0.05).Conclusion The increasing of IL-15 in peripheral blood after MP infection may play a role in bronchitic asthma pathogenesis.

Dissent and Disputes ; Humans ; Occupational Diseases ; diagnosis

Objective To evaluate effects of simultaneous inhibition of mammalian target of rapamycin complex 1(mTORC1)kinase and glycogen synthase kinase-3β(GSK-3β)on phosphorylation of 4E-binding protein-1(4EBP1), cap-dependent translation, as well as survival and apoptosis of melanoma cells. Methods Cultured A375 cells were classified into several groups to be treated with dimethyl sulfoxide (DMSO group), the mTORC1 kinase inhibitor everolimus at a concentration of 5 nmol/L (everolimus group), the GSK-3β kinase inhibitor AR-A014418 at a concentration of 10 μmol/L (AR-A014418 group), or 5 nmol/L everolimus and 10 μmol/L AR-A014418(combined treatment group). After additional culture, Western-blot analysis was performed to measure protein expressions of phosphorylated 4EBP1 (p4EBP1)and survivin in A375 cells, m7GTP pull down assay to estimate interaction between eukaryotic initiation factor-4E (eIF4E)and eIF4G, cell counting kit 8 (CCK8)assay to evaluate cell proliferation, and flow cytometry to detect cell apoptosis. Results Both everolimus and AR-A014418 had inhibitory effects on 4EBP1 phosphorylation and survivin expression. The expressions of p4EBP1-65 and survivin were both significantly decreased in the everolimus group (0.74 ± 0.05 and 0.71 ± 0.06 respectively), AR-A014418 group (0.62 ± 0.06 and 0.58 ± 0.07 respectively)and combined treatment group (0.14 ± 0.04 and 0.09 ± 0.05 respectively)compared with the DMSO group (1.00 ± 0.07 and 1.00 ± 0.06, respectively, all P < 0.001), with the most significant decrease observed in the combined treatment group. As m7GTP pull-down assay showed, the everolimus group, AR-A014418 group and combined treatment group all showed significantly lower relative expression levels of eIF4G(0.72 ± 0.04, 0.67 ± 0.05 and 0.12 ± 0.05 vs. 1.00 ± 0.06, all P < 0.001), but significantly higher relative expression levels of 4EBP1 (1.98 ± 0.16, 2.32 ± 0.17 and 7.58 ± 0.25 vs. 1.00 ± 0.08, all P < 0.001)than the DMSO group, and the combined treatment group showed the lowest eIF4G expression but highest 4EBP1 expression. After 24-hour culture, the proliferation of A375 cells was inhibited by 18.5% ± 1.3% in the everolimus group, 19.8% ± 1.8% in the AR-A014418 group, and 61.2% ± 2.1% in the combined treatment group compared with the DMSO group, with the strongest inhibition noted in the combined treatment group. The inhibitory effects of everolimus and AR-A014418 on cell proliferation increased over time, and showed the same trend at 48 hours. Flow cytometry showed that the apoptosis of A375 cells was accelerated by the 24-hour treatments with everolimus and AR-A014418 alone or in combination, with the apoptosis rate being 14.28% ± 2.18%, 14.57% ± 2.35% and 55.18% ± 6.27% in the everolimus group, AR-A014418 group and combined treatment group respectively, and the combined treatment showed the strongest accelerating effect. Conclusion The combined treatment with everolimus and AR-A014418 can evidently inhibit 4EBP1 phosphorylation and eIF4F complex formation in A375 cells, which then suppress cap-dependent translation and promote apoptosis of melanoma cells.

Juvenile idiopathic arthritis(JIA)is the most common rheumatology disease in childhood period with poor prognosis.The biological agents are newly developed drugs with features of clear therapeutic targets and fast effects.But its use in JIA is still limited,so this article focuses on the clinical use experience,timming and sideffects of the biological agents on JIA.

OBJECTIVETo observe the effect of ruthenium red (RR) on the body temperature of rats with lipopolysaccharide (LPS)-induced fever and investigate the possible mechanism.

METHODSRat models of fever were established with lipopolysaccharide and the effects of RR at different doses were observed on the body temperature of the rats and the content of TRPV4 in the hypothalamus.

RESULTSCompared with those in LPS group, the rats with LPS-induced fever receiving RR treatment showed a dose-dependent lowering of the body temperature. The rats with RR treatment had lower body temperature than those with saline injection. The content of TRPV4 in the saline group was significantly higher than that in RR+LPS and RR group.

