1.The efficacy of blinatumomab in the treatment of pediatric B-cell acute lymphoblastic leukemia: a multicenter study
Weiling YAN ; Jun LU ; Hua WANG ; Lihua YU ; Huidi FENG ; Bai LI ; Wenguang JIA ; Jian WANG ; Wenting HU ; Xue TANG ; Jing FAN ; Yujie GUAN ; Xiaolan LI ; Yalan YOU ; Yongmin TANG ; Xiaojun XU
Chinese Journal of Pediatrics 2025;63(11):1194-1200
Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.
2.The efficacy of blinatumomab in the treatment of pediatric B-cell acute lymphoblastic leukemia: a multicenter study
Weiling YAN ; Jun LU ; Hua WANG ; Lihua YU ; Huidi FENG ; Bai LI ; Wenguang JIA ; Jian WANG ; Wenting HU ; Xue TANG ; Jing FAN ; Yujie GUAN ; Xiaolan LI ; Yalan YOU ; Yongmin TANG ; Xiaojun XU
Chinese Journal of Pediatrics 2025;63(11):1194-1200
Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.
3.The significance of detecting human cytomegalovirus UL95 antigenic epitope peptide in the diagnosis of SLE
Ya HU ; Chenyu XU ; Wei QIANG ; Huidi ZHANG ; Fangfang FENG
Chinese Journal of Laboratory Medicine 2024;47(9):1042-1051
Objective:To explore the clinical significance of the dominant B-cell epitope peptide of the human cytomegalovirus (HCMV) UL95 gene, as well as the correlation between the plasma UL95 specific antibody levels and clinical indicators in systemic lupus erythematosus (SLE) patients, in order to find auxiliary diagnostic indicators for SLE.Methods:A non-randomized control study was conducted to analyze the sequencial characteristics and polymorphisms of HCMV UL95 gene, and bioinformatics analysis and chemical synthesis were used to synthesize UL95 dominant B cell epitope short peptides, which were used as coating antigens. Enzyme-linked immunosorbent assay (ELISA) assay was used to detect the specific antibody levels of plasma UL95 of 97 SLE patients and 35 healthy controls (HC). Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of UL95 short peptide antibodies for SLE diagnosis. Pearson correlation test was used to analyze the correlation between UL95 specific antibody levels and clinical indicators in SLE patients.Results:The nucleotide sequence similarity of UL95 gene was 92.9%-100%, and the amino acid sequence similarity was 92.1%-100%, whose sequences were highly conserved and homologous. A comprehensive prediction of multiple parameters resulted in 6 possible dominant B cell epitopes, named (Bp1, Bp2, Bp3, Bp4, Bp5, Bp6) respectively. The ELISA results showed that the levels of plasma UL95 specific antibodies (0.35±0.12) in SLE patients were significantly higher than those of the HC group (0.28±0.10)( t=3.091, P=0.002). The area under the ROC curve for distinguishing SLE and HC was 0.703, with a sensitivity of 54.6% and a specificity of 88.6%. In addition, the UL95 specifific antibody levels ( OD value) in the middle-high activity subgroup (systemic lupus erythematosus disease activity index, SLEDAI≥4) were higher (0.36±0.10) than those in the low activity subgroup (SLEDAI<4)(0.30±0.07) ( t=?2.055, P=0.044). UL95 specific antibody levels were positively correlated with clinical indicators such as total immunoglobulin G (IgG) and total immunoglobulin M (IgM), while negatively correlated with complement component 3 (C3), complement component 4 (C4), and platelet count. Conclusions:The antibody level of UL95 is closely related to the activity of lupus disease. The Bp1 (10-21) peptide segment of UL95 has important significance for the auxiliary diagnosis of SLE and is expected to become a new reference indicator.
