1.Effect of Huanglian Jiedutang in Regulating Ferroptosis in Mice with Atherosclerosis Based on Nrf2/GPX4 Signaling Pathway
Zhaohui GONG ; Li GAO ; Huiqi ZHAI ; Jinzi YU ; Qingmin CHU ; Chuanjin LUO ; Lijin QING ; Wei WU ; Rong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):22-28
ObjectiveTo study the mechanism of Huanglian Jiedutang (HLJDT) in treating mice with atherosclerosis (AS) by improving ferroptosis. MethodsA total of 10 SPF C57BL/6J mice were selected as a normal group, and 50 ApoE-/- mice were randomly divided into five groups: model group, low-dose group of HLJDT, medium-dose group of HLJDT, high-dose group of HLJDT, and atorvastatin (ATV) group. ApoE-/- mice were fed a high-fat diet for eight weeks to establish the AS model, and at the 9th week, they were given normal saline, low, medium, and high doses of HLJDT (3.9, 7.8, 15.6 g·kg-1·d-1), and atorvastatin calcium tablets (0.01 g·kg-1·d-1), respectively, for a total of eight weeks. The formation of aortic plaque in mice was observed by gross oil red O staining and Masson staining. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) in blood fat were measured by the automatic biochemical analyzer, and the mitochondrial structure of the aorta was observed by transmission electron microscopy. The content of serum superoxide dismutase (SOD) in serum was detected by enzyme-linked immunosorbent assay (ELISA). The content of reduced glutathione (GSH) in serum was detected by the microplate method, and that of malondialdehyde (MDA) in serum was detected by the TBA method. The protein expression of nuclear factor E2-associated factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway was detected by Western blot. ResultsCompared with those of the normal group, the contents of TC, LDL-C, TG, HDL-C, and MDA in the serum and the aortic vascular plaque deposition of the model group were significantly increased (P<0.01), while the expression levels of SOD and GSH in serum, as well as Nrf2, solute carrier family 7 member 11 (SLC7A11), and GPX4 in aorta were significantly decreased (P<0.01). Mice in the model group appeared mitochondrial fragmentation and vacuolation in the aorta, volume atrophy, mitochondrial crista reduction, or a loose and disorganized form. Compared with those in the model group, the aortic vascular plaque deposition was significantly decreased in the low-dose, medium-dose, and high-dose groups of HLJDT and ATV group, and the contents of serum TC, LDL-C, TG, and MDA in serum were significantly decreased (P<0.05, P<0.01). The contents of serum SOD and GSH and the expression levels of Nrf2, SLC7A11, and GPX4 in the aorta were increased (P<0.05, P<0.01), and the symptoms of aortic mitochondrial vacuolation were alleviated. The number of cristae was increased, and they were ordered neatly. ConclusionHLJDT can reduce aortic vascular plaque deposition, decrease blood lipid and MDA expression, increase SOD and GSH expression, and ameliorate the pathological changes of ferroptosis, the mechanism of which is related to the Nrf2/GPX4 signaling pathway.
