ObjectiveTo explore the mechanisms of Yangjing Tongluo prescription （YJTL） in the treatment of intrauterine adhesion （IUA） from the perspective of oxidative stress mediated by the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Keap1/Nrf2/HO-1） signaling pathway. MethodsA total of 48 rats with normal estrous cycles were selected and randomly divided into a normal group （n=8） and a modeling group （n=40）. An IUA rat model was established using a dual-injury method combining surgical curettage and infection. Eight rats were randomly selected from the modeling group for a pilot experiment to confirm successful model establishment. After successful modeling， the remaining 32 rats were randomly divided into a model group， a low-dose YJTL group （YJTL-L）， a high-dose YJTL group （YJTL-H）， and a Progynova group. Rats in the normal and model groups were administered purified water （15 mL·kg^-1） by gavage daily， while rats in the YJTL-L， YJTL-H， and Progynova groups received YJTL at doses of 6.43 and 12.86 g·kg^-1 and Progynova at 2.06 × 10^-4 g·kg^-1， respectively， for 14 consecutive days. The general condition， uterine morphology， and uterine index of the rats were monitored. Histopathological changes in uterine tissue were observed using hematoxylin-eosin （HE） staining. Serum levels of reactive oxygen species （ROS） and glutathione peroxidase （GSH-Px） were measured by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of Keap1， Nrf2， and HO-1 in endometrial tissue were detected by Western blot. Immunofluorescence （IF） was used to assess the distribution of Nrf2 and HO-1， as well as the expression of Nrf2 in the cytoplasm and nucleus. ResultsCompared with the normal group， rats in the model group exhibited poor mental status and reduced mobility， markedly edematous and tortuous uterine morphology， decreased gland number， and inflammatory reactions in the endometrium， along with an increased uterine organ index （P<0.05）. Serum ROS levels were significantly increased （P<0.05）， while serum GSH-Px levels were significantly decreased （P<0.05）. In endometrial tissue， Keap1 protein expression was increased （P<0.05）， whereas Nrf2 and HO-1 protein expression was decreased. Mild nuclear translocation of Nrf2 was observed， accompanied by increased relative fluorescence intensity of nuclear Nrf2 and decreased relative fluorescence intensity of cytoplasmic HO-1. Compared with the model group， all treatment groups showed varying degrees of improvement in the above symptoms and pathological changes. Serum ROS levels were reduced （P<0.05）， serum GSH-Px levels were increased （P<0.05）， Keap1 protein expression in endometrial tissue was decreased， and Nrf2 and HO-1 protein expression was increased in a dose-dependent manner （P<0.05）. Notably， significant nuclear translocation of Nrf2 was observed， with correspondingly increased relative fluorescence intensity of nuclear Nrf2 and enhanced relative fluorescence intensity of cytoplasmic HO-1. ConclusionYJTL may enhance antioxidant capacity and repair oxidative damage to the endometrial basal layer by regulating the Keap1/Nrf2/HO-1 signaling pathway.

