Overexpression of hSNF2H in glioma promotes cell proliferation, invasion, and chemoresistance through its interaction with Rsf-1.

hSNF2H partners with Rsf-1 to compose the Rsf complex to regulate gene expression. Recent studies indicated that hSNF2H was overexpressed in several human cancers. However, its expression pattern and biological mechanism in glioma remain unexplored. In this study, we found that hSNF2H was overexpressed in 32 % of glioma specimens. hSNF2H overexpression correlated with advanced tumor grade (p = 0.0338) and Rsf-1 positivity in glioma tissues (p = 0.016). Small interfering RNA (siRNA) knockdown was performed in A172 and U87 cell lines. MTT, colony formation assay, and cell cycle analysis showed that knockdown of hSNF2H inhibited cell proliferation, colony formation ability, and cell cycle transition. Matrigel invasion assay showed that hSNF2H depletion inhibited invasive ability of glioma cells. In addition, we demonstrated that hSNF2H depletion decreased temozolomide resistance of A172 and U87 cell lines and increased temozolomide induced apoptosis. Furthermore, hSNF2H depletion decreased cyclin D1, cyclin E, p-Rb, MMP2, cIAP1, Bcl-2 expression, and phosphorylation of IκBα and p65, suggesting hSNF2H regulates apoptosis through NF-κB pathway. Immunoprecipitation showed that hSNF2H could interact with Rsf-1 in both cell lines. To validate the involvement of Rsf-1, we checked the change of its downstream targets in Rsf-1 depleted cells. In Rsf-1 depleted cells, changes of cyclin E, Bcl-2, and p-IκBα were not significant using hSNF2H siRNA treatment. In conclusion, our study demonstrated that hSNF2H was overexpressed in human gliomas and contributed to glioma proliferation, invasion, and chemoresistance through regulation of cyclin E and NF-κB pathway, which is dependent on its interaction with Rsf-1.

A retrospective study of anesthesia during rigid bronchoscopy for airway foreign body removal in children: propofol and sevoflurane with spontaneous ventilation.

BACKGROUND: Tracheobronchial foreign body aspiration is a significant cause of childhood morbidity and mortality. We analyzed our experience in management of aspirated foreign bodies, including methods of anesthesia used, over a 4-year period. METHODS: We retrospectively reviewed the records of tracheobronchial foreign body removal by rigid bronchoscopy with spontaneous ventilation in 435 children. All patients had received initial anesthesia with inhaled sevoflurane. One hundred and ninety-seven patients (Group PropRemi) then received intravenous propofol and remifentanyl for maintenance of anesthesia; the remaining 238 patients (Group PropSevo) received propofol and sevoflurane. RESULTS: Tracheobronchial foreign body was found in 405 children (93.1%) and successfully removed from 402 (99.3%) children. Among three patients who failed bronchoscopy, one child suffered cardiac arrest and died during the bronchoscopy, and two required subsequent tracheotomy for foreign body removal. Adverse effects (intraoperative coughing, breath holding, body movement, bronchospasm, and laryngospasm) were significantly more frequent in Group PropRemi than in Group PropSevo. No complications such as bleeding, pneumothorax, pneumomediastinum, or the need for thoracotomy were encountered. CONCLUSION: Sevoflurane induction followed by a combination of sevoflurane and continuous infusion of propofol resulted in fewer adverse events than sevoflurane induction followed by TIVA with propofol and remifentanyl during rigid bronchoscopy for airway foreign body removal in children with spontaneous ventilation.

Myosin VI contributes to maintaining epithelial barrier function.

BACKGROUND: Epithelial barrier dysfunction is associated with the pathogenesis of a number of immune inflammations; the etiology is not fully understood. The fusion of endosome/lysosome is a critical process in the degradation of endocytic antigens in epithelial cells. Recent reports indicate that myosin VI (myo6) is involved in the activities of endosomes. The present study aims to investigate the role of myo6 in epithelial barrier dysfunction. RESULTS: The endosome accumulation was observed in myo6-deficient Rmcs. More than 80% endosomes were fused with lysosomes in naïve Rmcs while less than 30% endosomes were fused with lysosomes in the myo6-deficient Rmcs. The myo6-deficient Rmc monolayers showed high permeability to a macromolecular antigen, ovalbumin, the latter still conserved the antigenicity, which induced strong T cell activation. CONCLUSIONS: We conclude that myo6 plays a critical role in the fusion of endosome/lysosome in Rmc epithelial cells. Deficiency of myo6 compromises the epithelial barrier function.

Ameliorative effects of curculigoside from Curculigo orchioides Gaertn on learning and memory in aged rats.

