High-risk factors for early failure of high-flow nasal cannula oxygen therapy in children / 中国当代儿科杂志

OBJECTIVE@#To determine the high-risk factors for early failure of high-flow nasal cannula (HFNC) oxygen therapy in children with acute respiratory insufficiency (ARI).@*METHODS@#The clinical data of 123 children with ARI were reviewed who received HFNC oxygen therapy in the pediatric intensive care unit from January to June, 2018. The children who did not require an upgrade of respiratory support during hospitalization and were successfully weaned from HFNC were classified as HFNC success group (69 cases). Of the remaining children (54 cases) who required an upgrade of their respiratory support during hospitalization, those that needed to upgrade their respiratory support within 48 hours of receiving HFNC were classified as early HFNC failure group (46 cases). Risk factors for early failure of HFNC were determined using multivariate logistic regression analysis.@*RESULTS@#The incidence rates of shock, sepsis, intracranial hypertension syndrome, and multiple organ dysfunction syndrome were significantly higher in the early HFNC failure group than in the HFNC success group (P4.5 and PaCO/PaO ratio >0.64 were independent risk factors for early HFNC failure (OR=5.535 and 9.089 respectively; P4.5 or PaCO/PaO ratio >0.64 have relatively high risk of early HFNC failure.

Role of c-Jun N-terminal kinase-mediated FOXO3a nuclear translocation in neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the mechanisms of neuroprotective effects of c-Jun N-terminal kinase (JNK)/FOXO3a transcription factor signaling pathway inhibition on hypoxic-ischemic neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage (HIBD).</p><p><b>METHODS</b>Sixty-four 7-day-old Sprague-Dawley rats were divided into four groups: hypoxia-ischemia (HI), sham-operated, JNK specific inhibitor AS601245-treated, and DMSO vehicle. Rats' cerebral cortexes were collected at 24 hours after HI. Western blot was used to detect the protein expression of JNK, p-JNK, FOXO3a, nuclear and cytoplasmic FOXO3a, Bim, and CC3. TUNEL staining was used to detect the apoptotic cells.</p><p><b>RESULTS</b>Compared with the sham-operated group, p-JNK protein increased (P<0.01), nuclear protein of FOXO3a increased (P<0.01), cytoplasmic protein decreased (P<0.01), and pro-apoptotic proteins Bim and CC3 increased 24 hours after HI (P<0.01). Compared with the HI and DMSO vehicle groups, p-JNK protein was reduced (P<0.01), nuclear protein of FOXO3a was also reduced (P<0.01), cytoplasmic protein increased (P<0.01), and Bim and CC3 proteins decreased (P<0.01) in the AS601245-treated group 24 hours after HI. TUNEL positive cells were reduced in the AS601245-treated rats compared with the HI and DMSO vehicle groups 24 hours after HI (P<0.01).</p><p><b>CONCLUSIONS</b>JNK activity increases in the neonatal rat brain with HI damage. JNK activity inhibition can inhibit FOXO3a translocation from cytoplasm to nucleus and downregulate the levels of pro-apoptotic proteins Bim and CC3, leading to the reduction of neuronal apoptosis.</p>

