Objective To investigate the effects of extracellular signal regulated kinase ( ERK)signaling pathway on cell cycle of airway smooth muscle cells( ASMCs) in asthmatic rats. Methods Thirty Wistar rats were randomly assigned to a control group and an asthma group( 15 rats in each group) . Asthma model was established by ovalbumim sensitization and challenge. ASMC were isolated and cultured in vitro. The ASMCs from the asthmatic rats were treated with ERK activator epidermal growth factor ( EGF)and inhibitor PD98059, respectively. The expressions of cyclin D1 and CDK2 in ASMCs were detected by immunocytochemical staining. The expressions of ERK1 /2 and p-ERK1 /2 protein were observed by western blotting for measurement of ERK activation rate. Results Compared with the control group[ 54. 17 ±6. 11,61. 04 ±4. 09, ( 49. 91 ±3. 26) % , respectively] , the expressions of cyclin D1 protein and CDK2 protein,and the rate of ERK activation of ASMCs from the asthmatic rats significantly increased[ 76. 15 ±4. 88,92. 30 ±7. 95, ( 82. 37 ±5. 78) % , respectively] ( P lt; 0. 05) . Furthermore, compared with those before treatment, the expression of cyclin D1 and CDK2, and the rate of ERK activation of ASMCs significantly decreased after treatment with PD98059 [ 58. 78 ±4. 60, 69. 15 ±5. 83, ( 54. 01 ±4. 12) % , respectively]( P lt; 0. 05) , and significantly increased after treatment with EGF[ 119. 28 ±8. 14, 134. 77 ±9. 26, ( 91. 57 ±5. 32) %, respectively] ( P lt;0. 05) . Conclusion ERK1/ 2 participates in proliferation regulation of ASMCs in asthma by enhancing the expressions of cyclin D1 and CDK2, which promotes quiescent cells into S phase.
ObjectiveTo explore the independent factors related to clinical severe events in community acquired pneumonia patients and to find out a simple, effective and more accurate prediction method.MethodsConsecutive patients admitted to our hospital from August 2018 to July 2019 were enrolled in this retrospective study. The endpoint was the occurrence of severe events defined as a condition as follows intensive care unit admission, the need for mechanical ventilation or vasoactive drugs, or 30-day mortality during hospitalization. The patients were divided into severe event group and non-severe event group, and general clinical data were compared between two groups. Multivariate logistic regression analysis was performed to identify the independent predictors of adverse outcomes. Receiver operating characteristic (ROC) curve was constructed to calculate and compare the area under curve (AUC) of different prediction methods.ResultsA total of 410 patients were enrolled, 96 (23.4%) of whom experienced clinical severe events. Age (OR: 1.035, 95%CI: 1.012 - 1.059, P=0.003), high-density lipoprotein (OR: 0.266, 95%CI: 0.088 - 0.802, P=0.019) and lactate dehydrogenase (OR: 1.006, 95%CI: 1.004 - 1.059, P<0.001) levels on admission were independent factors associated with clinical severe events in CAP patients. The AUCs in the prediction of clinical severe events were 0.744 (95%CI: 0.699 - 0.785, P=0.028) and 0.814 (95%CI: 0.772 - 0.850, P=0.025) for CURB65 and PSI respectively. CURB65-LH, combining CURB65, HDL and LDH simultaneously, had the largest AUC of 0.843 (95%CI: 0.804 - 0.876, P=0.022) among these prediction methods and its sensitivity (69.8%) and specificity (81.5%) were higher than that of CURB65 (61.5% and 76.1%) respectively.ConclusionCURB65-LH is a simple, effective and more accurate prediction method of clinical severe events in CAP patients, which not only has higher sensitivity and specificity, but also significantly improves the predictive value when compared with CURB65.