[A pilot study on the effects of early use of valproate sodium on neuroinflammation after traumatic brain injury]. / æ—©æœŸä½¿ç”¨ä¸™æˆŠé ¸é’ å¯¹åˆ›ä¼¤æ€§è„‘æŸä¼¤åŽç¥žç»ç‚Žç—‡å½±å“çš„æŽ¢ç´¢æ€§ç ”ç©¶.

OBJECTIVES: To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI). METHODS: A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge. RESULTS: Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF-α, and IL-1ß on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1ß on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1ß than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05). CONCLUSIONS: Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI.

[Effect of somatostatin on gastrointestinal hormone levels and clinical outcomes in critically ill infants after gastrointestinal surgery: a prospective randomized controlled study]. / ç”Ÿé•¿æŠ‘ç´ å¯¹é‡ç—‡æ¶ˆåŒ–é“æœ¯åŽå©´å„¿èƒƒè‚ æ¿€ç´ æ°´å¹³å’Œä¸´åºŠé¢„åŽçš„å½±å“ï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To explore the effects of somatostatin on the levels of gastrointestinal hormones and clinical outcomes in critically ill infants after gastrointestinal surgery. METHODS: Using a random number table method, critically ill infants after gastrointestinal surgery who were admitted to the Intensive Care Unit of Xuzhou Children's Hospital from June 2019 to June 2021 were randomly divided into an observation group (29 cases) and a control group (30 cases). The control group received routine treatment such as anti-infection and hemostasis after surgery, while the observation group received somatostatin in addition to the routine treatment [3.5 µg/(kg·h) infusion for 7 days]. The levels of serum gastrin (GAS), motilin (MTL), insulin, and glucagon-like peptide-1 (GLP-1) before surgery, on the 3rd day after surgery, and on the 7th day after surgery were compared between the two groups. The recovery progress and incidence of complications after surgery were also compared between the two groups. RESULTS: There was no significant difference in the levels of serum GAS, MTL, insulin, and GLP-1 between the two groups before surgery (P>0.05). On the 3rd and 7th day after surgery, the levels of serum GAS, MTL, insulin, and GLP-1 in the observation group were higher than those in the control group (P<0.05). In the observation group, the levels of GAS, MTL, insulin, and GLP-1 on the 7th day after surgery were higher than those before surgery and on the 3rd day after surgery (P<0.05), and the levels on the 3rd day after surgery were higher than those before surgery (P<0.05). There was no significant difference in the levels of serum GAS, MTL, and insulin before surgery, on the 3rd day after surgery, and on the 7th day after surgery in the control group (P>0.05). The level of GLP-1 on the 7th day after surgery was higher than that before surgery and on the 3rd day after surgery (P<0.05), and the level on the 3rd day after surgery was higher than that before surgery (P<0.05) in the control group. The observation group had shorter first time of anal exhaust, recovery time of bowel sounds, and first time of defecation after surgery compared to the control group (P<0.05). The incidence of complications after surgery in the observation group was lower than that in the control group (10% vs 33%, P<0.05). CONCLUSIONS: Somatostatin can increase the levels of serum GAS, MTL, insulin, and GLP-1 in critically ill infants after gastrointestinal surgery, promote the recovery of gastrointestinal function, and reduce the incidence of postoperative complications.

Distinct expression and clinical value of aquaporin 4 in children with hand, foot and mouth disease caused by enterovirus 71.

