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Introduction: Although intradialytic exercise is considered a form of "nonpharmacological medicine" for patients receiving maintenance hemodialysis (MHD), this practice has not been widely implemented in most dialysis centers because of clinical limitations. We, therefore, aimed to design an intradialytic exercise training program to improve the implementation of this practice and determine its impact on physical performance and cardiovascular risk factors in patients receiving MHD. Methods: A total of 132 MHD patients at 4 outpatient dialysis units were enrolled and assigned randomly into exercise (n = 67) and control groups (n = 65). During a 2-year period, patients in the exercise group participated in 20-min exercise training sessions within dialysis sessions on 3 days per week. All patients underwent assessments of physical function (6-min walk test) and cardiovascular risk factors (blood pressure [BP], total cholesterol [TC], low-density lipoprotein [LDL], high-sensitivity C-reactive protein [hsCRP], albumin [Alb], hemoglobin [Hb], and erythropoietin [EPO] dose) at the baseline and annually thereafter. Results: Of the participants, 50.8% had completed the study after 2 years. No statistically significant intragroup or intergroup differences were observed in the measures of 6MD, BP, TC, hsCRP, Alb, Hb, and EPO dose. Conclusion: The results suggest that although this low-intensity, nonprogressive intradialytic exercise program may be practical, it was not sufficient to improve physiological function and reduce cardiovascular disease risk factors in patients receiving MHD. [ABSTRACT FROM AUTHOR]

To develop an equation to predict dual plasma sample method (DPSM)99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) plasma clearance from single plasma sample method (SPSM), and to clarify the condition in which DPSM can be substituted by SPSM in measurement of glomerular filtration rate (GFR). Patients with chronic kidney disease (CKD) were selected. Watson modified Christensen and Groth equation was used to calculate99mTc-DTPA plasma clearance by SPSM (sGFR). The equation recommended by the Nephrourology Committee of the Society of Nuclear Medicine was used to calculate99mTc-DTPA plasma clearance by DPSM (tGFR) in each patient. The difference between sGFR and tGFR was expressed as percent of the average of these two methods, and tGFR was predicted from sGFR. Plasma creatinine was measured by the kinetic picrate method, and GFR estimated by abbreviated modification of diet in renal disease (MDRD) equation (aGFR) and Cockcroft-Gault equation (cGFR) were evaluated as criteria in selection of DPSM and SPSM. Three hundred and sixty-nine patients with CKD were selected (208 male and 161 female). The average age and body weight were 51.4 ± 15.5 years and 67.2 ± 12.5 kg, respectively. The causes of CKD were glomerular disease, renal arterial stenosis, chronic tubulointerstitial disease, and other causes or causes unknown. The average tGFR was 62.9 ± 36.5 ml/min/1.73 m2, ranging from 1–180 ml/min/1.73 m2. sGFR was significantly correlated with tGFR (r = 0.9194, p < 0.001), but widely scattered when tGFR <30 ml/min/1.73 m2; in contrast, then tGFR was >30 m//min/1.73 m2, the difference was constant (-1.1%, 95% confidence interval-18.3%, 16.1%), and tGFR could be predicted from sGFR using the equation: predicted tGFR (ml/ min/1.73 m2) = 7.4244 + 0.7318 x sGFR + 0.0022 x sGFR2 (n = 299, r2 = 0.9428, p < 0.001), and the difference decreased to 0.1%, 95% confidence interval (-15.8%, 16.0%). aGFR was better than cGFR in diagnosis of tGFR <30 ml/min/l.73 m2, the diagnostic sensitivity of a cut off value of aGFR = 45 ml/min/1.73 m2was 91.8%, and recommended as a criterion in the selection of DPSM and SPSM. When GFR ≥30 ml/min/1.73 m2, tGFR can be predicted from sGFR, which will simplify the reference GFR measurement in clinical trials. sGFR becomes widely scattered when tGFR is less than 30 ml/min/1.73 m2. To obtain reliable reference GFR values, it is recommended that DPSM be used in clinical trials when aGFR is less than 45 ml/min/1.73 m2. [ABSTRACT FROM AUTHOR]

