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This paper is aimed at figuring out the elements which a technology-based small and medium-sized enterprise should have in order to further growth. Based on the deconstruction of the development of this kind of enterprise, the paper summarizes the current development problems of domestic technology-based small and medium-sized enterprises. The development of science and technology small and medium-sized enterprises in China is mainly faced with the problems of limited number and regional imbalance. In some undeveloped regions, the local governments are relatively more willing to invest their restricted capital to infrastructure construction and do not pay enough emphasis on innovation activities. Taking TianJin Chase Sun Pharmaceutical as an example, this paper investigates the management mechanism and financial information to study the development factors of Chase Sun Pharmaceutical, using SWOT analysis and financial indicators analysis. CSP has converted from an enterprise on the verge of bankruptcy to a “Little Giant” enterprise that has strong research and development abilities. The case analysis reflects the development hindrance factors such as achievement transformation level, financing difficulties, and management defects, and further puts forward countermeasures and suggestions. Through this analysis, more specific information and experience on the development of science and technology in small and medium-sized enterprises in China is expected to be verified.

The continued development of the automotive industry has led to a rapid increase in the amount of waste rubber tires, the problem of “black pollution” has become more serious but is often ignored. In this study, the emission characteristics, health risks, and environmental effects of volatile organic compounds (VOCs) from a typical, recycled rubber plant were studied. A total of 15 samples were collected by summa canisters, and 100 VOC species were detected by the GC/MS-FID system. In this study, the total VOCs (TVOCs) concentration ranged from 1000 ± 99 to 19,700 ± 19,000 µg/m3, aromatics and alkanes were the predominant components, and m/p-xylene (14.63 ± 4.07%–48.87 ± 3.20%) could be possibly regarded as a VOCs emission marker. We also found that specific similarities and differences in VOCs emission characteristics in each process were affected by raw materials, production conditions, and process equipment. The assessment of health risks showed that devulcanizing and cooling had both non-carcinogenic and carcinogenic risks, yarding had carcinogenic risks, and open training and refining had potential carcinogenic risks. Moreover, m/p-xylene and benzene were the main non-carcinogenic species, while benzene, ethylbenzene, and carbon tetrachloride were the dominant risk compounds. In the evaluation results of LOH, m/p-xylene (25.26–67.87%) was identified as the most key individual species and should be prioritized for control. In conclusion, the research results will provide the necessary reference to standardize the measurement method of the VOCs source component spectrum and build a localized source component spectrum.

Aim The accumulation of uremic toxins, such as asymmetric dimethylarginine (ADMA), has emerged as one of the major cardiovascular disease-related risk factors in patients with end-stage renal disease (ESRD). Based on the low molecular weight of ADMA, hemodialysis (HD) should theoretically effectively remove ADMA. In this study, we investigated the clearance behavior of ADMA during high-flux HD. Methods Eight HD patients without residual renal function were included. Blood samples were collected at 0, 30, 60, 120 and 240 min after dialysis started, as well as 1 h and 48 h after dialysis. ADMA level was detected by HPLC-MS/MS. Herein, the ADMA level in blood cells and the ADMA protein binding rate were measured. Accordingly, the dialyzer extraction ratio was also determined. Results The reduction ratio (RR) of ADMA (corrected for hemoconcentration) was significantly lower, at only 37.21 ± 6.44%, than that of urea and creatinine (p .05). Urea and creatinine had a slight rebound ratio of less than 10% at 1 h after the completion of HD. In contrast, considerable rebound of approximately 30% was detected in ADMA. Conclusion This study suggests that ADMA may present a multicompartmental distribution that cannot be representatively reflected by the urea kinetics model.

Background: Acute kidney injury (AKI) is a common post-cardiac surgery complication. It leads to increased morbidity and mortality. The aim of our study is to identify the prevalence and risk facto...

Background/Aims: Cardiac surgery-associated severe acute kidney injury (SAKI) is associated with high mortality and poor quality of life. A prognostic score for SAKI may enable prevention of complications. Methods: This observational study of 2,552 patients undergoing cardiac surgery from January 2006 to December 2011 in our institution established associations between predictor variables and postoperative SAKI from a cohort of 1,692 patients and developed a clinical score that was assessed in a validation cohort of 860 patients. Results: Postoperative SAKI occurred in 262 ­patients (10.3%). We identified 7 independent and significant risk factors in the derivation model (adjusted OR 95% CI): age ≥81 years (vs. age < 40 years, 4.30, 1.52–12.21), age 61–80 years (vs. age 2O (3.53, 2.38–5.23), and low postoperative cardiac output (4.78, 2.97–7.69). The 7-variable risk prediction model had acceptable performance characteristics in the validation cohort (C statistic 0.80, 95% CI 0.74–0.85). The difference in the C statistic was 0.21 (95% CI 0.12–0.29, p < 0.001) compared with the Cleveland Clinic score. Conclusion: We developed and validated a practical risk prediction model for SAKI after cardiac surgery based on routinely available perioperative clinical and laboratory data. The prediction model can be easily applied at the bedside and provides a simple and interpretable estimation of risk.

Background/Aims: Klotho is a multifunctional protein expressed predominantly in kidney tubular epithelium. Here, we investigated the protective effects of Klotho on necroptosis in renal ischemic-reperfusion injury (IRI) and the role of oxidative stress in this process. Methods: Mice were subjected to bilateral renal pedicle clamping. Mouse renal tubular epithelial (TCMK-1) cells were exposed to hypoxia/reoxygenation (H/R) or H2O2. Kidney samples from acute kidney injury (AKI) patients and controls were examined by immunofluorescence. Klotho protein and N-acetyl-L-cysteine (NAC) were used to define their roles in mediating necroptosis. Necroptosis was assessed by TUNEL staining, immunoblotting, and real-time PCR. Oxidative stress was studied via ELISA, immunoblotting, colorimetric, and thiobarbituric acid reactive substances assays. Results: Renal IRI induced Klotho deficiency in the serum and kidney, but an increase in the urine. The levels of the necroptotic markers receptor-interacting protein kinase (RIP) 1, RIP3, IL-1β, and TUNEL-positive cells increased after IRI; all increases were ameliorated by Klotho. In TCMK-1 cells, Klotho and NAC attenuated the elevation in RIP1, RIP3, and LDH release induced by H/R or H2O2. Moreover, Klotho decreased the levels of oxidative stress biomarkers and elevated superoxide dismutase 2 expression in both in vivo and in vitro experiments. Studies in human samples further confirmed the Klotho deficiency and increased formation of RIP3 puncta in AKI kidneys. Conclusion: Klotho protects tubular epithelial cells from IRI and its anti-necroptotic role may be associated with oxidative stress inhibition.