4.Effects of Jianpi Bushen Jiedu Prescription regulating JAK2/STAT3 pathway on proliferation and migration of hepatocellular carcinoma cells
Huidi LI ; Yuanyuan FENG ; Youying LAI ; Ru JIA ; Pingping ZHANG ; Xiaojun ZHU ; Hongjie LIU
International Journal of Traditional Chinese Medicine 2024;46(2):186-190
Objective:To explore the effects of Jianpi Bushen Jiedu Prescription on the proliferation and migration of hepatocellular carcinoma cells; To discuss its possible mechanism.Methods:Using human highly metastatic liver cancer cell line (HCCLM3) as the research object, they were randomly divided into control group and TCM group (100, 200, 400, 800, 1 600, 3 200 μg/ml Jianpi Bushen Jiedu Prescription) and Western medicine group (2.5, 5, 10, 20, 40 μmol/L sorafenib) using a random number table method. Cell viability was detected using cell counting reagent (CCK-8) method; HCCLM3 cells were divided into control group and TCM (Jianpi Bushen Jiedu Prescription 800 μg/ml) group and combined group (Jianpi Bushen Jiedu Prescription 800 μg/ml +sorafenib 20 μmol/L). Western blot method was used to detect the protein expressions of kinase/signaling transducer and transcriptional activator (JAK2/STAT3) pathway related proteins (p-JAK2, JAK2, p-STAT3, STAT3) in each group.Results:Compared with the control group, viability and mobility of HCCLM cell in TCM group and Western medicine group decreased ( P<0.01 or P<0.05); compared with the control group, the protein expressions of P-JAK2, JAK2, P-STAT3 and STAT3 in the TCM group and the combined group decreased ( P<0.05), and the JAK2 protein expression in the combined group was lower than that in the TCM group ( P<0.05). Conclusion:Jianpi Bushen Jiedu Prescription can inhibit the proliferation and migration of HCC cells by regulating JAK2/STAT3 pathway.
5.Construction of evaluation form with syndrome differentiation for lumbar disc herniation
Yuaner CHEN ; Xiaoyan XU ; Ying FENG ; Baoyu WANG ; Huidi CHENG
Chinese Journal of Nursing 2018;53(2):207-211
Objective To construct Evaluation Form for TCM Nursing with Syndrome Differentiation for Lumbar Disc Herniation in order to provide references for better nursing care of patients with lumbar disc herniation with syndrome differentiation.Methods According to the principle of "discern Yin and Yang,grasp the main symptoms",literature analysis and Delphi method were used to draft the primary and secondary symptoms of lumbar disc herniation's common syndromes,and Evaluation Form for TCM Nursing with Syndrome Differentiation for Lumbar Disc Herniation was developed.Totally 84 patients were recruited,and results evaluated by clinical physicians and nurses using the evaluation form were compared.Results By means of the evaluation form,80 patients were considered as the type of "Xue yu qi zhi",1 patient as the type of "Han shi bi zu",the others three as the type of "Gan shen kui xu";according to clinical physicians,83 patients were the type of "Xue yu qi zhi",and 1 patient was the type of "Gan shen kui xu".The consistency rate of two methods was 96.43%,and there was no significant difference (P>0.05).Conclusion There was no statistically significant difference between the results from clinical physicians and nurses using the evaluation form.The evaluation form is applicable in clinical practice,which can lay the foundation for nurses to carry out nursing with syndrome differentiation.
