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To investigate the effects of apigenin on the injury caused by oxygen and glucose deprivation in neurons and the underlying mechanisms, primary cultured rat hippocampal neurons were incubated with apigenin for 90 min before a 2-h oxygen and glucose deprivation followed by a 24-h reperfusion (OGD/R). Subsequently, cell viability, lactate dehydrogenase (LDH) leakage rate, apoptotic rate of neurons and activity of the sodium pump were assessed. In addition, activity of the sodium pump was also examined in the hippocampus of SD rats injected intraperitoneally with apigenin 90 min before a 10-min global cerebral ischemia/24-h reperfusion. The results showed that cell viability and activity of the sodium pump markedly decreased but LDH leakage rate and apoptotic rate significantly increased in OGD/R-treated neurons. However, pretreatment with apigenin (20-50μmol/L) reversed the changes dose-dependently. Compared to sham controls, activity of the sodium pump was significantly suppressed in global ischemia/reperfusion rats; application of apigenin (200mg/kg) restored the activity of the sodium pump. Furthermore, the neuroprotective effect of apigenin was blocked partly by the sodium pump inhibitor ouabain. Our findings provide the evidence that apigenin has a neuroprotective effect against OGD/R injury and the protective effect may be associated with its ability to improve sodium pump activity.

To investigate the association of clinical and histological characteristics and the development of ESRD in T2DM patients with renal involvement.We conducted a retrospective analysis of clinical and pathologic data from T2DM patients who underwent renal biopsy (n = 120).The mean age, duration of diabetes, and eGFR were 50.9 ± 11.2 years, 92.8 ± 41.3 months, 55.1 ± 42.3 mL/min/1.73 mThe prognosis of DN patients is significantly worse than that of NDRD patients. Compared with glomerular lesions, tubulointerstitial lesions were associated with higher risk for renal death in DN patients.

Atrial structural and electrical remodelling play important roles in atrial fibrillation (AF). Sacubitril/valsartan attenuates cardiac remodelling in heart failure. However, the effect of sacubitril/valsartan on AF is unclear. The aim of this study was to evaluate the effect of sacubitril/valsartan on atrial electrical and structural remodelling in AF and investigate the underlying mechanism of action. Thirty-three rabbits were randomized into sham, RAP, and sac/val groups. HL-1 cells were subjected to control treatment or rapid pacing with or without LBQ657 and valsartan. Echocardiography, atrial electrophysiology, and histological examination were performed. The concentration of Ca2+ and expression levels of calcineurin, NFAT, p-NFAT, Cav1.2, collagen Ⅰ and Ⅲ, ANP, BNP, CNP, NT-proBNP, and ST2 in HL-1 cells, and IcaL in left atrial cells, were determined. We observed that compared to that in the sham group, the atrium and right ventricle were enlarged, myocardial fibrosis was markedly higher, AF inducibility was significantly elevated, and atrial effective refractory periods were shortened in the RAP group. These effects were significantly reversed by sacubitril/valsartan. Compared to that in the sham group, collagen Ⅰ and Ⅲ, NT-proBNP, ST2, calcineurin, and NFAT were significantly up-regulated, while p-NFAT and Cav1.2 were down-regulated in the RAP group, and sacubitril/valsartan inhibited these changes. Ca2+ concentration increased and ICaL density decreased in in vivo and in vitro AF models, reversed by sacubitril/valsartan. Sacubitril/valsartan attenuates atrial electrical remodelling and ameliorates structure remodelling in AF. This study paves the way for the possibility of clinical use of sacubitril/valsartan in AF patients.

An increase in oxidative stress is an important pathological mechanism of heart injury induced by doxorubicin (DOX). Tranilast is an anti-allergy drug that has been shown to possess good antioxidant activity in previous studies. The overexpression and secretion of chymase by mast cells (MCs) increase the pathological overexpression of angiotensin II (Ang II), which plays a crucial role in myocardial hypertrophy and the deterioration of heart disease. The MC stabilizer tranilast (N-(3,4-dimethoxycinnamoyl) anthranilic acid; tran) prevents mast cells from degranulating, which may reduce DOX-induced Ang II synthesis. Therefore, in the present study, we hypothesized that tranilast will protect rats from DOX-induced myocardial damage via its antioxidant activity, thereby inhibiting Ang II expression. Thirty male Wistar rats were divided into three groups (n = 10 in each group) that received DOX, a combination of DOX and tranilast or saline (the control group) to test this hypothesis. Tranilast suppressed chymase expression, reduced Ang II levels and prevented the myocardial hypertrophy and the deterioration of heart function induced by DOX. Based on the findings of the present study, the suppression of chymase-dependent Ang-II production and the direct effect of tranilast on the inhibition of apoptosis and fibrosis because of its antioxidant stress capacity may contribute to the protective effect of tranilast against DOX-induced myocardial hypertrophy.