With the development of neutron detection technology, the demand for real-time and fast neutron gamma discrimination has become of increasing importance. In this study, neutron and gamma pulse signals measured by an EJ299-33A plastic scintillator detector were analyzed via Matlab off-line. This study compares the effects of seven fast neutron and gamma (n/ γ ) discrimination methods; (i) charge comparison method, (ii) time-domain oriented method, (iii) amplitude oriented method, (iv) pulse time–amplitude two types of width method, (v) angle difference method, (vi) falling-edge numerical integral method, and, lastly, (vii) falling-edge percentage slope method proposed in this study. We verified that filtering and amplitude normalization improve the discrimination quality but consume much time that accounts for 99.6 % of the total discrimination time. The proposed method was compared with other six methods in two aspects: (i) the figure of merit ( F o M ), (ii) the discrimination time. The F o M value and time consumption of the falling-edge percentage slope method with amplitude normalization are 1.26 and 0.0621s, respectively, while an unnormalized F o M value is 1.02. Experimental results showed that compared with all aforementioned methods, the F O M value of our proposed method is the second high followed the charge comparison method, retaining a short discrimination time which is only half of that of the charge comparison method. This relatively short time consuming is on account of its low volume of data storage and calculation. Generally, the falling-edge percentage slope method has a good discrimination performance while consumes little time, which is capable to be implemented on real-time discrimination applications.

Defects in Klotho gene expression in mice result in a vulnerability to oxidative injuries. We aimed to identify the expression of Klotho in a mouse tubular epithelial (TCMK-1) cell line, and also to investigate changes in Klotho expression induced by oxidative stress and the potential role of intra- and extracellular Klotho protein. During exposure to hydrogen peroxide (H2O2), an overexpression of the Klotho gene was induced and exogenous Klotho protein was added in TCMK-1 cells. The generation of reactive oxidative species (ROS) was examined by flow cytometry, and cell viability was assessed by Cell Counting Kit-8. Cellular apoptosis was determined by flow cytometry and Hoechst 33258 staining followed by Western blotting to evaluate the expression of Klotho, antioxidant enzymes, and apoptosis-associated proteins. While H2O2 significantly suppressed Klotho expression, cell viability, and the expression of antioxidant enzymes in a concentration-dependent manner, cellular apoptosis was increased and p38/MAPK and JNK/MAPK were activated. Intra- and extracellular Klotho remarkably ameliorated viability inhibition, ROS generation, and cellular apoptosis induced by H2O2. Intra- and extracellular Klotho also reversed the loss of antioxidant enzymes, the elevation of cleaved Caspase-3 and Bax/Bcl-2, and the phosphorylation of JNK/MAPK and p38/MAPK. Klotho has posed antioxidant and anti-apoptotic effects on oxidative injuries in TCMK-1 cells, which might be partially related to its inhibition of JNK/MAPK and p38/MAPK phosphorylation and subsequent elevation of antioxidant enzymes. Increasing Klotho expression has played a protective role against oxidative stress in tubular epithelial cells.

Cumulative evidence indicates it may be worthwhile revisiting the twice-weekly hemodialysis (HD) regimen as a valid option for individualized or incremental treatments for selected patients with end-stage renal disease. In this article, we will review the current evidences on the potential pros and cons of twice-weekly HD compared to thrice-weekly HD including China's experience in the practice of twice-weekly HD. A prudent patient selection and close dialysis adequacy monitoring might be necessary for this medical treatment choice. More randomized prospective controlled studies for the critical evaluation of twice-weekly dialysis are encouraged.

Background Current paradigms of detecting acute kidney injury (AKI) are insensitive and non-specific. Klotho is a pleiotropic protein that is predominantly expressed in renal tubules. In this study, we evaluated the diagnostic and prognostic roles of urine Klotho for AKI following cardiac surgery. Methods We conducted a prospective study involving 91 patients undergoing cardiac surgery. AKI was defined according to the AKIN definition. The renal outcomes within 7 days after operation were evaluated. Perioperative levels of urine Klotho and urine neutrophil gelatinase-associated lipocalin (NGAL) were measured by using ELISA. Results Of 91 participants, 33 patients (36.26%) developed AKI. Of these AKI patients, 21 (63.64%), 8 (24.24%), and 4 (12.12%) were staged 1, 2, and 3, respectively. Serum creatinine in AKI patients began to slightly increase at first postoperative time and reached the AKI diagnostic value 1 day after operation. Postoperative urine Klotho peaked at the first postoperative time (0 h after admission to the intensive care unit (ICU)) in patients with AKI, and was higher than that in non-AKI patients up to day 3. The AUC of detecting AKI for urine Klotho was higher than urine NGAL at the first postoperative time and 4 h after admission to the ICU. In a multivariate model, increased first postoperative urine Klotho may be an independent predictor for AKI occurrence following cardiac surgery. The concentrations of first postoperative urine Klotho were higher in AKI stage 2 and 3 than those in stage 1 (p

Background: As the utilization of hemodialysis increases in China, it is critical to examine anemia management. Methods: Using data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS), we describe hemoglobin (Hgb) distribution and anemia-related therapies. Results: Twenty one percent of China's DOPPS patients had Hgb Conclusion: A large proportion of hemodialysis patients in China's DOPPS do not meet the expressed Hgb targets. Less frequent hemodialysis, patient financial contribution, and lack of a substantial increase in ESA dose at lower Hgb concentrations may partially explain this gap. Video Journal Club ‘Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=442741.

