OBJECTIVE:To analyze the influential factors for blood concentration of vancomycin in neonates,and to provide reference for clinical medication. METHODS:In retrospective study,114 cases of blood concentration monitoring of vancomycin were collected from neonatal department of our hospital during Jul. 1st 2014 to Jun. 30th 2015,and general information were record-ed;the influential factors for blood concentration of vancomycin were analyzed by multiple factors linear regression analysis. RE-SULTS:The blood concentrations of vancomycin in 114 neonates were 2-39 μg/ml,and average blood concentration was(13.24± 8.66)μg/ml. The blood concentrations of 43 cases were within effective range(10-20 μg/ml),accounting for 37.72%. Premature (r=0.264) and serum creatinine level (r=0.289) of neonates were positively correlated with blood concentration (P<0.05), while birth weight(r=-0.264)and body weight on monitoring day(r=-0.236)were negatively correlated with blood concentra-tion (P<0.05). The serum creatinine level (r=0.304) of prematures was positively correlated with blood concentration (P<0.05),and gestational age(r=-0.373),correct gestational age(r=-0.431)and body weight on monitoring day(r=-0.263) were negatively correlated with blood concentration(P<0.05). CONCLUSIONS:Premature,body weight,gestational age,serum creatinine level and other factors all influence the blood concentration of vancomycin. The influential factors should be considered when using vancomycin. Treatment plan should be adjusted according to the results of blood concentration and clinical symptom.

OBJECTIVE:To provide baseline data for the formulation of the strategy for medical institutions in China. METH-ODS:3 600 discharged medical records were randomly collected from our hospital in 2013. According to drug package inserts,the judgment was carried out about whether off-label drug use existed in medical orders. The types of off-label drug use,off-label drug use of children in different age groups and of various drugs were all analyzed. RESULTS:A total of 3 268 hospitalized children were includ-ed,and 35 523 medical orders were analyzed,involving 468 types. Based on children,medical orders and drug types,the incidence of off-label drug use were 91.34%,35.72%and 48.72%,respectively. The types of off-label drug use mainly included pediatric medica-tion information(74.21%), exceeding route of administration(8.12%)and overage(8.45%). The top 3 age groups with respect to the incidence of off-label drug use were adolescents(42.42%),neonate(37.97%)and infant(35.48%). Top 4 drugs of off-label use in the list of medical orders were anti-infective drugs(23.65%),electrolytic,drugs for acid-base balance and nutrition(12.21%), drugs for respiratory system(36.84%)and cardiovascular drugs(63.21%). CONCLUSIONS:The off-label drug use of hospitalized children is common in our hospital. It is urgent to develop related laws and regulations or guidelines to regulate off-label drug use in or-der to ensure the safety of pediatric drug use.

Objective To investigate the pathogen characteristics of perforated appendicitis in children and the perioperative use of antimicrobials in order to provide evidence for the rational use of perioperative antibiotics. Methods The perioperative usage of antibiotics was analyzed to determine the reasonableness of antimicrobial use in children with perforated appendicitis who were discharged from July 2011 to August 2014,based on“guidelines of clinical use of antibiotics”and results of bacterial culture. Results Inflammatory secretions obtained from 126 children(126/ 149)were sent for examination and the examination rate was 84.56%.A total of 117 cases were found positive for cultured pathogens,and the detection positive rate was 92.86%.Three types of bacteria ranking the first three places were Escherichia coli,Pseudomonas aeruginosa and CitroBacter freundii.The utilization rate of antibacterial agents was 100.00%,with a dominant use of cephalosporins and nitrate imidazoles. Rational use of antimicrobial agents was found in 144 cases(accounting for 96.64%). Conclusion The major pathogen in perforated appendicitis is still Escherichia coli,which is highly sensitive to commonly used antibiotics,and drug-sensitivity testing results can help guide the treatment programs and antibiotics selection.

