1.Efficacy and safety of Tripterygium wilfordii polyglycoside combined with finerenone in the treatment of diabetic nephropathy
Xincheng ZHAO ; Ruimin LI ; Shuxia CUI
China Pharmacy 2026;37(4):486-490
OBJECTIVE To explore the efficacy and safe ty of Tripterygium wilfordii polyglycoside combined with finerenone in the treatment of diabetic nephropathy (DN). METHODS This study selected 104 DN patients admitted to the Nephrology Department of Handan Central Hospital from January 2023 to May 2024 as the subjects and randomly assigned them into the control group (52 cases) and the combination group (52 cases). All patients received basic treatment such as lipid-lowering and blood glucose control. On this basis, patients in the control group received finerenone, while those in the combination group received a combination therapy of T. wilfordii polyglycoside and finerenone. Both groups underwent treatment for a duration of three months. The two groups were compared in terms of clinical efficacy, renal function indicators [24-hour urine protein excretion (24 h UPE), urinary albumin-to-creatinine ratio (UACR), urinary albumin excretion rate (UAER) ] , inflammatory factors [high mobility group box 1 protein (HMGB1), interleukin-6 (IL-6), nuclear factor-κB (NF-κB), high-sensitivity C reactive protein (hs-CRP) ] , and oxidative stress indicators [total antioxidant capacity (T-AOC), superoxide dismutase (SOD), advanced oxidation protein products (AOPP), malondialdehyde (MDA) ] before and after treatment. Additionally, the occurrence of adverse drug reactions was recorded. RESULTS In terms of efficacy, the total effective rate of patients in the combination group was higher than that of the control group ( P <0.05). After treatment, the levels of 24-h UPE, UACR, UAER, HMGB1, IL-6, NF-κB, hs-CRP, AOPP and MDA in the two groups were significantly lower than those in the same group before treatment; the levels of T-AOC and SOD in the two groups were significantly higher than those in the same group before treatment, with the combination group showing superior changes in the above indicators compared to the control group at the corresponding time point ( P <0.05). In terms of safety, there was no statistical significance in the total incidence of adverse drug reactions between the two groups ( P >0.05). CONCLUSIONS Compared to finerenone monotherapy, the combination therapy of T. wilfordii polyglycoside and finerenone demonstrates significant efficacy in treating DN. It effectively reduces proteinuria levels, alleviates inflammatory reaction, mitigates oxidative stress, and does not increase the risk of adverse reactions.
2.Practice and analysis of implementing drug traceability code management in outpatient pharmacy
Liwen LIAO ; Yuqi WANG ; Yuzi WANG ; Kang CHEN ; Shuxia LI ; Kejing TANG ; Wei YANG
China Pharmacy 2025;36(7):858-862
OBJECTIVE To explore optimization pathways for the drug traceability code management model in outpatient pharmacy workflows, providing practical evidence for enhancing the efficiency of pharmaceutical service. METHODS Taking the outpatient pharmacy of the First Affiliated Hospital of Sun Yat-sen University as the research subject, a comprehensive drug traceability system was established through three key interventions: upgrading the information system architecture [including integration of the hospital information system (HIS) with the traceability platform], workflow optimization (reorganizing the inventory-dispensing-verification tripartite process), and designing a dual-mode traceability data collection mechanism (primary data capture at dispensing stations and supplementary capture at verification stations). Operational efficiency differences before and after implementation were analyzed using the medical insurance data and service timeliness metrics in September 2024. RESULTS After the implementation of drug traceability code management, in terms of data collection: Mode Ⅰ (verification-stage capture) uploaded 26 144 records, while Mode Ⅲ (inventory-as-sales capture) uploaded 443 061 records, totaling 469 205 entries; in terms of time efficiency: average drug dispensing time increased from 28.74 s to 43.37 s (enhanced by 51%). Through dynamic staffing adjustments, patient wait time only extended from 8.04 min to 8.67 min (enhanced by 8%). CONCLUSIONS Drug traceability code management can be effectively implemented via a “system reconstruction-process reengineering-human-machine collaboration” trinity strategy, leveraging informatization (e.g., dual-mode data capture) to offset manual operation delays, which validates the feasibility of balancing national traceability demands with service efficiency in outpatient pharmacies.
