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ObjectiveTo explore the mechanism of Wenyang Jieyu prescription in regulating hippocampal neuron apoptosis and improving synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 （PD0） were randomly assigned into a control group （n=10） and a modeling group （n=50）. Maternal separation combined with restraint stress was adopted to establish the mouse model of depression， and the modeled mice were randomized into model， Wenyang prescription， Jieyu prescription， Wenyang Jieyu prescription， and fluoxetine groups （n=10） on the weaning day （PD21）. From PD21 to PD111， the mice were fed with the diets mixed with corresponding medicines. The sucrose preference test， open field test， O-maze test， and novel object recognition test were then conducted to evaluate the depression， memory， and learning abilities of mice. Immunohistochemistry （IHC） was employed to measure the atomic absorbance （AA） of postsynaptic density protein 95 （PSD95） in the hippocampus. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to detect the apoptosis of hippocampal neurons. Western blot was employed to determine the protein levels of brain-derived neurotrophic factor （BDNF）， phosphorylated tyrosine kinase receptor B/tyrosine kinase receptor B （p-TrkB/TrkB）， phosphorylated protein kinase B/protein kinase B （p-Akt/Akt）， phosphorylated mammalian target of rapamycin/mammalian target of rapamycin （p-mTOR/mTOR）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X （Bax）， cysteinyl aspartate-specific proteinase-3 （Caspase-3）， synaptophysin （Syn）， and PSD95. ResultCompared with the control group， the modeling decreased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.01）. Furthermore， it decreased the expression of PSD95， increased the neuron apoptosis in the hippocampus （P<0.01）， down-regulated the protein levels of BDNF， p-TrkB/TrkB， p-Akt/Akt， p-mTOR/mTOR， Bcl-2， PSD95， and Syn （P<0.01）， and up-regulated the protein levels of Bax and Caspase-3 （P<0.05） in the hippocampus. Compared with the model group， Wenyang Jieyu prescription and fluoxetine increased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. Moreover， the drugs increased the expression of PSD95， reduced the neuron apoptosis （P<0.01）， up-regulated the protein levels of BDNF， p-TrkB/TrkB， p-Akt/Akt， p-mTOR/mTOR， Bcl-2， PSD95， and Syn （P<0.01）， and down-regulated the protein levels of Bax and Caspase-3 （P<0.01）. ConclusionWenyang Jieyu prescription outperformed Wenyang prescription and Jieyu prescription in the treatment of the depressive behavior induced by maternal separation combined with restraint stress in mice. It exerted the therapeutic effect by reducing the hippocampal neuron apoptosis and improving the synaptic plasticity via the BDNF/Akt/mTOR pathway.
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ObjectiveTo explore the effects of Wenyang Jieyu prescription （WJP） on neuroinflammation and synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 （PD0） were randomized into a control group and a modeling group. Maternal separation combined with restraint stress was employed to establish the mouse model of depression. After the removal of female mice， the modeled mice were randomized into model， Wenyang prescription （5.85 g·kg-1）， Jieyu prescription （12.03 g·kg-1）， WJP （16.71 g·kg-1）， and fluoxetine （2.6 mg·kg-1） groups on the weaning day （PD21）， with 15 mice in each group. The mice were administrated with corresponding drugs mixed with the diet from PD21 to PD111. The sucrose preference test， open field test， O-maze test， and novel object recognition test were then carried out to evaluate the depression state， memory， and learning ability of the mice. Immunohistochemistry （IHC） was employed to observe the ionized calcium-binding adapter molecule-1 （Iba-1） in hippocampal microglia. High performance liquid chromatography （HPLC） was employed to measure the content of noradrenaline （NE） and epinephrine （E） in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the content of interleukin （IL）-18 and IL-1β in the hippocampus. Western blot was employed to determine the protein levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteine aspartate-specific protease-1 （Caspase-1）， IL-1β， synaptophysin （Syn）， and postsynaptic density 95 （PSD95）. ResultCompared with control group， the model group showed decreased sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. The microglia in the model group presented amoeba-like appearance， the Iba1 increased. Moreover， the model group showed decreased content of NE and E （P<0.01）， elevated levels of IL-1β and IL-18 （P<0.01）， down-regulated protein levels of PSD95 and Syn （P<0.05， P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and IL-1β （P<0.05， P<0.01）. Compared with model group， WJP and fluoxetine increased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. They recovered the microglia and the Iba1 decreased. Moreover， the drugs increased the content of NE and E （P<0.05， P<0.01）， lowered the levels of IL-1β and IL-18 （P<0.01）， up-regulated the protein levels of PSD95 and Syn （P<0.01）， down-regulated the protein levels of NLRP3， ASC， Caspase-1， and IL-1β （P<0.05， P<0.01）. ConclusionWJP can treat the depressive behavior induced by maternal separation combined with restraint stress in mice， with the performance outperforming Wenyang prescription and Jieyu prescription. It may alleviate the neuroinflammation induced by microglia and improve the synaptic plasticity by regulating the NLRP3 pathway and increasing neurotransmitters in the hippocampus.
