1.Feasibility study on the construction of predictive models of knee joint cartilage thickness
Zhi-ming CHENG ; Zhong-hua XU ; Xiao-jun MAN ; Yu-heng LI ; Zai-yang LIU ; Yuan ZHANG
Journal of Regional Anatomy and Operative Surgery 2025;34(7):563-569
Objective To determine the knee joint cartilage thickness using different methods and explore the feasibility of mathematical statistical models of dataset for the prediction of cartilage thickness.Methods A total of 304 patients diagnosed as knee osteoarthritis(OA)combined with varus deformity and undergoing unilateral total knee arthroplasty at the Second Affiliated Hospital of Army Medical University from March 2023 to March 2024 were selected for the study.All patients had complete preoperative and postoperative clinical data.The healthy cartilage at four anatomical sites of patients,including the distal femur lateral condyle,lateral tibial plateau,posterior medial femoral condyle,and posterior lateral femoral condyle were selected,and the knee joint cartilage thickness was determined based on preoperative MRI analysis,robotic navigation system tracing,tissue section of surgical specimen and digital vernier caliper.The baseline indicators of demographics,disease and imaging ffor patients were collected to construct a dataset,and four models of linear regression analysis,principal component analysis,Least Absolute Shrinkage and Selection Operator(LASSO)regression analysis,and K-nearest neighbors(KNN)analysis were established for predicting the accuracy,determination coefficient(R2)and root mean square error(RMSE),and the regression equation for predicting cartilage thickness was established.Results The knee joint cartilage thicknesses determined by preoperative MRI analysis,robotic navigation system tracing,tissue section of surgical specimen had no statistically significant difference with that by digital vernier caliper(P>0.05).The predictive efficiencies of models of linear regression analysis,principal component analysis,and LASSO regression analysis for the knee joint cartilage thickness all failed to meet the expectations(R2<0.3,RMSE>0.03).The predictive effect of KNN model on the cartilage thickness of the distal femur lateral condyle and lateral tibial plateau was not ideal(R2=0.23,RMSE=0.29),while it had potential predictive value(accuracy=0.21,accuracy=0.15).Conclusion The prediction model of knee joint cartilage thickness based on individual parameters has certain scientificity,and the feasibility of KNN model is relatively high.However,due to insufficient sample size and unclear individual parameter weight,the efficiencies of the four established prediction models are not ideal,which fails to provide definite prediction equations.Therefore,the construction scheme of the prediction model still needs to be further optimized.
2.Risk prediction of Reduning Injection batches by near-infrared spectroscopy combined with multiple machine learning algorithms.
Wen-Yu JIA ; Feng TONG ; Heng-Xu LIU ; Shu-Qin JIN ; Yong-Chao ZHANG ; Chen-Feng ZHANG ; Zhen-Zhong WANG ; Xin ZHANG ; Wei XIAO
China Journal of Chinese Materia Medica 2025;50(2):430-438
In this paper, near-infrared spectroscopy(NIRS) was employed to analyze 129 batches of commercial products of Reduning Injection. The batch reporting rate was estimated according to the report of Reduning Injection in the direct adverse drug reaction(ADR) reporting system of the drug marketing authorization holder of the Center for Drug Reevaluation of the National Medical Products Administration(National Center for ADR Monitoring) from August 2021 to August 2022. According to the batch reporting rate, the samples of Reduning Injection were classified into those with potential risks and those being safe. No processing, random oversampling(ROS), random undersampling(RUS), and synthetic minority over-sampling technique(SMOTE) were then employed to balance the unbalanced data. After the samples were classified according to appropriate sampling methods, competitive adaptive reweighted sampling(CARS), successive projections algorithm(SPA), uninformative variables elimination(UVE), and genetic algorithm(GA) were respectively adopted to screen the features of spectral data. Then, support vector machine(SVM), logistic regression(LR), k-nearest neighbors(KNN), naive bayes(NB), random forest(RF), and artificial neural network(ANN) were adopted to establish the risk prediction models. The effects of the four feature extraction methods on the accuracy of the models were compared. The optimal method was selected, and bayesian optimization was performned to optimize the model parameters to improve the accuracy and robustness of model prediction. To explore the correlations between potential risks of clinical use and quality test data, TreeNet was employed to identify potential quality parameters affecting the clinical safety of Reduning Injection. The results showed that the models established with the SVM, LR, KNN, NB, RF, and ANN algorithms had the F1 scores of 0.85, 0.85, 0.86, 0.80, 0.88, and 0.85 and the accuracy of 88%, 88%, 88%, 85%, 91%, and 88%, respectively, and the prediction time was less than 5 s. The results indicated that the established models were accurate and efficient. Therefore, near infrared spectroscopy combined with machine learning algorithms can quickly predict the potential risks of clinical use of Reduning Injection in batches. Three key quality parameters that may affect clinical safety were identified by TreeNet, which provided a scientific basis for improving the safety standards of Reduning Injection.