2.Short-term efficacy of oblique lateral interbody fusion combined with lateral plate fixation in treatment of single-level lumbar degenerative disease
Xiaoyin LIU ; Jianqun ZHANG ; Zhen CHEN ; Simin LIANG ; Zhiqiang WANG ; Zongjun MA ; Rong MA ; Zhaohui GE
Chinese Journal of Tissue Engineering Research 2025;29(3):531-537
BACKGROUND:Stand-alone oblique lateral interbody fusion has a high rate of complications of fusion segment sink.Oblique lateral interbody fusion with posterior fixation can provide stable support,but intraoperative position changes and double incisions weaken the advantages of this technique.Oblique lateral interbody fusion combined with lateral plate fixation can achieve one-stage decompression in the same incision,while the lateral internal fixation provides stable support. OBJECTIVE:To analyze the short-term efficacy of oblique lateral interbody fusion combined with lateral plate fixation in the treatment of single-level lumbar degenerative disease. METHODS:The clinical data of 34 patients with single-level lumbar degenerative disease treated with oblique lateral interbody fusion combined with lateral plate fixation were collected from May 2020 to October 2022.Among them,14 were males and 20 were females aged from 41 to 72 years at the mean age of(58.6±9.9)years.There were 11 cases of lumbar spondylolisthesis(Ⅰ°),7 cases of lumbar disc herniation with segmental instability,and 16 cases of lumbar spinal stenosis.Operation time,blood loss,and complications were recorded.Visual analog scale scores of lumbago,radiative pain of both lower limbs,and Oswestry disability index scores were evaluated before surgery,3 months after surgery,and the last follow-up.Dural sac cross-sectional area,intervertebral height,and intervertebral fusion were measured and observed. RESULTS AND CONCLUSION:(1)The 34 patients were followed up for 14-36 months,with an average of(21.3±5.2)months.(2)The operation time ranged from 50 to 92 minutes,with an average of(68.5±11.1)minutes.Intraoperative blood loss was 50-170 mL,with an average of(71.6±25.3)mL.(3)Compared with the preoperative results,the visual analog scale scores and Oswestry disability index scores were significantly decreased at 3 months after surgery and at the last follow-up(P<0.001),and the maximum Oswestry disability index scores were improved by nearly 50%.(4)Bone fusion was achieved in all patients during half-year follow-up.The overall complication rate was 21%(7/34),including 1 case of plate displacement,3 cases of cage subsidence,1 case of psoas weakness,and 2 cases of anterior thigh pain.(5)It is concluded that oblique lateral interbody fusion combined with lateral plate fixation for the treatment of lumbar degenerative diseases has the characteristics of less blood loss,short operation time,rapid postoperative recovery,and significant short-term clinical efficacy with the stable support to a certain extent.The long-term curative effect needs further follow-up observation.
3.One-stage posterior hemivertebra resection and pedicle screw fixation in treatment of congenital scoliosis:a 2-year follow-up of correction effect
Wanzhong YANG ; Rong MA ; Wei GUO ; Zhiqiang WANG ; Wei YANG ; Zhen CHEN ; Zemin WANG ; Honglai ZHANG ; Zhaohui GE
Chinese Journal of Tissue Engineering Research 2025;29(33):7173-7180
BACKGROUND:Hemivertebra deformity should be treated surgically at an early age,but the risk factors for progression of deformity after hemivertebral resection have not been established.OBJECTIVE:To investigate the curative effect of one-stage posterior hemivertebrae resection and pedicle screw fixation in the treatment of congenital scoliosis,and to further explore the risk factors causing the progression of postoperative deformity.METHODS:The medical records of patients who underwent pedicle screw-rod fixation for unilateral hemivertebral deformity from January 2012 to February 2020 and were followed up for at least 2 years were retrospectively analyzed,and a total of 116 patients met the inclusion criteria.All patients were treated with standing anterior and lateral spinal radiographs taken before,after and at each follow-up time point.The segment Cobb angle,the total scoliosis Cobb angle,the proximal complementary Cobb angle,the distal complementary Cobb angle,and the coronal balance distance,apical vertebra distance,upper instrumented vertebra tilt,upper instrumented vertebra disc angle,lower instrumented vertebra tilt,lower instrumented vertebra disc angle,segmental kyphosis/lordosis,thoracic kyphosis,lumbar lordosis and sagittal vertical axis were measured.The progression of deformity and complications were also recorded.RESULTS AND CONCLUSION:(1)Segment Cobb,total scoliosis Cobb,segmental kyphosis,proximal complementary Cobb,and distal complementary Cobb were significantly corrected after operation(P<0.05),and remained corrected at the last follow-up.Thoracic kyphosis,lumbar lordosis,coronal balance distance,and sagittal vertical axis were all in the normal range pre-operation,after operation and at the last follow-up.(2)During follow-up,10 patients developed coronary decompensation,which was characterized by abnormal progression.(3)Independent sample t-test showed that preoperative total scoliosis Cobb,preoperative apical vertebra distance,age,Risser sign,postoperative upper instrument vertebra tilt and postoperative lowest instrumented vertebra tilt were correlated with postoperative malformation progression(P<0.05).(4)Multivariate Logistic regression analysis showed that postoperative lowest instrumented vertebra tilt was an independent risk factor for postoperative malformation progression(P=0.002,OR=1.526).(5)Receiver operating characteristic curve analysis showed that a postoperative lowest instrumented vertebra tilt of 8.14° was the optimal threshold for deformity progression after hemivertebrae resection and pedicle rod fixation(sensitivity 0.900,specificity 0.906,area under curve:0.926).(6)It is indicated that the treatment of congenital scoliosis with one-stage posterior hemivertebrae resection and pedicle nail fixation can achieve satisfactory orthopedic effect.Postoperative lowest instrumented vertebra tilt greater than 8.14° was an independent risk factor for postoperative coronal decompensation.