Brain dysfunction is a prerequisite for critical complications in children with hand, foot, and mouth disease (HFMD). Aquaporin 4 (AQP-4) may be involved in the pathological process of cerebral oedema and injury in children with severe and critical HFMD. This study aimed to assess the association of AQP-4 with the severity of enterovirus 71 (EV71)-associated HFMD. Children with EV71-infected HFMD were divided into a common group (clinical stage 1), a severe group (clinical stage 2), and a critical group (clinical stage 3) according to Chinese guidelines. The levels of AQP-4, interleukin-6 (IL-6), norepinephrine (NE), and neuron-specific enolase (NSE) before and after treatment were tested. Serum AQP-4, IL-6, NE, and NSE levels showed significant differences among the critical, severe, and common groups before and after treatment (P < 0.01). No significant differences in AQP-4 levels in cerebrospinal fluid (CSF) were observed between the critical and severe groups before and after treatment, but the CSF AQP-4 levels in these two groups were higher than those in the common group before treatment (P < 0.01). Serum AQP-4 levels, but not CSF AQP-4 levels, closely correlated with serum IL-6, NE, and NSE levels. These results suggest that the level of AQP-4 in serum, but not in CSF, is a candidate biomarker for evaluating the severity and prognosis of EV71-associated HFMD.

[Effect of somatostatin on postoperative gastrointestinal function and stress level in children with acute abdomen: a prospective randomized controlled study]. / ç”Ÿé•¿æŠ‘ç´ å¯¹æ€¥è ¹ç—‡æ‚£å„¿æœ¯åŽèƒƒè‚ åŠŸèƒ½åŠåº”æ¿€æ°´å¹³å½±å“çš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the effect of somatostatin on postoperative gastrointestinal function and stress level in children with acute abdomen. METHODS: A total of 102 children with acute abdomen who underwent surgery in Xuzhou Children's Hospital from August 2019 to June 2021 were enrolled as subjects and were randomly divided into an observation group and a control group, with 51 children in each group. The children in the control group were given conventional treatment such as hemostasis and anti-infective therapy after surgery, and those in the observation group were given somatostatin in addition to conventional treatment. Peripheral blood samples were collected from both groups before surgery and on days 1 and 5 after surgery. The two groups were compared in terms of the serum levels of endothelin-1 (ET-1), adrenocorticotropic hormone (ACTH), cortisol, gastrin, and motilin, postoperative recovery, and the incidence rate of complications. RESULTS: There was no significant difference in the serum levels of ET-1, ACTH, cortisol, gastrin, and motilin between the two groups before surgery (P>0.05). Compared with the control group, the observation group had significantly lower serum levels of ET-1, ACTH, and cortisol on days 1 and 5 after surgery (P<0.05) and significantly higher levels of motilin and gastrin on day 5 after surgery (P<0.05). Compared with the control group, the observation group had significantly shorter time to first passage of flatus, first bowel sounds, and first defecation after surgery, as well as a significantly shorter length of hospital stay (P<0.05). The incidence rate of complications in the observation group was significantly lower than that in the control group (6% vs 24%, P<0.05). CONCLUSIONS: In children with acute abdomen, somatostatin can significantly reduce postoperative stress response, improve gastrointestinal function, and reduce the incidence rate of complications, thereby helping to achieve a good prognosis.

The clinical value of aquaporin-4 in children with hand, foot, and mouth disease and the effect of magnesium sulfate on its expression: a prospective randomized clinical trial.

To evaluate the clinical value of aquaporin-4 (AQP-4) in hand, foot, and mouth disease (HFMD) and to evaluate therapeutic efficacy of magnesium sulfate (MgSO4) and its effect on AQP-4 expression. Children with HFMD were divided into a common group, a severe group and a critical group according to Chinese guidelines; children in the critical group were further divided into two subgroups: routine treatment group and MgSO4 group. Outcome measures included systolic blood pressure (SBP), Heart rate (HR), the levels of AQP-4, interleukin-6 (IL-6), norepinephrine (NE), and neuron-specific enolase (NSE). Serum AQP-4, IL-6, NE, and NSE levels varied significantly among the critical, severe, and common groups before and after treatment. There were no significant differences in AQP-4 levels in cerebrospinal fluid (CSF) between the critical and severe groups before and after treatment; however, CSF AQP-4 levels in these two groups were higher than those in the common group before treatment. Serum and CSF AQP-4 levels in convalescence decreased significantly in the critical and severe groups. SBP, HR and serum AQP-4, IL-6, NE, NSE levels, but not CSF AQP-4 levels, were significantly lower in MgSO4 group than in the routine treatment group. AQP-4 in serum, but not in CSF, is a candidate biomarker for evaluating the severity and prognosis of HFMD; MgSO4 can provide protection on children with critical HFMD.