The human induced pluripotent stem cell (iPSC) line ZJUCHi002-A was established from renal epithelial cells present in urine (urinary cells) collected from an 8-year-old Charcot-Marie-Tooth disease type 2A (CMT2A) patient carrying point mutation in MFN2 (c.752C > T). Urinary cells were reprogrammed by retrovirus vectors containing reprogramming factors: OCT4, SOX2, KLF4 and c-MYC. The pluripotency, capacity of differentiation into 3 germ layers, silence of reprogramming factors and normal karyotype were all confirmed in this study.

We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10(-11), OR = 1.21; rs4227, P = 4.31 × 10(-10), OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10(-14), OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10(-20), OR = 1.34; rs1794275, P = 3.43 × 10(-13), OR = 1.30; rs2523946, P = 1.74 × 10(-11), OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10(-11), OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.

The human iPSC cell line ZJUCHi001-A was established from renal epithelial cells present in urine (urinary cells) harvested from a 2-year-old Charcot-Marie-Tooth disease type 1B (CMT1B) patient carrying point mutation in MPZ (c.292C>T). Urinary cells were reprogrammed by retrovirus vectors containing reprogramming factors: OCT4, SOX2, KLF4 and c-MYC. The pluripotency, capacity of differentiation into 3 germ layers, silence of reprogramming factors and normal karyotype for this cell line were all confirmed in this study.

Chronic liver injury is an important clinical problem which eventually leads to cirrhosis, hepatocellular carcinoma and end-stage liver failure. It is well known that cell damage induced by reactive oxygen species (ROS) is an important mechanism of hepatocyte injure. N-acetylcysteine (NAC), a precursor of glutathione (GSH), is well-known role as the antidote to acetaminophen toxicity in clinic. NAC is now being utilized more widely in the clinical setting for non-acetaminophen (APAP) related causes of liver injure. However, the mechanisms underlying its beneficial effects are poorly defined. Thus, Aim of the present study was to investigate potential hepatic protective role of NAC and to delineate its mechanism of action against carbon tetrachloride (CCl4)-induced liver injury in models of rat. Our results showed that the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as malondialdehyde (MDA) contents decreased significantly in CCl4-induced rats with NAC treatment. GSH content and superoxide dismutase (SOD) activities remarkably increased in the NAC groups compared with those in CCl4-induced group. Treatment with NAC had been shown to an increase in nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA levels. In conclusion, these results suggested that NAC upregulated HO-1 through the activation of Nrf2 pathway and protected rat against CCl4-induced liver injure. The results of this study provided pharmacological evidence to support the clinical application of NAC.

Background The ambulatory arterial stiffness index (AASI) can be used to predict cardiovascular morbidity and mortality in hypertensive patients. However, data on AASI in Chinese patients with chronic kidney disease (CKD) is not available. Methods This cross-sectional study enrolled 583 CKD patients. Univariate and multivariate analyses were used to evaluate the relationship between AASI and renal function and parameters of cardiovascular injury. Results Patients with a higher AASI had a higher systolic blood pressure, a lower estimated glomerular filtration rate (eGFR), a higher serum cystatin C, a higher left ventricular mass index (LVMI) and carotid intima-media thickness (cIMT). Univariate analyses showed that AASI was positively correlated with serum cystatin C (r=0.296, P r=0.182, P r = 0.205, P r = –0.200, P Conclusions These data suggest that AASI was closely correlated with renal function and parameters of cardiovascular injury in Chinese CKD patients. Good quality, long-term, large longitudinal trials to validate the role of AASI in clinical practice for Chinese CKD patients.