4.One-stage posterior hemivertebra resection and pedicle screw fixation in treatment of congenital scoliosis:a 2-year follow-up of correction effect
Wanzhong YANG ; Rong MA ; Wei GUO ; Zhiqiang WANG ; Wei YANG ; Zhen CHEN ; Zemin WANG ; Honglai ZHANG ; Zhaohui GE
Chinese Journal of Tissue Engineering Research 2025;29(33):7173-7180
BACKGROUND:Hemivertebra deformity should be treated surgically at an early age,but the risk factors for progression of deformity after hemivertebral resection have not been established.OBJECTIVE:To investigate the curative effect of one-stage posterior hemivertebrae resection and pedicle screw fixation in the treatment of congenital scoliosis,and to further explore the risk factors causing the progression of postoperative deformity.METHODS:The medical records of patients who underwent pedicle screw-rod fixation for unilateral hemivertebral deformity from January 2012 to February 2020 and were followed up for at least 2 years were retrospectively analyzed,and a total of 116 patients met the inclusion criteria.All patients were treated with standing anterior and lateral spinal radiographs taken before,after and at each follow-up time point.The segment Cobb angle,the total scoliosis Cobb angle,the proximal complementary Cobb angle,the distal complementary Cobb angle,and the coronal balance distance,apical vertebra distance,upper instrumented vertebra tilt,upper instrumented vertebra disc angle,lower instrumented vertebra tilt,lower instrumented vertebra disc angle,segmental kyphosis/lordosis,thoracic kyphosis,lumbar lordosis and sagittal vertical axis were measured.The progression of deformity and complications were also recorded.RESULTS AND CONCLUSION:(1)Segment Cobb,total scoliosis Cobb,segmental kyphosis,proximal complementary Cobb,and distal complementary Cobb were significantly corrected after operation(P<0.05),and remained corrected at the last follow-up.Thoracic kyphosis,lumbar lordosis,coronal balance distance,and sagittal vertical axis were all in the normal range pre-operation,after operation and at the last follow-up.(2)During follow-up,10 patients developed coronary decompensation,which was characterized by abnormal progression.(3)Independent sample t-test showed that preoperative total scoliosis Cobb,preoperative apical vertebra distance,age,Risser sign,postoperative upper instrument vertebra tilt and postoperative lowest instrumented vertebra tilt were correlated with postoperative malformation progression(P<0.05).(4)Multivariate Logistic regression analysis showed that postoperative lowest instrumented vertebra tilt was an independent risk factor for postoperative malformation progression(P=0.002,OR=1.526).(5)Receiver operating characteristic curve analysis showed that a postoperative lowest instrumented vertebra tilt of 8.14° was the optimal threshold for deformity progression after hemivertebrae resection and pedicle rod fixation(sensitivity 0.900,specificity 0.906,area under curve:0.926).(6)It is indicated that the treatment of congenital scoliosis with one-stage posterior hemivertebrae resection and pedicle nail fixation can achieve satisfactory orthopedic effect.Postoperative lowest instrumented vertebra tilt greater than 8.14° was an independent risk factor for postoperative coronal decompensation.