Spectroscopy, Near-Infrared/methods*
;
Drugs, Chinese Herbal/administration & dosage*
;
Machine Learning
;
Algorithms
;
Humans
;
Quality Control
3.Preliminary application of human-computer interaction CT imaging AI recognition and positioning technology in the treatment of type C1 distal radius fractures.
Yong-Zhong CHENG ; Xiao-Dong YIN ; Fei LIU ; Xin-Heng DENG ; Chao-Lu WANG ; Shu-Ke CUI ; Yong-Yao LI ; Wei YAN
China Journal of Orthopaedics and Traumatology 2025;38(1):31-40
OBJECTIVE:
To explore the accuracy of human-computer interaction software in identifying and locating type C1 distal radius fractures.
METHODS:
Based on relevant inclusion and exclusion criteria, 14 cases of type C1 distal radius fractures between September 2023 and March 2024 were retrospectively analyzed, comprising 3 males and 11 females(aged from 27 to 82 years). The data were assigned randomized identifiers. A senior orthopedic physician reviewed the films and measured the ulnar deviation angle, radial height, palmar inclination angle, intra-articular step, and intra-articular gap for each case on the hospital's imaging system. Based on the reduction standard for distal radius fractures, cases were divided into reduction group and non-reduction group. Then, the data were sequentially imported into a human-computer interaction intelligent software, where a junior orthopedic physician analyzed the same radiological parameters, categorized cases, and measured fracture details. The categorization results from the software were consistent with manual classifications (6 reduction cases and 8 non-reduction cases). For non-reduction cases, the software performed further analyses, including bone segmentation and fracture recognition, generating 8 diagnostic reports containing fracture recognition information. For the 6 reduction cases, the senior and junior orthopedic physicians independently analyzed the data on the hospital's imaging system and the AI software, respectively. Bone segments requiring reduction were identified, verified by two senior physicians, and measured for displacement and rotation along the X (inward and outward), Z (front and back), and Y (up and down) axes. The AI software generated comprehensive diagnostic reports for these cases, which included all measurements and fracture recognition details.
RESULTS:
Both the manual and AI software methods consistently categorized the 14 cases into 6 reduction and 8 non-reduction groups, with identical data distributions. A paired sample t-test revealed no statistically significant differences (P>0.05) between the manual and software-based measurements for ulnar deviation angle, radial ulnar bone height, palmar inclination angle, intra-articular step, and joint space. In fracture recognition, the AI software correctly identified 10 C-type fractures and 4 B-type fractures. For the 6 reduction cases, a total of 24 bone fragments were analyzed across both methods. After verification, it was found that the bone fragments identified by the two methods were consistent. A paired sample t-tests revealed that the identified bone fragments and measured displacement and rotation angles along the X, Y, and Z axes were consistent between the two methods. No statistically significant differences(P>0.05) were found between manual and software measurements for these parameters.
CONCLUSION
Human-computer interaction software employing AI technology demonstrated comparable accuracy to manual measurement in identifying and locating type C1 distal radius fractures on CT imaging.
Humans
;
Male
;
Female
;
Radius Fractures/surgery*
;
Middle Aged
;
Adult
;
Aged
;
Aged, 80 and over
;
Tomography, X-Ray Computed/methods*
;
Retrospective Studies
;
Software
;
Wrist Fractures
4.Biomimetic dual-cell membrane nanoprobes employed for bimodal fluorescence-MR imaging of pancreatic cancer
Yanqi ZHONG ; Yingying MA ; Wenzheng LU ; Heng ZHANG ; Yuxi GE ; Peng WANG ; Jing ZHAO ; Jianying QIAN ; Jingxiao CHEN ; Shudong HU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(2):88-93
Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.