Data on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.The survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP140/90 mmHg and130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.The analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to140/90 mmHg and130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P0.001). When the threshold of BP130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P0.05). Using the threshold of140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P0.05).The prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Xun Liu,1,2,* Mu-hua Cheng,3,* Cheng-gang Shi,1 Cheng Wang,1 Cai-lian Cheng,1 Jin-xia Chen,1 Hua Tang,1 Zhu-jiang Chen,1 Zeng-chun Ye,1 Tan-qi Lou11Division of Nephrology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yet-sun University, Guangzhou, China; 2College of Biology Engineering, South China University of Technology, Guangzhou, China; 3Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yet-sun University, Guangzhou, China *These authors contributed equally to this paperBackground: Chronic kidney disease (CKD) is recognized worldwide as a public health problem, and its prevalence increases as the population ages. However, the applicability of formulas for estimating the glomerular filtration rate (GFR) based on serum creatinine (SC) levels in elderly Chinese patients with CKD is limited.Materials and methods: Based on values obtained with the technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA) renal dynamic imaging method, 319 elderly Chinese patients with CKD were enrolled in this study. Serum creatinine was determined by the enzymatic method. The GFR was estimated using the Cockroft–Gault (CG) equation, the Modification of Diet in Renal Disease (MDRD) equations, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the Jelliffe-1973 equation, and the Hull equation.Results: The median of difference ranged from −0.3–4.3 mL/min/1.73 m2. The interquartile range (IQR) of differences ranged from 13.9–17.6 mL/min/1.73 m2. Accuracy with a deviation less than 15% ranged from 27.6%–32.9%. Accuracy with a deviation less than 30% ranged from 53.6%–57.7%. Accuracy with a deviation less than 50% ranged from 74.9%–81.5%. None of the equations had accuracy up to the 70% level with a deviation less than 30% from the standard glomerular filtration rate (sGFR). Bland–Altman analysis demonstrated that the mean difference ranged from −3.0–2.4 mL/min/1.73 m2. However, the agreement limits of all the equations, except the CG equation, exceeded the prior acceptable tolerances defined as 60 mL/min/1.73 m2. When the overall performance and accuracy were compared in different stages of CKD, GFR estimated using the CG equation showed promising results.Conclusions: Our study indicated that none of these equations were suitable for estimating GFR in the elderly Chinese population investigated. At present, based on overall performance, as well as performance in different CKD stages, the CG equation may be the most accurate for estimating GFR in elderly Chinese patients with CKD.Keywords: elderly, equation, glomerular filtration rate, serum creatinine, Chinese

The serum immunoglobulin A (IgA)/C3 ratio has been shown to be a good predictor of histological lesions and prognosis for patients with IgA nephropathy (IgAN) in Japanese. But its validity in the Chinese population is unclear. We sought to explore the long-term outcomes of IgAN, its clinical and histopathological predictors in Chinese patients. In particular, the role of serum IgA/C3 ratio in the course of IgAN was addressed.A total of 217 biopsy-diagnosed IgAN patients were recruited into this prospective cohort with a mean follow-up of 36 months (25-75th percentile, 27-48). Sociodemographics, serum IgA/C3 level, other clinical examinations and Lee's histological grade were measured. The patients with a decline of estimated glomerular filtration rate (eGFR) 50% or developing end-stage renal disease (ESRD) were defined as progression.A total of 21 patients was found to progress (9.7%). In multivariate analysis, renal end point of IgAN was significantly predicted by proteinuria ≥1 g/day (relative risk (RR) = 2.65, 95% confidence interval (CI) 1.01-7.68), hypertension (RR = 3.15, 95% CI 1.07-9.29), higher Lee's histological grade (RR = 4.67, 95% CI 1.43-15.25) and serum IgA/C3 ratio ≥ 3.32 (RR = 4.31, 95% CI 1.33-13.96).A proportion of patients with IgAN developed end stage renal disease in a Chinese group. In addition to some traditional risk factors, we also confirmed that IgA/C3 ratio is a useful predictor of poor outcomes of IgAN in Chinese patients.

Background Perceptions of exercise benefits and barriers affect exercise behavior. Because of the clinical course and treatment, dialysis patients differ from the general population in their perceptions of exercise benefits and barriers, especially the latter. At present, no valid instruments for assessing perceived exercise benefits and barriers in dialysis patients are available. Objectives Our goal was to develop and test the psychometric properties of the Dialysis patient-perceived Exercise Benefits and Barriers Scale (DPEBBS). Methods A literature review and two focus groups were conducted to generate the initial item pool. An expert panel examined the content validity. Then, 269 Chinese hemodialysis patients were recruited by convenience sampling. Exploratory and confirmatory factor analyses were used to test construct validity. Finally, internal consistency and test–retest reliability were assessed. Results The expert panel determined that the content validity index was satisfactory. The final 24-item scale consisted of six factors explaining 57% of the total variance in the data. Confirmative factor analysis supported the six-factor structure and a higher-order model. Cronbach's alpha was 0.87 for the total scale, and 0.84 for test–retest reliability. Conclusion The DPEBBS was a valid and reliable instrument for evaluating dialysis patients' perceived benefits and barriers to exercise. The application value of this scale remains to be investigated by increasing the sample size and evaluating patients undergoing different dialysis modalities and coming from different regions and cultural backgrounds.