Background: Previous studies have indicated that creatinine (Cr)-based glomerular filtration rate (GFR) estimating equations - including the new Chronic Kidney Disease Epidemiology creatinine (CKD-EPI cr ) equation without race and the estimated glomerular filtration rate (eGFR) equation developed for the Chinese population - displayed suboptimal performance in patients with neurogenic lower urinary tract dysfunction (NLUTD), which limited their clinical application for detecting changes in GFR levels in all cohorts., Objective: To develop a neural network model based on multilayer perceptron (MLP) for evaluating GFR in Chinese NLUTD patients, and compare the diagnostic performance with Cr-based multiple linear regression equations for Chinese and the CKD-EPI cr equation without race., Design: Single-center, cross-sectional study of GFR estimation from serum Cr, demographic data, and clinical characteristics in Chinese patients with NLUTD., Patients: A total of 204 NLUTD patients, from 27 different geographic regions of China, were selected. A random sample of 141 of these subjects was included in the training sample set, and the remaining 63 patients were included in the testing sample set., Methods: The reference GFR (rGFR) was assessed by the technetium-99m-labeled diethylenetriaminepentaacetic acid ( 99m Tc-DTPA) double plasma sample method. A neural network model based on MLP was developed to evaluate GFR in the training sample set, which was then validated in the testing sample set and compared with Cr-based GFR equations., Results: The MLP-based model showed significant performance improvement in evaluating the difference, absolute difference, precision, and accuracy of GFR estimation compared with the Cr-based GFR equations. Additionally, compared with the rGFR, we found that the MLP-based model provided an acceptable level of accuracy (greater than 85%, which was within a 30% deviation from the rGFR)., Conclusion: The MLP-based model offered significant advantages in estimating GFR in Chinese NLUTD patients, and its application could be suggested in clinical practice.

Background: The liver plays a central role in the synthesis and metabolism of homocysteine (Hcy). The present study aimed to determine the prognostic role of serum Hcy levels in patients with HBV-related acute-on-chronic liver failure (AoCLF)., Methods: Fifty-two AoCLF and 52 chronic hepatitis B (CHB) patients were recruited. The virological parameters and biochemical examination of blood were obtained after 12 hours of fasting. In the AoCLF group, the relationships between the prognosis and the Hcy level were analyzed. The primary end-point was 3-month in-hospital mortality., Results: A significantly higher Hcy level was detected in AoCLF patients than in the healthy controls (HCs) and CHB groups (both p < 0.01). The Hcy level was positively correlated with the model of end-stage liver disease (MELD) score and the creatinine levels and was inversely correlated with the estimated glomerular filtration rate. Moreover, Hcy levels at presentation were higher among non-survivors than survivors in AoCLF patients. Multivariate analysis suggested that both Hcy level and MELD score were independent predictors of 3-month mortality in patients with AoCLF (p < 0.001)., Conclusions: Serum Hcy level measured at admission may serve as a biomarker for 3-month mortality rate in patients with HBV-AoCLF.

Objective: To investigate the expression of mRNA and protein of Calcium activated chloride channel (CLCA2) in hypoxic pulmonary artery smooth muscle cell (PASMCs) of rat and it's relationship with ERK1/2 signal pathway., Methods: PASMCs were randomly divided into 5 groups including normal group(N group), hypoxia group(H group), DMSO group(D group), U0126 group (U group) and Staurosporine aglycone group(SA group). The protein expression of CLCA2 in PASMCs was detected by Western blot.The mRNA expression of CLCA2 was detected by half quantitative reverse transcription polymerase chain reaction (RT-PCR)., Results: The mRNA and protein expressions of CLCA2 in H group were significantly higher than N group ( P <0.01). Comparing with D group,the mRNA and protein expressions of CLCA2 were significantly increased in U group ( P <0.01),the mRNA expression of CLCA2 in SA group was obviously decreased ( P <0.01) with slightly decreasing of its protein expression., Conclusions: Hypoxia promotes the expressions of mRNA and protein of CLCA2 in rat PASMCs. The ERK1/2 pathway activator Staurosporine aglycone reduces the mRNA and protein expression of CLCA2 in rats PASMCs and the ERK1/2 pathway inhibitor U0126 induces the upregulation of the mRNA and protein expressiosn of CLCA2 in rats PASMCs.