Objective: To investigate the incidence and the prognosis of cognitive impairment (CI) and to find out the risk factors associated with the outcome in maintenance haemodialysis (MHD) patients. Methods: Enrolled the patients who met the criteria as below: MHD (≥3 months) patients before July 2014, ≥18 years old and could carry on the cognitive function test (Montreal Cognitive Assessment [MoCA]). All enrolled patients were divided into 2 groups: CI group (MoCA < 26) and non-CI group (MoCA ≥26). All patients were followed up for 36 months. The incidence, demography data, medical history, haemodialysis data, laboratory examination and prognosis of CI in haemodialysis patients were prospectively compared and analyzed. Multivariate logistic regression analysis was used to investigate the risk factors of CI. Kaplan-Meier survival curve was used for survival analysis. Results: In the present study, 219 patients were enrolled. The ratio of male to female was 1.46: 1. Age was 60.07 ± 12.44 and dialysis vintage was 100.79 ± 70.23 months. One hundred thirteen patients’ MoCA scores were lower than 26 were divided into CI group. Education status (OR 3.428), post-dialysis diastolic pressure (OR 2.234) and spKt/V (OR 1.982) were independent risk factors for CI in MHD patients. During the follow-up period, 15 patients died (13.2%) in the CI group and 5 died (4.72%) in the non-CI group (p < 0.05). The Kaplan-Meier survival curve analysis showed that the survival rate of patients with CI was lower than that of non-CI group in MHD patients during 3 years follow-up (p = 0.046). Conclusion: CI is one of the most common complications in MHD patients. The mortality is high in patients who had CI. Education status, post-dialysis diastolic pressure and spKt/V are independent risk factors for CI in MHD patients.

Background/Aims: Clinical manifestation and renal histology serve as the current “gold standard” for evaluation of renal lesions in IgA nephropathy. MiR-192 is regarded as a potential noninvasive biomarker for kidney disease. We sought to elucidate a relationship between intrarenal, serum, and urinary exosomal miR-192 with renal lesions and disease progression in IgA nephropathy. Methods: Serum and urinary exosomal miR-192 were detected and correlated with clinical and pathological parameters from consecutive IgA nephropathy patients (n = 50) and healthy control patients (n = 25). Patients then received a follow-up of 24 months after biopsy. Disease progression was defined as a 40% reduction in estimated glomerular filtration rate. Expression of miR-192 was quantified by Taqman RT-PCR. Intrarenal ­miR-192 was detected in 8 IgA nephropathy patients and 4 matched patients receiving kidney nephrectomy as controls via in situ hybridization. TGF-β1 and E-cadherin expression in renal tissue was evaluated using immunohistochemistry. Results: Intrarenal miR-192 was correlated with serum miR-192 (r = 0.690, p = 0.013). Both intrarenal and serum miR-192 decreased in IgA nephropathy patients and were correlated with estimated glomerular filtration ratio. Patients with lower intrarenal and serum miR-192 levels had a higher interstitial fibrosis and tubular atrophy score, more severe lesions in tubular atrophy, and interstitial inflammation. Renal E-cadherin expression was correlated (r = 0.484, p = 0.004) and TGF-β1 was inversely correlated (r = –0.527, p < 0.001) with serum miR-192 in IgA. Patients with higher serum miR-192 had a lower disease progression rate over the course of 2 years (0 vs. 16%, p = 0.028). No correlation was found in urinary exosomal miR-192 with the clinical and pathological parameters mentioned earlier. Conclusions: Lower serum miR-192 in IgA nephropathy patients indicates lower intrarenal miR-192 expression, more severe tubular atrophy, interstitial inflammation, and fibrotic tendency (with higher TGF-β and E-cadherin in renal miR-192). IgA nephropathy patients with higher serum miR-192 are less likely to have renal function decline over the course of 2 years.

Introduction: Given that it is difficult to randomize end-stage renal disease (ESRD) patients to either hemodialysis (HD) or peritoneal dialysis (PD), differences between these renal replacement therapy (RRT) modalities are of major interest and remain controversial. Methods: All data on maintenance dialysis patients during 2009 to 2013 in the Renji Hospital in Shanghai, China and in the San Bortolo Hospital in Vicenza, Italy were selected. Patients who changed their therapy from HD to PD or PD to HD during this study were excluded. Results: 919 maintenance dialysis patients were included in the present study, including 509 patients on HD and 410 on PD. During the 5-year follow-up, mean arterial pressure (MAP) was higher in HD patients. The level of serum HCO3- was significantly better in PD patients than in HD patients. Phosphate was significantly higher in HD patients than in PD patients. With respect to lipid metabolism, triglyceride, total cholesterol and LDL were significantly higher in PD patients. Serum protein and albumin were higher in HD patients than in PD patients. Overall, 236 patients died (25.7%); 150 (16.3%) on HD and 86 (9.4%) on PD. The main cause of death in HD and PD patients was cerebral vascular disease and infection, respectively. After adjusting for dialysis vintage, the Kaplan-Meier patient survival was similar between HD and PD patients. Conclusions: Based on 5 years of data, we demonstrate that lipid metabolism and nutritional status were better in HD patients. However, blood pressure control, acid-base balance, phosphate (P) control were better in PD patients. The main cause of death in HD and PD was cerebral vascular disease and infection, respectively. Considering the dialysis vintage, the Kaplan-Meier patient survival was similar between HD and PD patients.

The aim was to identify the risk factors of long-term vascular access complications. The study cohort consisted of 239 incident hemodialysis (HD) patients from 1998 to 2010 in a single center. Among these patients, 59.8% had initially been dialyzing with a temporary catheter. Within 3 months after starting dialysis, all catheters had been converted into permanent accesses. 45 patients incurred long-term access complications after the first 2 years of dialysis, and 34 (75.6%) had used a temporary catheter starting HD. Complication occurrence was associated with age, initiation dialysis with a catheter and heart failure by logistic regression (odds ratios were 1.04, 2.77 and 2.23, respectively; p < 0.05). The 2-year primary patency rates of arteriovenous fistulae were significantly higher than those of arteriovenous grafts (79.5 vs. 50%, p = 0.002). We concluded that age, using a catheter and heart failure in HD initiation had a strong impact on long-term access complications.