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ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.
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Objective:To study the predictive value of total serum bilirubin (TSB) and the ratio of bilirubin to albumin (B/A) in neonatal acute bilirubin encephalopathy (ABE).Methods:Neonates with extremely severe hyperbilirubinemia (TSB≥425 μmol/L) treated in the Nanjing Maternal and Child Health Hospital, Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Northwest Women and Children's Hospital, Yinchuan Maternal and Child Health Hospital and Liaocheng People's Hospital from March 2018 to August 2019 were selected as prospective subjects for this study. According to the score of brain injury induced by bilirubin, the subjects were divided into ABE group and non-ABE group, and the predictive value of TSB peak and B/A for neonatal ABE were analyzed.Results:A total of 194 infants with extremely severe hyperbilirubinemia were recruited in this study, including 20 in ABE group and 174 in non-ABE group. The peak value of bilirubin ranged from 427 to 979 μmol/L. The optimal critical values of TSB peak value and B/A for ABE prediction were 530 μmol/L and 9.48, respectively. The sensitivity and specificity of ABE prediction were 85.0% and 92.8% when combined with TSB peak and B/A values.Conclusions:TSB peak combined with B/A value can effectively identify neonatal ABE. When the TSB peak value was greater than 530 μmol/L and the B/A value was greater than 9.48, the neonates had a higher risk of neonatal ABE.
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ObjectiveTo observe the behavioral and pain threshold alterations， as well as the changes in indexes related to depression and pain in the serum and central system in mice stressed by maternal separation and chronic neuropathic pain， and explore the underlying mechanism of Wenyang prescription （WY）， Jieyu prescription （JY）， and Wenyang Jieyu prescription （WYJY） in improving depression and pain sensitivity. MethodThe birth date of mice was recorded as PD0. After birth， the mice were divided into a blank group and an experimental group. The neonatal mice in the experimental group underwent maternal separation in PD5-14 at 8 h·d-1. After ablactation， the mice were divided into a maternal separation group， a WY group （Erxian decoction， 5.84 g·kg-1）， a JY group （Xiaoyaosan， 12.00 g·kg-1）， a WYJY group （16.68 g·kg-1）， and a fluoxetine group （2.60 mg·kg-1）， with 15 mice in each group. Meanwhile， 15 male mice of the same age without maternal separation were assigned to the normal control group. Mice in the blank group and the maternal separation group were fed on a regular chow diet in PD21-PD90， while the remaining groups were fed on the corresponding drugs. In PD91， sciatic nerve ligation was performed to induce a model of maternal separation and chronic neuropathic pain. The open field test was used to observe the depression-like behaviors of mice in each group， and the mechanical and temperature pain thresholds were measured to detect the pain sensitivity of mice in each group. The serum levels of corticosterone （CORT）， substance P， and β-endorphin （β-EP） were determined by enzyme-linked immunosorbent assay （ELISA）， and the expression of the glucocorticoid receptor （GR） in the amygdala and β-EP protein in the hypothalamus was detected by immunohistochemistry. The mRNA expression levels of amygdala GR gene （Nr3c1）， FK506 binding protein 5 gene （FKBP5）， metabolic glutamate receptor 5 gene （GRM5）， and brain-derived neurotrophic factor （BDNF） were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with the blank group， the maternal separation group showed reduced stay time and total distance traveled in the 5-min open field test （P<0.01）， reduced mechanical pain threshold （P<0.01）， increased serum CORT and β-EP （P<0.01）， declining FKBP5 mRNA expression （P<0.01）， and increased hypothalamic β-EP expression （P<0.05）. Compared with the maternal separation group， the groups with drug intervention showed prolonged stay time （P<0.05， P<0.01） and up-regulated pain thresholds to different degrees. The total distance traveled in the 5-min open field test increased in the WY group， the WYJY group， and the fluoxetine group （P<0.05， P<0.01）. The JY group showed decreased serum CORT （P<0.01）， reduced β-EP ， and increased BDNF mRNA （P<0.01）. Nr3c1 and GRM5 mRNA decreased in the WY group （P<0.05， P<0.01）. The WYJY group showed decreased serum CORT （P<0.05）and decreased Nr3c1， GRM5， and BDNF mRNA （P<0.05， P<0.01）. The levels of β-EP expression were elevated to different degrees in the groups with drug intervention， but the differences were not significant. The levels of GR expression in the WY group， the JY group， and the WYJY group increased （P<0.05）. ConclusionWYJY can inhibit central pain sensitization and regulate hypothalamic-pituitary-adrenal gland （HPA） axis function by enhancing the expression of GR in the amygdala and inhibiting neuroplasticity and excitability in the amygdala to relieve depression-like behaviors and improve somatic hyperalgesia.