The aim of the present study is to investigate the expressions of ATP-sensitive K(+) channels (KATP) in pulmonary artery smooth muscle cells (PASMCs) and the relationship with p38 MAPK signal pathway in rats. Male SD rat PASMCs were cultured in vitro, and a model of hypoxia and hypercapnia was reconstructed. PASMCs were divided to normal (N), hypoxia-hypercapnia (H), hypoxia-hypercapnia+DMSO incubation (HD), hypoxia-hypercapnia+SB203580 (inhibitor of p38 MAPK pathway) incubation (HS) and hypoxia-hypercapnia+Anisomycin (agonist of p38 MAPK pathway) incubation (HA) groups. Western blot was used to detect the protein expression of SUR2B and Kir6.1; semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of SUR2B and Kir6.1. The results demonstrated that: (1) Compared with N, H, HD and HS groups, the expressions of Kir6.1 mRNA and protein in PASMCs of HA group were decreased significantly (P < 0.01), but there were no differences among N, H, HD and HS groups (P > 0.05); (2) Compared with N group, the expressions of SUR2B mRNA and protein in H, HD, HS and HA groups were increased significantly (P < 0.05), but there were no differences among H, HD, HS and HA groups (P > 0.05). The results imply that: (1) Hypoxia-hypercapnia, SB203580 didn't change the expressions of Kir6.1 mRNA and protein in PASMCs, but Anisomycin decreased the expressions of Kir6.1 mRNA and protein, so Kir6.1 may be regulated by the other subfamily of MAPK pathway; (2) Hypoxia-hypercapnia raised SUR2B mRNA and protein expressions in PASMCs, but SB203580 and Anisomycin did not affect the changes, so the increasing of SUR2B mRNA and protein induced by hypoxia-hypercapnia may be not depend on p38 MAPK pathway.

Objective: To investigate the role of p38 MAPK on ischemic postconditioning (IPO) attenuating pneumocyte apoptosis after lung ischemia/reperfusion injury (LIRI)., Methods: Forty adult male SD rats were randomly divided into 5 groups based upon the intervention (n = 8): control group (C), LIR group (I/R), LIR + IPO group (IPO), IPO + solution control group (D), IPO + SB203580 group (SB). Left lung tissue was isolated after the 2 hours of reperfusion, the ratio of wet lung weight to dry lung weight (W/D), and total lung water content (TLW) were measured. The histological structure of the left lung was observed under light and electron transmission microscopes, and scored by alveolar damage index of quantitative assessment (IQA). Apoptosis index (AI) of lung tissue was determined by terminal deoxynuleotidyl transferase mediated dUTP nick end and labeling (TUNEL) method. The mRNA expression and protein levels of and Bax were measured by RT-PCR and quantitative immunohistochemistry (IHC)., Results: Compared with C group, W/D, TLW, IQA, AI and the expression of Bax of I/R were significantly increased, the expression of Bcl-2 and Bcl-2/Bax were significantly decreased (P < 0.05, P < 0.01), and was obviously morphological abnormality in lung tissue. Compared with I/R group, all the indexes of IPO except for the expression of Bcl-2 and Bcl-2/ Bax were obviously reduced, the expression of Bcl-2 and Bcl-2/Bax were increased (P < 0.05, P < 0.01). All the indexes between D and IPO were little or not significant( P > 0.05). The expression of Bcl-2 and Bcl-2/Bax of SB were significantly increased and other indexes were reduced than those of IPO (P < 0.05, P < 0.01)., Conclusion: IPO may attenuate pneumocyte apoptosis in LIRI by inactivation of p38 MAPK, up-regulating expression of Bcl-2/Bax ratio.

The aim of the present study was to investigate the roles of calcium-activated chloride channels (Cl(Ca)) in the two-phase hypoxic pulmonary vasoconstriction (HPV). The second pulmonary artery branches were dissected from male Sprague-Dawley rats, and the changes in vascular tone were measured by using routine blood vascular perfusion in vitro. The result showed that, under normoxic conditions, Cl(Ca) inhibitors (NFA and IAA-94) significantly relaxed second pulmonary artery contracted by norepinephrine (P < 0.01), but merely had effects on KCl-induced second pulmonary artery contractions. A biphasic contraction response was induced in second pulmonary artery ring pre-contracted with norepinephrine exposed to hypoxic conditions for at least one hour, but no biphasic contraction was observed in pulmonary rings pre-contracted with KCl. NFA and IAA-94 significantly attenuated phase II sustained hypoxic contraction (P < 0.01), and also attenuated phase I vasodilation, but had little effect on phase I contraction. These results suggest that Cl(Ca) is an important component forming phase II contraction in secondary pulmonary artery, but not involved in phase I contraction.