Role of STAT3 signaling pathway in hypoxic-ischemic brain damage of neonatal rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the role and mechanisms of STAT3 signaling pathway in hypoxic-ischemic brain damage (HIBD) of neonatal rats.</p><p><b>METHODS</b>Eighty 7-day-old Sprague-Dawley rats were randomly divided into two groups: HI and sham-operated (n=40 each). The rats in the HI group were subjected to right carotid artery ligation and subsequent hypoxia exposure (8% O2) for 2.5 hours, and the rats in the sham-operated group underwent the right carotid artery dissection without subsequent ligation or hypoxia treatment. Brain tissue samples were collected at 4, 6, 8, 12 and 24 hours after operation and hypoxic exposure. Immunohistochemistry and Western blot were used to detect the expression of STAT3, phosphorylated STAT3 (p-STAT3) and vascular endothelial growth factor (VEGF) proteins. TUNEL staining was used to detect apoptotic cells.</p><p><b>RESULTS</b>No significant difference in STAT3 expression was observed at all time points between the HI and sham-operated groups (P>0.05). Compared with the sham-operated group, the expression of p-STAT3 protein in the HI group was significantly upregulated at 4, 6, 8, 12 hours after operation and hypoxic exposure, and peaked at 6 hours (P<0.01). The VEGF expression in the HI group was higher than that in the sham-operated group at all time points, which peaked at 8 hours (P<0.05). TUNEL staining showed that the apoptotic cells increased significantly in a time-dependent manner compared with the sham-operated group (P<0.01).</p><p><b>CONCLUSIONS</b>HI may lead to phosphorylation of STAT3 which probably induces the VEGF expression in the brain of neonatal rats. The activated STAT3 signaling pathway may be involved in the apoptosis regulation of nerve cells, and related to apoptosis inhibition of nerve cells.</p>

Effect of integrin β8 on TGF-β1 activation in astrocytes with oxygen glucose deprivation / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effect of β8 expression on transforming growth factor β1(TGF-β1) activation in astrocytes with oxygen glucose deprivation (OGD).</p><p><b>METHODS</b>Astrocytes were cultured and then subjected to OGD to generate hypoxia-ischemia (HI) model in vitro. Immunocytochemistry was used to detect the expression and distribution of β8 in nomoxia cultured cells. β8 protein expression was quantified by Western blot at 12 hours, 1 day and 2 days after OGD. Astrocytes and luciferase reporter cells (TMLC) were co-cultured. β8 RNA interference system was established to specifically inhibit β8 expression in cultured astrocytes. TGF-β1 activation was then detected in the co-culture system.</p><p><b>RESULTS</b>β8 was mainly located in the cytoplasm and neurites of astrocytes. OGD resulted in increase of β8 protein expression at 12 hours after reoxygenation in astrocytes, which was peaked at 1 day after reoxygenation. TGF-β1 activation was in accordance with β8 expression in astrocyte-TMLC co-culture system after reoxygenation. After the inhibition of β8, TGF-β1 activation was significantly reduced in all time points.</p><p><b>CONCLUSIONS</b>The highly expressed β8 plays important roles in the regulation of TGF-β1 activation in neonatal rats with hypoxic-ischemic brain damage.</p>

Role of the FOXO3a transcription factor in neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the role and mechanisms of FOXO3a nuclear translocation in neuronal apoptosis after hypoxia-ischemia (HI).</p><p><b>METHODS</b>One hundred and sixty 10-day-old Sprague-Dawly rats were randomly divided into two groups: HI and sham-operated. The right common carotid artery was ligated followed by hypoxia exposure for 2.5 hours in the HI group. The sham-operated group rats were not subjected to carotid artery ligation or hypoxia treatment. Rat cerebral cortex was collected at 0.5, 2, 4, 8 and 24 hours after hypoxia. Western blot was used to detect expression of total FOXO3a protein, pnuclear and cytoplasmic FOXO3a and Bim. TUNEL staining was used to detect apoptotic cells.</p><p><b>RESULTS</b>The nuclear protein of FOXO3a obviously increased from 0.5 to 24 hours after HI in a time-dependent manner compared with the sham-operated group (P<0.01). On the contrary, cytoplasmic protein evidently decreased from 0.5 to 24 hours in the HI group compared with the sham-operated group (P<0.01). Bim protein increased from 0.5 hour, peaked at 2 hours, started to decline at 4 hours (P<0.01), and returned to baseline level at 8 and 24 hours after HI in the HI group compared with the sham-operated group. TUNEL positive cells started to express at 4 hours, and peaked at 24 hours after HI (P<0.01). However, TUNEL positive cells were rarely found in the sham-operated group.</p><p><b>CONCLUSIONS</b>HI induces FOXO3a translocation from cytoplasm to nucleus, and enhances protein expression of its target gene Bim in the neonatal rat brain. The upregulation of Bim expression might be related to neuronal apoptosis.</p>