Introduction: The value of biomarkers at the time of nephrology consultation in predicting the prognosis of acute kidney injury (AKI) in hospitalized patients has not been well described. This study aimed to evaluate the possibility of biomarkers at the time of nephrology consultation in predicting the prognosis of AKI. Methods: We prospectively enrolled 103 hospitalized patients who developed AKI. Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL), IL-6, IL-18, N-Acetyl-F-D-Glucosaminidase (NAG), and serum Cystatin C (CysC) were measured at the time of nephrology consultation. Baseline values of serum creatinine (bScr), serum creatinine on consultation (cScr) and the peak level of serum creatinine (pScr) were recorded. All the patients were followed-up till 28 days since consultation. Serum and urinary levels of the biomarkers were compared according to the patient or kidney prognosis. Each marker was assessed for its predictive value using receiver operator characteristic (ROC) curves to predict AKI prognosis. Results: Patients were aged 54.28 w 19.05. Male patients constituted 65% of the study group and baseline Scr was 93.54 w 35.98 Vmol/l. The mortality rate of the patients was 25.2% and kidney loss rate was 18.8% at 28 days after consultation. The level of urinary NGAL was significantly higher in death patients than that in survival patients [147.00 (31.59, 221.87) Vg/ml vs. 22.43 (6.48, 89.77) Vg/ml, p = 0.001], while the level of bScr, cScr, pScr, urinary IL-6 and NAG were similar in both these groups. The AUC of urinary NGAL for predicting patients' death was 0.723 (p = 0.001). Serum CysC and urinary IL-18 concentration was higher in the death patients with a marginal p value (p = 0.065 and 0.059 respectively). All the urinary markers, including NAG, NGAL, IL-6 and IL-18 were significantly higher in patients with kidney loss than in those with kidney survival, while no difference was found in Scr and serum CysC levels. The AUCs of these urinary biomarkers for predicting kidney survival were 0.663, 0.655, 0.705 and 0.663 respectively (p < 0.05). The concentrations of cScr, pScr, serum CysC, urinary IL-6 and NGAL were significantly higher in RRT patients (p < 0.05). The AUCs for predicting RRT were 0.628, 0.781, 0.768, 0.672 and 0.775 respectively. Conclusions: The level of biomarkers at the time of nephrology consultation might predict the prognosis of AKI in hospitalized patients. Further studies should be done to understand the role of the serum and urinary markers in the prognosis of AKI. i 2014 S. Karger AG, Basel

The main aim of this study is to investigate the incidence and prognosis of acute kidney injury (AKI) and to clarify the risk factors associated with the prognosis of AKI in hospitalized patients.All patients hospitalized from January 1st to December 31st 2012 in Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University were screened by the Lab Administration Network. All the patients with an intact medical history of AKI according to the Acute Kidney Injury Network (AKIN) were enrolled in the study cohort. AKI's incidence and etiology, as well as the patient's characteristics and prognosis, were retrospectively analyzed. Logistic regression analysis was used to investigate the risk factors on the patient prognosis and renal outcome.934 AKI patients were enrolled. The incidence of AKI in hospitalized patients was 2.41%. The ratio of males to females of patients was 1.88:1 and the mean age was 60.82 ± 16.94. The incidence of AKI increased with increase in age. Among hospitalized patients, 63.4% were from the surgical department, 35.4% from the internal medicine department, and 1.2% from the obstetric and gynecologic department. Regarding the cause of AKI, pre-renal AKI, acute tubular necrosis (ATN), acute glomerulonephritis and vasculitis (AGV), acute interstitial nephritis (AIN), and post-renal AKI contributed with 51.7, 37.7, 3.8, 3.5, and 3.3%, respectively. The survival rate on the day 28 after AKI was 71.8%. In addition, 65.7% patients got complete renal recovery, while 16.9% got partial renal recovery and 17.4% got renal loss. The mortality of AKI in hospitalized patients at Stage I, Stage II and Stage III was 24.8, 31.2 and 43.7%, respectively. Multivariate Logistic regression analysis showed that use of nephrotoxic drugs, [Odds Ratio (OR) = 2.313], hypotension in the previous week (OR = 4.482), oliguria (OR = 5.267), the number of extra-renal organ failures (OR = 1.376), and need for renal replacement therapy (RRT) (OR = 4.221) were independent risk factors for mortality. The number of extra-renal organ failures (OR = 1.529) and RRT (OR = 2.117) were independent risk factors for renal loss.AKI is one of the most common complications in hospitalized patients. The mortality is high and renal prognosis is poor after AKI. The prognosis is closely associated with the severity of AKI. Nephrotoxic drugs, hypotension within the last week, oliguria, the number of extra-renal organ failures, and RRT are independent risk factors for mortality, while the number of extra-renal organ failures and RRT are independent risk factors for renal loss.

Background Renal replacement therapy is rapidly expanding in China, and two-times weekly dialysis is common, but detailed data on practice patterns are currently limited. Using cross-sectional data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS), we describe the hemodialysis practice in China compared with other DOPPS countries, examining demographic, social and clinical characteristics of patients on two-times weekly dialysis.

Purpose Ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) with poor outcomes. While many important functions of microRNAs (miRNAs) have been identified in various diseases, few studies reported miRNAs in acute kidney IRI, especially the dynamic changes in their expression and their implications during disease progression. Methods The expression of miR-192, a specific kidney-enriched miRNA, was assessed in both the plasma and kidney of IRI rats at different time points after kidney injury and compared to renal function and kidney histological changes. The results were validated in the plasma of the selected patients with AKI after cardiac surgery compared with those matched patients without AKI. The performance characteristics of miR-192 were summarized using area under the receiver operator characteristic (ROC) curves (AUC-ROC). Results MiRNA profiling in plasma led to the identification of 42 differentially expressed miRNAs in the IRI group compared to the sham group. MiR-192 was kidney-enriched and chosen for further validation. Real-time PCR showed that miR-192 levels increased by fourfold in the plasma and decreased by about 40% in the kidney of IRI rats. Plasma miR-192 expression started increasing at 3 h and peaked at 12 h, while kidney miR-192 expression started decreasing at 6 h and remained at a low level for 7 days after reperfusion. Plasma miR-192 level in patients with AKI increased at the time of ICU admission, was stable for 2 h and decreased after 24 h. AUC-ROC was 0.673 (95% CI: 0.540–0.806, p = 0.014). Conclusions Plasma miR-192 expression was induced in a time-dependent manner after IRI in rats and patients with AKI after cardiac surgery, comparably to the kidney injury development and recovery process, and may be useful for the detection of AKI.