6.Dynamic changes of brain natriuretic peptide concentration and its diagnostic value for heart failure in early phase of acute myocardial infarction
Huidi LI ; Dingcheng XIANG ; Jinxia ZHANG ; Tianbing DUAN ; Feng LONG ; Aimin LI
Journal of Southern Medical University 2018;38(1):112-116
Objective To explore the dynamic changes in brain natriuretic peptide (BNP) concentration and the diagnostic value of BNP for heart failure at different time points in the early phase of acute myocardial infarction (AMI). Methods AMI patients who were admitted in our department between January 1, 2016 and July 31, 2016 and underwent emergency percutaneous coronary intervention (PCI) within 12 h after onset were enrolled in this study. All the patients received bedside examinations of BNP concentration and clinical cardiac function within 1 h after PCI and at 12, 20, 24 and 48 h after the onset of AMI. According to the peak BNP concentration, the patients were divided into high peak BNP group (>400 pg/mL) and normal peak BNP group (≤400 pg/mL). Results Seventy patients were enrolled in the study. Within 48 h after AMI onset, BNP concentration variations followed a pattern of an initial increase till reaching the peak concentration at 20 to 24 h, with subsequent gradual decrease. BNP concentrations differed significantly among the indicated time points (χ2=141.7, P<0.05) except for those between 20 h and 24 h (χ2=0.173, P>0.05). Compared with those in normal peak BNP group, the patients in high peak BNP group had an older age, a lower BMI, a longer time to perfusion, and a higher likeliness of anterior myocardial infarction and pulmonary infection (P<0.05). Logistic regression analysis showed that age, BMI and anterior myocardial infarction were independently associated with the increase of peak BNP concentration. ROC curve analysis showed that BNP concentration within 1 h after emergency PCI was unable to diagnose heart failure at that time (P>0.05), while BNP concentrations at 12, 20, 24 and 48 h after AMI onset had significant diagnostic values for heart failure (P<0.05) with areas under ROC of 0.860, 0.786, 0.768 and 0.863, and optimal cutoff values of 156.5, 313.7, 240.9 and 285.9 pg/mL, respectively. Conclusions BNP concentration increases first and then decreases in the early phase of AMI, and the peak concentration occurs at 20-24 h after the onset. The diagnostic values of BNP concentrations at different time points also vary.
7.Dynamic changes of brain natriuretic peptide concentration and its diagnostic value for heart failure in early phase of acute myocardial infarction
Huidi LI ; Dingcheng XIANG ; Jinxia ZHANG ; Tianbing DUAN ; Feng LONG ; Aimin LI
Journal of Southern Medical University 2018;38(1):112-116
Objective To explore the dynamic changes in brain natriuretic peptide (BNP) concentration and the diagnostic value of BNP for heart failure at different time points in the early phase of acute myocardial infarction (AMI). Methods AMI patients who were admitted in our department between January 1, 2016 and July 31, 2016 and underwent emergency percutaneous coronary intervention (PCI) within 12 h after onset were enrolled in this study. All the patients received bedside examinations of BNP concentration and clinical cardiac function within 1 h after PCI and at 12, 20, 24 and 48 h after the onset of AMI. According to the peak BNP concentration, the patients were divided into high peak BNP group (>400 pg/mL) and normal peak BNP group (≤400 pg/mL). Results Seventy patients were enrolled in the study. Within 48 h after AMI onset, BNP concentration variations followed a pattern of an initial increase till reaching the peak concentration at 20 to 24 h, with subsequent gradual decrease. BNP concentrations differed significantly among the indicated time points (χ2=141.7, P<0.05) except for those between 20 h and 24 h (χ2=0.173, P>0.05). Compared with those in normal peak BNP group, the patients in high peak BNP group had an older age, a lower BMI, a longer time to perfusion, and a higher likeliness of anterior myocardial infarction and pulmonary infection (P<0.05). Logistic regression analysis showed that age, BMI and anterior myocardial infarction were independently associated with the increase of peak BNP concentration. ROC curve analysis showed that BNP concentration within 1 h after emergency PCI was unable to diagnose heart failure at that time (P>0.05), while BNP concentrations at 12, 20, 24 and 48 h after AMI onset had significant diagnostic values for heart failure (P<0.05) with areas under ROC of 0.860, 0.786, 0.768 and 0.863, and optimal cutoff values of 156.5, 313.7, 240.9 and 285.9 pg/mL, respectively. Conclusions BNP concentration increases first and then decreases in the early phase of AMI, and the peak concentration occurs at 20-24 h after the onset. The diagnostic values of BNP concentrations at different time points also vary.

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