Roles of glutamate receptor 2 and cellular free calcium in the pathogenesis of periventricular leukomalacia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the expression of the AMPA receptor subunit glutamate receptor 2 (GluR2) and the cellular free calcium concentration in the white matter of neonatal rats with periventricular leukomalacia (PVL) and their roles in the pathogenesis of PVL.</p><p><b>METHODS</b>A PVL model was prepared by unilateral carotid artery ligation (UCL) followed by exposure to 6% oxygen for 4 hrs in 2-day-old rats. The neonatal rats performed a sham operation, without hypoxia-ischemia (HI), were used as the control group. At 12, 24, 48 and 72 hrs of HI, the expressions of GluR2 mRNA and protein in the white matter were detected using real time quantitative PCR and Western blot respectively. Spectrophotofluorimetry and Fura 2/AM were used to detect the cellular free calcium concentration.</p><p><b>RESULTS</b>The expressions of GluR2 mRNA and protein in the white matter were significantly reduced in the PVL group at 24 hrs of HI, and remained at lower expressions until 72 hrs of HI compared with the control group (P < 0.05). The cellular free calcium concentrations increased significantly in the PVL group at 12 hrs of HI, and remained at higher levels until 72 hrs of HI compared with the control group (P < 0.05).</p><p><b>CONCLUSIONS</b>The expressions of GluR2 mRNA and protein in the white matter decreased whereas the cellular free calcium concentration increased in neonatal rats with PVL. The decreased expression of GluR2 might lead to the overloading of cellular calcium in the white matter, which may cause neuronal damage and death.</p>

Expression of P75NTR protein and RhoA mRNA in the brain of neonatal rats with white matter damage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Recent studies have indicated that the signal pathway of NgR-P75NTR- RhoA plays a key role in nerve injury and remodeling, but its exact mechanism and the role of the downstream molecule RhoA regulated by P75NTR remain unclear in hypoxia-ischemia (HI) neonatal animals. The present study was designed to assess the expression of P75NTR protein and RhoA mRNA in neonatal white matter and to investigate their relationship in newborn rats with white matter damage (WMD).</p><p><b>METHODS</b>The rat WMD model was established by the ligation of right common carotid artery, followed by 6% hypoxia exposure for 4 hrs. The control group was sham-operated, without HI treatment. The histological changes of brain tissue were observed under light and electron microscopes. Expression of P75NTR protein and RhoA mRNA in the brain white matter after 12, 24, 48 and 72 hrs and 7 days of HI were detected by RT-PCR and immunohistochemistry, respectively.</p><p><b>RESULTS</b>Periventricular white matter damage was observed by 48 hrs of HI. Expression of P75NTR protein increased in the striatum and callosum zones at 12 hrs, peaked at 48 hrs, and remained at a higher level than control until 72 hrs of HI in the WMD group (P < 0.01). After 7 days of HI expression of P75NTR protein was no longer statistically different from controls. The RhoA mRNA was higher in the WMD group for the first 72 hrs and then declined to control values.</p><p><b>CONCLUSIONS</b>Increased P75NTR protein might mediate apoptosis of nerve cells and inhibit the regeneration of neuron axons. The subsequent decline back to control value may be correlated with the aggregation of necrosis of nerve cells after HI. The patterns of RhoA mRNA expression were consistent with those of P75NTR protein, suggesting that the increased P75NTR level may promote RhoA mRNA expression.</p>

Expression of F-actin and RhoA in experimental hypoxic-ischemic white matter damage in premature SD rats / 中华儿科杂志

