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Objective The transcriptome sequencing results of brain tissues of olanzapine-treated mice were analyzed to screen out differentially-expressed genes and explore potential targets of atypical antipsychotics leading to body weight gain.Methods Twenty female C57BL/6 mice were randomly divided into control group (Ctrl) and Olanzapine administration group (Olz), which were given saline and Olanzapine solution by gavage, respectively. The whole brain tissues were collected 8 weeks later for Transcriptome sequencing (RNA-Seq). The possible targets of olanzapine-induced body weight gain were identified by the Gene Ontology (GO) functional annotation analysis, the Kyoto Encyclopedia of Genes and Gnomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis. Differential expression levels of mRNAs were further verified by real-time quantitative fluorescence PCR (RT-qPCR).Results Compared with Ctrl group, 591 differentially expressed genes were screened in Olz group, including 251 up-regulated genes and 340 down-regulated genes. GO analysis showed that differential genes were widely involved in transcriptional process, among which the expression of genes related to the regulation of digestive system and cold-induced thermogenesis were significantly enriched. KEGG analysis showed that differential genes were widely involved in the interaction between neuroactive ligands and receptors, and the differential genes were significantly enriched in oxytocin signaling, fat digestion and absorption, and cholesterol metabolism pathways. RT-qPCR were performed to verify the expression levels of genes enriched in feeding regulation, gastric kinesis, thermogenesis, fat metabolism and other processes (Oxt, Trpv1, Adipoq, Phox2b, Abcg5, Mogat2, Dbh, Plac8 and Neurog1) as well as hub genes in PPI network (Fos, Dusp1 and Egr2), and the results were consistent with the trend of RNA-Seq.Conclusion Olanzapine administration resulted in changes in central feeding regulation, gastrointestinal motility, thermogenesis and other physiological processes in mice, which might be involved in body weight gain induced by olanzapine.
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ObjectiveTo explore the beneficial role and potential mechanism of intermittent fasting in olanzapine-induced metabolic disorders. MethodsC57BL/6J mice were randomly divided into four groups: Saline + ad libitum (Saline+Ad libitum), Saline + intermittent fasting (Saline +IF), olanzapine administration + ad libitum (Olanzapine+ Ad libitum), and olanzapine administration + intermittent fasting (Olanzapine+IF)， with eight mice in each group. The IF group adopted the 5∶2 scheme, that is, fasting on Monday and Thursday every week, and eating freely in the rest of the time. Ad libitum feeding as the control of intermittent fasting, Saline gavage as the control of olanzapine administration. The experiment lasted for 12 weeks. The differences of body mass, liver mass and epididymal adipose tissue mass were compared between the olanzapine-treated group and the control group after IF intervention. The body fat mass, lean body mass, and visceral fat infiltration of mice were analyzed by nuclear magnetic resonance and HE staining, respectively. Furthermore, the levels of fasting blood glucose, insulin, and insulin resistance index (HOMA-IR) in the process of glucose metabolism were also measured by glucose oxidase method and radioimmunoassay, respectively. The effects of IF on H2O2 release and the level of cytochrome C mRNA, a marker related to mitochondrial damage, were detected by ELISA and real-time fluorescence quantitative PCR. ResultsAfter 12 weeks of treatment, olanzapine induced a significant increase in body mass, body fat, lean body mass and visceral fat infiltration (P<0.05), as well as fasting blood glucose, insulin, and HOMA-IR (P<0.05); however, IF significantly reduced the above indicators (P<0.05). Further studies showed that the release of H2O2 and the expression of Cytochrome C mRNA in adipose tissue of mice after intermittent fasting treatment were significantly decreased (P<0.05). ConclusionIntermittent fasting therapy can alleviate olanzapine-induced metabolic disorders in mice. The underlying mechanism may involve the inhibition of oxidative stress level and the maintenance of mitochondrial functions.
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Objective To study the clinical efficacy of caffeine in premature infants receiving mechanical ventilation and related complications .Method From January 2014 to September 2016, preterm infants (28w≤GA<33w) treated with nasal continuous positive airway pressure (NCPAP) or conventional mechanical ventilation ( CMV ) in neonatal intensive care unit were studied .They were randomly assigned into the caffeine group and the control group .The caffeine group received caffeine when NCPAP ventilation was applied or adjusting to synchronized intermittent mandatory ventilation ( SIMV) mode.The control group was injected with 5%glucose without caffeine .The t test andχ2 test were used to analyze the clinical efficacy and related complications .Result A total of 96 patients receiving NCPAP ventilation were collected ( birth weight between 1300~2100 g), including 51 cases in caffeine group and 45 cases in the control group. 84 cases received CMV ventilation (birth weight between 1000~1499 g), with 43 cases in the caffeine group and 41 cases the control group.Among the NCPAP infants, the incidence of failure to withdraw ventilator (0% vs.13.3%) and the incidence of bronchopulmonary dysplasia (3.9% vs.17.8%) were lower in the caffeine group than the control group .The duration of assisted ventilation and hospital stay in the caffeine group were shorter than the control group [(6.2 ±3.1) d vs.(8.2 ±3.2) d, (16.3 ±8.7) d vs. (19.5 ±9.2) d], the differences were statistically significant (P<0.05).Among the CMV infants, the incidence of failure of A/C to SIMV mode transition and bronchopulmonary dysplasia were lower in the caffeine group than the control group and the duration of assisted ventilation and hospital stay were shorter . The differences were statistically significant ( P <0.05 ) . No differences were found in the related complications in each group ( P>0.05) . Conclusion Caffeine can help reduce the incidences of withdrawal failure, bronchopulmonary dysplasia , ventilation duration and hospital stay when using NCPAP and CMV ventilation.
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Objective To observe the clinical application of combined detection of troponin T(cTnT),myoglobin(Myo) and NT-ProBNP in the diagnosis of myocardial infarction(MI).Methods A total of 913 cases of acute chest pain complaints to our hospital for examination and treatment from January 2012 to December 2015 were selected and divided into the acute MI group and non-acute MI group according to the final diagnostic results.The cTnT,Myo and NT proBNP levels were detected in all subjects.The differences of cTnT,Myo and NT-proBNP levels were observed in the two groups.The sensitivity and specificity of single indicator detection,2-indicator combined detection and 3-indicator combined detection for diagnosing MI were observed.Results The levels of cTnT,Myo and NT-proBNP in the acute MI group were significantly higher than those in the non-acute MI group,the difference was statistically significant(P<0.05).The sensitivity and specificity of the two-indicator combined detection were higher than those of cTnT,Myo and NT-proBNP single detection,the sensitivity and specificity of the 3-indicator combined detection were 95.18% and 89.86% respectively,which were significantly higher than those of the single indicator test and the two-indicator combined detection.Conclusion The combined examination of cTnT,Myo and NT-proBNP has important significance in the diagnosis of MI,can improve the specificity and sensitivity of MI diagnosis and provides a reliable basis for clinical treatment.