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ObjectiveTo predict the molecular mechanism of Erxian decoction and Wenshen prescription （modified Erxian decoction） in the treatment of depression based on network pharmacology and explore the feasibility of Wenshen prescription in the treatment of depression by comparing the efficacy and mechanism of the two decoctions based on a depression model induced by maternal separation combined with chronic restraint stress. MethodActive components and targets of Erxian decoction and Wenshen prescription were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Targets related to depression were screened out from databases such as GeneCards， Online Mendelian Inheritance in Man database （OMIM）， and DrugBank. Common targets of drugs and disease were obtained and imported to Cytoscape 3.8.2 to plot the drug-active component-target-disease network. STRING platform was used to construct a protein-protein interaction （PPI） network and core targets and related core components were screened out. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） functional enrichment analysis were performed on common targets through Metascape platform. The depression model was induced in mice by maternal separation combined with chronic restraint stress. From the 21st day of maternal separation （PD21） to the 111th day of restraint stress completion （PD111）， mice were fed with the diet mixed with Erxian decoction or Wenshen prescription for intervention. The depressive state of mice was evaluated according to the sucrose preference test， tail suspension test， open field test， and elevated O-maze test. The expression of ionized calcium-binding adapter molecule 1 （Iba1） in the microglia was observed by immunohistochemistry （IHC）. Western blot and Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression levels of protein kinase B1（Akt1）， brain-derived neurotrophic factor （BDNF）， postsynaptic density-95 （PSD95）， and synaptophysin （Syn）. ResultA total of 126 and 118 targets of Erxian decoction and Wenshen prescription in the treatment of depression were screened out， with only eight more targets of Erxian decoction than Wenshen prescription. The two decoctions shared the same core targets， mainly including Akt1， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）. KEGG pathway enrichment analysis predicted that Erxian decoction and Wenshen prescription mainly treated depression through the phosphatidylinositol-3 kinase （PI3K）/Akt signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and neuroactive ligand-receptor interaction pathway. Animal experiments showed that compared with the results in the model group， Erxian decoction and Wenshen prescription could up-regulate the sucrose preference index， prolong the time spent in the central zone， increase the number of crossings， prolong the time spent in opened arm， increase the number of crossings in the opened arm， elevate the expression levels of p-Akt1， BDNF， PSD95， and Syn （P<0.05， P<0.01）， shorten the immobility time of tail suspension， and reduce the expression level of Iba-1 in the hippocampal microglia （P<0.05， P<0.01）. No significant difference between the two decoctions was found. ConclusionUnder the pathogenesis and syndrome law of depression dominated by kidney yang deficiency， Wenshen prescription modified from Erxian decoction is feasible in the treatment of depression. The mechanism may be attributed to the fact that both decoctions can improve neuroinflammation and synaptic plasticity in the hippocampus by affecting Akt1， IL-1β， IL-6， TNF-α， and other core targets and regulating the PI3K/Akt， MAPK， and neuroactive ligand-receptor interaction signaling pathways.