CONCLUSIONSRR inhibits LPS-induced fever in rats and regulates the hypothalamal expression of TRPV4 channels, which may participate in the maintenance of normal body temperature.

Animals ; Blotting, Western ; Body Temperature ; drug effects ; Dose-Response Relationship, Drug ; Fever ; chemically induced ; metabolism ; physiopathology ; Hypothalamus ; drug effects ; metabolism ; Lipopolysaccharides ; Male ; Rats ; Rats, Sprague-Dawley ; Ruthenium Red ; pharmacology ; TRPV Cation Channels ; biosynthesis

We describe two cases in which a forceps imprintdeveloped in the AcrySof ReSTOR IOL optic whileinserting these IOLs into the cartridge with straightclamping forceps. In case 1 ,the AcrySof ReSTOR IOL wasexplanted and observed under scanning electronmicroscopy (SEM). The SEM showed that the stepdesign of ReSTOR Multifocal IOL was well maintained. Incase 2, visual acuity, contrast sensitivity and wavefrontmeasurements were performed and no specific changeswere found. Strong evidence does not exist that suggeststhe on-axis forceps imprint can significantly compromisevisual acuity.

Objective To explore the effect of gastrin_(17) on E cadherin/?-catenin complex,a down- stream effector of FAK pathway,in colonic carcinoma cell line CoLo320WT.Methods pCR3.1/GR plasmid expressing gastrin receptor CCK 2R was transfected into colonic carcinoma cell line CoLo320 by Lipofectamine~(TM) 2000 and expressing stably CCK 2R clones was screened by G418.The expression levels of gastrin receptor of Coi.o320 and the transfected cell line Colo320WT were assayed by RT PCR. CoLo320WT cells were treated by 10~(-8)mmol/L gastrin_(17) at distinct time points (0 hr,1 hr,6 hr,12 hr, 24 hr,48 hr),whilst treated by 10_(-6) mmol/L L365,260 (gastrin_(17) receptor blocker) simultaneously for 30 minutes and then treated by gastrin_(17) again for 12 hr.Expression levels of phosphorylated FAK Tyr397 and total FAK in CoLo320WT under gastrin_(17)intervention were detected hy Western blot.Ex- pression levels of E-cadherin and?-catenin complex in TX-100 solution fraction and TX-100 insolution fraction of CoLo320WT cells were detected by coimmunoprecipitation and Western blot.Distribution of E-cadherin and?-catenin in CoLoWT320 were observed by immunocytochemistry.Results Phosphoryla- ted FAK Tyr397 expression in CoLo320WT cells increased in time dependent fashion under gastrin_(17) intervention and peaked at 12 hour after intervention,while decreased by L365,260 inhibition.But gas trine_(17) had no effect on total FAK in CoLo320WT cells.Expresion levels of E-cadherin and?-catenin com- plex in TX-100 solution fraction were decreased apparently,but increased again after L365,260 block- ing.On the contrary,the expression levels of E-cadherin and?-eatenin complex in TX-100 solution frac tion differed from that in TX-100 solution.Cytoehemistry observation had revealed that E-cadherin and?-catenin transferred from cell membranes into cndochylemas,nuclei and cytoskeleton under gastrin_(17) in- tervention.Conclusions Gastrin_(17)affected significantly the distribution of E cadherin/?-catenin complex in CoLo320WT by phosphorating FAK Tyr397 and activating FAK pathway when it bound to its recep- tor CCK-2,therefore promoted invasion and metastasis of CoLo320WT.

Arthritis, Juvenile ; complications ; immunology ; Child ; Humans ; Macrophage Activation ; Male ; Syndrome

Objective To investigate the effectiveness of the combined electrical stimulation and nursing interventions for female stress urinary incontinence.Methods The study is qusi-experimental design.48 patients with stress urinary incontinence were allocated to the intervention group and the control group with 24 patients in each group.The control group was given electrical stimulation,the intervention group was given 12-week electrical stimulation and comprehensive nursing interventions.The outcome indicators were 1-hour pad test urine loss,pelvic floor muscle (PFM) strength,the grade of subjective urinary incontinence,quality of life (I-QOL).Results Compared with the control group,no significant subjective urinary incontinence score was seen,but pelvic floor muscle (PFM ) strength and the score of the QOL evidently improved and 1-hour pad test urine loss decreased in the intervention group.Conclusions Combined electrical stimulation and nursing interventions for female stress urinary incontinence is effective treatment.