Objective: To investigate the role and significance of ATP-sensitive K+ channels in the pathological process of hypoxia hypercapnia-induced pulmonary vasoconstriction (HHPV) and the relationship with ERK1/2 signal pathway in rats., Methods: We made the third pulmonary artery rings of SD rats, used the model of pulmonary artery rings perfusion in vitro. Under acute hypoxia hypercapnia condition, and observed the effects of the three stages of HHPV incubated by glybenclamide(Gly) and the combined application of Gly and U0126. At the same time, the values of rings' tension changes were recorded via the method of hypoxia hypercapnia conditions reactivity., Results: Under the normoxia condition, the values of the third pulmonary artery rings tension were relatively stable, but under the hypoxia hypercapnia condition, we observed a biphasic pulmonary artery contractile response compared with N group (P < 0.05, P < 0.01). When the third pulmonary artery rings incubated by Gly, it's phase II persistent vasoconstriction was enhanced compared with the H group (P < 0.05, P < 0.01), and the phase I vasoconstriction was also heightened. Moreover, under the hypoxia hypercapnia condition, U0126 could significantly relieve the phase II persistent vasoconstriction compared with HD group (P < 0.05, P < 0.01) induced by Gly, but the phase I acute vasoconstriction and the phase I vasodilation had no changes (P > 0.05)., Conclusion: Gly may mediate HHPV via activating ERK1/2 signal transduction pathway.

Objective: The tumor suppressor gene, Ras-association domain family (RASSF)2A, is inactivated by promoter hypermethylation in many cancers. The current study was performed to evaluate the methylation status of RASSF2A in epithelial ovarian cancer (EOC) tissues and plasma, and correlations with gene expression and clinicopathologic characteristics., Method: We detected methylation of the RASSF2A gene in tissues and corresponding plasma samples from 47 EOC patients and 14 patients with benign ovarian tumors and 10 with normal ovarian tissues. The methylation status was determined by methylation-specific PCR while gene expression of mRNA was examined by RT-PCR. The EOC cell line, SKOV3, was treated with 5-aza-2'-deoxycytidine (5-aza- dC)., Results: RASSF2A mRNA expression was significantly low in EOC tissues. The frequency of aberrant methylation of RASSF2A was 51.1% in EOC tissues and 36.2% in corresponding plasma samples, whereas such hypermethylation was not detected in the benign ovarial tumors and normal ovarian samples. The expression of RASSF2A mRNA was significantly down-regulated or lost in the methylated group compared to the unmethylated group (p<0.05). After treatment with 5-aza-dC, RASSF2A mRNA expression was significantly restored in the Skov3 cell line., Conclusion: Epigenetic inactivation of RASSF2A through aberrant promoter methylation may play an important role in the pathogenesis of EOC. Methylation of the RASSF2A gene in plasma may be a valuable molecular marker for the early detection of EOC.

Objective: To investigate the effects of ischemic postconditioning (IPostC) on pneumocyte apoptosis after lung ischemia/reperfusion injury in rats., Methods: Adult male SD rats were randomly divided into 3 groups based upon the intervention (n = 8): control group (C), lung ischemic reperfusion group (LIR), LIR+ IPostC group (IPostC). At the end of the experiment, blood specimens drawn from the arteria carotis were tested for the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and myeloperoxidase (MPO); the pneumocyte apoptosis index (AI) was achieved by tennrminal deoxynucleotidyl transferase mediated dUTP nick end abeling (TUNEL); the expression of Bcl-2, Bax protein in lung tissue was accessed by quantitative immunohistochemistry (MHC) and Bcl-2, Bax mRNA by RT-PCR., Results: IPostC could significantly attenuate the MDA level, MPO activity and improve SOD activity in blood serum which was comparable to I/R and significantly reduced the number of TUNEL-positive cells compared with I/R group, expressed as Al (% total nuclei) from (39.0 +/- 3.46) to (8.0 +/- 0.88) (P < 0.01). The protein and mRNA expression of Bcl-2 and Bax showed that IPO significantly attenuated the ischemia/reperfusion-upregulated expression of Bax protein but improved the expression of Bcl-2 that improved the Bcl-2/Bax ratio (P < 0.01) ., Conclusion: IPostC may attenuate pneumocyte apoptosis in LIRI by up-regulating expression of Bcl-2/Bax ratio and by inhibiting oxidant generation and neutrophils filtration.

