Risk factors on admission associated with hospital length of stay in patients with COVID-19: a retrospective cohort study.

Treating patients with COVID-19 is expensive, thus it is essential to identify factors on admission associated with hospital length of stay (LOS) and provide a risk assessment for clinical treatment. To address this, we conduct a retrospective study, which involved patients with laboratory-confirmed COVID-19 infection in Hefei, China and being discharged between January 20 2020 and March 16 2020. Demographic information, clinical treatment, and laboratory data for the participants were extracted from medical records. A prolonged LOS was defined as equal to or greater than the median length of hospitable stay. The median LOS for the 75 patients was 17 days (IQR 13-22). We used univariable and multivariable logistic regressions to explore the risk factors associated with a prolonged hospital LOS. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated. The median age of the 75 patients was 47 years. Approximately 75% of the patients had mild or general disease. The univariate logistic regression model showed that female sex and having a fever on admission were significantly associated with longer duration of hospitalization. The multivariate logistic regression model enhances these associations. Odds of a prolonged LOS were associated with male sex (aOR 0.19, 95% CI 0.05-0.63, p = 0.01), having fever on admission (aOR 8.27, 95% CI 1.47-72.16, p = 0.028) and pre-existing chronic kidney or liver disease (aOR 13.73 95% CI 1.95-145.4, p = 0.015) as well as each 1-unit increase in creatinine level (aOR 0.94, 95% CI 0.9-0.98, p = 0.007). We also found that a prolonged LOS was associated with increased creatinine levels in patients with chronic kidney or liver disease (p < 0.001). In conclusion, female sex, fever, chronic kidney or liver disease before admission and increasing creatinine levels were associated with prolonged LOS in patients with COVID-19.

Urotensin II promotes monocyte chemoattractant protein-1 expression in aortic adventitial fibroblasts of rat.

BACKGROUND: Urotensin II (UII), a potent vasoconstrictive peptide, is able to stimulate phenotypic differentiation of adventitial fibroblasts. This study aimed to determine the effect of UII on monocyte chemoattractant protein-1 (MCP-1) expression in rat aortic adventitial fibroblasts, so as to explore possible mechanisms in the development of vascular inflammation. METHODS: Growth-arrested adventitial fibroblasts were incubated in serum-free medium with UII (10(-10)-10(-7) mol/L) and inhibitors of signal transduction pathways for 1 to 24 hours. MCP-1 mRNA and protein expression and secretion were determined by RT-PCR, Western blotting analysis and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: UII dose- and time-dependently promoted MCP-1 mRNA and protein expression and secretion in cells, with maximal effect at 10(-8) mol/L at 3 hours for mRNA expression, 24 hours for protein expression in the cells, and 12 hours for protein secretion from the cells. Furthermore, the UII effects were significantly inhibited by treatment with its receptor antagonist SB710411, Rho kinase inhibitor Y27632, protein kinase C (PKC) inhibitor H7, mitogen-activated protein kinase inhibitor PD98059, calcineurin inhibitor cyclosporine A, and the Ca(2+)channel blocker nicardipine. CONCLUSION: UII may stimulate MCP-1 expression in rat aortic adventitial fibroblasts through its receptor and Rho kinase, PKC, mitogen-activated protein kinase, calcineurin and Ca(2+) channel signal transduction, thus contributing to adventitial inflammation.

Osteopontin is involved in urotensin II-induced migration of rat aortic adventitial fibroblasts.

Recent studies suggest that both osteopontin and urotensin II (UII) play critical roles in vascular remodeling. We previously showed that UII could stimulate the migration of aortic adventitial fibroblasts. In this study, we examined whether osteopontin is involved in UII-induced migration of rat aortic adventitial fibroblasts and examined the effects and mechanisms of UII on osteopontin expression in adventitial fibroblasts. Migration of adventitial fibroblasts induced by UII could be inhibited significantly by osteopontin antisense oligonucleotide (P<0.01) but not sense or mismatch oligonucleotides (P>0.05). Moreover, UII dose- and time-dependently promoted osteopontin mRNA expression and protein secretion in the cells, with maximal effect at 10(-8)mol/l at 3h for mRNA expression or at 12h for protein secretion (both P<0.01). Furthermore, the UII effects were significantly inhibited by its receptor antagonist SB710411 (10(-6)mol/l), and Ca(2+) channel blocker nicardipine (10(-5)mol/l), protein kinase C (PKC) inhibitor H7 (10(-5)mol/l), calcineurin inhibitor cyclosporine A (10(-5)mol/l), mitogen-activated protein kinase (MAPK) inhibitor PD98059 (10(-5)mol/l) and Rho kinase inhibitor Y-27632 (10(-5)mol/l). Thus, osteopontin is involved in the UII-induced migration of adventitial fibroblasts, and UII could upregulate osteopontin gene expression and protein synthesis in rat aortic adventitial fibroblasts by activating its receptor and the Ca(2+) channel, PKC, calcineurin, MAPK and Rho kinase signal transduction pathways.

Transforming growth factor-ß1 involved in urotensin II-induced phenotypic differentiation of adventitial fibroblasts from rat aorta.

BACKGROUND: Urotensin II (UII) is a new vasoconstrictive peptide that may activate the adventitial fibroblasts. Transforming growth factor-ß1 (TGF-ß1) is an important factor that could induce the phenotypical transdifferentiation of adventitial fibroblasts. This study aimed to explore whether TGF-ß1 is involved in UII-induced phenotypic differentiation of adventitial fibroblasts from rat aorta. METHODS: Adventitial fibroblasts were prepared by the explant culture method. TGF-ß1 protein secretion from the cells was determined by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression of α-smooth nuscle actin (α-SM-actin), the marker of phenotypic differentiation from fibroblasts to myofibroblasts, were determined using real-time quantitative RT-PCR (real-time RT-PCR) and Western blotting, respectively. RESULTS: UII stimulated the secretion of TGF-ß1 in cultured adventitial fibroblasts in a time-dependent manner. The secretion reached a peak at 24 hours, was higher by 69.8% (P < 0.01), than the control group. This effect was also concentration dependent. Maximal stimulation was reached at 10(-8) mol/L of UII (P < 0.01), which was increased by 59.9%, compared with in the control group (P < 0.01). The secretion of TGF-ß1 induced by UII was significantly blocked by SB-710411 (10(-7) mol/L), a specific antagonist of UII receptor. In addition, both UII (10(-8) mol/L) and TGF-ß1 significantly stimulated α-SM-actin mRNA and protein expression. Moreover, the α-SM-actin induced by UII was inhibited by the specific neutralizing antibody (20 µg/ml) of TGF-ß1, while the α-SM-actin expression stimulated by TGF-ß1 (20 ng/ml) was inhibited by SB-710411 (10(-7) mol/L), the UII receptor antagonist. CONCLUSION: This study suggests that UII could induce TGF-ß1 secretion in adventitial fibroblasts via UT activation, and TGF-ß1 might be involved in phenotypic differentiation from adventitial fibroblasts into myofibroblasts induced by UII, and TGF-ß1 signaling might be one of the important pathways by which UII is involved in vascular fibrosis.