This study was designed to evaluate the ameliorating effects of curculigoside from Curculigo orchioides Gaertn on learning and memory in aged rats. In the present study, the ameliorating effects of curculigoside were determined through animal behaviour studies (including step-down test and Y-maze test), and the possible mechanisms were explored by evaluation of the activity of acetylcholinesterase (AchE) and determination of the expression of BACE1. Oral adminstration of the curculigoside (20, 40 mg/kg/day) for 14 days can significantly improve the latency and number of errors in aged rats based on the behaviour study results. In addition, the activity of AchE can be decreased by treatment of the curculigoside (10, 20, 40 mg/kg/day). Moreover, the expression of BACE1 can be down-regulated in the hippocampus of aged rats treated with curculigoside. The results of our present work have indicated that curculigoside can improve cognitive function in aged animals, possibly by decreasing the activity of AchE in the cerebra and inhibiting the expression of BACE1 in the hippocampus. In conclusion, our results suggested that curculigoside can be possible developed as a new drug for the treatment of Alzheimer's disease in the future.

A clinical trial evaluating the laryngeal mask airway-Supreme in obese children during general anesthesia.

INTRODUCTION: The laryngeal mask airway (LMA)-Supreme is a disposable double-lumen laryngeal mask airway that is widely used in clinical practice. However, its use in obese children has not been evaluated. The aim of this study was to determine whether the LMA-Supreme could perform equally as well as endotracheal intubation in obese children having a minor surgical procedure. MATERIAL AND METHODS: After ethical board approval, 100 obese male children receiving non-emergent appendectomy for chronic appendicitis or surgery to correct concealed penis were randomly divided into an endotracheal intubation group and an LMA-Supreme group. Endotracheal intubation was performed under direct vision laryngoscopy. In the LMA group, a size-3 LMA-Supreme was placed and a stomach tube inserted via the drainage tube of the mask. Cardiovascular and respiratory parameters, time taken for placement, placement attempts, time to removal of the endotracheal tube/LMA, length of stay in the post-anesthesia care unit (PACU), and complications were recorded. RESULTS: Insertion time was significantly longer (p < 0.001) in the LMA-Supreme group than in the endotracheal intubation group. Peak airway pressure was significantly higher, and pulmonary compliance and PACU stay time lower in the LMA-Supreme group. No significant differences between endotracheal intubation and the LMA-Supreme were seen in other parameters, except for a higher incidence of coughing in the endotracheal intubation group. CONCLUSIONS: The LMA-Supreme can be easily inserted and effectively used for airway management in obese children undergoing minor surgery.

[Excretion of beta-elemene from rat respiratory tracts].

AIM: To investigate the excretion of beta-elemene from the respiratory tracts in male Spraque-Dawley rats. METHODS: After a single administration of beta-elemene to rats at the dosage of 75 mg x kg(-1) (i.v. or i.p.), the exhaled gases were collected and concentrated at various time points. The residues were analyzed by gas chromatography. RESULTS: A minor amount of unchanged beta-elemene was excreted via rat respiratory tracts after iv and ip administration of a single dose. The cumulative excretion were 1.41% and 0.51% respectively. CONCLUSION: The results demonstrated that unchanged beta-elemene excretes from rat respiratory tracts, but may not be the main elimination pathway in rats.

Propofol exerts anti-inflammatory effects in rats with lipopolysaccharide-induced acute lung injury by inhibition of CD14 and TLR4 expression.

We investigated the effect of propofol (Prop) administration (10 mg kg-1 h-1, intravenously) on lipopolysaccharide (LPS)-induced acute lung injury and its effect on cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4 expression in lung tissue of anesthetized, ventilated rats. Twenty-four male Wistar rats were randomly divided into three groups of 8 rats each: control, LPS, and LPS+Prop. Lung injury was assayed via blood gas analysis and lung histology, and tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels were determined in bronchoalveolar lavage fluid using ELISA. Real-time polymerase chain reaction was used to detect CD14 and TLR4 mRNA levels, and CD14 and TLR4 protein expression was determined by Western blot. The pathological scores were 1.2 ± 0.9, 3.3 ± 1.1, and 1.9 ± 1.0 for the control, LPS, and LPS+Prop groups, respectively, with statistically significant differences between control and LPS groups (P < 0.05) and between LPS and LPS+Prop groups (P < 0.05). The administration of LPS resulted in a significant increase in TNF-α and IL-1ß levels, 7- and 3.5-fold, respectively (P < 0.05), while treatment with propofol partially blunted the secretion of both cytokines (P < 0.05). CD14 and TLR4 mRNA levels were increased in the LPS group (1.48 ± 0.05 and 1.26 ± 0.03, respectively) compared to the control group (1.00 ± 0.20 and 1.00 ± 0.02, respectively; P < 0.05), while propofol treatment blunted this effect (1.16 ± 0.05 and 1.12 ± 0.05, respectively; P < 0.05). Both CD14 and TLR4 protein levels were elevated in the LPS group compared to the control group (P < 0.05), while propofol treatment partially decreased the expression of CD14 and TLR4 protein versus LPS alone (P < 0.05). Our study indicates that propofol prevents lung injury, most likely by inhibition of CD14 and TLR4 expression.