3.Mechanism of Zuogui Jiangtang Jieyu Formula in treating diabetes-related depression by regulating GluR2-mediated mitophagy
Jian LIU ; Shuxia YAO ; Hui YANG ; Wei LI ; Yuhong WANG ; Hu TAN
Journal of Beijing University of Traditional Chinese Medicine 2025;48(9):1242-1256
Objective To explore the effect and mechanism of Zuogui Jiangtang Jieyu Formula(ZGJTJYF)in treating diabetes-related depression by regulating glutamate receptor 2(GluR2).Methods The primary isolated and cultured hippocampal neurons of SD rats were used.The experiment consisted of normal,model,blank serum(10%blank serum),positive drug(10%[metformin+fluoxetine]drug-containing serum),20%ZGJTJYF group,10%ZGJTJYF group,10%ZGJTJYF+GluR2 knockdown group,and 10%ZGJTJYF+GluR2 overexpression group(with corresponding volume fractions of ZGJTJYF drug-containing serum added).The ZGJTJYF+GluR2 knockdown and overexpression groups,were transfected with lentivirus to obtain hippocampal neurons with either GluR2 overexpression or knockdown.The glucose(150 mmol/L)and corticosterone(200 μmol/L)were used for 18 h to establish an in vitro cell model of hippocampal neurons in diabetes-related depression.After 24 h of successful modeling,the corresponding serum was added to each group for intervention.After 24 h of intervention,the morphological structure of hippocampal neurons was observed using an optical microscope.Biochemical methods were used to determine the glucose and insulin content in cell supernatant.An enzyme-linked immunosorbent assay was used to detect 5-hydroxytryptamine(5-HT)and dopamine(DA)levels in the cell supernatant,and the microtubule-associated protein 1A/1B light chain 3 autophagy double-labeled adenovirus(mRFP-GFP-LC3)autophagy fluorescence double labeling method was used to detect the average fluorescence intensity of LC3 protein in hippocampal neurons.Nissl staining was used to observe synaptic damage in hippocampal neurons,and an immunofluorescence method was used to detect the protein expression of Parkin,phosphatase and tensin homolog-induced putative kinase 1(PINK1),regulating synaptic membrane exocytosis 3(RIMS3),synapsin 1(SYN1),postsynaptic density-95(PSD-95),synapse-associated protein 102(SAP 102),and GluR2 in hippocampal neurons.Realtime fluorescence PCR was used to detect GluR2 mRNA expression in hippocampal neurons,while Western blotting was employed to assess the expression of mitophagy proteins Parkin and PINK1 in these neurons.Results Compared to the normal group,the model group and blank serum group showed structural damage to hippocampal neurons,increased glucose content in cell supernatant,decreased insulin,5-HT,and DA content,increased average fluorescence intensity of LC3,Parkin,and PINK1,decreased average fluorescence intensity of RIMS3,SYN1,PSD-95,SAP 102,and GluR2,decreased GluR2 mRNA expression,increased protein expression of Parkin and PINK1(P<0.05),and decreased Nissl bodies.Compared to the model group and blank serum group,the above indicators in each administration group were improved to varying degrees(P<0.05).Compared to the positive drug group,the average fluorescence intensity of LC3,Parkin,and PINK1 decreased,Parkin and PINK1 protein expression decreased,and the average fluorescence intensity of GluR2,SYN1,and PSD-95 increased in 10%ZGJTJYF,20%ZGJTJYF group,and 10%ZGJTJYF+GluR2 overexpression group(P<0.05).Compared to 10%and 20%ZGJTJYF groups,10%ZGJTJYF+GluR2 knockdown group showed a decrease in 5-HT content,an increase in average fluorescence intensity of LC3 and Parkin,a decrease in average fluorescence intensity of SYN1,PSD-95,and GluR2,a decreased in GluR2 mRNA expression,and an increase of Parkin and PINK1 protein expression(P<0.05).In contrast,the above indicators were improved to varying degrees in 10%ZGJTJYF+GluR2 overexpression group(P<0.05).Compared to 10%ZGJTJYF+GluR2 knockdown group,the above abnormal indicators in 10%ZGJTJYF+GluR2 overexpression group were reversed to varying degrees(P<0.05).Conclusion ZGJTJYF has a protective effect on synaptic damage of hippocampal neurons in diabetes-related depression,and its mechanism may be related to the upregulation of GluR2 and the inhibition of mitophagy over activation.