Current views of the Pediatric Intensive Care Unit.

International best practice endorses the use of standardized approaches in the management of pediatric patients in the Pediatric Intensive Care Unit (PICU). There is increasing awareness of the risk of prolonged duration of mechanical ventilation as a consequence of morphine use leading to ventilator-associated pneumonia, extended PICU and hospital length of stay and increased morbidity and mortality. Accordingly, a fundamental outcome measure of this study was to determine whether raising awareness of these issues and the introduction of analgesia and sedation guidelines led to a reduction in the amount of analgesics and sedatives administered to PICU patients, while not exposing them to pain and distress. The present review article is devoted to discussing all important aspects of PICU.

Metformin Attenuates Cognitive Impairments in Hypoxia-Ischemia Neonatal Rats via Improving Remyelination.

Perinatal hypoxia-ischemia (H/I) causes brain injury and myelination damage. Finding efficient methods to restore myelination is critical for the recovery of brain impairments. By applying an H/I rat model, we demonstrate that metformin (Met) treatment significantly ameliorates the loss of locomotor activity and cognition of H/I rat in the Morris water maze and open field task tests. After administration of Met to H/I rat, the proliferation of Olig2+ oligodendrocyte progenitor cells and the expression of myelin basic protein are obviously increased in the corpus callosum. Additionally, the myelin sheaths are more compact and the impairments are evidently attenuated. These data indicate that Met is beneficial for the amelioration of H/I-induced myelination and behavior deficits.

Metformin Attenuates Neurological Deficit after Intracerebral Hemorrhage by Inhibiting Apoptosis, Oxidative Stress and Neuroinflammation in Rats.

Intracerebral hemorrhage (ICH) can lead to brain damage and even death, and there is lack of effective therapeutic methods for treating ICH. Although recent studies have focused on the administration of metformin in treating stroke, there is no literature to support whether it can be used to treat ICH. Therefore, the aim of this study was to evaluate the possible effects of metformin on ICH and the underlying mechanisms of those effects. An ICH model was established in adult male Sprague-Dawley rats. Rats were randomly divided into three groups: sham group, ICH group, and ICH+metformin group. The neurobehavioral deficit scoring method was used to examine neurological function in rats. The levels of lipid peroxidation antioxidant enzyme and 8-iso-PGF2α were detected to evaluate oxidative stress. Survival of striatal neurons was examined by TUNEL staining, immunohistochemistry and HE staining. The levels of p-JNK, p-c-Jun and cleaved caspase-3 in the striatum were measured by western blotting. The results demonstrated that metformin protected rats from neurological deficits induced by ICH. Moreover, metformin reduced oxidative stress and preserved the survival of striatal neurons under ICH conditions. Furthermore, metformin downregulated the levels of apoptotic factors (p-JNK3, p-c-Jun and cleaved caspase-3) as well as pro-inflammatory cytokines (IL-1ß, IL-4 and IL-6 and TNF-α). Collectively, we speculate that metformin may be a potential clinical treatment for ICH patients.

[Application of esmolol in severe hand, foot, and mouth disease].