5.Mid-term analysis of a randomized controlled clinical trial on different transfusion strategies for cardiac valve surgery
Zhaolong ZHANG ; Xuankun XIE ; Yanji QU ; Lishan ZHONG ; Shanwen PANG ; Linbin HUA ; Qiuji WANG ; Heng ZUO ; Junqiang QIU ; Huanlei HUANG
Chinese Journal of Surgery 2025;63(8):695-703
Objective:To compare the clinical effects of restrictive transfusion strategy and liberal transfusion strategy for cardiac valve surgery.Methods:This study employed a prospective, randomized controlled superiority design, enrolling 439 patients undergoing non-emergency cardiac valve surgery with cardiopulmonary bypass at Department of Cardiovascular Surgery, Guangdong Provincial People′s Hospital, Southern Medical University from June 2023 to October 2024 who met the inclusion and exclusion criteria. While all the patients appeared hematocrit (Hct)≤24% or hemoglobin (Hb)≤80 g/L during the cardiopulmonary bypass. A simple random design was adopted to generate a random sequence and participants were randomized into a restrictive transfusion group (restrictive criteria: Hct≤18% or Hb≤60 g/L during cardiopulmonary bypass, and Hct≤21% or Hb≤70 g/L postoperatively) or a liberal transfusion group (liberal criteria: Hct≤24% or Hb≤80 g/L during cardiopulmonary bypass and Hct≤30% or Hb≤100 g/L postoperatively). If Hb or Hct fell below the respective thresholds, 2 units of red blood cells were transfused, followed by re-evaluation. If levels remained below the threshold, an additional 2 units were transfused until the criteria were met. The primary outcome was a composite of postoperative 3-month mortality, infection, ischemic events, and new-onset renal failure requiring dialysis. Secondary outcomes included blood product utilization, length of stay in the ICU and so on. Intergroup comparisons were performed using independent sample t-test, Mann-Whitney U test, χ2 test, or Fisher′s exact test, and analyses were conducted using a binary multivariable Logistic regression model. Results:A total of 439 patients were included in this study. The restrictive roup included 221 patients, including 75 males and 146 females, aged ( M(IQR)) 57.0 (14.0) years (range: 21 to 76 years). The liberal group included 218 patients, including 67 males and 151 females, aged 56.0 (20.0) years (range: 19 to 74 years). No statistically significant difference was observed in the incidence of primary outcome (restrictive group: 10.9%(24/221) vs. liberal group: 9.6%(21/218), χ2=0.180, P>0.05), 2 patints in the restrictive group died and 3 patints in liberal group died ( P=0.684). The transfusion rate was significantly lower in the restrictive group(19.0%(42/221) vs. 100%(218/218), P<0.01), with no significant differences in other secondary outcomes (all P>0.05). Subgroup analysis revealed an interaction between sex and transfusion strategy ( P=0.023), suggesting that using liberal transfusion strategy in male patients might increase the risk of the primary outcome. Conclusion:The mid-term results do not show that the restrictive transfusion strategy is superior to the liberal transfusion strategy in reducing the incidence of postoperative outcome events in patients undergoing cardiac valve surgery.
