Objective:Lung cancer has emerged as a leading cause of cancer death in the world.Eyes Absent (EYA) is an important and conserved transcriptional regulator of development.The aim of the present study was to identify t...Objective:Lung cancer has emerged as a leading cause of cancer death in the world.Eyes Absent (EYA) is an important and conserved transcriptional regulator of development.The aim of the present study was to identify the expression of Drosophila Eyes Absent Homologue 2 (EYA2) in non-small cell lung cancer (NSCLC) and to investigate their correlation with clinical parameters.Methods:Fresh,paired lung samples (n=59) of NSCLC were obtained by surgical resection at the Department of Thoracic Surgery of the People's Liberation Army General Hospital.Expression of EYA2 were examined by Western blot and immunohistochemical analysis in specimens of NSCLC and paired normal lung tissue.Clinical data,patho-logic result and Ki67 expression were collected and subsequent correlation with EYA2 expression was analyzed.Results:EYA2 expression was found located in cytoplasm and nucleus,but mostly in cytoplasm.The expression of EYA2 increased in NSCLC by Western blot and immunohistochemistry,which was correlated with histology type,but not correlated with gender,age,pTNM stage,histological differentiation and lymph node metastasis.Compared with normal lung tissue,the expres-sion of EYA2 significantly was up-regulated in lung adenocarcinoma,while no significant difference in lung squamous cell carcinoma.Expression of EYA2 was uncorrelated with expression of Ki67 in NSCLC.Conclusion:Expression of EYA2 was augmented in lung adenocarcinoma.EYA2 is likely participating in tumorigenesis and development of lung adenocarcinoma as transcriptional activator.展开更多
Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PD...Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.展开更多
Background:Acute kidney injury(AKI)is a common and serious complication following lung transplantation(LTx),and it is associated with high mortality and morbidity.This study assessed the incidence of AKI after LTx and...Background:Acute kidney injury(AKI)is a common and serious complication following lung transplantation(LTx),and it is associated with high mortality and morbidity.This study assessed the incidence of AKI after LTx and analyzed the associated perioperative factors and clinical outcomes.Methods:This retrospective study included all adult LTx recipients at the China-Japan Friendship Hospital in Beijing between March 2017 and December 2019.The outcomes were AKI incidence,risk factors,mortality,and kidney recovery.Multivariate analysis was performed to identify independent risk factors.Survival analysis was presented using the Kaplan-Meier curves.Results:AKI occurred in 137 of the 191 patients(71.7%),with transient AKI in 43(22.5%)and persistent AKI in 94(49.2%).AKI stage 1 occurred in 27/191(14.1%),stage 2 in 46/191(24.1%),and stage 3 in 64/191(33.5%)of the AKI patients.Renal replacement therapy(RRT)was administered to 35/191(18.3%)of the patients.Male sex,older age,mechanical ventilation(MV),severe hypotension,septic shock,multiple organ dysfunction(MODS),prolonged extracorporeal membrane oxygenation(ECMO),reintubation,and nephrotoxic agents were associated with AKI(P<0.050).Persistent AKI was independently associated with pre-operative pulmonary hypertension,severe hypotension,post-operative MODS,and nephrotoxic agents.Severe hypotension,septic shock,MODS,reintubation,prolonged MV,and ECMO during or after LTx were related to severe AKI(stage 3)(P<0.050).Patients with persistent and severe AKI had a significantly longer duration of MV,longer duration in the intensive care unit(ICU),worse downstream kidney function,and reduced survival(P<0.050).Conclusions:AKI is common after LTx,but the pathogenic mechanism of AKI is complicated,and prerenal causes are important.Persistent and severe AKI were associated with poor short-and long-term kidney function and reduced survival in LTx patients.展开更多