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ObjectiveTo predict the potential molecular mechanism of Erxian decoction in the treatment of anxiety disorder based on network pharmacology， and to verify the efficacy and mechanism using the animal model of maternal separation combined with restraint stress. MethodActive components and related targets of Erxian decoction were obtained by traditional Chinese medicine system pharmacology database and analysis platform （TCMSP） and SwissTargetPrediction. The targets related to anxiety disorder were screened out through GeneCards， therapeutic target database （TTD）， online mendelian inheritance in man database （OMIM）， and DrugBank， and the drug-disease intersection targets were obtained by taking intersections with the drug targets. The protein-protein interaction （PPI） network was constructed by the STRING database， and the core targets were screened out based on topological parameter analysis. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out for the intersection targets through the Metascape platform. Maternal separation combined with restraint stress was used to induce the mouse model of anxiety disorder. From the end of lactation on the 21st postnatal day （PD21） to the completion of restraint stress on the 97th postnatal day （PD97）， the mice were fed with Erxian decoction mixed with diet. The anxiety state of mice was evaluated by open field test and elevated O-maze test. The content of plasma corticosterone （CORT） in mice was detected by enzyme-linked immunosorbent assay （ELISA）. The expression levels of protein kinase B （Akt1）， mammalian target of rapamycin （mTOR）， brain-derived neurotrophic factor （BDNF）， postsynaptic density-95 （PSD95）， and synaptophysin in the hippocampus of mice were detected by Western blot and real-time quantitative polymerase chain reaction （Real-time PCR）. ResultNinty-seven active components and 227 action targets of Erxian decoction were obtained. There were 3 863 targets related to anxiety disorder， with 161 drug-disease intersection targets. Among these intersection targets， core targets such as Akt1， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor （TNF）， and mTOR were presumedly closely related to anxiety disorder. The results of KEGG pathway analysis showed that Erxian decoction mainly treated anxiety disorder through phosphatidylinositol 3-kinase （PI3K）/Akt， mitogen-activated protein kinase （MAPK）， and neuroactive ligand-receptor interaction signaling pathways. The results of animal experiments showed that compared with the model group， the Erxian decoction group significantly increased the time of mice spent in the central zone and central crossing times and time spent in the opened arm and opened arm crossing times， with significantly increased expression levels of p-Akt1， p-mTOR， BDNF， PSD95， and synaptophysin （Syp）. ConclusionErxian decoction has the multi-target and multi-pathway characteristics in the treatment of anxiety disorder， and its mechanism may be related to the improvement of synaptic plasticity and neuroinflammation by affecting Akt1， IL-1β， IL-6， TNF， mTOR， and other core targets and modulating PI3K/Akt， MAPK， as well as neuroactive ligand-receptor interaction signal pathways.
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ObjectiveTo predict the potential molecular mechanism of Erxian decoction in the treatment of anxiety disorder based on network pharmacology， and to verify the efficacy and mechanism using the animal model of maternal separation combined with restraint stress. MethodActive components and related targets of Erxian decoction were obtained by traditional Chinese medicine system pharmacology database and analysis platform （TCMSP） and SwissTargetPrediction. The targets related to anxiety disorder were screened out through GeneCards， therapeutic target database （TTD）， online mendelian inheritance in man database （OMIM）， and DrugBank， and the drug-disease intersection targets were obtained by taking intersections with the drug targets. The protein-protein interaction （PPI） network was constructed by the STRING database， and the core targets were screened out based on topological parameter analysis. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out for the intersection targets through the Metascape platform. Maternal separation combined with restraint stress was used to induce the mouse model of anxiety disorder. From the end of lactation on the 21st postnatal day （PD21） to the completion of restraint stress on the 97th postnatal day （PD97）， the mice were fed with Erxian decoction mixed with diet. The anxiety state of mice was evaluated by open field test and elevated O-maze test. The content of plasma corticosterone （CORT） in mice was detected by enzyme-linked immunosorbent assay （ELISA）. The expression levels of protein kinase B （Akt1）， mammalian target of rapamycin （mTOR）， brain-derived neurotrophic factor （BDNF）， postsynaptic density-95 （PSD95）， and synaptophysin in the hippocampus of mice were detected by Western blot and real-time quantitative polymerase chain reaction （Real-time PCR）. ResultNinty-seven active components and 227 action targets of Erxian decoction were obtained. There were 3 863 targets related to anxiety disorder， with 161 drug-disease intersection targets. Among these intersection targets， core targets such as Akt1， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor （TNF）， and mTOR were presumedly closely related to anxiety disorder. The results of KEGG pathway analysis showed that Erxian decoction mainly treated anxiety disorder through phosphatidylinositol 3-kinase （PI3K）/Akt， mitogen-activated protein kinase （MAPK）， and neuroactive ligand-receptor interaction signaling pathways. The results of animal experiments showed that compared with the model group， the Erxian decoction group significantly increased the time of mice spent in the central zone and central crossing times and time spent in the opened arm and opened arm crossing times， with significantly increased expression levels of p-Akt1， p-mTOR， BDNF， PSD95， and synaptophysin （Syp）. ConclusionErxian decoction has the multi-target and multi-pathway characteristics in the treatment of anxiety disorder， and its mechanism may be related to the improvement of synaptic plasticity and neuroinflammation by affecting Akt1， IL-1β， IL-6， TNF， mTOR， and other core targets and modulating PI3K/Akt， MAPK， as well as neuroactive ligand-receptor interaction signal pathways.