To observe the effects of leflunomide on renal pathology and expression of transforming growth factor-beta1 (TGF-beta1), monocyte chemotaxis peptide 1 (MCP-1) in renal tissue of experimental IgA nephropathy in rat.IgA nephropathy model was reproduced in rats. They were randomly divided into leflunomide group, prednisone group, nephropathy control group, and normal control group. The deposition of immunocomplex in renal tissue and degree of mesangial matrix hyperplasia in mesangial region were detected by immunofluorescence and light microscope; the level of expression of gene and protein of TGF-beta1 and MCP-1 in renal tissue were determined by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) methods.Compared with model group, leflunomide lessened the deposit of immunocomplex in renal tissue, alleviated the hyperplasia of mesangial matrix (all P0.01). Leflunomide could also inhibit the expression of TGF-beta1, MCP-1 at the level of gene and protein in renal tissue (P0.05 or P0.01).Leflunomide can decrease the deposit of immunocomplex, down regulate the expression of TGF-beta1, MCP-1 in kidney, diminish local inflammatory reaction, relieve hyperplasia of mesangial matrix, related the process of nephrotic fibrosis, and protect renal function.

To investigate the changes in blood pressure in hemodialysis patients treated with low calcium dialysate or high calcium dialysate for long time.Fifteen patients undergoing hemodialysis were enrolled in this study. High calcium dialysate (1.75 mmol/L, Dca1.75) was first used for 6 months, then low calcium dialysate (1.25 mmol/L, Dca1.25) was used for 6 months. Serum calcium, phosphate, blood urea nitrogen, and creatinine were measured, blood pressure was recorded before and after hemodialysis at the beginning, and also at 1, 2, 3 and 4 hours after hemodialysis.Compared with that before the treatment, systolic and diastolic blood pressure lowered significantly after single low calcium hemodialysis for 4 hours (both P0.05), while systolic and diastolic blood pressure rose significantly after single high calcium hemodialysis (both P0.05). Systolic blood pressure changed more obviously after two hemodialyses (both P0.05). Changes in systolic, diastolic and mean blood pressure were positively related to changes in serum total calcium (r(1)=0.326, P(1)=0.054; r(2)=0.383, P(2)=0.037; r(3)=0.391, P(3)=0.032). During 6 months of hemodialysis with low calcium dialysate, blood pressure lowered slightly with no significant difference in it (P0.05), while systolic blood pressure rose during 6 months of hemodialysis with high calcium dialysate (P0.05). Changes in systolic blood pressure were significantly different between two groups using dialysates with different calcium concentrations (P0.05).Systolic blood pressure and incidence of hypertension decrease after single low calcium hemodialysis.

To evaluate the effect of different blood purification techniques on serum parathyroid hormone (PTH) level in chronic hemodialysis (HD) patients with renal failure.Ninety patients were randomly divided into three groups: absorption (AP) group, hemodiafiltration (HDF) group, and HD group. Patients in AP group received therapy with resin absorptive devices associated with HD, patients in HDF group received HDF, while patients in HD group received HD. Blood routine examination, serum albumin, globulin, blood urea nitrogen, creatinine and PTH were measured before and after these treatments, and vital signs and side effects were recorded during HD. Glomerular filtration rate (GFR) and the length of HD were compared among three group.(1)Serum PTH in AP group was decrease from (291.7+/-237.5)ng/L to (122.2+/-114.5)ng/L, the difference was statistically significant. The mean single clearance rate was 48.6%+/-55.2%, the rate of relief from skin discomfort was 83.3%e10/12 cases). (2)Serum PTH in HDF group was decreased from(325.9+/-423.1)ng/L to (90.9+/-93.7)ng/L, the difference was statistically significant. The mean single clearance rate was 59.5%+/-22.7%, and the rate of relief from skin discomfort was 50.0%(4/8 cases).(3)Serum PTH in HD group was decreased from (297.7+/-211.3)ng/L to (248.1+/-105.5)ng/L, which showed no statistically significant difference. The mean single clearance rate was 13.1%+/-30.2%, the rate of relief from skin discomfort was 14.3%(1/7 cases).Resin absorptive devices and HDF can safely and effectively clear PTH, relieve skin discomfort; while hemodialysis alone can not.