Background: Few studies have evaluated the prognostic value of dialysis dose in twice-weekly hemodialysis (HD). A single-pool Kt/V (spKt/V) over 1.70 may benefit patients receiving twice-weekly maintenance HD. Methods: This is a multicenter randomized controlled trial performed on 163 patients from 17 dialysis centers in Shanghai who were allocated to high- (n = 98) and standard-dose groups (n = 65) and followed through 96 weeks of study period. Therapeutic approaches were given to increase spKt/V to over 1.70 in the high-dose group. Data were collected every 12-24 weeks. The primary outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACEs) occurrence, and secondary outcomes included residual kidney function (RKF) and health-related quality of life (HR-QOL). Results: The spKt/V in high-dose and standard-dose groups were 1.80 ± 0.23 and 1.55 ± 0.19, respectively, after an 8-week intervention (p < 0.001). At the end of the study, SF-36 physical function and total score in high-dose group were 82 (69-90) and 74 (47-84), respectively, both of which were higher than those in the standard-dose group. Decline in urine volume was observed in both groups with no significant difference (p = 0.431). No difference was found in overall survival between the 2 groups (p = 0.580). The 1-year MACE-free survival for high-dose group was 84.49%, better than 76.72% for standard-dose group (p = 0.029). Conclusions: Higher spKt/V is also associated with MACE-free survival and better HR-QOL, especially in physical function aspect for twice-weekly dialysis patients. Increasing spKt/V over 1.70 in twice-weekly HD population does not cause loss of RKF.

In non-neuronal cells, glutamate is an extracellular signaling mediator. Since podocytes have glutamate-containing vesicles, we sought to determine glutamate receptor presence and action in glomerular cells. The metabotropic glutamate receptors (mGluR) 1, 5, 6, and 8 were found to be expressed in mouse brain and glomeruli; predominantly in podocytes. In two models of proteinuria (BalB/C mice with puromycin aminonucleoside- and doxorubicin-induced podocyte injury) we found that the selective mGluR1/5 agonist (S)-3,5-dihydroxyphenylglycine (DHPG) attenuated albuminuria and improved the expression of the podocyte marker WT-1. TUNEL staining showed that the number of podocytes undergoing apoptosis was inversely correlated with the number of WT-1–positive cells in glomeruli. When podocytes were treated with DHPG in vitro , they generated cyclic AMP and activated CREB (cyclic AMP response element binding protein). The selective mGluR1/5 antagonist ( RS )-1-aminoindan-1,5-dicarboxylic acid, the adenylate cyclase inhibitor SQ22536, and RNA interference knockdown of mGluR1 or mGluR5 all prevented DHPG-induced cAMP generation and CREB activation. DHPG inhibited apoptosis and the decrease of aminonucleoside-induced mitochondrial membrane potential in podocytes but had no effect in the presence of SQ22536 with knockdown mGluR1 or mGluR5. Thus, functional mGluR1 and mGluR5 are expressed in podocytes and their activation protects against albuminuria and podocyte apoptosis, processes that are, at least in part, dependent on cAMP.

Hemodialysis is an important alternative for renal replacement therapy to remove uremic retention solutes (URS) for the uremic syndrome. The metabolites in the hemodialysate directly reflect the efficiency of URS clearance. Here we report a highly sensitive and reliable metabolomic procedure for the measurement of small molecule metabolites in hemodialysate using gas chromatography coupled with time-of-flight mass spectrometry (GC/TOF/MS). The method was developed and evaluated through orthogonal experimental design using multivariate statistical analysis. The optimized method involves the use of methanol and water in the ratio of 3:1 (v/v) for dissolving the lyophilized solid of the hemodialysate after degradation of urea with urease (no less than 50 U) for 10 min. Validation of the method demonstrated a good linearity with regression coefficients greater than 0.99. Relative standard deviations of precision and stability of proposed method were less than 15%, and recoveries ranged from 71.8 to 115.8%. This method was successfully applied in the metabolite profiling of human hemodialysate samples which was able to differentiate the patients treated with high-flux hemodialysis from those with low-flux hemodialysis. The metabolomic results reveal a higher concentration of URS, and thus, better URS removal, from the patients under high-flux dialysis than those under low-flux dialysis.

Background/Aims: Acute kidney injury (AKI) following surgery is a major complication, but the prevalence and risk factors in the Asian population are unclear. Recently, a consensus definition of AKI (AKIN) was proposed. We studied a cohort of cardiac surgery patients and identified AKI by AKIN and associated risk factors. Methods: We retrospectively evaluated 1,056 consecutive patients undergoing cardiac surgery in Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from January 1, 2004 to June 30, 2007. We recorded AKIN stage, clinical characteristics, perioperative variables and complications, as well as clinical outcomes. Univariate and multivariate regression as well as survival analysis was performed. Results: AKI occurred in 328 (31.1%) patients, stage 1 in 21.1%, stage 2 in 6.3% and stage 3 in 3.7%. Patients with AKI were older (65.8 vs. 53.5 years, p < 0.001), more often male (66.8 vs. 54.1%, p < 0.001), and had higher Charlson Comorbidity Index (CCI) (CCI >2: 22.6 vs. 7.8%, p < 0.001). In logistic regression, advanced age (OR 1.48 per decade, 95% CI 1.32–1.67), CCI >2 (OR 2.82, 95% CI 1.80–4.41), hypertension (OR 2.13, 95% CI 1.47–3.09), left ventricular ejection fraction (LVEF) 2O (OR 13.28, 95% CI 8.72–20.14) and postoperative use of ACEI/ARB (OR 1.90, 95% CI 1.27–2.85) were risk factors of AKI. Mortality rose progressively with increased AKIN stage (non-AKI 0.7%, stage 1 4.9%, stage 2 12.1% and stage 3 48.7%). In ROC analysis, AKIN classification was identified to be associated with in-hospital mortality with an AUC of 0.865 (95% CI 0.801–0.929, sensitivity 0.884, specificity 0.714, p < 0.001). Finally, in a Cox proportional hazards model, AKIN stage (HR 2.40, p < 0.001), re-exploration (HR 6.30, p = 0.002) and multiple organ dysfunction syndrome (MODS) (HR 4.42, p = 0.001) were associated risk factors for in-hospital mortality. Conclusion: We evaluated AKIN as a marker of AKI and mortality risk in a large, unselected Chinese cohort of incident patients undergoing cardiac surgery. AKI following cardiac surgery was diagnosed by AKIN criteria in around one third of the patients, and AKI may be associated with outcome. The value of preventative strategies to reduce AKI and their effect on in-hospital mortality should be studied.