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Objective To investigate the diagnostic correlation and sensitivity of amplitude integrated electroencephalogram (aEEG),brainstem auditory evoked potential (BAEP) and cranial magnetic resonance imaging (MRI) for acute bilirubin encephalopathy (ABE) in the newborn.Method Term and near-term neonates (gestational age ≥ 35 weeks) with hyperbilirubinemia (the level of bilirubin over than 95th percentile) of high and intermediate risk group admitted in the neonatal ward of Guangxi Maternal and Child Health Care Hospital from Jan 2014 to Dec 2015 were recruited retrospectively.The infants were assigned to ABE group and non-ABE group according to the diagnostic criteria of ABE.The clinical data of the newborns were collected and the diagnostic correlation between clinical diagnosis and aEEG,BAEP and cranial MRI were analyzed.The receiver operating characteristic (ROC) curve was adopted to assess the diagnostic efficiency of the peak level of serum bilirubin,aEEG,BAEP and cranial MRI on the early diagnosis of ABE.Result A total of 152 newborns with hyperbilirubinemia were recruited,including 33 cases in the ABE group and 119 cases in non-ABE group.(1) The results of aEEG and MRI were marginally positively correlated with clinical diagnosis of ABE (aEEG:r =0.487,P ＜ 0.001;MRI:r =0.220,P=0.018),while the results of BAEP were closely related to the clinical diagnosis of ABE (r =0.593,P ＜ 0.001);(2) The results of BAEP and MRI on the diagnosis of ABE were positively correlated with those of aEEG (BAEP:r =0.424,P ＜ 0.001;MRI:r =0.307,P ＜ 0.001).(3) The area under the ROC curves for predicting the onset of ABE were 0.899 for the peak level of serum bilirubin,0.767 for BAEP,0.738 for aEEG and 0.590 for MRI.Conclusion There was the correlation on the diagnosis of ABE among the methods of aEEG,BAEP and MRI.The combined diagnosis of the three methods could play a complementary role.The aEEG contributed to the early diagnosis of ABE with high sensitivity.
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Objective To evaluate the levels of total serum bilirubin(TSB),amplitude integrated electroencephalogram(aEEG) monitoring and brainstem auditory evoked potential(BAEP) individually and in combination for the early diagnosis of neonatal acute bilirubin encephalopathy by receiver operating charac-teristic( ROC) curve. Methods Clinical data was retrospectively analyzed. A total of 152 infants were diag-nosed with hyperbilirubinemia,including 119 cases of non-bilirubin encephalopathy group and 33 cases of bil-irubin encephalopathy group. The detection results of peak serum bilirubin,aEEG,BAEP combined with the three methods were determined with ROC curve analysis. Results The areas under ROC curve of TSB lev-el,aEEG,BAEP and in combination were 0. 900,0. 738,0. 767,0. 925,respectively,the corresponding sensi-tivity(specificity) in the cut-off point were 90. 91%(78. 15%),87. 88%(59. 66%),65. 52%(87. 91%), 93. 10%(82. 42%),respectively. It showed that the area under ROC curve of the maximum,the comprehen-sive assessment in diagnostic sensitivity and specificity of the combination of three methods were better than any single detection method by ROC curve. Conclusion The methods of TSB level,aEEG and BAEP play an important role in the diagnosis of neonatal bilirubin encephalopathy,and combination with the three meth-ods can improve the accuracy of diagnosis.
