Objective To observe the changes of invariant natural killer T(iNK T)cells in visceral adipose tissue and blood lipids of high-fat diet-fed mice,and to analyze the correlation between iNK T cells and lipid metabolism.Methods Fifty-two C57BL/6 mice were selected as the high-fat diet group,and 51 C57BL/6 mice as the normal control group.The high-fat diet intervention lasted for 12 weeks.At weeks 1,4,8,and 12,the epididymal and perirenal fats of mice in both groups were collected and weighed to record the visceral fat mass(VFM),and the changes in body fat content(BFC)were calculated.Flow cytometry and laser scanning confocal microscopy were used to detect the changes of invariant natural killer T(iNK T)cells in visceral adipose tissue.An automatic biochemical analyzer was used to measure the lipid levels in mice,and the correlations of iNKT cells in visceral adipose tissue with VFM,BFC,and serum lipid levels were analyzed.Results At 12 weeks after high-fat diet feeding,the body weight,VFM,BFC,serum total cholesterol(TC),triglyceride(TG)and high-density lipoprotein cholesterol(HDL-C)increased significantly,while the content of invariant natural killer T(iNK T)cells in visceral adipose tissue decreased obviously in the high-fat diet group,as compared with the control group(P＜0.01).The iNKT cell number in visceral adipose tissue of mice was negatively correlated with VFM,BFC,serum HDL-C and serum TG(r=-0.293,-0.289,-0.337,-0.199,P＜0.05),and was not correlated with serum TC and LDL-C(r=-0.122,-0.082,P＞0.05).Conclution VFM is increased and iNK T cell number is decreased in in adipose tissue of high-fat diet-fed mice.The number of iNK T cells is negatively correlated with VFM,BFC,serum HDL-C and TG.

Objective To observe the changes of invariant natural killer T(iNK T)cells in visceral adipose tissue and blood lipids of high-fat diet-fed mice,and to analyze the correlation between iNK T cells and lipid metabolism.Methods Fifty-two C57BL/6 mice were selected as the high-fat diet group,and 51 C57BL/6 mice as the normal control group.The high-fat diet intervention lasted for 12 weeks.At weeks 1,4,8,and 12,the epididymal and perirenal fats of mice in both groups were collected and weighed to record the visceral fat mass(VFM),and the changes in body fat content(BFC)were calculated.Flow cytometry and laser scanning confocal microscopy were used to detect the changes of invariant natural killer T(iNK T)cells in visceral adipose tissue.An automatic biochemical analyzer was used to measure the lipid levels in mice,and the correlations of iNKT cells in visceral adipose tissue with VFM,BFC,and serum lipid levels were analyzed.Results At 12 weeks after high-fat diet feeding,the body weight,VFM,BFC,serum total cholesterol(TC),triglyceride(TG)and high-density lipoprotein cholesterol(HDL-C)increased significantly,while the content of invariant natural killer T(iNK T)cells in visceral adipose tissue decreased obviously in the high-fat diet group,as compared with the control group(P＜0.01).The iNKT cell number in visceral adipose tissue of mice was negatively correlated with VFM,BFC,serum HDL-C and serum TG(r=-0.293,-0.289,-0.337,-0.199,P＜0.05),and was not correlated with serum TC and LDL-C(r=-0.122,-0.082,P＞0.05).Conclution VFM is increased and iNK T cell number is decreased in in adipose tissue of high-fat diet-fed mice.The number of iNK T cells is negatively correlated with VFM,BFC,serum HDL-C and TG.

Background::Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia.Methods::Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients ( n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group ( n = 56) and a twice or three times per week intravenous epoetin alfa group ( n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion::Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Background::Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia.Methods::Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients ( n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group ( n = 56) and a twice or three times per week intravenous epoetin alfa group ( n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion::Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Animals ; Biological Transport, Active/physiology* ; Centrioles/metabolism* ; Cilia/metabolism* ; Mice ; Mice, Mutant Strains ; N-Acetylglucosaminyltransferases/metabolism*

Objective To assess the efficacy and safety of ultrasound-guided percutaneous transluminal angioplasty (PTA) for treatment of stenosis of autogenous arteriovenous fistulas in maintenance hemdialysis patients. Methods From September 2016 to August 2017, thirty patients with autologous arteriovenous fistula (AVF) stenosis diagnosed in Guangzhou First People′s Hospital underwent PTA under the guidance of ultrasound for the first time. The vascular diameter of AVF stenosis and the blood flow of AVF before and after operation were evaluated. During the follow-up period,the patency time and complications were recorded. Results In 93. 3%( 28/30) patients, primary ultrasound-guided PTA procedures were successfully performed. The internal diameter of the stenosis increased from (1. 62±0. 30) mm preoperatively to (3. 61±0. 66) mm postoperatively (t＝18. 205,P＜0. 001),and the natural blood flow increased from (270. 0±36. 5) ml/min preoperatively to (611. 4±46. 6) ml/min postoperatively (t＝50. 221,P＜0. 001). The post-intervention primary patency rates at 90 and 180 d were 96. 4%(27/28) and 85. 7%(24/28), respectively. There was no rupture of the vein,or other severe complication during the PTA procedure. One patient had perilesional swelling,and one patient had extravasation after the PTA procedure. Conclusion Ultrasound-guided PTA is a safe and effective method for treatment of stenosis of autogenous arteriovenous fistulas in maintenance hemdialysis patients.

Animals ; Embryonic Stem Cells ; metabolism ; Histone Deacetylase 6 ; deficiency ; genetics ; metabolism ; Mice ; Reproduction ; genetics

Objective To investigate the role of miR-155 in diabetic nephropathy(DN)and its mecha-nism. Methods MiR-155 expression level in kidney was detected by real-time PCR and in situ hybridization. The target gene of miR-155 was predicted by bioinformatics and verified by Western Blot and double luciferase reporter activity. Western Blot was used to detect the related marker proteins of mesangial cells proliferation and mesangial matrix. Results (1)The expression of miR-155 increased in DN renal tissue and high glucose-stimulated renal cells.(2)MiR-155 was related to the regulation of Smad5 gene expression.(3)MiR-155 promoted the mesangial cells proliferation and increased extracellular matrix by down-regulating Smad5 expression. Conclusions MiR-155 can promote the mesangial cells proliferation and renal fibrosis by regulating Smad5 gene,providing a basis for further understanding the pathogenesis of DN.