Objective:To investigate the off-label drug use in the outpatients of Zhengzhou children's hospital in 2013 to provide the evidence for improving the rational drug use in pediatrics. Methods:The prescriptions of outpatients were randomly selected from January to December in 2013. According to the drug instruction, the off-label drug uses were analyzed in the following aspects: sam-pling conditions, the kinds of off-label drug use, the incidence of off-label drug use in different age groups and drug categories. Re-sults:A total of 8 684 prescriptions with 16 344 medical records involving 410 kinds of drugs were analyzed, and the rate of off-label drug use was 70. 87% for prescription, 51. 21% for medical orders and 71. 95% for category, respectively. The primary types of off-label drug use were over applicable people (50. 83%), dosage(21. 00%) and frequency (19. 04%). The top 3 age groups with high-est off-label drug use rate were neonates (63. 27%), infants (56. 20%) and school-age (44. 98%). The top 5 drugs with highest off-label drug use rate were cardiovascular system medicines (99. 02%), anti-infective agents (64. 14%), vitamin and mineral drugs (62. 89%), hematological system medicines (59. 48%) and Chinese patent drugs (53. 43%). Conclusion: Off-label drug use in outpatients is prevalent. Physicians should master indications, usage and dosage described in instructions, select suitable dosage form, reduce off-label drug use and improve drug safety in pediatrics.

Objective To investigate the molecular mechanism of Shema Zhichuan Liquid in the treatment of neutrophilic asthma(NA)based on network pharmacology and in vivo experiments.Methods(1)The TCMSP,literature search and Swiss ADME and Swiss Target Prediction databases were used to search and screen the active components and their targets of Shema Zhichuan Liquid.OMIM,GeneCards,DisGeNET and DrugBank databases were used to search and screen NA disease-related targets.The intersection of the active components and NA disease-related targets of Shema Zhichuan Liquid was obtained through the microbiology platform to obtain the potential targets of Shema Zhichuan Liquid for the treatment of NA(common targets).Cytoscape 3.8 software was used to construct the network of"Chinese medicinals-active components-potential targets".The PPI network of potential targets was established by STRING database,and the core targets were obtained by analysing the built-in Mcode plug-in.The Metascape platform was used to enrich the gene ontology(GO),Kyoto Encyclopaedia of Genes and Genomes(KEGG)pathways for the potential targets.(2)BALB/C mice were acclimatised and fed for 1 week and randomly divided into a blank group,NA model group,low-dose group(2.5 g·kg-1)and high-dose group of Shema Zhichuan Liquid(10 g·kg-1),and control group of Dexamethasone(1 mg·kg-1);the NA mouse model was replicated by intraperitoneal injection of sensitizer(OVA+CFA)and nebulized inhalation excitation.OVA/CFA(20 μg OVA+75 μg CFA,0.3 mL)was injected intraperitoneally to sensitize on days 0,7 and 14 respectively,and 5%OVA suspension was nebulized on days 21-30(8 mL each time,40 minutes each time,once a day);1 hour before nebulisation,each group was administered by gastric gavage,and the Dexamethasone control group was administered by intraperitoneal injection once a day.The pathological changes of mouse lung tissue were observed by HE staining;IL-8 content in alveolar lavage fluid was detected by ELISA;mRNA expression levels of NLRP3 and CXCR2 were detected by RT-qPCR;and p-mTOR protein expression levels was detected by immunohistochemistry.Results(1)A total of 826 active component targets and 154 NA disease-related targets were obtained,and 51 potential targets(common targets)for the treatment of NA were obtained from the intersection of the active component and the NA disease-related targets of Shema Zhichuan Liquid.Through the network analysis of"Chinese medicinals-active components-potential targets",quercetin,lignocerotoxin,kaempferol,stigmasterol,naringenin and other key active components were obtained.The PPI network analysis of potential targets yielded 29 core targets,including AKT1,IL6,TNF,EGFR,NLRP3,RELA,MIF,CXCR2,VEGFA,etc..The GO functional enrichment analysis yielded 882 biological process entries,33 cellular component entries,and 61 molecular function entries;KEGG analysis yielded 142 signaling pathways,mainly involving TNF signaling pathway,influenza A signaling pathway,Toll-like receptor pathway,MAPK signaling pathway,mTOR signaling pathway and so on.(2)Results of animal experiments:compared with the blank group,mice in the NA model group showed obvious damage to the airway mucosa,structural disorders,a large number of inflammatory cells infiltration,mucosal congestion,oedema,obvious thickening of the alveolar wall,and narrowing of the alveolar lumen;the level of the inflammatory factor IL-8 in the alveolar lavage fluid was significantly elevated(P＜0.05);the mRNA expressions of NLRP3 and CXCR2 in the lung tissues of the mice were significantly up-regulated(P＜0.01),and the protein expression of p-mTOR was significantly increased.Compared with the NA model group,the structural arrangement of bronchial epithelial cells in the mice in the low-and high-dose groups of Shema Zhichuan Liquid was slightly disordered,with a small amount of inflammatory cell infiltration around the airways and blood vessels,and the congestion and edema of the bronchial mucosa were significantly reduced;the mRNA expression of CXCR2 in the lung tissues of the mice was significantly down-regulated(P＜0.01),and the level of expression of p-mTOR protein was significantly reduced.The IL-8 level in the vesicular lavage fluid of mice in the high-dose group was significantly reduced(P＜0.05);the mRNA expression of NLRP3 in the lung tissue of mice in the low-dose group was significantly down-regulated(P＜0.05).Conclusion The therapeutic effect of Shema Zhichuan Liquid on NA may be achieved through the key active components,such as quercetin,lignocerol and kaempferol,acting on the core targets,such as NLRP3 and CXCR2,and regulating the key signaling pathways,such as the TNF signaling pathway,the MAPK signaling pathway,the Toll-like signaling pathway,and the mTOR pathway.