OBJECTIVE: To study the clinical effect and mechanism of action of esmolol in the treatment of severe hand, foot, and mouth disease (HFMD). METHODS: A prospective randomized controlled trial was performed. A total of 102 children with severe HFMD were enrolled in the study and were randomly divided into conventional treatment and esmolol treatment groups (n=51 each). The children in the conventional treatment group were given conventional treatment according to the guidelines for the diagnosis and treatment of HFMD. Those in the esmolol treatment group were given esmolol in addition to the conventional treatment. The heart rate (HR), systolic blood pressure (SBP), and respiratory rate (RR) were continuously monitored for all children. Blood samples were collected from all children before treatment and 1, 3, and 5 days after treatment to measure the levels of norepinephrine (NE), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB) p65 in mononuclear cells. Serum levels of myocardial enzymes and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before treatment and after 5 days of treatment. RESULTS: There were no significant differences in HR, SBP, RR, NE, TNF-α, IL-6, NF-κB p65, serum myocardial enzymes, and NT-proBNP before treatment between the conventional treatment and esmolol treatment groups. Both groups had significant reductions in these parameters at each time point (P<0.05). Compared with the conventional treatment group, the esmolol treatment group had significant improvements in the above parameters after 1 and 3 days of treatment (P<0.05). After 5 days of treatment, the esmolol treatment group had significant improvements in serum levels of myocardial enzymes and NT-proBNP compared with the conventional treatment group (P<0.05). CONCLUSIONS: Early application of esmolol can effectively stabilize the vital signs of the children with severe HFMD. Its mechanism of action may be related to reducing serum catecholamine concentration, alleviating myocardial damage, improving cardiac function, and reducing inflammatory response.

[Clinical effect and safety of somatostatin in treatment of postoperative gastrointestinal bleeding in neonates].

OBJECTIVE: To investigate the clinical effect and safety of somatostatin in the treatment of postoperative gastrointestinal bleeding in neonates. METHODS: A prospective randomized study was performed, and 126 neonates who underwent surgery for congenital gastrointestinal anomalies were randomly divided into control group, treatment group A, and treatment group B. The neonates in the control group were given routine postoperative hemostasis, and those in the treatment groups were given somatostatin in addition to the treatment for the control group. The neonates in treatment group A were given intravenous injection of somatostatin 0.25 mg as the initial dose and 0.25 mg/h for maintenance, and those in treatment group B were given continuous intravenous pumping of somatostatin at a dose of 3.5 µg/(kg·h). The clinical outcome and complications were compared between the three groups. RESULTS: Compared with the control group, the treatment groups had significantly shortened clearance time in occult blood test for gastrointestinal decompression drainage and a significantly lower degree of the reduction in 24-hour hemoglobin (P<0.05), while there were no significant differences between treatment groups A and B. Compared with the control group, treatment group A had significant reductions in heart rate (HR), respiratory rate (RR), blood pressure (BP), and SaO2 after one hour of treatment (P<0.05 ), but there were no significant differences at the other time points between the two groups (P>0.05). There were no significant differences in monitoring indices between the control group and treatment group B (P>0.05). No neonates in the control group experienced hypoglycemia reaction, and treatment group A had a significantly higher incidence rate of hypoglycemia (20%) than treatment group B (P<0.05). CONCLUSIONS: Somatostatin has a marked clinical effect and good safety in the treatment of neonates with postoperative gastrointestinal bleeding, and the administration of somatostatin by continuous intravenous pumping leads to fewer side effects.

Differential effects of paraoxonase 1 (PON1) polymorphisms on cancer risk: evidence from 25 published studies.

Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stress, which is thought to contribute to cancer development. PON1 activity varies widely among individuals, which is in part related to two common nonsynonymous polymorphisms in the PON1 gene (Q192R and L55M). The polymorphisms in PON1 have been implicated in cancer risk. However, results from the studies to date have been conflicting. To clarify the association, a meta-analysis was performed for 7,073 cases and 9,520 controls from 25 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Significant associations between PON1-L55M but not Q192R polymorphism and total cancer were observed from all the comparisons. In stratified analyses, PON1-55M allele was a risk factor for breast cancer. Similarly, increased risk was observed for prostate cancer (OR = 1.18, 95% CI: 1.01-1.36, P (heterogeneity) = 0.260) and Caucasian population (OR = 1.18, 95% CI: 1.02-1.38, P (heterogeneity) = 0.1) of the LM genotype, compared with the LL genotype. For PON1-Q192R polymorphism, PON1-192R allele was a decreased risk factor for cancer in the Asian group (RR vs QQ: OR = 0.61, 95% CI: 0.38-0.98, P (heterogeneity) = 0.268; QR vs QQ: OR = 0.71, 95% CI: 0.52-0.96, P (heterogeneity) = 0.130; RR + QR vs QQ: OR = 0.71, 95% CI: 0.53-0.95, P (heterogeneity) = 0.135). Although some modest bias could not be eliminated, this meta-analysis suggests that the PON1-55M allele is a risk factor for the development of cancer, in particular for breast cancer. Future studies with larger sample sizes are warranted to further evaluate these associations.