4.Mechanism of Compound Baimai Powder protecting neurons against glucose and oxygen deprivation/reoxygenation injury
Shuyao WANG ; Jia LIU ; Yue YUAN ; Yang LI ; Shuhai HAN ; Yuchuan MENG ; Shuxia WANG ; Jianhua BAO ; Mo YAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(9):1263-1268
Objective To explore the protective effect and related mechanism of Compound Baimai Powder(CBMP,a compound description of Mongolian medicine)on astrocytes after oxygen glu-cose deprivation and reoxygenation(OGD/R)injury.Methods Astrocyte model of OGD/R injury was subjected to simulate in vitro cerebral ischemia/reperfusion injury.Cultured astrocytes were randomly divided into normal group,OGD/R group,OGD/R+nimodipine group(10 μmol/L),OGD/R+low-and high-dose CBMP groups(25,50 μmol/L).Cell viability and apoptosis were de-tected with CCK-8 assay and flow cytometry,respectively.Western blotting was used to measure the expression levels of the proteins related to the nuclear factor erythroid-2-related factor-2(NRF2)/antioxidant response element and Janus kinase(J AK)/signal transducer and activator of transcription(STAT)signaling pathways.ELISA was employed to examine the levels of inflam-matory factors IL-1β,IL-6,and TNF-α,as well as oxidative stress molecules ROS,GSH,MDA and SOD.Results Compared to the normal group,the OGD/R group showed significant decreases in cell viability,NRF2 protein level,and SOD and GSH activities(P<0.05,P<0.01),and obvious increases in p-JAK and p-STAT proteins levels,contents of IL-1β,IL-6 and TNF-α,and ROS and MDA levels(P<0.05,P<0.01).High-dose CBMP treatment resulted in notably elevated cell via-bility and NRF2 protein level,while reduced levels of p-JAK[(1.20±0.20)vs(2.50±0.26)]and p-STAT[(1.15±0.25)vs(2.10±0.21)]proteins,IL-6[(30.33±5.20)vs(180.35±18.50)]and TNF-α[(50.12±8.24)vs(160.45±15.20)]when compared to the OGD/R group(P<0.05,P<0.01).Conclusion CBMP exerts protective effect on astrocytes against OGD/R injury.
5.Analysis of the associated factors and cumulative effects of cardiometabolic multimorbidity among residents in southern Xinjiang
Silin CHEN ; Dilimulati MUHETAER ; Rulin MA ; Bo YANG ; Xuelian WU ; Leyao JIAN ; Jiahang LI ; Jing CHENG ; Shuxia GUO ; Heng GUO
Chinese Journal of Preventive Medicine 2025;59(3):292-301
Objective:To analyze the associated factors and cumulative effects of cardiometabolic multimorbidity (CMM) among residents in southern Xinjiang.Methods:A stratified random cluster sampling method was used to conduct questionnaire surveys, physical examinations and laboratory tests among the personnel of the 51st Brigade, 3rd Division, Xinjiang, in 2016. The multivariate logistic regression, multivariate linear regression, restricted cubic spline, and network analysis methods were used to study the association of lifestyle (smoking, alcohol consumption and physical activity), socioeconomic (occupation, education and marital status) and clinical factors (waist circumference, body mass index and family history) with CMM.Results:A total of 12 773 study subjects were included. The prevalence of cardiovascular metabolic diseases among residents in southern Xinjiang was 52.49%. Specifically, the prevalence rates of dyslipidemia, hypertension, coronary heart disease, diabetes, and stroke were 31.14%, 29.95%, 6.78%, 6.26%, and 2.47%, respectively, and the prevalence of CMM was 19.06%. Multivariate logistic regression analysis revealed that the associations between clinical and socioeconomic factors and CMM significantly increased with higher scores. Specifically, the OR rose from 1.75 (clinical factors) and 1.07 (socioeconomic factors) on a score of 1 to 