Objective To investigate the role and mechanism of urate in chronic kidney disease complicated with renal interstitial fibrosis(CKD-RIF).Methods Mice were continuously fed with a diet containing 0.2％adenine for a duration of 9 weeks to establish mice models with CKD-RIF.By the end of the 9-week experimental periods,collected blood samples from the posterior orbital venous plexus of mice to measure renal functions and serum urate concentrations prior to euthanizing the mice.Hematoxylin-eosin(HE)staining and periodic acid-Schiff staining(PAS)were used to investigate the pathological alternations in kidney tissues.Masson's trichrome staining was used to observe the extent of renal fibrosis.Urate staining was used to detect urate deposition in renal tissues.Western blot and immunohistochemistry were used to detect the expression of target molecules.Scratch tests were used to ex-amine the migration abilities of cells treated with different concentrations of uric acid.Results The kidney function analysis showed that a significant increase in the levels of serum urea nitrogen(P=0.006 4),creatinine(P=0.008 0)and urate(P=0.000 7)in the CKD-RIF mice compared with the normal control group.The results of HE staining and PAS staining showed a significance of renal tubule injury and infiltration of inflammatory cells in the model group.Masson's trichrome staining showed that a marked increase in collagen deposition in the model group.The results of urate staining showed a significant presence of urate crystals in kidney tissue of the model group when compared to the control group.Animal tissue immunoblotting and immunohistochemistry analysis showed a significant increase in the expression levels of vimentin,α-SMA and TGF-β1 in the model group in comparison to the control group.Conversely,in the model group,E-cadherin levels exhibited a dramatic reduction compared to the control group.The findings from the scratching tests showed that uric acid significantly enhanced cell migration.Western blot analysis showed a dramatic increase in the expression levels of vimentin and α-SMA,while E-cadherin exhibited significant decrease in the cells subjected to uric acid treatment.Conclusion Urate stimulates the secre-tion of TGF-β1 by renal tubule epithelial cells and induces epithelial-mesenchymal transdifferentiation,thereby ex-acerbating renal interstitial fibrosis in CKD.

Objective:To evaluate the effects of different doses of dexmedetomidine infused at nighttime on early postoperative cognitive dysfunction (POCD) in elderly patients undergoing radical resection of malignant gastrointestinal tumors.Methods:Eighty American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients of either sex, aged 65-75 yr, with body mass index of 18-24 kg/m 2, scheduled for elective radical resection of malignant gastrointestinal tumors, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C) and different doses of dexmedetomidine groups (D 1-3 groups). Dexmedetomidine 0.1, 0.2 and 0.3 μg·kg -1·h -1 (infusion rate 4 ml/h) were intravenously infused from 21: 00 on the day of surgery and the first day after surgery until 6: 00 in the next morning.Normal saline was given instead of dexmedetomidine in group C. The period of sleep and the number of awakening at night were recorded before surgery and at 2 and 7 days after surgery.Cognitive function was assessed at 1 day before surgery and 7 days after surgery.The concentrations of plasma cortisol were measured at 16: 00 before surgery and 2 and 7 days after surgery and at 8: 00 in the corresponding morning of the next day.The difference in the plasma cortisol concentration measured at 8: 00 every day and at 16: 00 of the previous day were calculated. Results:The incidence of POCD was significantly lower in D 2, 3 groups than in group C ( P<0.05). The number of awakening at night was significantly decreased at 2 days after surgery in group D 3 as compared with the other three groups ( P<0.05). The difference in the plasma cortisol concentration was significantly decreased at 2 and 7 days after surgery in D 2, 3 groups when compared with group C and group D 1 ( P<0.05). Compared with group D 2, no significant change was found in the difference in the plasma cortisol concentration at each time point in group D 3 ( P>0.05). There were no significant differences in the incidence of hypotension, hypertension, bradycardia, and tachycardia among the four groups ( P>0.05). Conclusion:Infusing dexmedetomidine 0.2 or 0.3 μg·kg -1·h -1 at the nighttime can reduce the development of POCD in the elderly patients undergoing radical resection of malignant gastrointestinal tumors.

Objective: To investigate the role and mechanism of Sigirr deletion in chronic kidney disease complicated with renal interstitial fibrosis (CKD⁃RIF) in mice. Methods: polymerase chain reaction (PCR) was used for identification of gene types of mice. Mice were continuously fed with the foods containing 0. 2% adenine for 12 weeks to establish the CKD⁃RIF models. Then , serum was collected to detect levels of creatinine and nitrogen when mice were killed. H&E staining was used to analyze the pathological changes of kidney tissues. Masson staining was used to observe the degree of renal fibrosis. Immunohistochemistry was used to detect the changes of the interest proteins , such as IL⁃1β , MyD88 , activated NF⁃κB , TGF⁃ β1 , E ⁃cadherin and Vimentin. Results: Serum creatinines and urea nitrogens of mice fed with high adenine (CKD⁃RIF groups) significantly increased , compared with those of the control groups. H&E and Masson staining results showed that there were more infiltrated inflammatory cells and more critical collagen fiber deposition in the renal tissues of the Sigirr - / - mice with CKD⁃RIF. Western blot and Immunohistochemical analysis showed that the expression of IL⁃1β and its downstream MyD88 increased , and the level of phosphorylated NF⁃κB (p⁃P65) significantly increased in the renal tissues of CKD⁃RIF mice compared with the controls. And upregulation of these proteins in renal tissues of Sigirr - / - mice with CKD⁃RIF was more obvious than that of the CKD⁃RIF Sigirr + / + mice. TGF⁃ β1 , as a key cytokine involved in renal interstitial fibrosis , significantly increased ,followed by the increase of vimentin , as well as the decrease of E ⁃cadherin . The results of vimentin and cadherin E detected by Western blot were consistent with those of immunohistochemistry , and α ⁃SMA also increased significantly. Conclusion Adenine diet successfully induces CKD⁃RIF mice models. Sigirr deletion is beneficial to activation of the IL⁃1β mediating NF⁃κB signal pathway ,which promotes TGF⁃ β1 expression in the renal interstitiums to induce renal interstitial fibrosis.