酶联免疫吸附法测定2组患儿血清白细胞介素-6(IL-6)、细胞间黏附分子-1(ICAM-1)、肿瘤坏死因子-α(TNF-α)、缺氧诱导因子-1α(HIF-1α)、神经元特异性烯醇化酶(NSE)水平。结果对照组和观察组患儿总有效率分别为69.23%(27/39)、94.87(37/39),观察组患儿治疗总有效率显著高于对照组(χ^(2)=8.705,P=0.003)。2组轻度患儿治疗总有效率均为100%;观察组中中、重度患儿总有效率显著高于对照组(χ^(2)=4.843、3.898,P=0.028、0.048)。2组患儿治疗前NBNA评分比较差异无统计学意义(P>0.05);2组患儿治疗后14、28 d NBNA评分显著高于治疗前(P<0.05);2组患儿治疗后28 d NBNA评分显著高于治疗后14 d(P<0.05)。观察组患儿治疗后14、28 d NBNA评分显著高于对照组(P<0.05)。治疗前2组患儿血清ICAM-1、IL-6、TNF-α、HIF-1α、NSE水平比较差异无统计学意义(P>0.05);2组患儿治疗后14、28 d血清ICAM-1、IL-6、TNF-α、HIF-1α、NSE水平显著低于治疗前(P<0.05);2组患儿治疗后28 d血清ICAM-1、IL-6、TNF-α、HIF-1α、NSE水平显著低于治疗后14 d(P<0.05)。治疗后14、28 d,观察组患儿血清ICAM-1、IL-6、TNF-α、HIF-1α、NSE水平显著低于对照组(P<0.05)。结论GM1联合rhEPO治疗新生儿HIE,能显著降低炎症因子及血清HIF-1α、NSE水平,促进神经功能恢复。

新生儿缺氧缺血性脑病患儿血清DNMT1、DNMT3a和BDNF检测对预后评估的临床价值

目的探讨血清DNA甲基化转移酶(DNMT)1、DNMT3a和脑源性神经营养因子(BDNF)检测在新生儿缺氧缺血性脑病(HIE)患儿预后评估中的价值。方法选取2016年1月至2023年1月在我院诊治的84例新生儿HIE患儿为观察组,并选取同期84例于我院出生的健康新生儿为对照组。根据患儿病情程度分为轻度组36例、中度组28例、重度组20例。采用酶联免疫吸附(ELISA)法检测血清DNMT1、DNMT3a和BDNF水平;多因素Logistic回归分析新生儿HIE患儿预后的影响因素;受试者工作特征(ROC)曲线分析血清DNMT1、DNMT3a和BDNF水平对新生儿HIE患儿预后的预测价值。结果与对照组相比,轻度、中度、重度组新生儿HIE患儿血清DNMT1、DNMT3a水平依次升高(P<0.05),BDNF水平依次降低(P<0.05);与预后良好组相比,预后不良组新生儿HIE患儿血清DNMT1、DNMT3a水平升高(P<0.05),BDNF水平降低(P<0.05);多因素Logistic回归分析发现,病情程度、DNMT1、DNMT3a是影响新生儿HIE患儿预后的危险因素(P<0.05),新生儿Apgar评分、BDNF是影响患儿预后的保护因素(P<0.05);血清DNMT1、DNMT3a、BDNF联合检测预测新生儿HIE患儿预后的ROC曲线下面积(AUC)为0.955,均优于其各自单独预测(Z_(联合检测-DNMT1)=2.046,P=0.020;Z_(联合检测-DNMT3a)=3.046,P=0.001;Z_(联合检测-BDNF)=2.073,P=0.019)。结论新生儿HIE患儿血清DNMT1、DNMT3a水平升高,BDNF水平降低,在新生儿HIE患儿预后评估中具有一定价值。

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。

针刺联合循经按摩治疗新生儿缺氧缺血性脑病恢复期临床研究

目的:观察针刺联合循经按摩治疗新生儿缺氧缺血性脑病(NHIE)恢复期的疗效。方法:选取102例NHIE恢复期患儿作为研究对象,按照治疗方案不同分为针刺组、抚触按摩组、联合组,各34例。3组均给予常规康复治疗,在此基础上,针刺组给予针刺治疗,抚触按摩组给予循经按摩,联合组给予针刺联合循经按摩治疗。比较3组临床疗效及预后情况,比较3组治疗前后血液流变学指标[全血高切黏度、全血低切黏度、血浆黏度]、血清炎性因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、可溶性细胞间黏附分子-1(sICAM-1)]、神经相关因子[Tau蛋白、生长激素(GH)、胰岛素生长因子-1 (IGF-1)、金属蛋白酶-9 (MMP-9)]、生长发育指标[智能发育(MDI)、运动发育(PDI)]值的变化。结果:联合组总有效率为94.12%,针刺组、抚触按摩组分别为76.47%、70.59%,针刺组、抚触按摩组与联合组比较,差异有统计学意义(P<0.05)。治疗4周、8周后,3组血浆全血高切黏度、全血低切黏度、血浆黏度均较治疗前下降(P<0.05);治疗4周、8周后,联合组血浆全血高切黏度、全血低切黏度、血浆黏度均低于同一时间段的针刺组、抚触按摩组(P<0.05)。治疗4周、8周后,3组血清IL-6、TNF-α、sICAM-1水平均较治疗前下降(P<0.05);治疗4周、8周后,联合组血清IL-6、TNF-α、sICAM-1水平均低于同一时间段的针刺组、抚触按摩组(P<0.05)。治疗4周、8周后,3组血清Tau蛋白、MMP-9水平均较治疗前下降,血清GH、IGF-1水平均较治疗前上升(P<0.05);治疗4周、8周后,联合组血清Tau蛋白、MMP-9水平低于同一时间段的针刺组、抚触按摩组,血清GH、IGF-1水平高于同一时间段的针刺组、抚触按摩组(P<0.05)。治疗4周、8周后,3组MDI、PDI评分均较治疗前升高(P<0.05);治疗4周、8周后,联合组MDI、PDI评分均大于同一时间段的针刺组、抚触按摩组。随访6个月,Ridit检验显示,联合组预后情况优于针刺组、抚触按摩组(P<0.05);针刺组与抚触按摩组预后情况比较,差异无统计学意义(P>0.05)。结论:针刺联合循经按摩疗效确切,可调节NHIE患儿血液流变情况,抑制炎症因子分泌,调节神经相关因子水平,有助于患儿智力及运动发育,预后良好。