4.41 and 1.93 on a score of 3, respectively. The association between lifestyle factors and CMM was only observed at higher scores ( OR=1.26, 95% CI:1.07~1.62). The trend test using the scores of each group as continuous variables in the model showed that the risk of disease increased with the accumulation of clinical, socioeconomic and lifestyle factors (all P<0.05). Restricted cubic spline analysis demonstrated a non-linear relationship between the total number of associated factors and CMM ( Poverall<0.05 and Pnon-linear<0.05). Network analysis identified hypertension (strength=0.42) as the “core node” among the five diseases. When analyzing the three types of influencing factors, hypertension (strength=0.68), dyslipidemia (strength=0.47), coronary heart disease (strength=0.37), and clinical factors (strength=0.53) emerged as “core nodes”. In the network of nine associated factors, abnormal waist circumference and BMI (strength=0.90 and 0.84) were identified as “key factors”, while hypertension (strength=0.68) and dyslipidemia (strength=0.52) were identified as “key diseases”. Conclusion:The prevalence of CMM among residents in southern Xinjiang is high, and there is a cumulative effect of multiple factors. Hypertension and dyslipidemia are key diseases in the multimorbidity network, while abnormal BMI and waist circumference are key associated factors.
6.A cohort study on the correlation between metabolic syndrome and cholecystolithiasis and gallbladder polyp in Uygur population in rural areas of southern Xinjiang
Jie GUO ; Jing YANG ; Minghan ZHANG ; Zhihao HOU ; Shilong LI ; Shijie ZHANG ; Hongwei ZHANG ; Jiang LI ; Yongguo ZHANG ; Xiangwei WU ; Shuxia GUO ; Xinyu PENG
Chinese Journal of Digestion 2025;45(5):338-344
Objective:To investigate the correlation between metabolic syndrome (MS), its different components and the risk of cholecystolithiasis and gallbladder polyp in Uygur population in rural areas of southern Xinjiang.Methods:This study was a prospective cohort study. A baseline survey was conducted in August 2016. A typical sampling method was used to select 10 476 Uygur people in rural areas of southern Xinjiang as the research objects. Baseline clinical data were collected, including demographic data such as age, gender, and education level, and laboratory examination indicators such as blood glucose and triglyceride levels. According to the MS diagnostic criteria of the relevant guidelines, 10 476 subjects were divided into the MS group (3 475 cases) and the non-MS group (7 001 cases). The incidence of cholecystolithiasis and gallbladder polyp was followed up in 2019, 2021 and 2023, respectively. Cox regression was used to analyze the correlation between MS, its different components and the risk of cholecystolithiasis and gallbladder polyp. Chi-square test and independent sample t test were used for statistical analysis. Results:The median follow-up time was 6.43 years in 10 476 subjects, and the overall cumulative incidence of cholecystolithiasis and gallbladder polyp was 5.43% (569/10 476). The cumulative incidence of cholecystolithiasis and gallbladder polyp in the MS group was 10.73% (373/ 3 475), which was significantly higher than that in the non-MS group (2.80% (196/7 001)); χ2= 284.62, P<0.001). The results of multivariate Cox regression analysis showed that, 41 to 59 years old ( HR=1.26, 95% confidence interval (95% CI): 1.03 to 1.54, P=0.025), ≥60 years old ( HR=1.88, 95% CI: 1.45 to 2.45, P<0.001), female ( HR=1.34, 95% CI: 1.13 to 1.60, P=0.001), MS ( HR=2.19, 95% CI: 1.59 to 3.01, P<0.001), hypertriglyceridemia ( HR=1.47, 95% CI: 1.18 to 1.83, P=0.001), hypertension ( HR=1.30, 95% CI: 1.04 to 1.62, P=0.023), and hyperglycemia ( HR=1.24, 95% CI: 1.01 to 1.52, P=0.041) were independent risk factors for cholecystolithiasis and gallbladder polyp. After the adjustment of age and gender, MS ( HR=3.39, 95% CI: 2.82 to 4.07, P<0.001), hypertriglyceridemia ( HR=2.37, 95% CI: 2.00 to 2.81, P<0.001), hypertension ( HR=2.00, 95% CI: 1.66 to 2.41, P<0.001), and hyperglycemia ( HR=1.86, 95% CI: 1.55 to 2.23, P<0.001) were still correlated with cholecystolithiasis and gallbladder polyp, and there was the srtongest correlation between MS and cholecystolithiasis and gallbladder polyp. The results of univariate Cox regression analysis showed that along with the increase of accumulated of MS components, the risk of cholecystolithiasis and gallbladder polyp significantly increased (1 to 5 components corresponding HR (95% CI) were 1.92 (1.13 to 3.24), 2.21 (1.32 to 3.69), 6.91 (4.22 to 11.30), 8.56 (5.15 to 14.22), and 10.73 (5.66 to 20.33); P=0.015, =0.002, <0.001, <0.001, and <0.001); after age and gender were adjusted, this trend still existed (1 to 5 components corresponding HR (95% CI) were 1.81(1.07 to 3.06), 1.95(1.16 to 3.27), 5.64(3.42 to 9.32), 6.69(3.97 to 11.25), and 7.76(4.04 to 14.91); P=0.028, =0.012, <0.001, <0.001, and <0.001). Conclusion:MS and its components can increase the risk of cholecystolithiasis and gallbladder polyp, and the risk of cholecystolithiasis and gallbladder polyp significantly increases along with the increase of accumulated of MS components.
7.Mechanism of Zuogui Jiangtang Jieyu Formula in treating diabetes-related depression by regulating GluR2-mediated mitophagy
Jian LIU ; Shuxia YAO ; Hui YANG ; Wei LI ; Yuhong WANG ; Hu TAN
Journal of Beijing University of Traditional Chinese Medicine 2025;48(9):1242-1256
Objective To explore the effect and mechanism of Zuogui Jiangtang Jieyu Formula(ZGJTJYF)in treating diabetes-related depression by regulating glutamate receptor 2(GluR2).Methods The primary isolated and cultured hippocampal neurons of SD rats were used.The experiment consisted of normal,model,blank serum(10%blank serum),positive drug(10%[metformin+fluoxetine]drug-containing serum),20%ZGJTJYF group,10%ZGJTJYF group,10%ZGJTJYF+GluR2 knockdown group,and 10%ZGJTJYF+GluR2 overexpression group(with corresponding volume fractions of ZGJTJYF drug-containing serum added).The ZGJTJYF+GluR2 knockdown and overexpression groups,were transfected with lentivirus to obtain hippocampal neurons with either GluR2 overexpression or knockdown.The glucose(150 mmol/L)and corticosterone(200 μmol/L)were used for 18 h to establish an in vitro cell model of hippocampal neurons in diabetes-related depression.After 24 h of successful modeling,the corresponding serum was added to each group for intervention.After 24 h of intervention,the morphological structure of hippocampal neurons was observed using an optical microscope.Biochemical methods were used to determine the glucose and insulin content in cell supernatant.An enzyme-linked immunosorbent assay was used to detect 5-hydroxytryptamine(5-HT)and dopamine(DA)levels in the cell supernatant,and the microtubule-associated protein 1A/1B light chain 3 autophagy double-labeled adenovirus(mRFP-GFP-LC3)autophagy fluorescence double labeling method was used to detect the average fluorescence intensity of LC3 protein in hippocampal neurons.Nissl staining was used to observe synaptic damage in hippocampal neurons,and an immunofluorescence method was used to detect the protein expression of Parkin,phosphatase and tensin homolog-induced putative kinase 1(PINK1),regulating synaptic membrane