ObjectiveThis paper aims to investigate the efficacy and related actions of Guizhi Fulingwan in intervening in the mice with colitis-associated colon cancer （CAC） based on the immunosuppressive microenvironment associated with myeloid-derived suppressor cells （MDSCs）. MethodsSixty male C57BL/6 mice were randomly assigned to a blank group， a model group， an aspirin group （0.04 g·kg^-1）， and low-， medium-， and high-dose Guizhi Fulingwan groups （4.87， 9.75， and 19.50 g·kg^-1）， with ten mice per group. The CAC mouse model was established via combined induction of azoxymethane （AOM）/dextran sulphate sodium （DSS）. Drug intervention commenced in week five， with continuous intragastric administration for nine weeks. The food intake， body weight， fecal characteristics， and haematochezia were observed and recorded， and disease activity index （DAI） scores were calculated according to scoring criteria. Hematoxylin and eosin （HE） staining was used to observe the histopathological changes in the colon tissues of the mice. Immunohistochemistry was used to determine proliferating cell nuclear antigen-67 （Ki67） expression in the colon tissues， and enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-6 （IL-6）， IL-1β， and tumor necrosis factor-α （TNF-α） in the serum of the mice. Flow cytometry was employed to determine the proportion levels of MDSCs， CD4⁺ T cells， and CD8⁺ T cells in the spleen tissues of the mice. The mRNA expressions of MDSC-associated effector molecules， including arginase 1 （Arg1） and inducible nitric oxide synthase （iNOS）， were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. After that， an in vitro co-culture model of MDSCs and CD8⁺ T cells was established， and drug-containing serum of Guizhi Fulingwan was used for intervention. The Flow cytometry was employed to assess the effects of drug-containing serum of Guizhi Fulingwan with different concentrations on the levels of reactive oxygen species （ROS） and iNOS in MDSCs and the proliferation of CD8⁺ T cells. The levels of granzyme B （GZMB） and interferon-γ （IFN-γ） in cell supernatant were detected by ELISA. ResultsCompared with those in the control group， the mice in the model group exhibited significantly reduced body weight， elevated DAI scores， shortened colon length （P<0.01）， increased number of tumors and Ki67 expression （P<0.01）， and significantly elevated contents of IL-6， IL-1β， and TNF-α in the serum （P<0.01）. Significant increases in the number of MDSCs were observed in mouse spleens， alongside marked reductions in the levels of CD4⁺ T and CD8⁺ T cells （P<0.01）. Furthermore， the mRNA expressions of MDSC function-associated effector molecules Arg1 and iNOS were significantly upregulated （P<0.01）. Compared with those in the model group， the mice in the middle-dose Guizhi Fulingwan group exhibited increased body weight and significantly decreased DAI scores （P<0.05， P<0.01）. The mice in the middle- and high-dose Guizhi Fulingwan groups exhibited significantly improved colon shortening， significantly decreased number of tumors and Ki67 expression （P<0.05， P<0.01）， and significantly decreased contents of IL-6， IL-1β， and TNF-α in the serum （P<0.05， P<0.01）. Furthermore， administration of Guizhi Fulingwan markedly reduced MDSC infiltration in the spleen of the mice， with different degrees of increase in the levels of both CD4⁺ T and CD8⁺ T cells （P<0.05， P<0.01）， alongside significant decreases in the mRNA expressions of Arg1 and iNOS （P<0.05， P<0.01）. In vitro cell co-culture shows that administration of drug-containing serum of Guizhi Fulingwan significantly decreases the activity levels of ROS and iNOS in MDSCs and promotes the proliferation of CD8⁺ T cells and the secretion of GZMB and IFN-γ （P<0.05， P<0.01）. ConclusionGuizhi Fulingwan can reduce pro-inflammatory cytokine secretion and inhibit tumor proliferation in the colon tissues of CAC mice. Its potential mechanism may involve reducing MDSC infiltration， enhancing effector T cells， particularly CD8⁺ T cell response， and improving the tumor immunosuppressive microenvironment.

ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.

Cytotoxicity, usually represented by cell viability, is a crucial parameter for evaluating drug safety in vitro. Accurate prediction of cell viability/cytotoxicity could accelerate drug development in the early stage. In this study, by integrating cellular transcriptome and cell viability data using four machine learning algorithms (support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM)) and two ensemble algorithms (voting and stacking), highly accurate prediction models of 50% and 80% cell viability were developed with area under the receiver operating characteristic curve (AUROC) of 0.90 and 0.84, respectively; these models also showed good performance when utilized for diverse cell lines. Concerning the characterization of the employed Feature Genes, the models were interpreted, and the mechanisms of bioactive compounds with a narrow therapeutic index (NTI) can also be analyzed. In summary, the models established in this research exhibit superior capacity to those of previous studies; these models enable accurate high-safety substance screening via cytotoxicity prediction across cell lines. Moreover, for the first time, Cytotoxicity Signature (CTS) genes were identified, which could provide additional clues for further study of mechanisms of action (MOA), especially for NTI compounds.

Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of forkhead box P3⁺ (FOXP3⁺) regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile, with an increased abundance of probiotics Bacteroides fragilis, while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL-17), IL-1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal B. fragilis was observed, correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1 (FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa238-335) and the FXR1 domain (aa82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3⁺ Tregs and curbs pro-inflammatory pathways.