5.Biomechanical Evaluation of Oblique Lateral Interbody Fusion Combined with Different Internal Fixation Methods for Treating Degenerative Lumbar Scoliosis:A Finite Element Analysis
Shulong YANG ; Rong MA ; Zhiqiang WANG ; Simin LIANG ; Zhen CHEN ; Xiaoyin LIU ; Jianqun ZHANG ; Zhaohui GE
Journal of Medical Biomechanics 2023;38(1):E052-E058
Objective To verify the biomechanical stability of oblique lateral interbody fusion ( OLIF) combinedwith different fixation methods for treating degenerative lumbar scoliosis (DLS) by three-dimensional (3D) finite element analysis. Methods The L1-S1 3D finite element DLS model ( Model 1) was established, and then the OLIF (L2-5) at 3 contiguous levels of fusion and its combination with different internal fixation methods were simulated, namely, stand-alone OLIF model ( Model 2), vertebral screw fixation model ( Model 3), unilateral pedicle screw fixation model (Model 4) and bilateral pedicle screw fixation model (Model 5) were established,respectively. Under upright, flexion, extension, lateral bending and axial rotation states, range of motion (ROM) of fusion segments, as well as cage stress, internal fixation stress, and stress distribution were recorded and analyzed. Results Under six motion states, the overall ROM of fusion segments in Models 2-5 was smaller than that of Model 1. Compared with Model 1, the overall ROM reduction of Model 3 and Model 4 was larger than that of Model 2 and smaller than that of Model 5. Under flexion and extension, the overall ROM reduction of Model 4 and Model 5 was basically equal. Under left and right lateral bending, the overall ROM reduction of Model 3 and Model 5 was basically equal. Under all motion states, the peak stress of Model 3 and Model 4 fusion cage was larger than that of Model 5 and smaller than that of Model 2. The peak stresses of L2-3, L3-4 and L4-5 fusion cages in Model 3 increased by 5. 52% , 10. 96% and 7. 99% respectively compared with Model 5 under left lateral bending, and the peak stresses of L2-3, L3-4 and L4-5 fusion cages in Model 4 increased by 8. 70% , 7. 00% and 6. 99% respectively under flexion. Under all motion states, the peak stress of screw rod in Model 5 was smaller than that of Model 3 and Model 4, and the peak stresses of screw rod in Models 3-5 were the smallest in upright state. Conclusions The OLIF with unilateral pedicle screw fixation or vertebral screw fixation can provide favorable biomechanical stability of the fusion segment. The results provide some references for clinical application of OLIF technology in the treatment of DLS.
6.Darbepoetin alfa injection versus epoetin alfa injection for treating anemia of Chinese hemodialysis patients with chronic kidney failure: A randomized, open-label, parallel-group, non-inferiority Phase III trail
Nan CHEN ; Changying XING ; Jianying NIU ; Bicheng LIU ; Junzhou FU ; Jiuyang ZHAO ; Zhaohui NI ; Mei WANG ; Wenhu LIU ; Jinghong ZHAO ; Ling ZHONG ; Xiongfei WU ; Wenge LI ; Yuqing CHEN ; Wei SHI ; Jianghua CHEN ; Aiping YIN ; Ping FU ; Rong WANG ; Gengru JIANG ; Fanfan HOU ; Guohua DING ; Jing CHEN ; Gang XU ; Yuichiro KONDO ; Yuliang SU ; Changlin MEI
Chronic Diseases and Translational Medicine 2022;08(1):59-70
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.
7.Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients: A randomized, open-label, parallel-group, noninferiority phase III trial
Bicheng LIU ; Nan CHEN ; Jinghong ZHAO ; Aiping YIN ; Xiongfei WU ; Changying XING ; Gengru JIANG ; Junzhou FU ; Mei WANG ; Rong WANG ; Jianying NIU ; Ping FU ; Zhaohui NI ; Fanfan HOU ; Jiuyang ZHAO ; Jing CHEN ; Yuqing CHEN ; Wei SHI ; Jianghua CHEN ; Wenge LI ; Gang XU ; Ling ZHONG ; Wenhu LIU ; Guohua DING ; Yuichiro KONDO ; Changhe YUE ; Changlin MEI
Chronic Diseases and Translational Medicine 2022;08(2):134-144
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.