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Objective To evaluate the levels of total serum bilirubin(TSB),amplitude integrated electroencephalogram(aEEG) monitoring and brainstem auditory evoked potential(BAEP) individually and in combination for the early diagnosis of neonatal acute bilirubin encephalopathy by receiver operating charac-teristic( ROC) curve. Methods Clinical data was retrospectively analyzed. A total of 152 infants were diag-nosed with hyperbilirubinemia,including 119 cases of non-bilirubin encephalopathy group and 33 cases of bil-irubin encephalopathy group. The detection results of peak serum bilirubin,aEEG,BAEP combined with the three methods were determined with ROC curve analysis. Results The areas under ROC curve of TSB lev-el,aEEG,BAEP and in combination were 0. 900,0. 738,0. 767,0. 925,respectively,the corresponding sensi-tivity(specificity) in the cut-off point were 90. 91%(78. 15%),87. 88%(59. 66%),65. 52%(87. 91%), 93. 10%(82. 42%),respectively. It showed that the area under ROC curve of the maximum,the comprehen-sive assessment in diagnostic sensitivity and specificity of the combination of three methods were better than any single detection method by ROC curve. Conclusion The methods of TSB level,aEEG and BAEP play an important role in the diagnosis of neonatal bilirubin encephalopathy,and combination with the three meth-ods can improve the accuracy of diagnosis.
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Objective To explore the clinical characteristics and genetic mutation types of the Mediterranean anemia in Guangxi region in the early neonatal period.Methods The observation group was the children who hospitalized in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomons Region during the period of January 2013 and November 2015,and diagnosed Mediterranean anemia were 85 cases.And 85 newborns that were in the hospital at the same time were selected as the control group.The matching condition between the observation group and the control group was the gestational age.We retrospectively analyzed the general situation (birth weight and gender) and the treatment procedure (the characteristic of blood routine examinations;the day-old of the onset of anemia;the endurance of jaundice;assisted ventilation;the time of oxygen therapy;the dayold of enteral feeding;the blood transfusion times) of the two groups.And the gene was detected in the observation group.Results The observation group's days of life [(13.00 ± 3.79) d] of the oral feeding were higher than that [(9.33 ± 1.95) d] of the control group's (t =2.730,P ＜ 0.05);the observation group's frequency [(3.0 ± 1.0) times] of the blood transfusion was higher than that [(1.0 ± 0.2) times] of the control group's (t =4.268,P ＜ 0.05).The observation group's days of life [(4 ± 1) d] of anaemic onset was shorter than that [(8 ± 2) d] of the control group's (t =-3.258,P ＜ 0.05).The mean corpuscular volume [(80 ± 12) fl] in the blood routine of the observation group was smaller than that [(91 ± 28) fl] of the control group (t =6.712,P ＜ 0.05).In the observation group,the mother's age of pregnancy was (29.19 ± 0.91) years,the birth weight of the newborns was (2.356 ± 0.748) kg,the service time of the ventilator was (7.11 ± 5.07) h,the time of continue positive airway pressure was (27.40 ± 15.17) h,the time of the oxygen provision was (84.98 ± 30.65) h,the time of duration of the jaundice last was (10 ± 3) d;and in the control group,the mother's age of pregnancy was (27.9i ± 0.88) years,the birth weight of the newborns was (2.507 ± 0.783) kg,the service time of the ventilator was (6.21 ± 2.55) h,the time of continue positive airway pressure was (9.64 ± 4.89) h,the time of the oxygen provision was(63.07 ± 21.87) h,the time of duration of the jaundice last was (15 ± 2) d.The parameters showed above were not statistically different between the two groups (all P ＞ 0.05).In 85 cases the detection of α-thalassemia in 60 cases,24 patients with β-thalassemia,1 cases of α-thalassemia combined with β-thalassemia.The logistic regression analysis showed that the age of the oral feeding completely (OR =0.233,95％ CI =0.081-0.673) and the times of blood transfusion (OR =6.621,95％ CI =2.777-15.784) were the independence factors of the Mediterranean anemia.Conclusion The early clinical performance of Mediterranean anemia is lack of specificity,and we must improve genetic testing and regulate blood transfusion as soon as possible to the one who has anemia and other clinical manifestations within a week immediately following birth or who is suspected of Mediterranean anemia patients by the blood routine examination.
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Objective To study the clinical characteristics and imaging features of perinatal autosomal recessive polycystic kidney disease ( ARPKD) and a systematic review of the literature was performed to improve awareness of the disease. Methods A newborn with infantile ARPKD admitted to the neonatal department of our hospital was studied and her clinical data and imaging features retrospectively reviewed. CNKI, CBMdisc, MEDLINE and Embase databases were searched using autosomal recessive, perinatal and polycystic kidney as keywords. 9 case reports were retrieved from 2005 to 2015 and a total of 9 patients were analyzed. Results The gestational age of patients with infantile ARPKD was from 33 to 37 weeks. 6 of them were diagnosed using prenatal ultrasound and one patient was diagnosed using genetic sequencing. One of 10 infants had a family history, 4 patientsˊ mothers had abnormal pregnancy history (spontaneous abortion or miscarriage) and 7 (70. 0%) patients with respiratory failure needed mechanical ventilation. The ultrasound of all the patients showed enlarged and hyperechogenic kidneys. 9 patients died, and only one patient was alive after renal transplant. Conclusions The characteristics of perinatal APRKD are enlarged and polycystic kidneys, hepatic cysts and liver fibrosis. Infants with this disease have poor outcomes and high mortality rate. Respiratory failure and renal failure are the main causes of death in the neonatal period and early diagnosis and treatment are necessary.