OBJECTIVE: To explore the early clinical outcomes of 3D printed individualised customised prostheses for in hip revision in patients with combined severe bone defects. METHODS: Twenty-two patients from January 2021 to May 2023 underwent hip revision using 3D printed personalised customised prostheses were retrospective analyzed, including 10 males and 12 females, age 28 to 78 with a mean of (58.9±12.8) years old. All of patients were combined with severe bone defects (Parprosky type Ⅲ). Among of them, 9 patients had periprosthetic infections and 13 patients had aseptic prosthesis loosening. All patients were treated with a 3D printed personalised prosthesis protocol, patients with the periprosthetic infection received a second stage revision after infection control. The operation time, preoperative waiting time, intraoperative and postoperative complications were recorded, and the clinical efficacy were evaluated at the final follow-up using the visual analogue scale (VAS) for pain, the Harris hip score. RESULTS: One patient was lost to follow-up and the remaining 21 patients were followed up for 10 to 15 with a mean of (12.91±1.44) months after surgery. All patients completed surgery as planned, with an operative time of 135 to 390 with a mean of (165.4±39.3) minutes and a preoperative waiting time of 7 to 16 with a mean of (10.5±3.3) days. Regarding patient complications:one patient had a severe intraoperative periprosthetic femoral fracture due to the combination of severe osteoporosis; one patient had an intraoperative greater trochanteric femur fracture. At the latest follow-up, all patients had good position of the custom-made prosthesis and no loosening of the prosthesis;all patients had good wound healing and no local redness or swelling. The total Harris score at the final follow-up (85.86±7.04) was significantly improved compared to the preoperative (44.86±2.36), P<0.001. The VAS at the last follow-up (2.19±0.87) was significantly improved compared with preoperative (7.41±0.96), P<0.001. CONCLUSION The clinical efficacy of 3D-printed personalised customised prosthesis in combined severe bone defect hip revision is satisfactory, but due to the increased preoperative waiting time of the patients and certain risks, certain indications should be mastered when applying in the clinic.
Humans ; Male ; Female ; Printing, Three-Dimensional ; Middle Aged ; Aged ; Adult ; Retrospective Studies ; Hip Prosthesis ; Arthroplasty, Replacement, Hip ; Reoperation ; Prosthesis Design ; Treatment Outcome

OBJECTIVE: Investigation on the clinical application of HURWA robot and Smith & Nephew Cori robot in total knee arthroplasty(TKA). METHODS: A retrospective analysis was performed on 84 patients with knee osteoarthritis who underwent robotic-assisted TKA (RATKA) between June 2023 and March 2025. According to the different robotic systems used, the patients were divided into the domestic HUARUN robotic-assisted total knee arthroplasty group (HRATKA group) and the Smith & Nephew Cori robotic-assisted total knee arthroplasty group (CRATKA group). There were 42 patients in the HRATKA group, including 16 males and 26 females; the age ranged from 56 to 73 years old, with an average of (64.70±8.30) years old;the body mass index (BMI) was (25.10±2.30) kg·m^-2;21 cases were on the right side and 21 cases on the left side;in terms of Kellgren-Lawrence(K-L) classification, there were 15 cases of Grade Ⅲ and 27 cases of Grade Ⅳ;the disease duration ranged from 3 to 25 years, with an average of (15.5±7.5) years. The CRATKA group also included 42 patients, with 14 males and 28 females;the age ranged from 58 to 74 years old, with an average of (65.60±7.50) years old;the BMI was (24.50±2.70) kg·m^-2; 20 cases were on the right side and 22 cases on the left side;regarding K-L classification, there were 11 cases of Grade Ⅲ and 31 cases of Grade Ⅳ;the disease duration ranged from 2 to 26 years, with an average of (16.5±8.8) years. Collect general data of all patients, including age, gender, height, weight, surgical site, K-L classification, incision length, and operation time. To evaluate prosthesis position, compare the frontal tibia component (FTC) angle, lateral femoral component (LFC) angle, lateral tibia component (LTC) angle, and frontal femoral component angle between the two groups of patients after surgery. Measure the deviation of the hip-knee-ankle (HKA) angle to assess lower limb alignment. Additionally, compare the following indicators between the two groups:Knee Society Score (KSS), Visual Analogue Scale (VAS) for pain, knee range of motion (ROM), hemoglobin (HB) level, hematocrit (HCT) level, complication rate, and in-hospital satisfaction. RESULTS: All patients successfully completed the surgery as scheduled, and all were followed up after the operation. The follow-up period ranged from 5 to 17 months with an average of (11.2±6.1) months. There were 4 cases of venous thrombosis in the HRATKA group and 3 cases in the CRATKA group;each group had 2 cases of wound exudation. No mechanical-related complications, pulmonary embolism, or other severe complications occurred. Comparison of the incision length and hospital stay between the HRATKA group and the CRATKA group showed no statistically significant difference (P>0.05). The operation time in the HRATKA group was (96.80±7.10) minutes, which was longer than that in the CRATKA group (90.10±8.80) minutes, and the difference was statistically significant (P<0.05). In the HRATKA group, the HKA angle was (178.93±1.11) degree, the FFC angle was (89.00±0.91)°, and the LFC angle was (7.31±2.17) degree;the corresponding values in the CRATKA group were (178.05±1.34)°, (87.88±1.74)°, and (10.60±2.84) degree respectively. The differences in these three indicators between the two groups were all statistically significant (P<0.05). However, there were no statistically significant differences in the FTC angle or LTC angle between the two groups (P>0.05). There was also no statistically significant difference in the total perioperative blood loss between the two groups (P>0.05). At 3 days after surgery, the VAS score for movement in the HRATKA group (5.95±1.45) points was higher than that in the CRATKA group (4.50±0.97) points, with a statistically significant difference (P<0.05);at 90 days after surgery, there was no statistically significant difference in the movement VAS score between the two groups (P>0.05). Additionally, no statistically significant differences were observed between the two groups in the KSS, ROM at 3 and 90 days after surgery, or satisfaction degree during hospitalization (all P>0.05). CONCLUSION The domestic HURWA robot demonstrates excellent performance in osteotomy efficiency and lower limb alignment recovery. The Smith & Nephew Cori robot has a significant advantage in soft tissue assessment and joint stability optimization. Both robotic systems offer high-quality surgical treatments that significantly improve short-term knee function.
Humans ; Male ; Female ; Arthroplasty, Replacement, Knee/instrumentation* ; Aged ; Middle Aged ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Osteoarthritis, Knee/surgery*

