Objective:To evaluate the role of interferon regulatory factor 3 (IRF3) in renal fibrosis in a mouse model of renal ischemia-reperfusion injury.Methods:Twelve male C57BL/6J wild-type mice and 12 macrophage IRF3 conditional knockout C57BL/6J mice, aged 8-10 weeks, weighing 20-25 g, were divided into 2 groups ( n=6 each) using a random number table method: wild-type sham operation group (WT-Sham group) and wild-type renal ischemia-reperfusion injury group (WT-I/R group); IRF3 conditional knockout sham operation group (cKO-Sham group) and IRF3 conditional knockout I/R group (cKO-I/R group). The model of renal I/R injury was established by occluding bilateral renal pedicles for 45 min followed by reperfusion in anesthetized animals. The orbital blood samples and renal tissues were collected at 14 days of reperfusion for determination of the concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in serum, expression of fibronectin, collagen-I, alpha-smooth muscle actin (α-SMA) (by immunofluorescence), F4/80-α-SMA double positive cell count, and mRNA expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in renal tissues (by real-time polymerase chain reaction) and for observation of pathological changes which were scored. The area of renal fibrosis was measured. Results:For two types of mice, compared with group Sham, the levels of serum BUN and Cr, area of renal fibrosis and renal injury score were significantly increased, the expression of fibronectin, COL-Ⅰ and α-SMA protein and IL-6, IL-1β, TNF-α and TGF-β1 mRNA was up-regulated, and the F4/80-α-SMA dual positive cell count was increased in group WT-I/R ( P<0.05). Compared with group WT-I/R, the concentrations of BUN and Cr in serum, area of renal fibrosis and renal injury score were significantly decreased, the expression of fibronectin, COL-Ⅰ and α-SMA protein and IL-6, IL-1β, TNF-α and TGF-β1 mRNA was down-regulated, and the F4/80-α-SMA dual positive cell count was decreased in cKO-I/R group ( P<0.05). Conclusions:IRF3 is involved in the process of renal fibrosis in a mouse model of renal ischemia-reperfusion injury, and the mechanism may be associated with the promotion of inflammatory responses and the transformation of macrophages into myofibroblasts.

Objective:To evaluate the role of interferon regulatory factor 3 (IRF3) in renal fibrosis in a mouse model of renal ischemia-reperfusion injury.Methods:Twelve male C57BL/6J wild-type mice and 12 macrophage IRF3 conditional knockout C57BL/6J mice, aged 8-10 weeks, weighing 20-25 g, were divided into 2 groups ( n=6 each) using a random number table method: wild-type sham operation group (WT-Sham group) and wild-type renal ischemia-reperfusion injury group (WT-I/R group); IRF3 conditional knockout sham operation group (cKO-Sham group) and IRF3 conditional knockout I/R group (cKO-I/R group). The model of renal I/R injury was established by occluding bilateral renal pedicles for 45 min followed by reperfusion in anesthetized animals. The orbital blood samples and renal tissues were collected at 14 days of reperfusion for determination of the concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in serum, expression of fibronectin, collagen-I, alpha-smooth muscle actin (α-SMA) (by immunofluorescence), F4/80-α-SMA double positive cell count, and mRNA expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in renal tissues (by real-time polymerase chain reaction) and for observation of pathological changes which were scored. The area of renal fibrosis was measured. Results:For two types of mice, compared with group Sham, the levels of serum BUN and Cr, area of renal fibrosis and renal injury score were significantly increased, the expression of fibronectin, COL-Ⅰ and α-SMA protein and IL-6, IL-1β, TNF-α and TGF-β1 mRNA was up-regulated, and the F4/80-α-SMA dual positive cell count was increased in group WT-I/R ( P<0.05). Compared with group WT-I/R, the concentrations of BUN and Cr in serum, area of renal fibrosis and renal injury score were significantly decreased, the expression of fibronectin, COL-Ⅰ and α-SMA protein and IL-6, IL-1β, TNF-α and TGF-β1 mRNA was down-regulated, and the F4/80-α-SMA dual positive cell count was decreased in cKO-I/R group ( P<0.05). Conclusions:IRF3 is involved in the process of renal fibrosis in a mouse model of renal ischemia-reperfusion injury, and the mechanism may be associated with the promotion of inflammatory responses and the transformation of macrophages into myofibroblasts.

Objective:To analyze the influencing factors of prognosis of early mixed signet ring cell carcinoma (SRCC) of the stomach with signet ring cell ratio less than 50%.Methods:The clinical data of 110 patients with SRCC who underwent radical resection of gastric cancer in the First People's Hospital of Ziyang from January 2014 to December 2016 were retrospectively analyzed. The postoperative pathology was confirmed as mixed SRCC of the stomach with signet ring cell ratio less than 50%. The patients were followed up, and the end point of the follow-up was all-cause death. The prognostic influencing factors of SRCC patients were analyzed.Results:The median follow-up time was 32.5 months (0.9-70.0 months), with the median overall survival (OS) time of 40.0 months (7.0-61.0 months) and the 3-year OS rate of 46.5%. Kaplan-Meier survival analysis showed that the 3-year OS rate of age ≥60 years, male, upper stomach, tumor diameter ≥5 cm, invasion of the gastric wall, lymph node metastasis, and vascular invasion of mixed SRCC of the stomach patients was 34.3%, 31.1%, 30.0%, 33.3%, 40.7%, 28.9%, 37.5%, respectively, which was all lower than that of those with age <60 years old, female, lower stomach, tumor diameter <5 cm, non-invasive whole stomach wall, no lymph node metastasis, no vascular invasion (57.6%, 57.5%, 52.9%, 57.6%, 56.7%, 74.6%, 62.3%), and there was no statistically significant difference (all P < 0.05). Cox multivariate results showed that age ≥60 years old ( OR = 1.225, 95% CI 1.089-3.481, P = 0.003), lymph node metastasis ( OR = 1.077, 95% CI 1.059-2.674, P = 0.034), invasion of the whole stomach wall ( OR = 1.342, 95% CI 1.117-7.225, P = 0.002), and vascular invasion ( OR = 1.104, 95% CI 1.087-2.541, P = 0.018) were independent factors affecting OS of mixed SRCC of the stomach. Conclusion:Mixed SRCC of the stomach patients with signet ring cell ratio less than 50% featured by advanced age, lymph node metastasis, invasion of the full thickness of the stomach wall, and vascular invasion have a poor prognosis.