OBJECTIVE：To study the protective effects of butein on oxidative stress injury of PC12 cell and its effects on mitochondrial function. METHODS：Rats PC12 cells were divided into normal control group，model group，solvent control group（1 ‰ dimethyl sulfoxide），butein high，medium and low concentration groups（2，1，0.5 μmol/L）. The latter 4 groups were given relevant reagent/medicine for intervention；24 h later，other groups were given 100 mU/mL glucose oxidase to induce oxidant stress model except for normal control group. After 4 h culture，cell survival rate，apoptosis rate，the levels or activities of ROS，MDA，SOD，CAT，GSH-Px，ATP，IL-1β and TNF-α as well as the change of MMP were detected. RESULTS：Compared with normal control group，cell survival rate，the levels or activities of SOD，CAT，GSH-Px and ATP were all decreased significantly，and apoptotic rate，the content of ROS，the levels of MDA，IL-1β and TNF-α were all increased significantly（P＜0.05 or P＜0.01），while the MMP was decreased significantly. Compared with model group，above indexes of solvent control group had no significant change （P＞0.05），cell survival rates，the levels or activities of SOD （except for medium and low concentration groups），CAT，GSH-Px（except for medium and low concentration groups），ATP（except for low concentration group）were increased significantly in butein high，medium and low concentration groups，while apoptotic rates，the content of ROS，the levels of MDA，IL-1 β and TNF-α were decreased significantly（P＜0.05 or P＜0.01），while the MMP were increased significantly. CONCLUSIONS：Butein can increase the antioxidant enzyme activity， stabilize mitochondrial function， inhibit oxidative stress and inflammationthus， increase energy generation inhibiting neuronal cell apoptosis ultimately exerting a neuroprotective effect.

Objective: To investigate the role of long non-coding RNA double homeobox A pseudogene 9 (DUXAP9) in head and neck squamous cell carcinoma (HNSCC) and to evaluate the expression level, molecular function and mechanism of DUXAP9 in HNSCC cells. Methods: Differential expression of lncRNAs between normal and tumor tissues in HNSCC tissues were screened using lncRNA microarray, the expression level of DUXAP9 in HNSCC tissues and its relationship with prognosis were analyzed in the TCGA database. The expression levels of DUXAP9 in HNSCC tissues and cell lines were detected using qRT-PCR. The function in HNSCC cells after DUXAP9 silencing was evaluated using the CCK-8 assay, wound healing assay, Transwell migration assay and subcutaneous xenograft assay in nude mice. Changes in the transcription and translation of epithelial-mesenchymal transition (EMT)-related proteins in head and neck squamous cell carcinoma cells after DUXAP9 silencing were detected using qRT-PCR and Western blot. Results: lncRNA microarray results showed that, compared to adjacent normal tissues, DUXAP9 was abnormally upregulated in HNSCC tissues. Analysis from TCGA database showed that, compared to HNSCC patients with low DUXAP9 expression, HNSCC patients with high DUXAP9 expression had poorer survival. The relative expression of DUXAP9 in HNSCC tissues and 4 HNSCC cell lines increased compared to paired adjacent normal tissues as detected using qRT-PCR. Silencing DUXAP9 significantly inhibited the proliferation, migration and expression of EMT-related genes in HNSCC cells. The silencing of DUXAP9 significantly inhibited subcutaneous tumorigenesis of the HNSCC cell line CAL27 in nude mice. Conclusion Silencing DUXAP9 significantly inhibited the proliferation of HNSCC cells and subcutaneous xenografts in nude mice. DUXAP9 may mediate the migration of head and neck squamous cell carcinoma cells via the EMT pathway.