Objective To investigate the effects of NVP-BEZ235 on proliferation and apoptosis of human cholangiocarcinoma(CCA) cell QBC939 in vitro and to reveal the antineoplastic mechanisms of NVP-BEZ235.Methods Human CCA cell line QBC939 was used in this study.Cell apoptosis by NVP-BEZ235 was analyzed using the flow cytometry.Cell growth inhibition by NVP-BEZ235 for 24h 48h 72h by MTT assay.The antineoplastic mechanisms of NVP-BEZ235 for 48h were assessed by western blotting for PARP、Bcl-2、Akt、p-Akt、c-FLIPL and Mcl-1 assay in QBC939 cell.Results NVP-BEZ235 treatment inhibited the proliferation and induced apoptosis of human CCA cell QBC939,which appeared time-dependent and concentration-dependent effects.NVP-BEZ235 reduced protein levels of Mcl-1、c-FLIPL and Bcl-2 and downregulate protein level of p-Akt significantly.Conclusion NVP-BEZ235 inhibited the phosphorylation of Akt.NVP-BEZ235 downregulated Bcl-2、c-FLIPL、Mcl-1 protein level via PI3K/AKT signaling pathway to induce apoptosis and inhibit the proliferation of human CCA cell QBC939.

Objective The purpose of this study was to investigate the efficacy and safety of bortezomib +doxorubicin + dexamethasone (PAD) regimen in the treatment of patients with multiple myeloma (MM) . Methods Thirty-eight patients with MM in our hospital were selected and randomly divided into observation group and control group with 19 cases in each. The observation group was treated with PAD regimen and the control group was treated with VAD regimen (vincristine+doxorubicin+dexamethasone) . Clinical efficacy and adverse reaction were compared between the two groups. Results The effective rate and total effective rate of the observation group were 52.63%and 78.95%respectively, which were significantly higher than those of the control group ( <0.05 and <0.05) . There was no statistical difference in the incidence of adverse events between the two groups ( >0.05) . Conclusion PAD regimen could improve the clinical effect of treating patients with MM, and the adverse reactions can be tolerated. It is safe and worthy of clinical application.

Objective To compare the clinical effects and side events between simple synchronal radiochemotherapy(group A) and cervical local implantation chemotherapy combined with synchronal radiochemotherapy(group B) in advanced cervical cancer.Methods Sixty patients with primary cervical cancer,admitted to our hospital from January 2009 to December 2009,were enrolled into the study.The clinical staging of these patients ranged from Ⅱb to Ⅲb.The patients were randomly divided into two different therapy groups.In group A,patients received external irradiation by X-rays and intracavitary by 192 Ir and PT chemotherapy(n=30).In group B,patients received cervical local implantation of fluorouracil palliative 400-500 mg in addition of external irradiation by X-rays and intracavitary by 192 Ir and PT chemotherapy(n=30).The short-term effect and complications were compared between the two groups.Results The effective rate of group A was significantly higher than the second group(97% vs.80%,x2=4.706,P＜ 0.05).The most common complication was myelosuppression.In group A we observed 8 cases had grade Ⅰ,10 cases had grade II,9 cases had grade Ⅲ,3 cases had grade Ⅳ myelosuppression.In group B we observed 8 cases had grade Ⅰ,12 cases had grade Ⅱ,7 cases had grade Ⅲ,3 cases had grade Ⅳ myelosuppression.There were no significantly differences in the comparisons of this complication between the two groups(x2=0.432,P＞0.05).Conclusion The cervical local implantation chemotherapy combined with synchronal radiochemotherapy might improve the prognosis in advanced cervical cancer patients without increasing toxic side effects.

OBJECTIVE: To study the expression of IL-33 and its receptor ST2 in the nasal mucosa of allergic rhinitis (AR) patients, and to explore the role of IL-33 and ST2 in the pathogenesis of AR. METHOD: Collected 24 cases of nasal septum deviation of patients with AR as AR group,and selected 20 patients with simple septum deviation as normal control. In addition, collected 20 cases diagnosed with AR, who accepted standardized specific immunotherapy(SIT). RESULT: Immunohistochemical results found more positively stained cells of IL-33 and ST2 in AR patients than normal control group, the difference was statistically significant (P < 0.05), Western-Blot detected that IL-33 and ST2 protein level were significantly higher in AR than the normal control group (P < 0.01), PCR detected that the expression of IL-33mRNA and ST2mRNA were increased in AR group compared with the control group, the difference was statistically significant (P < 0.05). While, the serum IL-33 levels in AR were decreased before treatment (72.37 ± 16.18) ng/L than after six months of SIT (47.35 ± 10.59) ng/L,and the difference was statistically significant (P < 0.05). CONCLUSION IL-33 and its receptor ST2 were highly expressed in the nasal mucosa of patients with AR, suggesting that IL-33/ST2 may play an important role in the pathogenesis of allergic rhinitis. Serum levels of IL-33 were significantly decreased after SIT treatment, suggesting that IL-33 may have a positive correlation with the severity of AR.
Case-Control Studies ; Humans ; Immunotherapy ; Interleukin-33 ; metabolism ; Nasal Mucosa ; metabolism ; Nasal Septum ; abnormalities ; Receptors, Interleukin ; metabolism ; Rhinitis, Allergic ; drug therapy ; metabolism ; pathology