6.Feasibility study on the construction of predictive models of knee joint cartilage thickness
Zhi-ming CHENG ; Zhong-hua XU ; Xiao-jun MAN ; Yu-heng LI ; Zai-yang LIU ; Yuan ZHANG
Journal of Regional Anatomy and Operative Surgery 2025;34(7):563-569
Objective To determine the knee joint cartilage thickness using different methods and explore the feasibility of mathematical statistical models of dataset for the prediction of cartilage thickness.Methods A total of 304 patients diagnosed as knee osteoarthritis(OA)combined with varus deformity and undergoing unilateral total knee arthroplasty at the Second Affiliated Hospital of Army Medical University from March 2023 to March 2024 were selected for the study.All patients had complete preoperative and postoperative clinical data.The healthy cartilage at four anatomical sites of patients,including the distal femur lateral condyle,lateral tibial plateau,posterior medial femoral condyle,and posterior lateral femoral condyle were selected,and the knee joint cartilage thickness was determined based on preoperative MRI analysis,robotic navigation system tracing,tissue section of surgical specimen and digital vernier caliper.The baseline indicators of demographics,disease and imaging ffor patients were collected to construct a dataset,and four models of linear regression analysis,principal component analysis,Least Absolute Shrinkage and Selection Operator(LASSO)regression analysis,and K-nearest neighbors(KNN)analysis were established for predicting the accuracy,determination coefficient(R2)and root mean square error(RMSE),and the regression equation for predicting cartilage thickness was established.Results The knee joint cartilage thicknesses determined by preoperative MRI analysis,robotic navigation system tracing,tissue section of surgical specimen had no statistically significant difference with that by digital vernier caliper(P>0.05).The predictive efficiencies of models of linear regression analysis,principal component analysis,and LASSO regression analysis for the knee joint cartilage thickness all failed to meet the expectations(R2<0.3,RMSE>0.03).The predictive effect of KNN model on the cartilage thickness of the distal femur lateral condyle and lateral tibial plateau was not ideal(R2=0.23,RMSE=0.29),while it had potential predictive value(accuracy=0.21,accuracy=0.15).Conclusion The prediction model of knee joint cartilage thickness based on individual parameters has certain scientificity,and the feasibility of KNN model is relatively high.However,due to insufficient sample size and unclear individual parameter weight,the efficiencies of the four established prediction models are not ideal,which fails to provide definite prediction equations.Therefore,the construction scheme of the prediction model still needs to be further optimized.
7.Biomimetic dual-cell membrane nanoprobes employed for bimodal fluorescence-MR imaging of pancreatic cancer
Yanqi ZHONG ; Yingying MA ; Wenzheng LU ; Heng ZHANG ; Yuxi GE ; Peng WANG ; Jing ZHAO ; Jianying QIAN ; Jingxiao CHEN ; Shudong HU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(2):88-93
Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.
8.Mid-term analysis of a randomized controlled clinical trial on different transfusion strategies for cardiac valve surgery
Zhaolong ZHANG ; Xuankun XIE ; Yanji QU ; Lishan ZHONG ; Shanwen PANG ; Linbin HUA ; Qiuji WANG ; Heng ZUO ; Junqiang QIU ; Huanlei HUANG
Chinese Journal of Surgery 2025;63(8):695-703
Objective:To compare the clinical effects of restrictive transfusion strategy and liberal transfusion strategy for cardiac valve surgery.Methods:This study employed a prospective, randomized controlled superiority design, enrolling 439 patients undergoing non-emergency cardiac valve surgery with cardiopulmonary bypass at Department of Cardiovascular Surgery, Guangdong Provincial People′s Hospital, Southern Medical University from June 2023 to October 2024 who met the inclusion and exclusion criteria. While all the patients appeared hematocrit (Hct)≤24% or hemoglobin (Hb)≤80 g/L during the cardiopulmonary bypass. A simple random design was adopted to generate a random sequence and participants were randomized into a restrictive transfusion group (restrictive criteria: Hct≤18% or Hb≤60 g/L during cardiopulmonary bypass, and Hct≤21% or Hb≤70 g/L postoperatively) or a liberal transfusion group (liberal criteria: Hct≤24% or Hb≤80 g/L during cardiopulmonary bypass and Hct≤30% or Hb≤100 g/L postoperatively). If Hb or Hct fell below the respective thresholds, 2 units of red blood cells were transfused, followed by re-evaluation. If levels remained below the threshold, an additional 2 units were transfused until the criteria were met. The primary outcome was a composite of postoperative 3-month mortality, infection, ischemic events, and new-onset renal failure requiring dialysis. Secondary outcomes included blood product utilization, length of stay in the ICU and so on. Intergroup comparisons were performed using independent sample t-test, Mann-Whitney U test, χ2 test, or Fisher′s exact test, and analyses were conducted using a binary multivariable Logistic regression model. Results:A total of 439 patients were included in this study. The restrictive roup included 221 patients, including 75 males and 146 females, aged ( M(IQR)) 57.0 (14.0) years (range: 21 to 76 years). The liberal group included 218 patients, including 67 males and 151 females, aged 56.0 (20.0) years (range: 19 to 74 years). No statistically significant difference was observed in the incidence of primary outcome (restrictive group: 10.9%(24/221) vs. liberal group: 9.6%(21/218), χ2=0.180, P>0.05), 2 patints in the restrictive group died and 3 patints in liberal group died ( P=0.684). The transfusion rate was significantly lower in the restrictive group(19.0%(42/221) vs. 100%(218/218), P<0.01), with no significant differences in other secondary outcomes (all P>0.05). Subgroup analysis revealed an interaction between sex and transfusion strategy ( P=0.023), suggesting that using liberal transfusion strategy in male patients might increase the risk of the primary outcome. Conclusion:The mid-term results do not show that the restrictive transfusion strategy is superior to the liberal transfusion strategy in reducing the incidence of postoperative outcome events in patients undergoing cardiac valve surgery.