<p><b>OBJECTIVE</b>White matter damage (WMD) in preterm infants is a well-recognized serious complication of prematurity. The collapse of cell skeleton of growth cone after hypoxia-ischemia (HI) is considered as the basic neuropathologic change of the long-term residuals of premature white matter damage. F-actin is the major component of cell skeleton and maintains the normal form of cells, its function and potential mechanism of WMD have not been reported. In this study, changes of F-actin and its influencing factor RhoA were investigated.</p><p><b>METHODS</b>Totally 184 Sprague-Dawley (SD) rats (age 2 days, body weight 6 to 8 grams) were randomly divided into 14 groups: 7 different time WMD groups (HI 12 h, 24 h, 48 h, 72 h, 7 d, 14 d, 28 d) and 7 corresponding control groups. The 2 day-old SD rats were subjected to ligation of right carotid artery (ischemia), and then they were put into a box full with 6% oxygen and 94% nitrogen for 4 hours (hypoxia). The light microscopy was used to observe the brain pathological changes and the electron microscopy was used to detect the brain ultrastructural changes after hypoxia and ischemia. Eighty SD rats were used for flurescent-immunohistochemical method to detect the distribution of F-actin in cell membrane and cytoplasm of both WMD groups and the control groups at 12 h, 24 h, 48 h, 72 h, 7 d after HI respectively. The distribution of F-actin was reflected by the percentage of non-integrity cells. Another 80 SD rats were used for real time RT-PCR to detect the expression of RhoAmRNA in the white matter tissue of both WMD groups (HI 12 h, 24 h, 48 h, 72 h, 7 d) and the control groups.</p><p><b>RESULTS</b>(1) Necrosis of lateral ventricle tissue was observed by 72 h after HI. Dilatation of ventricle and formation of capsular space beneath white matter had been observed by 14 d after HI. (2) Disregulation, pyknosis, mitochondrion swelling and chromatin agglutination were observed in WMD groups. The maldevelopment of myelins in WMD groups was detected at 1 h after HI. (3) The fluorescent stains decreased on cellular membrane, but increased in cytoplasm with time. The percentage of non-integrity cells was significantly higher (P < 0.05) in HI groups (0.32 +/- 0.04, 0.43 +/- 0.04, 0.56 +/- 0.03, 0.65 +/- 0.04, 0.87 +/- 0.03) than the controls (0.02 +/- 0.01, 0.02 +/- 0.01, 0.01 +/- 0.01, 0.02 +/- 0.01, 0.02 +/- 0.01). (4) The expression of RhoA mRNA was significantly increased (P < 0.05) in HI groups (1.205, 2.415, 4.830, 1.500) in the white matter tissue compared with the controls (0.300, 0.375, 0.375, 0.530) at 12 h, 24 h, 48 h, 72 h after HI. The expression of RhoA mRNA reached the peak value at HI 48 h, and then gradually decreased. The expression of RhoA mRNA at HI 7 d in WMD group (0.500) was not significantly different from the control (P > 0.05).</p><p><b>CONCLUSION</b>(1) The pathological and ultrastructural changes of white matter in WMD groups after HI suggest that the WMD model was successfully set up in premature 2 days SD rats. (2) F-actin is redistributed within cells after HI: expression in membrane is decreased and expression in plasma was increased. The redistribution possibly results in the collapse and retraction of cells. (3) The expression of RhoA mRNA is increased significantly after HI, which may lead to the redistribution of F-actin. (4) The increase of the expression of RhoA mRNA is not persistent, but the redistribution of F-actin is continued, which suggests that RhoA may not be the only factor affecting the redistribution of F-actin.</p>

Function of Phosphatase and Tensin Homologue Deleted on Chromosome 10 in Formation and Maintenance of Neuronal Circuits in Brain / 实用儿科临床杂志

Phosphatase and tensin homologue deleted on chromosome 10(PTEN) is a tumor suppressor which can inhibit proliferation and migration and control apoptosis in a number of cell types,mainly through inhibiting the phosphoinositide 3-kinase(PI3K) signaling pathway.A number of in vitro and in vivo studies has been instrumental in uncovering a direct correlation between deregulated PTEN/PI3K signaling and changes in neuronal morphogenesis,which is likely to have profound bearings upon the pathogenesis of neurological symptoms.This review outlines recent work on the function of PTEN during the formation and maintenance of neuronal circuits in the brain.

