Objective:To explore the evaluation value of sequential organ failure assessment (SOFA) score at different time points in the prognosis of patients with severe pneumonia combined with acute respiratory distress syndrome (ARDS).Methods:A retrospective cohort study method was conducted, including patients with severe pneumonia and ARDS admitted to the emergency intensive care unit (ICU) of General Hospital of Ningxia Medical University from January 2015 to December 2019. General clinical data such as gender, age, and the SOFA scores at 1, 2, 3, and 7 days after admission were recorded. According to the diagnostic test, the prognostic evaluation value of SOFA score in patients with severe pneumonia combined with ARDS at different time points and different ages was analyzed.Results:A total of 88 cases were included in this study, eventually, 42 cases were survived and 46 cases died, the mortality was 52.27%. The age of the death group was significantly older than the survival group (years old: 60.67±14.66 vs. 51.91±15.97), the SOFA score at each time point were significantly higher than those in the survival group (9.83±3.50 vs. 7.54±2.67, 9.98±3.75 vs. 7.48±2.92, 10.84±4.14 vs. 7.23±2.94, 11.71±4.03 vs. 6.51±3.22, respectively at 1, 2, 3, 7 days after admission, all P < 0.01). The receiver operator characteristic curve (ROC curve) showed that the SOFA score at 1, 2, 3, and 7 days after admission had a certain predictive value for the prognosis of patients with severe pneumonia combined with ARDS (all P < 0.01), and with the prolong of ICU stay, the area under ROC curve (AUC) of SOFA score had gradually increased. On the 7th day after admission, the SOFA score had the highest sensitivity in predicting severe pneumonia combined with ARDS patients, which was 92.86%, and the specificity was the highest on the 3rd day after admission, which was 88.10%. The AUC in day 7 was significantly higher than day 2 (0.85 vs. 0.72) , there was no statistically significant difference of AUC at other time points. After stratifying by age, the diagnostic of sensitivity, specificity, accuracy, and AUC of SOFA score for the prognosis had gradually increased, and the predictive value was better. However, only on day 3 after admission, the AUC of SOFA score was significantly higher than day 1 (0.80 vs. 0.77, P < 0.05), and there was no significant difference in AUC at other time points. In patients older than 60 years old, the AUC of the SOFA score predicting the prognosis of patients was relatively small on day 1 and day 2 (0.67, 0.68, respectively), the ability was poor. There was no statistically significant difference in the AUC of SOFA scores at each time point in evaluating the prognosis of patients. The trends over time of patients at different ages and time points showed that regardless of age, the SOFA scores of the patients in the death group showed an upward trend, while showed a downward trend in the survival group, the difference reached the largest on the 7th day after admission, and the death group was significantly higher than the survival group (age < 60 years old: 12.50 vs. 6.69; age≥60 years old: 11.58 vs. 6.21). Conclusion:The initial SOFA score has a certain value in the evaluation of prognosis of severe pneumonia patients combined with ARDS, but the effect is poor for elderly patients.

OBJECTIVETo study the signaling pathways associated with lipopolysaccharide (LPS)-induced inflammation in islet micro-endothelial cells (IMECs) and the mechanism of pravastatin intervention.

METHODSIMECs exposed to LPS, SB203580, pravastatin, or SB203580+pravastatin were examined for cell apoptosis with Hoechst staining and flow cytometry and for expression levels of total-p38, photophosphorylation-p38 (p-p38) and iNOS with Western blotting.

RESULTSThe apoptosis rate and expression levels of total-p38, p-p38, iNOS in IMECs all increased after LPS exposure. Pravastatin, SB203580, and their combination significantly attenuated LPS-induced enhancement of cell apoptosis and total-p38, p-p38, and iNOS expressions in IMECs.

CONCLUSIONLPS-induced inflammatory toxicity in IMECs is associated with the activation of P38MAPK and iNOS/NO signaling pathways. Pravastatin can inhibit these pathways and suppress the apoptosis and necrosis of IMECs to relieve the cell inflammatory injuries.

Animals ; Apoptosis ; Endothelial Cells ; drug effects ; metabolism ; Endothelium, Vascular ; cytology ; Inflammation ; Islets of Langerhans ; blood supply ; MAP Kinase Signaling System ; drug effects ; Mice ; Nitric Oxide Synthase Type II ; metabolism ; Phosphorylation ; Pravastatin ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; metabolism

Pannexin-1 (Panx1) forms nonselective large channel in cell plasma membrane and has been shown to be associated with NLRP3 inflammasome activation, ATP release and phagocytes recruitment. In the current study, by manipulation of Panx1 expression in human myeloid cells and application of Panx1 deficient mice, we failed to find a correlation between Panx1 and NLRP3 inflammasome activation, although an interaction between these two proteins was evident. However, in thioglycollate induced peritonitis, Panx1 deficient mice showed much more phagocytes infiltration. Further analyses showed that mice deficient for Panx1 exhibited enlarged F4/80(low)Gr1(-)Ly6C(-)cell population in the peritonea. Our study thus reveals an important role for Panx1 in regulation of peritoneal cell population and peritonitis development.
Animals ; Carrier Proteins ; metabolism ; Cell Line ; Connexins ; antagonists & inhibitors ; deficiency ; genetics ; metabolism ; HEK293 Cells ; Humans ; Inflammasomes ; metabolism ; Macrophages ; cytology ; metabolism ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nerve Tissue Proteins ; antagonists & inhibitors ; deficiency ; genetics ; metabolism ; Peritoneal Cavity ; cytology ; Peritonitis ; chemically induced ; metabolism ; pathology ; RNA Interference ; RNA, Small Interfering ; metabolism ; Thioglycolates ; toxicity