Isoflurane post-conditioning protects primary cultures of cortical neurons against oxygen and glucose deprivation injury via upregulation of Slit2/Robo1.

Different mechanisms have been suggested to contribute to isoflurane-mediated neuroprotection. Previous studies have suggested that the protein Slit can abrogate neuronal death in mixed neuronal-glial cultures exposed to oxygen-glucose deprivation (OGD) and reperfusion (OGD/R). We hypothesized that isoflurane increases the expression of Slit and its receptor Robo when cortical neurons are exposed to OGD/R. To test this hypothesis, we exposed primary cortical neurons to OGD for 90 min and reperfusion for 24h and investigated how isoflurane post-conditioning affected cell survival and expression of Slit2 and receptors Robo1 and Robo4. Cell survival increased after administration of isoflurane, as assessed by the lactate dehydrogenase assay, trypan blue analysis, and propidium iodide staining. Western blot analysis showed that cleaved caspase-3 was increased after OGD/R(P<0.01) but reduced by isoflurane post-conditioning. Real-time PCR and Western blot analysis showed that the expression levels of Slit2 and Robo1, but not Robo4, were increased after OGD/R (P<0.5) and increased even further by isoflurane post-conditioning (P<0.01). Our results suggest that isoflurane post-conditioning markedly attenuates apoptosis and necrosis of cortical neurons exposed to OGD/R possibly in part via elevation of Slit2 and Robo1 expression. These findings provide a novel explanation for the pleiotropic effects of isoflurane that could benefit the central nervous system.

Expression of N-methyl-d-aspartate receptor 1 and its phosphorylated state in basal ganglia of a neonatal piglet hypoxic-ischemic brain injury model: a controlled study of (1)H MRS.

Excitatory amino acids (EAAs) and excitotoxicity medicated by receptors of these amino acids play an important role in hypoxic-ischemic brain injury (HIBI), but most studies were ex vivo experiments, the mechanism in vivo is not well understood. We sought to study the expression of N-methyl-d-aspartate receptor 1 (NR1) and phosphorylated N-methyl-d-aspartate receptor 1 (P-NR1) in basal ganglia in a piglet model of HIBI and to investigate the correlation between Glx(Glu/Gln) value measured by magnetic resonance spectroscopy (MRS) and NR1/P-NR1 expression. Multi-voxel (1)H MRS was applied to detect change in Glx in basal ganglia of the newborn piglets in vivo. Automatic amino acid analyzer was applied to accurately quantify the Glu concentration. Immunohistochemical method was used to examine the expression of NR1 and P-NR1. The NR1 receptors in basal ganglia of the newborn piglets were significantly activated after HIBI. P-NR1 expression in the basal ganglia was consistent with the change in brain Glu content, so the activation status of NMDA receptor in the brain could be indirectly reflected by ß-, γ-Glx/NAA measured by (1)H MRS.

Propofol exerts anti-inflammatory effects in rats with lipopolysaccharide-induced acute lung injury by inhibition of CD14 and TLR4 expression

We investigated the effect of propofol (Prop) administration (10 mg kg-1 h-1, intravenously) on lipopolysaccharide (LPS)-induced acute lung injury and its effect on cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4 expression in lung tissue of anesthetized, ventilated rats. Twenty-four male Wistar rats were randomly divided into three groups of 8 rats each: control, LPS, and LPS+Prop. Lung injury was assayed via blood gas analysis and lung histology, and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were determined in bronchoalveolar lavage fluid using ELISA. Real-time polymerase chain reaction was used to detect CD14 and TLR4 mRNA levels, and CD14 and TLR4 protein expression was determined by Western blot. The pathological scores were 1.2 ± 0.9, 3.3 ± 1.1, and 1.9 ± 1.0 for the control, LPS, and LPS+Prop groups, respectively, with statistically significant differences between control and LPS groups (P < 0.05) and between LPS and LPS+Prop groups (P < 0.05). The administration of LPS resulted in a significant increase in TNF-α and IL-1β levels, 7- and 3.5-fold, respectively (P < 0.05), while treatment with propofol partially blunted the secretion of both cytokines (P < 0.05). CD14 and TLR4 mRNA levels were increased in the LPS group (1.48 ± 0.05 and 1.26 ± 0.03, respectively) compared to the control group (1.00 ± 0.20 and 1.00 ± 0.02, respectively; P < 0.05), while propofol treatment blunted this effect (1.16 ± 0.05 and 1.12 ± 0.05, respectively; P < 0.05). Both CD14 and TLR4 protein levels were elevated in the LPS group compared to the control group (P < 0.05), while propofol treatment partially decreased the expression of CD14 and TLR4 protein versus LPS alone (P < 0.05). Our study indicates that propofol prevents lung injury, most likely by inhibition of CD14 and TLR4 expression.