OBJECTIVE: To explore the expression of IL-35, Epstein-Barr virus-induced gene 3 (EBI3) mRNA and IL-12A mRNA in peripheral blood of patients with allergic rhinitis and its significance. METHOD: Peripheral blood were collected from patients with allergic rhinitis (46 cases) and healthy human controls(30 cases). The level of IL-35 in serum was measured by enzyme-linked immunosorbent assay. The subunit EB13 and IL-12A of IL-35 mRNA expressions in peripheral blood mononuclear cell(PBMC) were detected by SYBR Green real-time quantitative PCR. RESULT: IL-35 level in AR group (251.22 +/- 46.27) ng/L was significantly lower compared with that in the normal control group (382.17 +/- 25.41) ng/L, (P < 0.01). The mRNA expression level of EBI3 in the patients with allergic rhinitis was significantly lower than that in the normal control group (P < 0.01), AR group EB13 mRNA level was about half of that in the normal control group. But the mRNA expression level of IL-12A in the patients with allergic rhinitis has not significant difference with that in the normal control group (P > 0. 05). CONCLUSION The decrease of IL-35 and EBI3 mRNA in AR,indicated that IL-35 and EBl3 mRNA may play an important role in allergic rhinitis.
Adolescent ; Adult ; Case-Control Studies ; Child ; Female ; Humans ; Interleukin-12 Subunit p35 ; blood ; Interleukins ; blood ; Male ; Middle Aged ; Minor Histocompatibility Antigens ; Rhinitis, Allergic ; blood ; Young Adult

Allergic rhinitis (AR) is a noninfectious inflammatory response in nasal mucosa caused by allergens, which is contacted by a specific individual. The immune imbalance of Th1/Th2 plays an important role in the pathogenesis of AR. In?terleukin (IL)-33, the novel cytokine of IL-1 family, is an important regulatory factor of allergic diseases, autoimmune diseas?es and various inflammatory diseases. IL-33 is a kind of alarm, which is mainly secreted and released by damaged tissues and cells, especially impaired epithelial cells and endothelial cells. IL-33 binding to its receptor ST2L can activate a variety of immune cells to produce Th2 cytokines, precipitating and maintaining Th2 polarization, increasing AR immune inflamma?tion, which is the new target of AR in research and treatment. In this article, we have done a brief overview for the biological functions of IL-33 and its receptor ST2L and the research progress in the AR.

Objective:To explore whether the deubiquitinating enzyme deubiquitin ligase 9X(USP9X)affects the proliferation of nasopharyngeal carcinoma(NPC)cells via regulating forkhead box Ml(FOXM1)mediated glycolysis. Methods:Western blotting and real-time fluorescence quantitative PCR,respectively,were used to detect the protein and mRNA expression levels of USP9X in NPC tissue and normal nasal mucosa tissue.NPC cells(CNE2 and HNE2)were infected with lentivirus carrying specific shRNA targeting USP9X gene(shUSP9X)or full-length USP9X gene(Flag-USP9X)for USP9X overexpression.CCK-8 assay was used to evaluate the effect of USP9X silencing or overexpression on the proliferation of NPC cells.Cellular energy metabolism assay and extracellular acidification rate(ECAR)assay were performed to investigate the impact of USP9X alteration on the glycolysis of NPC cells.The interaction between USP9X and FOXM1 was analyzed using ubibrowser_v3/database,co-immunoprecipitation,and ZDOCK software,and the changes in FOXM1 protein ubiquitination levels upon USP9X silencing was examined.Real-time fluorescence quantitative PCR and Western blotting,respectively,were used to detect the effect of USP9X alteration on the expression of FOXM1 mRNA and protein in NPC cells.Finally,FOXM1 expression was restored in USP9X silencing CNE2 cells by expression of recombinant plasmid Flag-FOXM1 carrying full-length FOXM1 gene through lentiviral infection.CCK-8 assay was used to evaluate the effect of FOXM1 upregulation on the proliferation of CNE2 cells.Cellular energy metabolism assay and ECAR assay were used to investigate the effect of FOXM1 upregulation on the glycolysis of CNE2 cells. Results:Compared with normal nasal mucosa tissue,the expression levels of USP9X mRNA and protein were significantly increased in NPC tissues(P＜0.05).After USP9X downregulation,the proliferation and glycolysis of CNE2 cells was significantly inhibited as indicated by the results of CCK-8 assay,cellular energy metabolism assay and ECAR assay(P＜0.05).In contrast,the proliferation and glycolysis of HNE2 cells was significantly enhanced after USP9X upregulation(P＜0.05).The interaction between USP9X and FOXM1 was confirmed by ubibrowser_v3/database,co-immunoprecipitation,and ZDOCK software analysis.Silencing USP9X could significantly increase FOXM1 ubiquitination in CNE2 cells.Overexpressing FOXM1 in low-USP9X CNE2 cells restored the proliferation and glycolysis activity of NPC cells(P＜0.05). Conclusion:USP9X can enhance NPC cell glycolysis by inhibiting FOXM1 ubiquitination and subsequent degradation,thereby promoting NCP cell proliferation.USP9X may be a potential novel therapeutic target for the treatment of NPC.