Background/Aims: Acute kidney injury (AKI) is common following cardiac surgery and predicts a poor outcome. However, the early detection of AKI has proved elusive and most cases are diagnosed only following a significant rise in serum creatinine (SCr). We compared a panel of early biomarkers of AKI for the detection of AKI in patients undergoing heart surgery. This study included serum cystatin C (CyC) and urinary levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), retinol-binding protein (RBP) and N-acetyl-β-D-glucosaminidase (NAG). Methods: We retrospectively identified 15 patients undergoing open cardiac surgery who developed AKI within 72 h postoperatively. For these, we identified 15 matched controls also having undergone surgery but without AKI. Serial serum and urine samples had prospectively been postoperatively obtained from all patients at 0, 2, 4, 6, 10, 24, 48 and 72 h after admission to the intensive care unit. AKI was defined as a >50% increase in SCr. CyC was measured by nephelometry, while NGAL, IL-18, and RBP were measured by ELISA and NAG was measured by spectrophotometry. The urinary biomarkers were normalized to urinary creatinine (UCr) concentration. Each marker was assessed at each time point for its predictive value using receiver operating characteristic curves to predict AKI. Results: Following the exclusion of 1 case due to a urinary tract infection, the final cohort consisted of 29 patients aged 62.9 ± 13.7 years with baseline SCr of 73.2 ± 11.9 µmol/l. While there were no differences in the demographics between cases and controls, the aortic clamp time was predictably higher in AKI cases than in controls (60.6 ± 13.9 vs. 43.0 ± 9.2 min, p < 0.05). Each biomarker differed significantly between cases and controls for at least one time point. The optimal area under the curve (AUC) was for CyC at 10 h (sensitivity 0.71, specificity 0.92, cutoff 1.31 mg/l), NGAL at 0 h (sensitivity 0.84, specificity 0.80, cutoff 49.15 µg/g UCr), IL-18 at 2 h (sensitivity 0.85, specificity 0.73, cutoff 285.65 ng/g UCr), RBP at 0 h (sensitivity 0.75, specificity 0.67, cutoff 2,934.65 µg/g UCr) and NAG at 4 h (sensitivity 0.86, specificity 0.67, cutoff 37.05 U/mg UCr). Using a combination of all 5 biomarkers analyzed at the optimal time point as above, we were able to obtain an AUC of 0.98 (0.93–1.02, p < 0.001) in this limited sample. Conclusion: The use of serum and urinary biomarkers for the prediction of AKI in patients undergoing cardiac surgery is highly dependent on the sampling time. Of the evaluated markers urinary NGAL had the best predictive profile. The previously unstudied marker of urinary RBP showed similar predictive power as more established markers. By combining all 5 studied biomarkers we were able to predict significantly more cases, suggesting that the use of more than one marker may be beneficial clinically.

Background. Maintenance dialysis therapy is the only way to remove excess fluid in patients with anuric end-stage renal disease. The optimal ultrafiltration (UF) volume in patients on peritoneal dialysis (PD) remains controversial. Methods. We retrospectively analysed a cohort of 86 prevalent anuric PD patients followed up for a median of 25.3 months (range, 6 to 54 months). Clinical and PD parameters were recorded yearly. Kaplan-Meier analysis and Cox proportional hazards models were used to identify risk factors of mortality and technique failure in patients with a UF ≥1 L/24 h or

OBJECTIVE To study the expression of angiopoietin receptor Tie-2 in the renal tissue of diabetic rats and the effects of Astragalus. METHODS SD rats were randomly divided into normal control group, diabetes group and Astragalus-treated group. The expression of receptor Tie-2 in the renal tissue was assessed by using real-time quantitative polymerase chain reaction and immunohistochemical method. RESULTS Glomerule Tie-2 protein expression was significantly elevated in the diabetes group as compared with the normal control group (P

Immunoglobulin A nephropathy (IgAN), the pathogenesis of which remained still unclear is one of the leading courses of end-stage renal disease in approximately 50% affected patients. On the basis of several researches, the activation of complement mannose-binding lectin (MBL) pathway might be the underlying mechanism in disease progress. In order to investigate the relationship between MBL pathway and IgAN, we discussed the MBL gene polymorphism as well as its expressed level in serum, urine and renal parenchymal, with renal outcome in IgAN patients. The significantly down-regulated expression of MBL was discovered, which may serve as a potential urinary biomarker in progressive IgAN according to the results of difference in gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The single nucleotide polymorphisms of MBL gene in promoter and exon region were found and confirmed relating with the poor prognosis of progressive IgAN patients. As a result, the deficient activation of MBL pathway caused by the mutation of MBL accompanied with low expressed level of MBL in serum might be the potential inspiring regulation in IgAN, and will attract a promising insight in remedy of IgAN to inhibit further progress.

