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Acute kidney injury (AKI) with maladaptive tubular repair leads to renal fibrosis and progresses to chronic kidney disease (CKD). At present, there is no curative drug to interrupt AKI-to-CKD progression. The nuclear factor of the activated T cell (NFAT) family was initially identified as a transcription factor expressed in most immune cells and involved in the transcription of cytokine genes and other genes critical for the immune response. NFAT2 is also expressed in renal tubular epithelial cells (RTECs) and podocytes and plays an important regulatory role in the kidney. In this study, we investigated the renoprotective effect of 11R-VIVIT, a peptide inhibitor of NFAT, on renal fibrosis in the AKI-to-CKD transition and the underlying mechanisms. We first examined human renal biopsy tissues and found that the expression of NFAT2 was significantly increased in RTECs in patients with severe renal fibrosis. We then established a mouse model of AKI-to-CKD transition using bilateral ischemia-reperfusion injury (Bi-IRI). The mice were treated with 11R-VIVIT (5 mg/kg, i.p.) on Days 1, 3, 10, 17 and 24 after Bi-IRI. We showed that the expression of NFAT2 was markedly increased in RTECs in the AKI-to-CKD transition. 11R-VIVIT administration significantly inhibited the nuclear translocation of NFAT2 in RTECs, decreased the levels of serum creatinine and blood urea nitrogen, and attenuated renal tubulointerstitial fibrosis but had no toxic side effects on the heart and liver. In addition, we showed that 11R-VIVIT administration alleviated RTEC apoptosis after Bi-IRI. Consistently, preapplication of 11R-VIVIT (100 nM) and transfection with NFAT2-targeted siRNA markedly suppressed TGFβ-induced HK-2 cell apoptosis in vitro. In conclusion, 11R-VIVIT administration inhibits IRI-induced NFAT2 activation and prevents AKI-to-CKD progression. Inhibiting NFAT2 may be a promising new therapeutic strategy for preventing renal fibrosis after IR-AKI.

Renal fibrosis is the final common pathway of all chronic kidney diseases progressing to end-stage renal diseases. Autophagy, a highly conserved lysosomal degradation pathway, plays important roles in maintaining cellular homeostasis in all major types of kidney cells including renal tubular cells as well as podocytes, mesangial cells and endothelial cells in glomeruli. Autophagy dysfunction is implicated in the pathogenesis of various renal pathologies. Here, we analyze the pathological role and regulation of autophagy in renal fibrosis and related kidney diseases in both glomeruli and tubulointerstitial compartments. Further research is expected to gain significant mechanistic insights and discover pathway-specific and kidney-selective therapies targeting autophagy to prevent renal fibrosis and related kidney diseases.

when the ballast track stretch with the bridge, ballast which is near expansion joint will move confusedly. As a result, rail produced vertical deformation. The deformation will affect the running safety and comfortability of train. At present, there are two kinds of treatments which are cover board structure and baffle structure to deal ballast’s movement. Aiming at the different modes of stretching when the two kinds of structures and different arrangement condition of bridge plate are applied, the rail-sleeper-ballast discrete element model is developed by the method of two-dimensional granular flow. The relationship between rail deformation and bridge expansion is analyzed on the foundation of the model. Results show as flows: when bridge extends or shortens, rail always produced upwarp deformation. Bridge plate should arrange asymmetrically. Like this, the rail deformation decrease by 40%. And adopting the baffle structure can effectively reduce the influence of bridge expansion in ballast truck.

To investigate the impact of heart valve calcification (HVC) on cardiovascular outcomes in patients on maintenance hemodialysis (MHD).We enrolled 302 Chinese patients on MHD between 2009 and 2011 including 99 with HVC identified by echocardiography screening. All the patients were followed up for 2 years and survival analysis was performed with all-cause mortality, cardiovascular mortality and new onset cardiovascular events as the endpoints. Cox regression analysis was used for analyzing the impact of heart valve calcification on the cardiovascular outcomes of the patients.The mean age of the total patients was 58.2∓15.0 years when receiving the initial MHD, and 53.6% were male patients. The overall mortality, cardiovascular mortality and new on-set cardiovascular events in HVC and non-HVC groups were 30.3% vs 16.3%, 22.2% vs 6.9%, and 48.5% vs 25.6%, respectively (P0.05). Kaplan-Meier survival analysis showed a significant difference in all-cause mortality (P=0.006), cardiovascular mortality (P0.001) and new-onset cardiovascular events (P0.001) between HVC and non-HVC groups. After adjustment, Cox regression analysis identified HVC as a risk factor for increased all-cause mortality (HR=1.88; 95%CI: 1.11-3.19), cardiovascular mortality (HR=3.47, 95%CI: 1.76-6.84) and cardiovascular events (HR=1.64, 95% CI: 1.09-2.47).HVC is an independent risk factor for increased cardiovascular mortality and new cardiovascular events in patients on MHD.