[Gastric acid reflux and reflux esophagitis in children].

OBJECTIVE: To evaluate the significance of gastric acid reflux in children with reflux esophagitis (RE). METHODS: Twenty-four-hour esophageal pH monitoring and gastroscopy were performed in 180 children suffered from vomiting. The relationship between RE, non-esophagitis (NE), non-erosive reflux disease (NERD) and gastroesophageal reflux (GER) was analyzed. RESULTS: Sixty-five of the 180 patients were confirmed as having RE by endoscopy. Among them, the number of cases with grades I, II and III RE according to the diagnostic criteria by endoscopy was 37, 19 and 9 cases, respectively, while the other 115 cases were diagnosed as NE. The positive rate of acid reflux in RE group was 58.5% (38/65), while it was 42.6% (49/115) in NE group (chi(2) = 4.179, P < 0.05). All parameters of acid reflux in RE group except for the episode of reflux and the number of reflux longer than 5 min were significantly higher than those in NE group. None of the parameters of acid reflux except for Boix-Ochoa score in grade III RE patients was significantly higher than that in both grade II and grade I RE cases. However, the difference in acid reflux parameter between grade I and grade II RE patients had not reached statistical significance. The results also showed that the positive rate of pathological acid reflux was 48.3% (87/180). Among them, 38 cases were RE, while other 49 cases were NERD. The difference in acid reflux between these two groups was not significant. CONCLUSIONS: Gastric acid reflux may play a major role in the development of RE in children, but may not be a sole pathogenic factor. The degree of acid reflux is not closely correspondent to the severity of RE. Acid reflux may not completely contribute to RE. Gastroscopy is very important for patients with reflux symptom.

[Long-term therapeutic effect of triple therapy consisted of omeperazole, clarithromycin and amoxycillin in children with Helicobacter pylori infection and approach to re-treatment after failure of the treatment].

OBJECTIVE: Helicobacter pylori (Hp) infection presents high prevalence in the world, but there are few pediatric assays evaluating antimicrobial treatment using a short regimen of triple therapy. To evaluate the eradication rate and long term therapeutic effect of a triple therapy consisted of omeperazole, clarithromycin (CLA) and amoxycillin (AMO) on Hp infection, the authors explored the alternative therapeutic programs and their effects after first therapeutic failure. METHODS: A total of 192 children with Hp infection were divided into two groups: 157 children were given the triple therapy for one week (CLA group); 35 children were given another triple therapy composed of omeperazole, metronidazole (MET) and AMO for two weeks (MET group). All of the children were followed up for 1 - 36 months after the therapies ended. Twenty-two children in whom Hp was eradicated with CLA triple therapy were followed up for 3 years. The children of the two groups who had therapeutic failure were given re-treatment as follows. CLA triple therapy was given for one week to the children who had failure after MET triple therapy; increased doses of CLA with longer treatment course was given to the children who had failure after CLA triple therapy. A tetra therapy consisted of omeperazole, colloidal bismuth subcitrate (CBS), furazolidone (FUR) and AMO was given to the children in whom the re-treatment failed. RESULTS: The Hp eradication and ulcer recovery rate of CLA group was 90.4% (142/157) and 96.9% (32/33), respectively; the Hp eradication rate of MET group was 77% (27/35). There was significant difference between eradication rates of the two groups (chi(2) = 4.69, P < 0.05). The recurrence rate of 22 Hp eradicated children treated with CLA triple therapy was 4.5% (1/22) during the 3-year follow-up. The eradication rate of the three re-treatment programs for 29 children was 75% (6/8), 77% (11/15) and 100% (6/6), respectively. CONCLUSION: (1) Omeperazole, CLA and AMO triple therapy for one week was the best to eradicate Hp infection with high eradication rate, few side effects, short period of treatment, good compliance and low recurrence rate. (2) Proper increase of CLA dose and longer therapeutic course may increase the eradication rate. Omeperazole, CBA, FUR and AMO tetra therapeutic program may be used as an alternative treatment in patients who develop resistance to CLA triple therapy.