Objective: To investigate the effect of chloride channel blocker--niflumic acid (NFA) on the pathological process of hypoxia hypercapnia-induced pulmonary vasoconstriction in rats., Methods: We used the model of hypoxia hypercapnia-induced pulmonary vasoconstriction rats, and divided the second, third branch pulmonary artery rings randomly into four groups (n = 8): control group (N group), hypoxia hypercapnia group (H group), DMSO incubation group (HD group), niflumic acid group (NFA group). Under acute hypoxia hypercapnia conditions, we observed the effects of the three stages of hypoxia hypercapnia-induced pulmonary vasoconstriction (HHPV) incubated by NFA in the second, third brach pulmonary artery rings. At the same time, the values of rings' tension changings were recorded via the method of hypoxia hypercapnia conditions reactivity. And investigated the effect of NFA to HHPV., Results: (1) Under the hypoxia hypercapnia condition, we observed a biphasic pulmonary artery contractile (the phase I rapid contraction and vasodilation; the phase II sustained contraction) response in both the second and the third branch pulmonary artery rings compared with the control group (P < 0.05 , P < 0.01); (2) The second and third pulmonary artery rings incubated by NFA which phase II persistent vasoconstriction were significantly attenuated compared with the H group (P < 0.05 , P < 0.01)., Conclusion: The blocker of the chloride channels attenuates the second and third branch pulmonary artery rings constriction in rat, especially the phase II persistent vasoconstriction, so then have an antagonistic effect on HHPV.

Objective: To find an applicable condition of the single-plasma-sample method (SPSM) to measure the glomerular filtration(GFR) with (99m)Tcj Diethylene Triamine Pentaacetic Acid ((99m)Tc-DTPA), and predict the value of (99m)Tc-DTPA plasma clearance by dual plasma sample method (DPSM ) from that by SPSM., Methods: Three hundred and thirty five patients with chronic kidney disease (CKD) were selected (192 males and 143 females). The average age was 51.91+/-14.76 years. The GFR was determined simultaneously by 2 methods: (1) SPSM (sGFR); (2) DPSM (tGFR), using DPSM as reference standard, sGFR calculated from the different SPSM was compared with tGFR. An equation was developed to predict tGFR from sGFR. GFR estimated by abbreviated Modification of Diet in Renal Disease (MDRD) equation (aGFR) was evaluated as the criterion in selection of DPSM and SPSM. The condition that DPSM could be substituted by SPSM in GFR measurement was given., Results: When tGFR >or= 30 mL/(minx1.73 m(2)), all of the sGFR were significantly correlated with tGFR. Among them, Watson modified Christensen and Groth's equation at sample time=240 min tended to be the most accurate (r=0.977, RMSE=10.91), and tGFR could be predicted from sGFR using the equation: Predicted tGFR [mL/(minx1.73 m(2))]=7.755 4+0.789 3xsGFR+0.002 4 xsGFR2 (n=297, r2=0.959 1, P<0.001). When aGFR was less than 50 mL/(minx1.73 m(2)), the diagnostic sensitivity of tGFR<30 mL/(minx1.73 m(2)) was 94.7%, and recommended as the criterion in selection of DPSM and SPSM., Conclusion: When aGFR >or=50 mL/(minx1.73 m(2)), DPSM can be substituted by SPSM in GFR measurement.

Objective: To understand the applicability of MDRD equation in Chinese patients with chronic kidney disease (CKD). Glomerular filtration rate (GFR) estimated with MDRD equation, abbreviated MDRD equation and Cockcroft-Gault equation was compared with (99m)Tc-DTPA plasma clearance by dual plasma sampling method in different stages of CKD., Methods: CKD were diagnosed according to K/DOQI guideline.298 patients with CKD were selected. Patients'sex, age, height and body weight were recorded and plasma creatinine, urea nitrogen and albumin were measured in a single clinical laboratory. (99m)Tc-DTPA plasma clearance was calculated and standardized by body surface area (sGFR). GFRs estimated with MDRD equation 7, abbreviated MDRD equation and Cockcroft-Gault equation (7GFR, aGFR and cGFR) were compared with sGFR in different stages of CKD., Results: There were 165 male and 133 female in the selected 298 patients with CKD;the average age was (52.5 +/- 15.5) years. There was significant difference between the GFRs of the 3 equations with sGFR in different stages of CKD (P < 0.001). 7GFR, aGFR and cGFR were significantly higher than sGFR in CKD stages 5-4; the lower the sGFR, the more the differences. 7GFR, aGFR and cGFR were significantly lower than sGFR in CKD stage 2-1; the higher the sGFR, the more the differences., Conclusion: Our results showed that in Chinese population with CKD, MDRD equation 7, abbreviated MDRD equation and Cockcroft-Gault equation overestimate actual GFR in CKD stages 4-5 and underestimate GFR in CKD stages 1-2. These results indicate that MDRD equation and its modifications for estimation of GFR should be amended when applying to Chinese patients with CKD in clinical practice.