The prognosis of acute kidney injury (AKI) is often adverse but varies markedly, underlying the need in clinical decision-making for biomarkers that, individually, stratify risk. At present, only a few biomarkers of AKI have the limited dual function of diagnostic and prognostic stratification, one of which is urine neutrophil gelatinase-associated lipocalin. Currently, the most feasible approach to clinically managing patients with AKI is to combine the predictive functions of several markers in order to diagnose AKI and predict short-term prognosis. Biomarkers for assessing the long-term prognosis of AKI remain to be identified.

To explore the incidence and possible risk factors of restless legs syndrome (RLS) in the maintenance hemodialysis patients.A total of 375 maintenance hemodialysis patients were enrolled in this study from September 1 to 30 in 2012. The diagnosis and assessment of severity were based on the International Restless Leg Syndrome Study Group (IRLSSG) standard. The relevant laboratory parameters and dialysis indicators were collected, such as hemoglobin, serum ferritin, parathyroid hormone, blood flow and dialysis mode. The clinical data were analyzed by multivariate logistic regression method.The incidence of RLS was 13.3% with the severity score of 18.69 ± 0.95. The logistic regression analysis showed that anuria (OR 0.292, 95%CI 0.114-0.750) and β2 microglobulin (OR 1.023, 95%CI 1.003-1.044) were the risk factors for RLS in the maintenance hemodialysis patients, while hemoglobin, serum iron and parathyroid hormone were not correlated with RLS.The incidence of RLS is high in the maintenance hemodialysis patients. The risk factors of RLS are anuria and β2 microglobulin. Therefore, the preservation of residual renal function and the improvement of dialysis adequacy, especially the removal of the middle molecular weight toxins, may reduce the occurrence of RLS and improve the quality of life in the hemodialysis patients.

To explore the influence of early postoperative use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) or diuretics on acute kidney injury (AKI) after cardiac surgery in elderly patients.Data from elderly patients (age≥60 years old) who underwent cardiac surgery with extracorporeal circulation in Guangdong General Hospital between January 2007 and December 2010 were analyzed in this retrospective research. The primary endpoint was AKI as diagnosed according to the serum creatinine criteria of RIFLE (risk, injury, failure, loss, end stage renal disease). The baseline serum creatinine was defined as the latest serum creatinine level before cardiac surgery. Multivariate analysis by logistic regression was used to obtain the independent risk factors for AKI.Among 618 elderly patients, 76 (12.3%) patients received ACEI/ARB during early postoperative period, 491 (79.4%) patients were given diuretics during early postoperative period, and postoperative AKI occurred in 394 (63.8%) patients. The incidence of AKI was 46.1% in patients who received early postoperative ACEI/ARB, and 66.2% in patients who did not (P0.001). Patients who received diuretics postoperatively were less likely to suffer from AKI compared with patients who did not (57.0% vs. 89.8%, P0.001). After adjustment of other potential factors of postoperative AKI, logistic regression analysis showed that early postoperative use of ACEI/ARB [odds ratio (OR)=0.131, 95% confidence interval (95%CI) 0.033-0.517, P=0.004], and early postoperative use of diuretics (OR=0.149, 95%CI 0.076-0.291, P0.001) independently predicted the occurrence of AKI.Early postoperative use of ACEI/ARB or diuretics is associated with a lower incidence of AKI after cardiac surgery with extracorporeal circulation in elderly patients.

To evaluate the sensitivity/accuracy of 2 different acute kidney injury (AKI) diagnosis/classification criteria, the RIFLE (risk, injury, failure, loss of kidney function, end-stage kidney disease) and the acute kidney injury network (AKIN), for patients in intensive care unit (ICU).Clinical data were collected from all adult patients admitted to the Department of Intensive Medicine in Guangdong General Hospital between October 2009 and July 2010, and AKI cases were identified/classified using RIFLE and AKIN criteria separately, for statistical evaluation of their diagnostic sensitivity, and accuracy in hospital mortality prediction.In all 524 patients evaluated, AKI were identified by RIFLE criteria in 95 of them, while by AKIN, 135. The AKI incidence by RIFLE (18.1%), and AKIN (25.8%) were significantly different (P0.05). Meanwhile, AKI incidence was found independent from the mortality, either by RIFLE or AKIN (both P0.001). In all patients, the area under the receiver operator characteristic curve (ROC curve), the index for hospital mortality prediction, was 0.7293 for RIFLE [with 95% confidence interval (95%CI) ranging from 0.6005 to 0.8581, P0.001], and for AKIN, 0.7777 (95%CI: 0.6664 - 0.8890, P0.001). No significant difference was found between the total hospital mortality by the two criteria (37.9% vs. 34.1%, P0.05).Although AKIN criteria has higher sensitivity in AKI diagnosis, it is not different from the RIFLE criteria in predicting hospital mortality in critically ill patients.