Acute kidney injury (AKI) is common following cardiac surgery and is associated with poor outcomes. However, the detection of those preoperative patients who will develop AKI is still difficult. In this study, we compared serum cystatin C combined with dipstick proteinuria as early markers to predict AKI available before surgery.We prospectively followed 616 patients undergoing cardiac surgery and identified 179 that developed AKI, defined as an increase in serum creatinine (SCr) of ≥ 0.3 mg/dL or ≥ 50% increase in creatinine level. Preoperative values for cystatin C were categorized into quartiles. We defined proteinuria, measured with a dipstick, as mild (trace to 1+) or heavy (2 + to 4+). Univariate as well as multivariate regression was performed. Cystatin C combined with dipstick proteinuria before surgery was assessed for its' predictive value of AKI using receiver operating characteristic (ROC) curves.The final cohort consisted of 616 patients aged 60.7 ± 13.2 years, and baseline SCr was 75.8 ± 26.4 μmol/L, estimated glomerular filtration rate (eGFR) 96.3 ± 29.0 mL/min/1.73 m(2) and cystatin C 1.05 ± 0.33 mg/L. Patients in higher cystatin C quartiles were older (p 0.001), more often to have heavy proteinuria (p = 0.021), hyperuricemia (p 0.001), heart failure (p 0.001) and recent myocardial infarction (p = 0.002). Those with heavy proteinuria were more often to have diabetes mellitus (p = 0.010), hyperuricemia (p = 0.043), worse cardiac function (p 0.05), higher creatinine levels (p 0.001) and lower eGFR levels (p 0.001). In a multiple logistic regression model, preoperative heavy proteinuria [OR: 3.14, 95% confidence interval (CI): 1.26-7.77] and preoperative cystatin C quartiles (Q2:OR: 1.60, 95% CI: 0.72-3.60; Q3:OR: 1.87, 95% CI: 0.85-4.14; Q4:OR: 3.10, 95% CI: 1.37-7.02) each associated with an increased odds of AKI, independent of advanced age (OR: 1.04, 95% CI: 1.01-1.06), hypertension (OR: 1.88, 95% CI: 1.13-3.12) and combined surgery (OR: 3.47, 95% CI: 1.35-8.89). The risk for adverse outcomes such as postoperative AKI, persistent AKI, severe AKI, dialysis and mortality were highest in patients with highest quartile of cystatin C (p 0.05, respectively) and heavy proteinuria (p 0.05, respectively). The area under the ROC curve for preoperative cystatin C combined with proteinuria to detect AKI, persistent AKI and severe AKI were 0.695 (p 0.001; 95% CI = 0.637-0.754), 0.753 (p 0.001; 95% CI = 0.693-0.812) and 0.718 (p 0.001; 95% CI = 0.642-0.795), respectively.These data suggest that preoperative serum cystatin C combined with dipstick proteinuria may improve prediction of AKI among patients undergoing cardiac surgery.

Background: Klotho is a single transmembrane protein originally identified as an ‘aging suppressor'. Emerging evidence reveals that soluble Klotho (sKl) in the circulation plays important roles in anti-aging, anti-oxidation, anti-apoptosis and Wnt signaling. However, the role of serum sKl in the vascular calcification in hemodialysis patients is not clear. The aim of this study was to determine the associations of sKl with abdominal aortic calcification in patients on maintenance hemodialysis (MHD). Methods: 129 MHD patients were enrolled prospectively. Serum sKl level was detected by ELISA. Abdominal aortic calcification was measured by abdomen lateral plain radiograph, and the abdominal aorta calcification (AAC) score was calculated. The sKl levels were observed in patients with different degrees of calcification. Logistic regression analysis was used to determine the risk factor of abdominal aortic calcification in MHD patients. The diagnostic value of sKl for abdominal aortic calcification was assessed using receiver operator characteristic (ROC). Results: Abdominal aortic calcification was seen in 87 of 129 patients. The median AAC score was 4.0 (0.00, 11.00) and the median sKl level was 616.29 (378.19, 821.61) pg/ml. Serum sKl levels were inversely associated with AAC. When evaluated as AAC categories (15) with ordinal logistic regression, each SD higher sKl was associated with 37.1% lower odds of AAC severity (proportional odds ratio: 0.629; 95% confidence interval: 0.413-0.959, p = 0.031) in models adjusted for demographic data, lifestyle factors, traditional CVD risk factors and uremic risk factors. Multivariate logistic regression analysis showed that serum sKl levels and smoking were independent risk factors for severe AAC. The area under the receiver-operating characteristic curve (AUC) of serum sKl for severe abdominal aortic calcification was 0.746 (0.612-0.880, p = 0.001), sensitivity was 0.885, and specificity was 0.562 for a cutoff value of 265.39 pg/ml. Conclusions: Lower serum sKl levels are independently associated with severe AAC. Serum sKl might have a diagnostic value for the severe AAC in MHD patients.

AIM Prevalence of secondary hyperparathyroidism (SHPT), a renal disease complication, is increasing in China. Available therapies may not optimally control SHPT, particularly in patients with hypercalcemia, hyperphosphatemia, and parathyroid hyperplasia. This study examined efficacy and safety of two dosing regimens of selective vitamin D receptor activator paricalcitol. MATERIALS AND METHODS Subjects with SHPT (n = 216) undergoing hemodialysis were treated with paricalcitol i.v. for 12 weeks. One group was treated according to the EU paricalcitol package insert (PI) (initial μg dose based on iPTH/80), and the other was treated according to the US PI (initial dose of 0.04 μg/kg). Dose titration was based on iPTH and serum calcium (Ca) and phosphorus (P) levels. RESULTS The primary endpoint of two consecutive ≥ 30% iPTH decreases was achieved by 88.6% and 55.9% of subjects in the EU and US PI groups, respectively. Noninferiority of the EU PI group vs. the US PI group was demonstrated (lower bound of the 1-sided 97.5% CI = 21.3%). Superiority of the EU PI group was shown (lower limit > 0%) and confirmed by Fisher's exact test (p < 0.001); both groups showed similar achievement of recommended KDIGO iPTH levels. Ca and P levels were relatively constant. CONCLUSION Both EU and US PI paricalcitol dosing strategies effectively reduced iPTH levels in Chinese subjects with SHPT, with minimal impact on Ca and P levels.

