OBJECTIVES: To elucidate the molecular mechanism by which villin-like protein VILL (VILL) inhibits proliferation of nasopharyngeal carcinoma (NPC) cells. METHODS: Co-immunoprecipitation (CO-IP) assay, mass spectrometry, Western blotting, immunofluorescence staining, and GST pull-down assay were employed to identify and confirm the protein interacting with VILL that had the highest abundance in NPC cell lines. Transgenic experiments were conducted in both NPC cell lines and nude mice to validate the regulatory role of VILL and its target protein in NPC proliferation. Immunohistochemistry was utilized to assess the correlation of the expression levels of VILL and its target protein in clinical tissue specimens of NPC with the clinical features of the patients. RESULTS: In NPC cell lines (HONE1 EBV and S18), VILL was found to interact most abundantly with the E3 ubiquitin ligase LMO7, and both proteins co-localized in the cytoplasm with direct interactions. Overexpression of LMO7 partially counteracted the inhibitory effect of VILL on NPC cell proliferation. The expression of VILL was significantly downregulated in 136 NPC tissue samples compared to 67 non-cancerous nasopharyngeal tissues (P<0.00001) with close correlation with clinical T stage (P=0.04), N stage (P=0.01), and M stage (P=0.013), whereas LMO7 was highly expressed in all the NPC tissues. CONCLUSIONS VILL overexpression inhibits NPC proliferation probably by suppressing the oncogenic function of LMO7.
Nasopharyngeal Neoplasms/metabolism* ; Humans ; LIM Domain Proteins/metabolism* ; Cell Proliferation ; Cell Line, Tumor ; Animals ; Mice ; Nasopharyngeal Carcinoma ; Mice, Nude ; Transcription Factors/metabolism* ; Carcinoma ; Female ; Microfilament Proteins/genetics* ; Male ; Middle Aged

Objective The objective of this study was to construct a new Bayesian information borrowing model based on the concept of elastic prior,evaluate the statistical properties of the method through simulation studies,and provide a new method for historical information borrowing.Methods The concept of elastic prior was introduced into the commensurate prior method to establish the elastic commensurate prior model.Simulations were conducted for clinical study outcomes as normal variables under situations where historical data was either consistent or inconsistent with the current study data.Type Ⅰ error,statistical power,and the 95％posterior highest density credible interval were used as evaluation criteria to compare the performance of the elastic commensurate prior method with non-informative prior,full-information prior,power prior,and commensurate prior methods.Results Through simulation studies in various scenarios,it was shown that the proposed elastic commensurate prior method,compared to other prior methods under similar conditions,provides better control of Type Ⅰ error,higher statistical power,and relatively narrower posterior highest density credible intervals.Conclusion The proposed elastic commensurate prior method not only better controls Type Ⅰ error but also ensures higher statistical power,improving the accuracy of estimating treatment effects.This method introduces a new approach for borrowing information from historical data in clinical trials.

Objective The objective of this study was to construct a new Bayesian information borrowing model based on the concept of elastic prior,evaluate the statistical properties of the method through simulation studies,and provide a new method for historical information borrowing.Methods The concept of elastic prior was introduced into the commensurate prior method to establish the elastic commensurate prior model.Simulations were conducted for clinical study outcomes as normal variables under situations where historical data was either consistent or inconsistent with the current study data.Type Ⅰ error,statistical power,and the 95％posterior highest density credible interval were used as evaluation criteria to compare the performance of the elastic commensurate prior method with non-informative prior,full-information prior,power prior,and commensurate prior methods.Results Through simulation studies in various scenarios,it was shown that the proposed elastic commensurate prior method,compared to other prior methods under similar conditions,provides better control of Type Ⅰ error,higher statistical power,and relatively narrower posterior highest density credible intervals.Conclusion The proposed elastic commensurate prior method not only better controls Type Ⅰ error but also ensures higher statistical power,improving the accuracy of estimating treatment effects.This method introduces a new approach for borrowing information from historical data in clinical trials.

Objective To observe the changes of cell apoptosis and levels of Bcl-2 and Bax protein in myocardium after cardiopulmonary resuscitation (CPR) in rats and to study the protective effects of different doses of exogenous phosphocreatine (creatine phosphate, CP) on cell apoptosis. Methods A total of 32 male adult SD rats were randomly divided into 4 groups, namely control group ( group A), CPR group (group B), low dose CP group (group C, phosphocreatine 0. 5 g/kg given at beginning of CPR and 1.0 g/ kg 2 hour after CPR) and high dose CP group ( group D, phosphocreatine 1.0 g/kg at beginning of CPR and 2. 0 g/kg 2 hours after CPR) . Cardiac arrest was induced by asphyxiation and CPR was started 7 min after asphyxiation it groups B, C and D. Myocardium samples were taken 24 hours after CPR for detecting myocardium cell apoptosis by TUNEL method. The levels of Bcl-2 and Bax protein were measured by using immunohistochemistry. Experimental data were processed with variance analysis in SPSS package. Results Compared with group A, myocardium cell apoptosis index (AI), and the levels of Bcl-2 and Bax proteinincreased significantly in groups B, C and D (P ＜0. 01 ), and Bcl-2/Bax ratio decreased significantly (P ＜0. 01 ) . Compared with group B, myocardium cell AI and levels of Bcl-2 and Bax protein decreased significantly in groups C and D ( P ＜ 0. 01 ), and Bcl-2/Bax ratio increased significantly ( P ＜ 0. 01 ) .Compared with group C, myocardium cell AI and levels of Bcl-2 and Bax decreased significantly in group D (P ＜ 0. 05 ), and Bcl-2/Bax ratio increased significantly ( P ＜ 0. 05 ) . Conclusion Exogenous phosphocreatine, especially inlarge dose, could inhibit apoptosis of myocardium cells and alleviate myocardium injury after CPR in rats.

Objective To study the factors influenceing patients' family members to make own relative fac-tors patients' families making decision on refusal of cardiopulmonary resuscitation (CPR) to the critical patients. Method Data were registered based on Utstein Style of 522 patients aged over 15 years, who subjected to in-hos-pital cardiac arrest(CA) in Department of Emergency of The First Affiliated Hospital of Wenzhou Medical College from January 2005 to December 2008. A total of 157 patients' family made refusal decision among the 522 pa-tients, who belonged to the refusal group, and others belonged to the attempt resuscitation group. The associated factors included age, sex, marriage, household register, cause of CA, underlying diseases, capability of activity before CA, life supported with mechanical ventilation, and administration of pressor agents. The refusal decisions were evaluated by using univariate Logistical regression analysis, and then the statistical significant variables were analyzed by using muhivanate Logistical regression analysis. Results Age, household register, cause of CA(car-diac or traumatic),stroke, sudden death, cancer, capability of activity before CA, life supported with mechanical ventilation,and administration of pressor agents were the important factors of making refusal decision (P < 0.01), but sexes or marriage was insignificant related to the refusal decision (P > 0. O5). The independent risk factors re-lated to refusal decision were age (P = 0.034),cancer (P = 0.006),stroke (P = 0.003), and life supported with mechanical ventilation (P = 0.000) in multivariate Logistical regression analysis, but the protective factors were sudden death (P =0.000),cardiac CA (P =0.020) and traumatic CA(P =0.000). Conclusions Age over 60 years, cancer, stroke, and life suppoted with assisted ventilation before CA were factors associated with re-fusal decision making, yet sudden death, cardiac CA and traumatic CA were factors of accepting CPR.