To investigate the prevalence of cardiovascular diseases (CVD) in patients with systemic lupus erythematosus (SLE) and estimate the associated risk factors for CVD.This cross-sectional study was conducted in 879 SLE patients treated in our hospital between March, 2006 and March, 2011. The demographic data and the clinical data including SLE duration, therapeutic regimen, renal pathological data, estimated glomerular filtration rate (eGFR), SLE Disease Activity Index (SLEDAI), and associated biochemical parameters were analyzed. Cardiovascular ultrasound was used for detecting and analyzing the cardiovascular structural and functional abnormalities.Eighty-five cases of CVD were found in the 879 SLE cases (9.7%). After age stratification, CVD was identified in 5.8%, 9.0%, 14.0% and 20.0% in SLE patients aged ≤19, 20-39, 40-59 and ≥60 years, respectively, showing a tendency to increase with age (P=0.002). The prevalence of CVD differed significantly between patients with and those without lupus nephritis (P=0.001). Among the 85 patients with CVD, 23.5% (20/85) had left ventricular hypertrophy, 49.5% (42/85) had congestive heart failure, 20.0% (17/85) had stroke, 3.5% (3/85) had angina pectoris, and 3.5% (3/85) had peripheral CVD. Compared to those without CVD, patients with CVD had a longer SLE duration (P=0.002), a longer time of steroids treatment (P=0.026), a higher blood pressure (P=0.0006), a lower eGFR (P=0.001), and a lower concentration of HDL (P=0.007). Logistic regression analysis showed that SBP, eGFR, HDL, SLE duration, SLEDAI index, serum C3 and hs-CRP were the risk factors for CVD in SLE patients (P=0.033).SLE is associated with a high risk of CVD which increases with age, and SLE patients with lupus nephritis have an even higher risk for CVD. SBP, eGFR, HDL, SLE duration, SLEDAI index, serum C3 and hs-CRP are the risk factors for CVD in SLE patients.

To explore the changes in the clinicopathological features of patients with IgA nephropathy with elevated uric acid level.A total of 171 patients with IgA nephropathy diagnosed at biopsy were classified into 3 groups, namely normotensive group with normal level uric acid (group 1), normotensive group with elevated uric acid level (group 2), and hypertensive group with elevated uric acid level (group 3). The clinicopathological features were compared between the 3 groups.From group 1 to group 3, the disease duration became elongated, body weight increased, systolic and diastolic pressures elevated, blood urea nitrogen and serum creatinine increased, glomerular filtration rate decreased, and 24-h urine protein increased; the apolipoprotein A, high-density lipoprotein and albumin levels decreased, while apolipoprotein B100, triglyceride, cholesterol and low-density lipoprotein increased. The glomerular damage, tubulointerstitial lesions and arteriole hypertrophy worsened, and Lee's grade III changes were predominant in group 1, grade III or IV in group 2 and grades III-V in group 3. Mesangial proliferative glomerulonephritis was the major pathological type in groups 1 and 2, as compared with focal segmental glomerulonephritis or sclerosing glomerulonephritis in group 3.Patients with IgA nephropathy and elevated uric acid level have greater clinicopathological damage than those with normal uric acid level, and hypertension further aggravates such damages.

1. Accumulating evidence suggests that vitamin D and its analogues are renoprotective. However, the precise mechanisms and the molecular targets by which active vitamin D exerts its beneficial effects remain obscure. The objective of the present study was to evaluate the effect of active vitamin D on rats with puromycin aminonucleoside (PAN) nephropathy, a model that is characterized by predominant podocyte injury. 2. The PAN nephropathy rats were created by a single intravenous injection of 100 mg/kg PAN. Changes in renal pathology and podocyte numbers were observed. Real-time polymerase chain reaction (PCR) was performed to examine mRNA expression of nephrin, transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP)-7. Protein expression of nephrin, TGF-beta1, BMP-7 and p-Smad2/3 and p-Smad1/5/8 was examined by immunofluorescence, immunohistochemistry and western blotting, respectively. Rats were treated with 1,25(OH)(2)D(3) by gastric gavage at a dose of 2.5 microg/kg per day, starting 2 days before PAN injection and continuing throughout the experiment. 3. A single injection of PAN induced massive proteinuria and elevated serum creatinine on Day 7, both of which were significantly suppressed by 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Immunofluorescence and real-time PCR of the podocyte-associated protein nephrin revealed reduced and discontinuous staining and this change was reversed by 1,25(OH)(2)D(3). In PAN nephropathy rats, TGF-beta1 and p-Smad2/3 expression was upregulated, whereas that of BMP-7 and p-Smad1/5/8 was downregulated. Treatment with 1,25(OH)(2)D(3) significantly restored BMP-7/Smad signalling while suppressing TGF-beta1/Smad signalling. 4. In conclusion, 1,25(OH)(2)D(3) can ameliorate podocyte damage and proteinuria induced by PAN. The beneficial effects of 1,25(OH)(2)D(3) on podocytes may be attributable, in part, to direct modulation of TGF-beta1/BMP-7 signalling.