Effect of HMGB1 on monocyte immune function in respiratory syncytial virus bronchiolitis.

Expression of high mobility group protein box 1 (HMGB1) in children with respiratory syncytial virus bronchiolitis and its effect on the inflammatory function of monocytes were investigated. A total of 30 cases of respiratory syncytial viral bronchitis and 30 cases of healthy persons from physical examination were collected from January 2017 to September 2019 in the pediatric department of Xuzhou Children's Hospital, Xuzhou Medical University. HMGB1 expression level in plasma was detected by ELISA. All participants in the study were followed up for 18 months. Human recombinant respiratory syncytial virus (RSV)-A2 virus was used to infect human bronchial epithelial cell line 16HBE, and cell culture supernatant was collected to detect HMGB1. Transwell plate was used to co-culture infected or no-infection groups of epithelial cells and monocytes THP-1. Western blot was used to detect the level of Toll-like receptor (TLR)4 and TLR7 in monocytes. HMGB1 expression level in peripheral blood of children with bronchiolitis was significantly increased compared with that in healthy controls (P<0.0001), and was significantly correlated with the severity of the children's condition (P<0.01). The expression level of HMGB1 was significantly correlated with the number of monocytes, lymphocytes and CRP expression level. HMGB1 was also significantly increased in cell culture supernatant compared with no-infection group (P<0.0001). TLR4 expression in monocytes could be activated by the virus infected cell lines. Follow-up results showed that children with bronchiolitis had a higher incidence of asthma within 18 months (P<0.05). The independent risk factors for children to develop asthma were age, number of monocytes and HMGB1 level. HMGB1 is highly expressed in peripheral blood of children with respiratory syncytial virus bronchitis, and RSV epithelial cells can activate TLR4 expression in monocytes, suggesting that HMGB1 plays an important role in monocyte mediated immune inflammation. HMGB1 expression level is related to the development of asthma in children, which is of great significance for understanding the pathogenesis of bronchiolitis and suggesting the prognosis of children.

Aquaporin­4 deletion ameliorates enterovirus 71 infection in mice.

Aquaporin-4 (AQP4) is a major water channel of the central nervous system. The present study was designed to determine whether AQP4 deletion could ameliorate enterovirus (EV) 71 infection­induced hand, foot and mouth disease (HFMD) by inhibiting inflammation and apoptosis in mice. EV 71 strains were injected into neonatal BALB/c mice to induce HFMD. Western blotting and ELISA were used to measure the protein expression and cytokine levels. The levels of AQP4 mRNA and protein in the brain were increased in EV 71­infected mice, while the survival rate and health score were improved in AQP4­knockout (KO) mice with EV 71 infection. The EV 71 infection­induced increases of tumor necrosis factor­α, interleukin (IL)­1ß, IL­6, monocyte chemotactic protein­1, interferon (IFN)­α and IFN­Î³ in plasma and brain were inhibited in AQP4­KO mice. AQP4 deletion reversed the decreased levels of Bcl2 and Bcl2/Bax, and the increased levels of Bax induced by EV 71 infection in the brain. These results demonstrated that AQP4 deletion ameliorated EV 71 induced­HFMD via inhibiting inflammation and apoptosis in mice.

Roles of HIF1α- and HIF2α-regulated BNIP3 in hypoxia-induced injury of neurons.