To study the histopathological effect of hepatic arterial infusion of lipiodol on transplanted hepatoma in rats.Fourty-one rats bearing Walker-256 transplanted hepatoma were randomly divided into embolization group (n = 35, divided in 5 subgroups, with 7 rats in each) and control group (n = 6). Lipiodol (0.5 ml/kg)emulsified with 0.2 - 0.3 ml of 76% urografin (v:v = 1:1) was infused via gastroduodenal artery into hepatic artery in embolization group. Rats in the control group were given via the same route urografin only. Histopathological changes of the treated tumors were examined by light and transmission electron microscopy.In the control rats treated with urografin alone, the average tumor size increased 2.8 fold on day 3, while that in the lipiodol treated rats increased 1.7 fold (P0.01). Compared with the control group, on day 3, 5, 10 after embolization treatment, tumor necrosis was more extensive (P0.01). In one of the treated rats, the tumor was completely necrotic on day 10. Inflammatory reaction was marked in the early post-embolic period, but it was replaced by fibrous tissue encapsulation. From day 1 on, in 17 of the 18 treated rats, apoptotic cells, identified by typical morphology under light and electronic microscopes, were observed, mainly in the tumor periphery.In addition to cellular necrosis, apoptosis may be another important mechanism leading to cell death in hepatoma treated with transarterial embolization.

To compare the serum Leptin clearance efficiency with different blood purification treatment.Thirty-one chronic end-stage renal failure hemodialysis (HD) patients (16 men, 15 women, mean age (54.0+/-11.0) years) were enrolled into the study. All the patients were treated with routine hemodialysis, the serum Leptin levels were examined before and after HD. Then they were divided into two groups, one was to be treated with hemodiafiltration (12 patients), and the other was to be treated with blood adsorption (8 patients). The same serum Leptin levels were examined before and after treatment. Serum Leptin concentration was detected by radioimmunoassay (RIA).The concentration of serum Leptin was not significantly decreased after routine hemodialysis in HD patients ((11.820+/-5.507) microg/L vs. (12.255+/-5.172) microg/L, P0.05). Leptin concentrations after hemodiafiltration and blood adsorption therapy were decreased to the levels of (29.07+/-8.56) percent and (40.29+/-8.33) percent respectively, and their curative effect was significantly different (P=0.001).Routine hemodialysis can influence serum Leptin levels in HD patients. Hemodiafiltration and blood adsorption therapy can lower serum Leptin levels. Blood adsorption therapy is better than hemodiafiltration in the clearance of serum Leptin.

To analyze the clinical presentation of venous diethylene glycol (DEG) poisoning in patients with preexisting severe liver disease and factors that correlate with DEG poisoning.Retrospective chart review was performed to analyze the epidemiology, clinical presentation, hepatorenal functions, hemodynamics and pathological characteristics of 64 patients with severe liver disease who received intravenous armillarisin-A, the solvent of which was DEG. Comparative analyses of correlating factors and causes for poisoning were based on the presence or absence of poisoning.Of the 64 patients who received armillarisin-A, 15 were found to have DEG poisoning. Twelve poisoned patients died. After a mean of 5 d, the poisoned patients displayed acute renal failure. Metabolic acidosis occurred in 13 cases. BUN, Cr, and CO2 values were significantly elevated and exacerbation of digestive tract symptoms and/or symptom was noted in 11 cases. Neurological system impairment was observed in 10 cases after 2 wk. Compared to the 49 non-poisoned patients, the poisoned patients exhibited significantly lower RBC and Hb values and higher WBC count. Renal biopsy from the poisoned patients revealed acute tubular necrosis and interstitial nephritis. Significant differences in preexisting severe hepatitis, ascites, renal disease, and diuretic therapy were found between groups. Prior to diethylene glycol injections, the mean values for neutral granular cells, BUN, Cr, calcium and phosphorous ions differed significantly between groups.Venous diethylene glycol poisoning is characterized by oliguric acute renal failure, metabolic acidosis, digestive symptoms, nervous system impairment, and a high probability of anemia and WBC proliferation. Mortality is high. Correlative factors include preexisting severe liver disease, renal disease, and infection.