8.Darbepoetin alfa injection versus epoetin alfa injection for treating anemia of Chinese hemodialysis patients with chronic kidney failure: A randomized, open-label, parallel-group, non-inferiority Phase III trail
Nan CHEN ; Changying XING ; Jianying NIU ; Bicheng LIU ; Junzhou FU ; Jiuyang ZHAO ; Zhaohui NI ; Mei WANG ; Wenhu LIU ; Jinghong ZHAO ; Ling ZHONG ; Xiongfei WU ; Wenge LI ; Yuqing CHEN ; Wei SHI ; Jianghua CHEN ; Aiping YIN ; Ping FU ; Rong WANG ; Gengru JIANG ; Fanfan HOU ; Guohua DING ; Jing CHEN ; Gang XU ; Yuichiro KONDO ; Yuliang SU ; Changlin MEI
Chronic Diseases and Translational Medicine 2022;08(1):59-70
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.
9.Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients: A randomized, open-label, parallel-group, noninferiority phase III trial
Bicheng LIU ; Nan CHEN ; Jinghong ZHAO ; Aiping YIN ; Xiongfei WU ; Changying XING ; Gengru JIANG ; Junzhou FU ; Mei WANG ; Rong WANG ; Jianying NIU ; Ping FU ; Zhaohui NI ; Fanfan HOU ; Jiuyang ZHAO ; Jing CHEN ; Yuqing CHEN ; Wei SHI ; Jianghua CHEN ; Wenge LI ; Gang XU ; Ling ZHONG ; Wenhu LIU ; Guohua DING ; Yuichiro KONDO ; Changhe YUE ; Changlin MEI
Chronic Diseases and Translational Medicine 2022;08(2):134-144
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.
10.Telehealth-based dialysis registration system for the improvement of renal anemia in maintenance hemodialysis:multicenter experiences
Zhaohui NI ; Haijiao JIN ; Gengru JIANG ; Niansong WANG ; Ai PENG ; Zhiyong GUO ; Shoujun BAI ; Rong ZHOU ; Jianrao LU ; Yi WANG ; Ying LI ; Shougang ZHUANG ; Chen YU ; Yueyi DENG ; Huimin JIN ; Xudong XU ; Junli ZHANG ; Junli ZHAO ; Xiuzhi YU ; Xiaoxia WANG ; Liming ZHANG ; Jianying NIU ; Kun LIU ; Xiaorong BAO ; Qin WANG ; Jun MA ; Chun HU ; Xiujuan ZANG ; Qing YU
Chinese Journal of Nephrology 2018;34(11):831-837
Objective To analyze the role of telehealth?based dialysis registration systems in real?time and dynamic reflection of renal anemia in hemodialysis (HD) patients, and discuss the prospect of its application in dialysis registration management. Methods The Red China project was to build up a dialysis registration system based on the WeChat mobile terminal platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, creatinine were recorded in this system. Hemoglobin (Hb) level was monthly recorded. The platform generated Hb statistics report for each HD center monthly, including the detection rate, target rate and the distribution level of Hb, and released it to physicians through the WeChat terminal of mobile phone. After that, physicians could change the treatment of anemia individually on basis of this report. Here the demographic and baseline laboratory parameters, the detection rate, target rate, the average level and the distribution of Hb from June 2015 to October 2017 after the project launched were analyzed. Results From June 2015 to October 2017, 8392 maintenance HD patients from 28 HD centers in Shanghai were enrolled, of whom 5059(60.3%) were male.The average rate age was (60.5 ± 13.7) years old. Baseline average Hb was (108.3±16.0) g/L. Baseline detection rate and target rate were 54.2%and 47.5%, respectively. After 28 months follow?up, the detection rate of Hb increased from 54.2% to 73.6% (P<0.001), the target rate of Hb increased from 47.5% to 56.1% (P<0.001), and the level of average Hb rose from (108.3±16.0) g/L to (110.7±16.0) g/L. The difference between average Hb in two consecutive months was less than 1.3 g/L. Conclusions The telehealth?based dialysis registration system can timely report the anemia situation of HD patients, which may improve the awareness rate of anemia, the degree of attention and the compliance of anemia monitoring, so as to improve the detection rate and target rate of Hb and reduce the fluctuation of Hb, which helps to maintain the HD patients to correct anemia in a timely, stable and long?term way. The telehealth?based dialysis registration system, as an improved mode of dialysis registration is a promising way for long?term management of renal anemia in dialysis patients.

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