文摘Objective:Lung cancer has emerged as a leading cause of cancer death in the world.Eyes Absent (EYA) is an important and conserved transcriptional regulator of development.The aim of the present study was to identify the expression of Drosophila Eyes Absent Homologue 2 (EYA2) in non-small cell lung cancer (NSCLC) and to investigate their correlation with clinical parameters.Methods:Fresh,paired lung samples (n=59) of NSCLC were obtained by surgical resection at the Department of Thoracic Surgery of the People's Liberation Army General Hospital.Expression of EYA2 were examined by Western blot and immunohistochemical analysis in specimens of NSCLC and paired normal lung tissue.Clinical data,patho-logic result and Ki67 expression were collected and subsequent correlation with EYA2 expression was analyzed.Results:EYA2 expression was found located in cytoplasm and nucleus,but mostly in cytoplasm.The expression of EYA2 increased in NSCLC by Western blot and immunohistochemistry,which was correlated with histology type,but not correlated with gender,age,pTNM stage,histological differentiation and lymph node metastasis.Compared with normal lung tissue,the expres-sion of EYA2 significantly was up-regulated in lung adenocarcinoma,while no significant difference in lung squamous cell carcinoma.Expression of EYA2 was uncorrelated with expression of Ki67 in NSCLC.Conclusion:Expression of EYA2 was augmented in lung adenocarcinoma.EYA2 is likely participating in tumorigenesis and development of lung adenocarcinoma as transcriptional activator.
基金This work was supported by Beijing Natural Science Foundation[Z220019 to Jing Wang,China]National High Level of Hospital Clinical Research Funding[2022-PUMCH-D-002 to Jing Wang,China]+3 种基金National Key Research and Development Program of China Grants[2019YFA0801703 and 2019YFA0801804 to Jing Wang]Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences[2022-I2M-JB-007 to Chen Wang,2021-I2M-1-016 to Hongmei Zhao,2021-I2M-1-049 to Jing Wang,2021-I2M-1-005 to Yanjiang Xing,China]Haihe Laboratory of Cell Ecosystem Innovation Fund[22HHXBSS00010 to Jing Wang,China]National Natural Science Foundation of China[82241004 to Jing Wang].
文摘Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.
基金This work was supported by the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(No.2019PT320020).
文摘Background:Acute kidney injury(AKI)is a common and serious complication following lung transplantation(LTx),and it is associated with high mortality and morbidity.This study assessed the incidence of AKI after LTx and analyzed the associated perioperative factors and clinical outcomes.Methods:This retrospective study included all adult LTx recipients at the China-Japan Friendship Hospital in Beijing between March 2017 and December 2019.The outcomes were AKI incidence,risk factors,mortality,and kidney recovery.Multivariate analysis was performed to identify independent risk factors.Survival analysis was presented using the Kaplan-Meier curves.Results:AKI occurred in 137 of the 191 patients(71.7%),with transient AKI in 43(22.5%)and persistent AKI in 94(49.2%).AKI stage 1 occurred in 27/191(14.1%),stage 2 in 46/191(24.1%),and stage 3 in 64/191(33.5%)of the AKI patients.Renal replacement therapy(RRT)was administered to 35/191(18.3%)of the patients.Male sex,older age,mechanical ventilation(MV),severe hypotension,septic shock,multiple organ dysfunction(MODS),prolonged extracorporeal membrane oxygenation(ECMO),reintubation,and nephrotoxic agents were associated with AKI(P<0.050).Persistent AKI was independently associated with pre-operative pulmonary hypertension,severe hypotension,post-operative MODS,and nephrotoxic agents.Severe hypotension,septic shock,MODS,reintubation,prolonged MV,and ECMO during or after LTx were related to severe AKI(stage 3)(P<0.050).Patients with persistent and severe AKI had a significantly longer duration of MV,longer duration in the intensive care unit(ICU),worse downstream kidney function,and reduced survival(P<0.050).Conclusions:AKI is common after LTx,but the pathogenic mechanism of AKI is complicated,and prerenal causes are important.Persistent and severe AKI were associated with poor short-and long-term kidney function and reduced survival in LTx patients.