To evaluate efficacy and safety of coupled plasma filtration adsorption (CPFA) combined with continuous veno-venous hemofiltration (CVVH) for the treatment of multiple organ dysfunction syndrome (MODS) patients with acute liver failure (ALF), and to evaluate the effect of CPFA plus CVVF on inflammatory mediators in these patients.A total of 38 cases of 11 MODS patients with ALF (male 6, female 5) were treated with CPFA plus CVVH, and the following clinical indicators including changes in mean arterial pressure (MAP), oxygen index (PaO(2)/FiO(2)), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, IL-8, biochemical parameters of liver and kidney function, parameters of systemic inflammatory response syndrome (SIRS) score, and acute physiology and chronic health evaluation II (APACHE II) score were determined before and after the treatment. The degree of improvement in clinical symptoms, feasibility, tolerance toward CPFA plus CVVH, therapy-related adverse reactions and security were simultaneously evaluated.MAP increased by 12 mmHg (1 mmHg=0.133 kPa), and PaO(2)/FiO(2) increased by 40 mmHg after the application of CPFA plus CVVH (both P0.05), along with significant decrease in TNF-alpha, IL-1 beta, IL-6, IL-8 and markedly lowered levels of serum total bilirubin (IBIL), direct bilirubin (DBIL), blood urea nitrogen (BUN), serum creatinine (SCr) and blood ammonia (all P0.05). Besides, clinical symptoms, including urinary volume, mental disturbance, jaundice, debility, nausea, vomiting, fever, abdominal distention, anepithymia, and SIRS, APACHE II scores were improved significantly after the CPFA plus CVVH (all P0.05). No therapy-related adverse reactions, including severe haemorrhage, shock, hypersensitivity, were noted, and patients tolerated well toward CPFA plus CVVH. The total survival rate of patients was 45.5% (5/11 cases) at the end of the treatment.Our data indicate that CPFA combined with CVVH is an effective and safe method to improve the prognosis of MODS patients with ALF, the mechanism of which may be related to its effective removal of inflammatory cytokines.

To determine bacterial endotoxin in the replacement solution of on-line hemodiafiltration (on-line HDF) using kinetic turbidimetric limulus test.Validation test was performed with the replacement solution of on-line HDF in which quantified standard endotoxin was added. The recovery rates of endotoxin from the replacement solution and its dilutions at 1/5, 1/10, and 1/20 were 58.17%, 106.7%, 99.00% and 98.79%, respectively, suggesting that the optimal dilution was at 1/10. Standard endotoxin was added into the replacement solution of on-line HDF of 3 batches (040408, 040511,040527), and the recovery rates in their dilution at 1/10 were 76.32%, 99.00% and 96.24%, respectively. The standard endotoxin in the working curve was 1.00, 0.125, and 0.0156 Eu/ml (endotoxin unit/ml), and the dilution at 1/10 of the replacement solution is effective to eliminate the interference in limulus test.Kinetic turbidimetric limulus test provide a means to detect endotoxin in the replacement solution of on-line HDF.

To investigate the value of emergency hysterectomy on arresting severe postpartum hemorrhage.A retrospective analysis was performed on 10 cases of hysterectomy by reason of postpartum hemorrhage between Jan 1990 and Dec 2000.All the patients were severe postpartum hemorrhage that couldn't be controlled by conservative treatment. Among them, there were 5 cases of DIC, 2 cases of placental adherence, 1 case each of uterine atony, uterine rupture and infection of uterine incision. Blood loss averaged 2,427 ml. All the 10 patients were recovered. Emergency hysterectomy was related to times of gestation and delivery and also to delivery pattern.Emergency hysterectomy is one of the effective methods on arresting severe postpartum hemorrhage.