Establishment and Evaluation on Experimental Newborn Rats Model of Periventricular Leukomalacia / 实用儿科临床杂志

Objective To establish the 2 day-old SD rats model of periventricular leukomalacia(PVL).Methods Sixty-five healthy 2 day-old SD rats were randomly divided into 3 experimental PVL groups and 3 control groups.The experimental PVL groups were subjected to right carotid ligation(RCL),and then they were suffered from hypoxia by 6% oxygen and 94% nitrogen for 4 hours.Meanwhile sham surgeries were performed on control groups without exposed to hypoxia.Light and electronic microscopy were used to observe brain pathological changes.Immunohistochemistry methods were used to detect the distribution and expression of glial fibrillary acidic protein(GFAP),?-amyloid precursor protein(?-APP),myelin basie protein(MBP) and O4 of brain at 72 hours post-operation.Han-(ging) test,inclined plane test,open field test and cylinder test were performed on the rats 28 days post-operation.Results 1.In the PVL groups,light and electronic microscopy showed that tissue necrosis was observed in the periventricular white matter area at early stage,and at later stage right ventricular dilation,decrease of the corpus callosum area and loss of medullary sheath were detected.The morphometrical analysis showed that GFAP and ?-APP integrated optical density(A) of PVL group was increased,and mean diameter of GFAP-immunoreactive cells was also increased in PVL group,while MBP A of PVL group was decreased compared with contral group.The density of O4-immunoreactive abnormal cells was dramatically increased in PVL group.The outcomes of neurobehavioral tests of PVL group were greatly abnormal compared with control group.Conclusion The changes in 2-day-old SD rats,RCL-hypoxia model are accor-(ded) with the pathology and behavior characeriatis of PVL.

Regulation of Phosphatase and Tensin Homology Deleted on Chromosome 10 / 实用儿科临床杂志

Phosphatase and tensin homology deleted on chromosome 10 (PTEN) is a tumor suppressor with dual protein and lipid phosphatase activity.PTEN is involved multisystem diseases and cancer,though the mechanisms of PTEN regulation are far from clear.Recent advances concerning regulation of PTEN including protein-protein interaction,phosphorylation,ubiquitination,oxidation and acetylation will be discussed.

Roles and Mechanisms of Tumor Suppressor PTEN in Ischemic Brain Injury / 实用儿科临床杂志

Recent studies have revealed that tumor suppressor PTEN does not only closely relate to the development and differentiation of brain but also get extensively involved into the pathophysiological processes of ischemic brain injury.Through research on the mechanisms of molecular regulation mediated by PTEN in ischemic brain injury will provide new perspectives for the treatment of ischemic brain injury.

Relative Factors of Intraventricular Hemorrhage in Premature Infants / 实用儿科临床杂志

Objective To analyze the etiologic factors and clinical manifestation of intraventricular hemorrhage (IVH) in preterm infants.Methods One hundred and seventy-two preterm infants from June 2005 to August 2006 were accrued to investigate their gestational age,birth weight,birth history,and clinical symptoms.Cranial chromatic ultrasound was used to scan the preterm infants and diagnose IVH.Results 1.The incidence of IVH was associated with gestational age (?2=6.40 P=0.011);2.The incidence of IVH was also associated with birth weight(?2=26.49 P=0);3.IVH usually occurred within 72 h with mild clinical manifestations and was diagnosed within 5 days after birth;4.IVH occurred more frequently and more severe in infants with severe asphyxia than those with mild asphyxia.Conclusions Early gestational age,low birth weight, and severe asphyxia are risk factors for IVH.The clinical symptoms of IVH are usually mild in most patients.Cranial chromatic ultrasound is a reliable,sensitive and convenient method of detection for IVH in preterm infants.