exocytosis 3(RIMS3),synapsin 1(SYN1),postsynaptic density-95(PSD-95),synapse-associated protein 102(SAP 102),and GluR2 in hippocampal neurons.Realtime fluorescence PCR was used to detect GluR2 mRNA expression in hippocampal neurons,while Western blotting was employed to assess the expression of mitophagy proteins Parkin and PINK1 in these neurons.Results Compared to the normal group,the model group and blank serum group showed structural damage to hippocampal neurons,increased glucose content in cell supernatant,decreased insulin,5-HT,and DA content,increased average fluorescence intensity of LC3,Parkin,and PINK1,decreased average fluorescence intensity of RIMS3,SYN1,PSD-95,SAP 102,and GluR2,decreased GluR2 mRNA expression,increased protein expression of Parkin and PINK1(P<0.05),and decreased Nissl bodies.Compared to the model group and blank serum group,the above indicators in each administration group were improved to varying degrees(P<0.05).Compared to the positive drug group,the average fluorescence intensity of LC3,Parkin,and PINK1 decreased,Parkin and PINK1 protein expression decreased,and the average fluorescence intensity of GluR2,SYN1,and PSD-95 increased in 10%ZGJTJYF,20%ZGJTJYF group,and 10%ZGJTJYF+GluR2 overexpression group(P<0.05).Compared to 10%and 20%ZGJTJYF groups,10%ZGJTJYF+GluR2 knockdown group showed a decrease in 5-HT content,an increase in average fluorescence intensity of LC3 and Parkin,a decrease in average fluorescence intensity of SYN1,PSD-95,and GluR2,a decreased in GluR2 mRNA expression,and an increase of Parkin and PINK1 protein expression(P<0.05).In contrast,the above indicators were improved to varying degrees in 10%ZGJTJYF+GluR2 overexpression group(P<0.05).Compared to 10%ZGJTJYF+GluR2 knockdown group,the above abnormal indicators in 10%ZGJTJYF+GluR2 overexpression group were reversed to varying degrees(P<0.05).Conclusion ZGJTJYF has a protective effect on synaptic damage of hippocampal neurons in diabetes-related depression,and its mechanism may be related to the upregulation of GluR2 and the inhibition of mitophagy over activation.
8.Anxiety as mediator between impulsive traits and symptoms of eating disorders
Dian CHEN ; Lei YANG ; Shuxia GENG ; Chao CHEN ; Peihua SONG ; Xueni LI ; Qingmei KONG ; Tianmei SI
Chinese Mental Health Journal 2025;39(8):671-676
Objective:To explore the relationship between impulsivity traits,anxiety,and symptoms of eating disorders,with a focus on the mediating effect of anxiety between impulsivity and eating disorder symptoms.Me-thods:A total of 244 patients with eating disorders meeting the DSM-5 diagnostic criteria for anorexia nervosa(AN)and bulimia nervosa(BN)were enrolled,and the Eating Disorder Inventory-1(EDI-1),Barratt Impulsive-ness Scale(BIS-11),and the State Anxiety Inventory(SAI)were assessed.Mediation role analysis was performed by SPSS macro PROCESS program.Results:There was a significant positive correlation between the total score of BIS-11,SAI and EDI-1 in AN and BN patients(AN,r=0.56,0.63,0.72;P<0.001.BN,r=0.51,0.31,0.56;P<0.001 or P<0.01).The total score of SAI played a mediating effect between the total score of BIS-11 and the total score of EDI-1,but the total score of SAI played a partial mediating effect(effect ratio was 46.9%)in patients with AN,and the total score of SAI played a full mediating effect in patients with BN.Conclusion:Impulsive trait and anxiety may be positive predictors of eating disorder symptoms.Anxiety mediates the relationship between impul-sivity trait and eating disorder symptoms,with a partial mediating effect in patients with AN and a full mediating effect in patients with BN.
