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Purposes: This study mainly explored the mechanism of capillary leakage caused by hypoxia-inducible factor-1 α through inducing high expression of matrix metalloproteinase-9. Method. We established a monolayer endothelial cell model by culturing human umbilical vein endothelial cells (HUVEC) in vitro, used tumor necrosis factor (TNF α ) and HIF-1 α inhibitor 2-methoxyestradiol (2ME2) to act on HUVEC, and at the same time constructed siRNA-transfected HUVEC to interfere with the expression of HIF-1 α . The permeability of monolayer endothelial cells was measured by transwell chamber method, the concentration of MMP-9 in the supernatant was measured by ELISA method, the expression of key molecules related to permeability (HIF- 1 α , MMP-9, claudin-5, and ZO-1) was measured by RT-PCR and Western blot method, and the localization and expression of claudin-5 and ZO-1 were measured by immunofluorescence method. We searched for 7 HIF-1 α hypoxia response elements within 4000 bp before the transcription start site in the MMP-9 promoter region, constructed the MMP-9 promoter-luciferase reporter gene recombinant plasmid, transfected and stimulated HUVEC with TNF α , and detected the effect of 7 hypoxia response element plasmids on the transcription activity of MMP-9 promoter., Results: Under the action of TNF α , the permeability of monolayer endothelial cells increased, and the concentration of MMP-9 in the cell supernatant increased. 2ME2 and HIF-1 α -siRNA transfection can improve the above situation ( P < 0.05). 2ME2 and HIF-1 α -siRNA transfection can inhibit the high expression of HIF-1 α and MMP-9 caused by TNF α , thereby increasing the expression of claudin-5 and ZO-1 ( P < 0.05). 2ME2 and HIF-1 α -siRNA transfection can reduce the inhibition of TNF α on the expression of cell membrane protein claudin-5 and tight junction protein ZO-1. Element 1, element 5, and element 7 are the sites where HIF-1 α interacts with MMP-9 at the transcription level., Conclusion: This study shows that HIF-1 α can increase the permeability of monolayer epithelial cells by inducing the high expression of MMP-9, leading to capillary leakage. Its target is at the -3798 bp, -1878 bp, and -1489 bp points of the transcription initiation site in the MMP-9 promoter region., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Huili Li et al.)

Objective: To predict the risk of 28- day mortality on septic patients in intensive care unit (ICU) with the combination of the Weighted index of comorbidities (WIC) and sepsis-related organ failure assessment (SOFA) score., Methods: The clinical data of adult sever sepsis/ septic shock patients in Department of Emergency Medicine of Chagzeng Hospital and Department of Clinical Care Medicine of Jinan Military General Hospital from October 2011 to February 2013 were analyzed retrospectively. The etiological factor, past history, having sever sepsis or not were recorded. Age score, WIC score, acute physiology and chronic health evaluation II (APACHE II) score and SOFA score were calculated at or 24 hours after admission. The logistic regression was used and the receiver operating characteristic curve (ROC curve) was drawn to calculate the patients' outcome., Results: In 310 enrolled patients, 223 (71.9%) patients survived and 87 (28.1%) died. Univariate analysis showed the P values of the age score, WIC score, APACHE II score and SOFA score. chronic cardiac insufficiency, type 2 diabetes, cerebrovascular disease, tumor, multiple injury, pulmonary infection and having severe sepsis or not were all less tha 0.2. The above 11 variables were put into the multivariate logistic regression equation 1, of which predicted probability was reserved. It revealed that 5 variables were independently associated with 28-day prognosis, of which influence power in descending order were SOFA score [odds ratio (OR)=1.308, 95 % confidence interval (95% CI): 1.158-1.478, P=0.000], having sever sepsis or not (OR=0.206, 95% Cl:0.100-0.424, P=0.000), APACHE II score (OR=1.090, 95% CI:1.021-1.164, P=0.010) WIC score (OR=1.441, 95% CI:1.067-1.947, P=0.017) age score (OR=1.228, 95% CI:1.027-1.468, P=0.024), the Wals were 18.554, 18.369, 6.725, 5.662, 5.067, respectively. The 3 variables, age score, WIC score and SOFA score, were brought into the multivariate logistic regression equation 2, of which predicted probability was reserved too. It revealed that age score (OR=1.330, 95 % CI: 1.145-1.546, P=0.000), WIC score (OR=1.496, 95% CI: 1.145-1.546, P=000) and SOFA score (OR=1.429, 95% CI: 1.303-1.567, P=0.000), were independently associated with the septic patients’ 28-day prognosis. There was no significant difference in the area under receiver operating characteristics curve (AUC) between the SOFA score and APACHE II score (0.784 vs. 0.780, Z=0.014, P=0.989). However, compared with APACHE II score, the AUC of equation 1 (0.888) and 2 (0.851) were much more (Z=4.333, P= 0.000; Z= 2.669, P= 0.008)., Conclusion: The sensitivity of 28-day prognosis 28-day prognosis by WIC score was improved greatly with the combination of SOFA score and age score.