This study aimed to investigate the anti-inflammatory and antioxidant effects of atractylon on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Changes in lung function parameters were measured in mice after intraperitoneal administration of atractylon. Pathological changes in lung tissue were observed by H&E staining, and the degree of pulmonary edema was assessed by the lung wet/dry weight ratio (W/D). Kit assays were used to detect changes in oxidative stress markers in mouse serum and the protein concentration in bronchoalveolar lavage fluid (BALF). ELISA was employed to measure the expression levels of inflammatory cytokines in BALF and serum. Western blot was used to detect the expression levels of proteins related to the cGAS-STING pathway and vascular cell adhesion molecule-1 (VCAM-1) in lung tissue. Results showed that, compared to the ALI model group, mice in the low-dose and high-dose atractylon groups exhibited significant improvement in lung function parameters, alleviated pulmonary edema, and reduced inflammatory cell infiltration in lung tissue. Protein content and inflammatory cytokine levels in serum and BALF were decreased, while serum oxidative stress indicators were improved. Western blot results further indicated that atractylon could regulate the cGAS-STING pathway, blocking the generation of inflammatory signals, and simultaneously inhibit VCAM-1 expression, thereby reducing pulmonary vascular injury. The results suggest that atractylon may alleviate LPS-induced ALI by modulating the cGAS-STING signaling pathway, reducing the expression of pro-inflammatory cytokines and the production of pro-inflammatory mediators, and improving vascular endothelial injury. This study provides a new potential target and theoretical basis for the treatment of ALI, as well as a potential drug candidate for ALI therapy.

Objective To analyze the risk factors of left atrial appendage(LAA)thrombosis in elderly patients with NVAF.Methods A total of 210 NVAF patients admitted to our hospital from January 2019 to June 2023 were enrolled in this study.Transesophageal echocardiography was applied used to detect the LAA thrombus,and then according to the presence or absence of thrombus,the patients were divided into a thrombus group(n=42)and a non-thrombus group(n=168).The indicators of routine blood test within 48 h of admission and the characteristics of LAA were recorded.Multivariate logistic regression analysis was performed to identify the risk factors related to the occurrence of LAA thrombus.Results The thrombus group exhibited sig-nificantly larger proportions of diabetes and nonparoxysmal AF,higher total bilirubin,increased left ventricular end-systolic diameter and left ventricular end-diastolic diameter values,and elevat-ed ratio of complex LAA,but lower INR and left ventricular ejection fraction value than the non-thrombus group(P＜0.05,P＜0.01).After adjusting for confounding factors,multivariate logistic regression analysis showed that diabetes(OR=3.585,95％CI:1.003-12.808,P=0.049)and complex LAA(OR=5.572,95％CI:2.101-14.777,P=0.001)were independent risk factors for LAA thrombosis.Conclusion LAA morphology and diabetes are independent risk factors for the occurrence of LAA thrombus in NVAF patients.

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.