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Objective To establish biological reference intervals of neonatal T lymphocyte subsets and IgG, IgA,IgMlevels in 24 -hour newborns in Guangxi.Methods Maternal history and neonatal clinical data were evalua-ted and recorded.Venous blood samplings were collected within 24 hours of birth and were sent for testing in half an hour.The neonates were divided into the early -preterm,the late -preterm and the term neonates group,1 1 0 cases for each group.The parturients were divided into Dexamethasone treatment group and without Dexamethasone treatment group.Data in neonates and the parturients and the sex were analyzed by SPSS 1 7.0 software and the biological refe-rence values were calculated.Results The two -sided reference intervals of 95% in the early -preterm group,the late -preterm group and the term neonates group were as follows:CD3 +:52.07 -88.92 g/L,58.1 6 -90.42 g/L, 56.1 5 -95.67 g/L;CD4 +:25.20 -59.26 g/L,31 .27 -72.91 g/L,28.44 -82.66 g/L;CD8 +:7.30 -36.26 g/L, 9.1 3 -38.49 g/L,1 1 .09 -48.99 g/L;CD4 +/CD8 +:0.34 -4.58,0.34 -4.58,0.32 -3.80;CD1 9 +:3.95 -27.59 g/L,4.04 -30.94 g/L,4.08 -38.70 g/L;NK cell:1 .34 -6.64 g/L,2.88 -8.92 g/L,3.07 -9.35 g/L;IgA:0.000 4 -0.039 6 g/L,0.000 0 -0.069 0 g/L,0.000 0 -0.069 0 g/L;IgM:0.001 6 -0.1 58 4 g/L,0.020 0 -0.1 40 0 g/L,0.020 0 -0.420 0 g/L;IgG:3.22 -1 0.98 g/L,1 .1 0 -1 4.62 g/L,5.00 -1 3.66 g/L.Moreover the ca-ses with Dexamethasone treatment were as follows:the late -preterm infants CD8 + 1 0.35 -40.33 g/L,NK 3.1 0 -9.46 g/L,term NK 6.60 -9.50 g/L;those in without Dexamethasone treatment:the late -preterm infants CD8 +8.42 -34.96 g/L,NK 2.94 -7.80 g/L,term NK 2.98 -8.94 g/L;according to gender,the males in the late -pre-term infants CD8 + 8.26 -35.66 g/L,term CD3 + 51 .90 -92.94 g/L;females in the late -preterm infants CD8 +1 1 .08 -40.68 g/L,term CD3 + 61 .1 0 -96.1 4 g/L.Conclusions Testing values of neonatal T lymphocyte subsets and IgG,IgA,IgM levels in 24 -hour newborns in Guangxi disperse largely and show some differences among the early -preterm neonates,the late -preterm neonates and the term neonates,and maternal Dexamethasone treatment during pregnancy and gender play a role in neonatal immunity.
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Objective To study the clinical characteristics and risk factors of cow's milk protein allergy(CMPA)in infants less than 3 months old in Guangxi District.Methods From July 1 ,2012,to December 30,2014,infants less than 3 months old suspected of CMPA visiting the pediatric outpatient depart-ment of Maternal and Children Hospital of Guangxi Zhuang Autonomous Region were recruited,which included initial diagnosis and being transported from peripheral hospitals.Observation scale was formulated, attending physician screened patients and their senior made a definite diagnosis.All the infants underwent diagnostic algorithms and were followed up constantly.Results A total of 137 cases were divided into aller-gy group(n =51 )and control group(n =86).Two groups shared some common symptoms such as diarrhea, constipation,bloody stool,stomachache,gastroesophageal reflux(GER),indigestion,anorexia,feeding diffi-culties.Between the allergy group and control group the parameters such as feeding patterns (including breast feeding,mix feeding,formula feeding),improper deeding of food supplement,long-term use of antibiotics in neonatal period and parental atopy showed no significant differences(P ﹥0.05).The parameters in neonatal period including GER [20 cases (39.2%)vs.7 cases (8.1 %)],intake of cow's milk formula [51 cases (100%)vs.71 cases (82.6%)],feeding intolerance (including GER)[17 cases (33.3%)vs.1 1 cases (12.8%)],gut infection[8 cases(15.7%)vs.4 cases(4.7%)],transfusion of blood or/and bloody prod-ucts[12 cases(23.5%)vs.1 1 cases(12.8%)]showed statistically significant differences between the aller-gy group and control group(χ2 =19.538,P =0.000;χ2 =9.989,P =0.002;χ2 =8.308,P =0.004;χ2 =4.691 ,P =0.030;χ2 =5.198,P =0.023 ).Conclusion Symptoms of CMPA in infants no more than 3 months old involve mainly digestive system such as diarrhea,bloody stool,GER.Intake of cow milk formula in neonatal period play an important role in triggering CMPA.