9.Anxiety as mediator between impulsive traits and symptoms of eating disorders
Dian CHEN ; Lei YANG ; Shuxia GENG ; Chao CHEN ; Peihua SONG ; Xueni LI ; Qingmei KONG ; Tianmei SI
Chinese Mental Health Journal 2025;39(8):671-676
Objective:To explore the relationship between impulsivity traits,anxiety,and symptoms of eating disorders,with a focus on the mediating effect of anxiety between impulsivity and eating disorder symptoms.Me-thods:A total of 244 patients with eating disorders meeting the DSM-5 diagnostic criteria for anorexia nervosa(AN)and bulimia nervosa(BN)were enrolled,and the Eating Disorder Inventory-1(EDI-1),Barratt Impulsive-ness Scale(BIS-11),and the State Anxiety Inventory(SAI)were assessed.Mediation role analysis was performed by SPSS macro PROCESS program.Results:There was a significant positive correlation between the total score of BIS-11,SAI and EDI-1 in AN and BN patients(AN,r=0.56,0.63,0.72;P<0.001.BN,r=0.51,0.31,0.56;P<0.001 or P<0.01).The total score of SAI played a mediating effect between the total score of BIS-11 and the total score of EDI-1,but the total score of SAI played a partial mediating effect(effect ratio was 46.9%)in patients with AN,and the total score of SAI played a full mediating effect in patients with BN.Conclusion:Impulsive trait and anxiety may be positive predictors of eating disorder symptoms.Anxiety mediates the relationship between impul-sivity trait and eating disorder symptoms,with a partial mediating effect in patients with AN and a full mediating effect in patients with BN.
10.Identify the factors associated with treatment-free remission outcomes after imatinib discontinuation in children and adolescent patients with chronic myeloid leukemia
Huifang ZHAO ; Qian JIANG ; Weiming LI ; Yu ZHU ; Bingcheng LIU ; Qingshu ZENG ; Shuxia GUO ; Lixin LIANG ; Chunlei ZHANG ; Yingling ZU ; Yongping SONG ; Yanli ZHANG
Chinese Journal of Hematology 2025;46(9):800-805
Objective:To identify factors influencing treatment-free remission (TFR) outcomes in children and adolescent patients with chronic myeloid leukemia (CML) after imatinib (IM) discontinuation.Methods:This multicenter retrospective study analyzed 36 children and adolescent patients with CML from eight hematology centers in China (December 1, 2016, to September 27, 2024) who discontinued IM therapy with documented post-cessation outcomes. Clinical characteristics and molecular response dynamics were assessed. Univariate analysis and multivariate Cox proportional hazards regression models were employed to assess factors associated with TFR outcomes.Results:A total of 36 patients were documented, comprising 17 males and 19 females. The median ages at CML diagnosis and IM discontinuation were 11 years ( IQR: 5,16) and 20 years ( IQR: 14,25), respectively. The median time from IM initiation to first deep molecular response (DMR) was 21 months ( IQR: 13, 38). Pre-discontinuation, patients received IM for a median duration of 96 months ( IQR: 84, 121) and maintained DMR for 74 months ( IQR: 63, 89). With a median post-discontinuation follow-up of 38 months ( IQR: 15, 68), cumulative TFR rates at 6, 12, 24, and 36 months were 74.1%, 60.7%, 60.7%, and 56.0%, respectively, generating an overall TFR rate of 58.3%. Fifteen patients lost major molecular response at a median of 5 months post-discontinuation ( IQR: 3, 11). All 15 patients resumed tyrosine kinase inhibitor therapy, comprising 13 who restarted IM and 2 who switched to dasatinib. By the last follow-up, 13 (86.7% ) patients regained DMR after a median treatment duration of 5 months ( IQR: 3, 17), and no disease progression occurred in any patient. Withdrawal syndrome occurred in 2 (5.6% ) patients. Univariate analysis revealed significantly higher TFR rates in patients with pre-discontinuation IM duration of ≥100 months vs <100 months (82.4% vs 36.8%, P=0.017) and pre-discontinuation DMR duration of ≥72 months vs <72 months (84.2% vs 29.4%, P=0.003). Multivariate Cox analysis identified pre-discontinuation DMR duration as an independent protective factor for TFR ( HR=5.419, 95% CI: 1.524–19.272, P=0.009) . Conclusion:DMR duration was identified as an independent protective factor influencing TFR outcomes in children and adolescent patients with CML after IM discontinuation. Patients who maintained DMR for ≥72 months before IM discontinuation demonstrated a significantly higher TFR rate.

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