BACKGROUND: To explore the roles of HIF1α- and HIF2α-regulated BNIP3 in hypoxia-induced injury of neurons. METHODS: The sera of neonates with hypoxic-ischemic encephalopathy (HIE) within 24 h after birth and full-term healthy newborns (n = 40) were collected. The BNIP3 levels were detected by ELISA. AGE1.HN cells were cultured in 1% O2 at 37 °C. The apoptosis of cells treated with 1, 5 and 10 ng/ml BNIP3 for 48 h was detected by flow cytometry. The proliferation of cells transfected with siBNIP3 was detected by CCK-8 assay. The mRNA level of BNIP3 in cells under hypoxic conditions was measured by RT-PCR. The protein level of BNIP3 in cells cultured under hypoxic conditions after pretreatment with HIF1α or HIF2α inhibitor was measured by Western blot. RESULTS: The serum BNIP3 concentration of HIE neonates ((4.5 ± 2.1) ng/ml) was significantly higher than that of healthy neonates ((1.2 ± 0.5) ng/ml) (P < 0.001). Compared with untreated group, the number of apoptotic AGE1.HN cells treated with BNIP3 significantly increased (P < 0.05). Under hypoxic conditions (1%), the mRNA and protein levels of BNIP3 increased significantly with prolonged time. After pretreatment with HIF1α or HIF2α inhibitor and hypoxic culture, BNIP3 expression was significantly lower than that of cells hypoxically cultured only. Inhibiting the expression of HIF1α or HIF2α or transfecting with siBNIP3 before hypoxic treatment significantly reduced the number of apoptotic cells. Under hypoxic conditions, HIF1α or HIF2α bound BNIP3 promoter, which did not occur under normal culture conditions. HIF1α or HIF2α was significantly enriched near the hypoxia response element (HRE) site of BNIP3 promoter. CONCLUSIONS: BNIP3 was involved in the apoptosis of cells undergoing HIE. The HRE site of BNIP3 promoter bound HIF to promote its transcription.

The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway.

Immunological response is thought to play a crucial role in the development of a severe hand-foot-and-mouth disease (HFMD) infection in children, but the mechanisms remain largely unknown. This study was designed to help in elucidating the immunopathological pathways involved in the disease by quantifying Toll-like receptor (TLR) mRNAs, MAPK factors and cytokine levels in children experiencing the disease. A total of 86 enterovirus 71 (EV71)-infected HFMD children (49 with mild and 27 with severe disease), along with 30 healthy children were involved in the study. Peripheral vein blood samples were collected from each individual, and used to isolate peripheral blood mononuclear cells (PBMCs) for mRNA extraction and sera for measuring levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6 and IL-10. The average expression levels of TLR3, TLR4, TLR7 and TLR8 mRNA in PBMCs of children with severe HFMD were significantly higher than those in the other children, the lowest values were found in the healthy control group (P<0.05). The expression levels of TLR2 and TLR9 mRNA were not significantly different (P>0.05) among the groups. Additionally, the expression levels of TNF-α, IFN-γ, IL-6 and IL-10 in the serum of the children in the severe group were significantly higher than those in the other two groups, and the lowest values were again found in the control group (P<0.05). Pearson correlation analysis showed that the TLR3, TLR4, TLR7 and TLR8 mRNA levels in PBMCs were positively correlated with the TNF-α, IFN-γ, IL-6 and IL-10 levels in the serum (P<0.05). Furthermore, the expression levels of the ERK, JNK and p38 mRNA in PBMCs of children in the severe group were significantly higher than those in the other two groups, with the lowest values being in the control group (P<0.05). Pearson correlation analysis showed that the TLR3, TLR4, TLR7 and TLR8 mRNA levels in PBMCs were positively correlated with ERK, JNK and p38 mRNA levels (P<0.05). The results of our study seem to indicate that the high expression levels of TLR3, TLR4, TLR7 and TLR8 induced in severe EV71 HFMD regulate the expression of cytokines by MAPK signaling pathway and negatively affect the ability of the organism to resolve the infection. Further studies are needed to test the hypothesis that immuno-modulation would be an effective treatment approach in pediatric cases of severe HFMD.

[Protective effects of baicalin pretreatment on hypoxic-ischemic brain damage in neonatal rats].