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Objective To discuss the safety of inhaled nitric oxide (iNO)for bronchopulmonary dysplasia (BPD).Methods We analysed 65newborns diagnosed as BPD from January 2012to December 2013in Maternal and Child Health Hospital of the Guangxi Zhuang Autonomous Region.They were divided into iNO group(n=35)and control group(n=30)according to whether administering iNO or not.The heart rate,blood pressure,oxygen supply time,assisted ventilation time,hospital stay,concentration of NO2 and methemoglobin,and the changes of coagulation function were observed dynamically before and after iNO treatment.Results There were significant differences in oxygen supply time[(37±9)d vs.(55±7)d], assisted ventilation time[(29±7)d vs.(35±9)d],hospital stay [(45±9)d vs.(54±7)d]between iNO group and control group(P﹤0.05).There were no obvious changes in heart rate,blood pressure and co-agulation function before and after iNO treatment(P﹥0.05).The incidences of the complications had no sig-nificant differences between the two groups (P﹥0.05).Conclusion Long-time iNO can shorten oxygen therapy time and assisted ventilation time,iNO therapy in BPD doesn′t found serious adverse effect to cardio-vascular function as well as coagulation function,and doesn′t increase the risk of intracranial hemorrhage and retinopathy of prematurity.
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The early clinical symptoms of newborns with acute bilirubin encephalopathy are absent or slight.In addition ,this diseaes is no specificity.So ne wborns with acute bil rubin encephalopaht y is easy to miss ni d iagnosis.If the best treatmetn opportunity of this disease is delayed,it can affect the long-term prog-nosis and survival.Neuros-pecfi ic nlo ase,cranial magnetic resonance imga ing,electroencpe halogram,amlp i-tude integrated electroencephalogram and rb ainstem auditory evoked potential can judge the position and in-tensity of brain injury from the different angle and level,which can provide important basis for the early diag-nosis and intervention of acute bilirubin encephalopathy.
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Due to the fact that early full term newborn has no specific clinical signs,early diagnosis of hypoxic-ischemic brain damage is difficult. Timely intervention will affect the longterm prognosis in patients with the treatment and survival. Amplitude integrated electroencephalography( aEEG) is a noninvasive monitoring and evaluation of brain function,simple and effective method,which can provide exact basis for full term newborn with hypoxic ischemic brain damage in early diagnosis and prediction of prognosis.
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ObjectiveTo analyze the incidence and risk factors of retinopathy of prematurity (ROP).Methods244 premature children 4 weeks after birth, which neonatal gestational age were ＜ 36 weeks, birth weight were ＜ 2 000g,were taken fundus examination.ROP stage at diagnosis, according to international law for the diagnosis and staging.Results244 patients with varying degrees of premature children with ROP in 49 cases(including 37 cases of ROP Ⅰ ,ROPⅡ of the 10 cases,ROP Ⅲ 2 ,ROP rate was 20.1％.Gestational age,birth weight,oxygen,mother pregnancy complications,acidosis, apnea,PaO2 changes, mechanical ventilation and infection on the incidence of ROP had a significant effect (all P ＜ 0.05) ;and shorter gestational age, birth weight, smaller, ROP incidence higher(all P ＜ 0.05).ConclusionThe incidence of ROP and gestational age, birth weight,oxygen, mother pregnancy complications, acidosis, apnea, PaO2 changes and infection, mechanical ventilation and other factors, and the gestational age, birth weight, oxygen, apnea were independent risk factors for ROP.