ObjectiveTo investigate the effects of losartan on angiotensin (Ang)Ⅱ-induced the generation of oxidative stress and expression of transforming growth factor β1(TGF-β1) in rat proximal tubular epithelial cells and to explore its underlying mechanism. MethodsNRK-52E cells, a rat proximal tubular epithelial cell line, were applied to explore the antioxidationand antifibrosis of losartan. The expression of three subunits of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, including p47phox, Nox-4, p22phox, and TGF-β1 were determined by real-time RT-PCR and/or Western blot. The generation of reactive oxygen species (ROS) was measured by DCF fluorescence analysis. Superoxide dismutase (SOD) in the supernatant was measured by colorimetric method. Results10-7 mol/L Ang Ⅱ up-regulated p22prox, p47phox and Nox-4 mRNA and protein expression, and the mRNA increased by 5.57-fold, 5.55-fold and 9.41-fold at 24 h (P<0.01, respectively) and the protein increased by 4.53-fold, 4.17-fold and 6.50-fold at 24 h (P<0.01, respectively) as compared with control. Losartan greatly reduced the mRNA elevation of p22prox, p47phox and Nox-4 by 2.71-fold, 2.18-fold and 5.23-fold (P<0.01, respectively) and reduced the protein elevation by 3.20-fold, 2.30-fold and 4.30-fold (P<0.01, respectively) as compared with control. Losartan also inhibited ROS generation induced by Ang Ⅱ in rat proximal tubular epithelial cells. SOD level in the supernatant was markedly decreased after Ang Ⅱ stimulation, while losartan could increase SOD levels (P<0.01). Furthermore, losartan signficantly inhibited Ang Ⅱ-induced TGF-β1 mRNA up-regulation by 64% (P<0.01). ConclusionsLosartan acts as an anti-oxidative and anti-fibrotic agent via the mechanisms of blocking NADPH oxidase-dependent oxidative stress and inhibiting TGF-β1 expression.

Objective:To analyze the trend relevant factors leading to death and their patterns over a 10-year period in inpatients with connective tissue diseases (CTDs).Methods:All clinical data about death in inpatients with CTDs were retrospectively reviewed between 2005 and 2014 at the Department of Rheumatology and Immunology in Xiangya Hospital of Central South University.Results:In the 10-year time period,the overall hospital mortality was 15.689‰.The disease itself accounted for 44.71% of the total causes of death,infection accounted for 42.94%,and comorbidities accounted for 12.35%.The constituent ratio of deaths and the average hospital mortality caused by the disease itself declined gradually year by year,and the constituent ratio of deaths caused by infection and comorbidities increased gradually year by year (P<0.05).In 2013-2014,infection was the leading cause of death,which accounted for 51.06%.The survival time for CTDs inpatients with interstitial lung disease (ILD) was shorter than that of CTDs inpatients without ILD,and even the risk of death was 1.722 times of the latter.The proportion of deaths caused by the disease itself was the highest in systemic sclerosis and systemic lupus erythematosus,that by infection was the highest in idiopathic inflammatory myopathy (IIM),and that by comorbidities was the highest in rheumatoid arthritis.Conclusion:The proportion of deaths and the hospital mortality in CTDs inpatients caused by the disease itself show a declining trend,while the proportion of deaths caused by infection and comorbidities increase.CTDs patients with ILD have shorter survival time and an increase in risk of death.

Taking nephrotic syndrome as an example, this paper analyzed the autonomy of patients with chronic diseases in medical decision-making, and recognized that patients have autonomy in five dimensions: information, expression, function, decision-making and implementation. Respecting patient autonomy can enable patients to make decisions in their best interests, which is the basis for relevant medical decision-making. However, respecting patient autonomy in medical decision-making of chronic diseases also faces some problems such as limited autonomy of some patients with chronic diseases, poor communication of medical information or lack of resources weakens the autonomy of medical decision-making of patients with chronic diseases, and the difference in health literacy and health management ability affects the play of patient autonomy. Taking the patients with nephrotic syndrome as an example, this paper proposed to recognize the limitations of the autonomy of patients with chronic diseases and flexibly use different ways to respect the autonomy of patients; improve the communication ability and joint decision-making experience of clinical medical staff to fully respect patients’ autonomy; enhance patients’ health literacy and health management ability to realize clinical practice strategy of respect for patients’ autonomy.

To observe the effect of enalapril on the apoptosis of renal tubular epithelial cells in renal interstitial fibrosis rats and to explore the mechanism of enalapril on renal interstitial fibrosis.
 Methods: Twenty-four SD male rats were randomly divided into a sham operation group, a model group and an enalapril group (n=8 in each group). The rats in the model group and the enalapril group underwent the operation of left urethral obstruction to establish the animal model of unilateral urethral obstruction (UUO). Fourteen days later after the operation, all rats were sacrificed and their obstructed kidneys were collected for HE and Masson staining to observe the pathological change of renal tissues. Terminal deoxynucleotidyl transferase-mediated (dUTP) nick end-labeling (TUNEL) staining was used to detect the apoptosis of renal tubular epithelial cells. Immunohistochemistry and Western blotting were used to detect the protein expression of Fas-associated death domain (FADD), apoptotic protease activating factor-1 (APAF-1) and C/EBP homologous protein (CHOP).
 Results: Compared with the sham operation group, the renal interstitial injury index and renal interstitial fibrosis index were significantly increased in the model group (P<0.05). Compared with the model group, the renal interstitial injury index and renal interstitial fibrosis index were both significantly decreased in the enalapril group (P<0.05). Compared with the sham group, the apoptosis rate of renal tubular epithelial cells was increased in the model group (P<0.05); compared with the model group, the apoptosis rate of renal tubular epithelial cells was significantly reduced in the enalapril group (P<0.05). The protein levels of FADD, APAF-1 and CHOP in the model group were significantly elevated than those in the sham group (all P<0.05), which were reversed in presence of enalapril (all P<0.05). 
 Conclusion: Enalapril can alleviate renal interstitial fibrosis through inhibiting apoptosis of renal tubular epithelial cells in UUO rats.
Animals ; Apoptosis ; Enalapril ; Epithelial Cells ; Fibrosis ; Kidney Tubules ; Male ; Rats ; Ureteral Obstruction