OBJECTIVE: Previous research suggests that dexamethasone (Dex) pretreatment protects neonatal rats against hypoxic-ischemic brain damage (HIBD). Some of the pharmacological effects of baicalin (a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi) are similar to Dex. This study was designed to explore the effect of baicalin on the neuronal apoptosis following HIBD in neonatal rats. METHODS: Six-day-old Sprague-Dawley rats were randomly assigned into Control (without HI), HIBD, Dex-pretreatment and post-treatment, Baicalin-pretreatment and -post-treatment groups. HIBD was induced by ligating the left common carotid artery, followed by exposure to hypoxia. In the pretreatment groups either baicalin (16 mg/kg) or Dex (0.1 mg/kg) was administered to the rats 24 hrs before HIBD; in the post-treatment groups baicalin or Dex was given 30 minutes after HIBD. The rat pups were sacrificed on postnatal day 10, and brain tissues were harvested. Brain water content was determined, morphological changes were observed under a light microscope, and neuronal apoptosis was measured by terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) staining. RESULTS: The brain water content and the number of apoptotic cells were significantly higher in the HIBD group than those of the Control group (P < 0.05). Both baicalin and Dex pretreatment decreased the brain water content from 88.9 +/- 1.7 % (HIBD group) to 87.4 +/- 0.7% (baicalin) or 87.3 +/- 0.6% (Dex) (P < 0.05) and the number of apoptotic cells were reduced from 251 +/- 28 (HIBD group) to 102 +/- 47 (baicalin) or 75 +/- 26 (Dex) (P < 0.05). Baicalin and Dex post-treatment had no effects on the brain water content and the number of apoptotic cells. Loss and degeneration of neurons could be observed in the HIBD group. Baicalin and Dex pretreatment significantly alleviated neuronal injury, but post-treatment did not. CONCLUSIONS: Pretreatment with baicalin, as with Dex, has a protective effect against HIBD in neonatal rats, but baicalin or Dex post-treatment do not reverse the neuronal injuries.

[Effect of hyperbaric oxygenation on neural stem cells and myelin in neonatal rats with hypoxic-ischemic brain damage].

OBJECTIVE: This study investigated the effect of hyperbaric oxygenation (HBO) on neural stem cells (NSCs) and myelin in neonatal rats following hypoxic-ischemic brain damage (HIBD) and aimed to explore the possible mechanism of the protective effect of HBO on HIBD. METHODS: Seven-day-old Sprague-Dawley rat pups were randomly assigned into 4 groups: Normal control, HIBD, hyperbaric air (HBA), and HBO groups (n=30 each). The HIBD model was produced by permanent occlusion of the left common carotid artery and 2 hrs hypoxemia exposure (8% O2 at 37 degrees C). HBA and HBO treatment was administered (2 ATA, once daily for 7 days) in the HBA and HBO groups respectively 1 hr after HIBD. BrdU immunohistochemistry was used to detect the NSCs in the sub-ventricle zone (SVZ) of the lateral ventricle and the dentate gyrus (DG) of the hippocampus. The myelin damage was assessed by myelin basic protein (MBP) immunostaining. RESULTS: The BrdU-positive cells in the SVZ and the DG of the ischemic hemisphere in the HIBD group were dramatically decreased compared with those of the Normal control group at 3 weeks post-HIBD (P < 0.01). The HBO treatment resulted in an increase of BrdU-positive cells in the DG from 153.7 +/- 37.0 to 193.7 +/- 38.8 (P < 0.05). The nestin expression in the HIBD and HBA groups was reduced compared with that in the Normal control group. There was no difference in the nestin expression between the HBO and the Normal control groups. Hypoxia-ischemia (HI) led to marked myelin damage at 1 week post-HIBD. HBO or HBA treatment alleviated the damage. CONCLUSIONS: The HBO treatment can result in the proliferation of BrdU-positive cells and alleviate the myelin damage following HIBD in neonatal rats, thereby offering neuroprotectivity against HI insults.