The early detection of acute kidney injury (AKI) may be become possible by several promising early biomarkers which may facilitate the early detection, differentiation and prognosis prediction of AKI. In this study, we investigated the value of urinary liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL) and their combination in predicting the occurrence and the severity of AKI following cardiac surgery.We prospectively followed 109 patients undergoing open heart surgery and identified 26 that developed AKI, defined as an increase in serum creatinine of ≥0.3 mg/dl or ≥150% of baseline creatinine. Serum creatinine (SCr), urinary L-FABP, and NGAL corrected by urine creatinine were tested pre-operation, at 0 hour and 2 hours post-operation. Each marker was assessed at each time point between patients with and without AKI. Receiver operating characteristic (ROC) curves and area under curves (AUC) were used to evaluate the diagnostic accuracy of urinary L-FABP, NGAL and their combination for predicting AKI.Patients were aged 63.0 ± 11.3 years, 66.1% were male and baseline SCr was 70.5 ± 19.1 umol/L. Of 109 patients, 26(23.9%) developed AKI (AKIN stage I, II and III were 46.2%, 34.6% and 19.2% separately). The levels of urinary L-FABP and NGAL were significantly higher in AKI patients than non-AKI patients at 0 hour and 2 hours postoperative. AUCs for L-FABP was 0.844 (sensitivity (ST) 0.846, specificity (SP) 0.819, cut-off (CO) 2226.50 μg/g Ucr) at 0 hours and 0.832 at 2 hours (ST 0.808, SP 0.747, CO 673.09 μg/g Ucr) while 0.866 for NGAL at 0 hours (ST 0.769, SP 0.819, CO 131.12 μg/g Ucr) and 0.871 at 2 hours (ST 0.808, SP 0.831, CO 33.73 μg/g Ucr) to predict AKI occurrence. Using a combination of L-FABP and NGAL analyzed at the same timepoint as above, we were able to obtain an AUC of 0.911-0.927, p0.001. Similar AUCs of 0.81-0.87 were found to predict AKI stage II-III.Urinary L-FABP and NGAL increased at an early stage after cardiac surgery. The combination of the two biomarkers enhanced the accuracy of the early detection of postoperative AKI after cardiac surgery before a rise in SCr.

We examined the value of two potential novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid binding protein (L-FABP), in diagnosing acute kidney injury (AKI) in liver transplant recipients.NGAL and L-FABP in urinary sample from Twenty-five patients before surgery and at 2, 4, 6, 12, 24, 48, 72 and 120 h after the anhepatic phase were tested. Standard statistics were used along with receiver-operating characteristic (ROC) analysis to evaluate the diagnostic value of selected markers.Urinary NGAL was only slightly elevated at 2 h in the non-AKI group while rose and stayed high from 2-6 h in the AKI group. However, urinary L-FABP rose transiently in both groups 2-120 h following surgery. The level of urinary NGAL presented differences at 2-6 h (p0.05) and urinary L-FABP at 4 h (p0.05) between AKI and non-AKI groups. ROC analysis showed that area under the curves (AUCs) of NGAL were 0.766, 0.773, and 0.773 at 2, 4 and 6 h respectively while 0.760 of L-FABP at 4 h.Urinary NGAL rather than L-FABP appeared to be a sensitive and specific marker of AKI in liver transplant recipients.

Background: Twice-weekly hemodialysis (HD) is prevalent in the developing countries and the clinical outcome of this population remains to be elucidated. Methods: Data were collected from Shanghai Renal Registry. 2,572 patients undergoing regular HD in Shanghai on January 2007 were enrolled into the cohort study with 2 years’ follow-up. Clinical and HD parameters obtained from the network were utilized to compare twice-weekly with thrice-weekly HD. Results: Compared with patients on thrice-weekly HD, the twice-weekly HD patients were significantly younger and had significantly longer HD session time, higher single-pool Kt/V (spKt/V) but shorter HD vintage (p < 0.001). Kaplan-Meier survival analysis indicated that the two groups had similar survival. Multivariate Cox regression analysis showed that age, body mass index, serum albumin and weekly Kt/V were predictors of patient mortality. Conclusions: The similar survival between twice-weekly HD and thrice-weekly HD is likely relating to patient selection; dialysis adequacy of twice-weekly HD remains to be elucidated.

Several studies have related the circulating level of asymmetric dimethylarginine (ADMA) to cardiac remodeling and cardiovascular (CV) events in end-stage renal disease (ESRD) patients. Studies investigating this relationship in patients with pre-dialysis chronic kidney disease (CKD) are lacking.We enrolled 76 CKD patients (age, 46.7+/-14.3 years, 39 females) and 15 controls (age, 40.1+/-18.5 years, 6 females). Clinical parameters, blood biochemistry and echocardiographic findings were recorded, and plasma ADMA concentrations measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Patients were prospectively followed up for a median of 15 (range, 6-24) months.Plasma ADMA was significantly elevated in CKD patients compared with controls (41.56+/-12.76 microg/mL vs 17.12+/-7.09 microg/mL, P0.001), and correlated with the left ventricular mass index (LVMI) (r=0.597, P0.001). During follow-up, 25 patients experienced new CV events and their plasma ADMA level was significantly elevated (48.27+/-13.70 vs 34.91+/-6.38 in CV event-free patients, P0.001). Cox regression analysis further confirmed that ADMA was an independent risk factor for CVD (HR=1.175, 95%CI[1.070-1.290], P=0.001).Similar to findings in ESRD patients, elevated circulating levels of ADMA may increase the risk of LVH and CV events in pre-dialysis CKD patients.

In this paper, a novel method to accelerate off-line Chinese writer identification by combining multi text-sensitive features and combining multi character level decisions is practiced. The used text-sensitive writer identification algorithm extracts Directional histogram feature, Moment feature and Wigner feature, reduces the dimensions using PCA and LDA, and adopts the simple Euclidean classifier. However the writer identification algorithms are text-sensitive, thus there are different mutual character combinations between writers. A method for retrieving in an amount of writers who has different handwriting script content is proposed in this paper, by combining and sorting the posterior probability measures of writing identification. An experiment, which is carried out in a handwriting script database, demonstrates the effectiveness of the proposed method.