9.Genetic diversity of GⅡ genogroup noroviruses linked to clustered infections in Northeast Chongqing,2021-2022
Zhong-Kai LANG ; Ai-Ping CHEN ; Heng-Qin WANG ; Yu-Lu GAN ; Yong-Jun ZHANG
Chinese Journal of Zoonoses 2024;40(5):448-453
Norovirus is the global leading cause of epidemic and endemic acute gastroenteritis in people of all ages.To inves-tigate the genetic diversity of GⅡ genogroup noroviruses linked to clustered infections in northeast Chongqing,we collected anal swabs or environmental smears from 11 norovirus outbreaks during 2021-2022.Norovirus RNA was detected by quantitative real-time PCR(qRT-PCR),and partial viral RdRp/capsid genes were amplified by reverse transcription PCR(RT-PCR)and sequenced.Among samples from 11 outbreaks in 4 districts and counties,55 strains of GⅡ genogroup norovirus were detected.Six genotypes were identified with an online norovirus genotyping tool(http://www.rivm.nl/mpf/norovirus/typingtool).Genotype GⅡ.17[P17]was associated with four outbreaks;the co-circulating GⅡ.17[P17]and GⅡ.1[P16]caused another out-break;GⅡ.6[P7]and GⅡ.8[P8]respectively were linked to two outbreaks;and GⅡ.3[P12]and GⅡ.2[P16]respectively ac-counted for one outbreak.Phylogenetic analysis also indicated that 55 GⅡ genogroup strains formed five clusters,with norovir-uses of identical genotypes from diverse events belonging to the same cluster,and that genetically distinct genotypes from di-verse events belonged to different clusters.Therefore,our results revealed that multiple genotypes associated with norovirus outbreaks were circulating in northeast Chongqing,and GⅡ.17[P17]was the predominant genotype linked to these out-breaks during 2021-2022.Most norovirus outbreak events were caused by single sources,and genetic relationships were demonstrated among noroviruses of identical genotypes from diverse events.
10.A Novel Trifluoromethyl Quinazoline Compound Inhibits Drug-resistant Glioblastoma Cells Proliferation
Xiao-Zhong CHEN ; Shi-Nan WEI ; Heng LUO ; Peng ZHANG ; Ping SUN ; Bao-Fei SUN
Chinese Journal of Biochemistry and Molecular Biology 2024;40(9):1250-1261
The current treatment of glioma is facing drug resistance,which limits the efficacy of traditional chemotherapy drugs.This study aims to explore the potential mechanisms of the trifluoromethylquinazoline compound(KZL204)against glioma.Through the Cell Counting Kit-8(CCK-8)assay,we found that KZL204 significantly inhibits the growth of drug-resistant cancer cells,with a 48-hour half-maximal inhibitory concentration(IC50)of 3.63±0.38 μmol/L,which is significantly better than the positive control drug temozolomide(TMZ)(IC50 value of 81.67±5.49 μmol/L).Additionally,flow cytometry analysis showed that KZL204 treatment significantly increased the apoptosis rate of drug-resistant tumor cells and arrested the cell cycle at the G2/M phase.At the same time,the Transwell assay confirmed the inhibitory effect of KZL204 on the migration and invasion of drug-resistant cancer cells.Transcriptome analysis revealed 2 435 differentially expressed genes in drug-resistant cancer cells treated with KZL204,of which 1 320 were upregulated,and 1 115 were downregulated.KEGG and GO enrichment analysis showed that these differential genes were significantly enriched in apoptosis-related signaling pathways.Further bioinformatics prediction and Venn diagram analysis identified 35 potential core targets,with the PI3K-AKT signaling pathway being the most significant among the differentially expressed genes.Quantitative real-time PCR(RT-qPCR)experiments confirmed the downregulating effects of KZL204 on genes such as CREB3L1,CSF1,CXCL5,BCL3,and the upregulating effects on genes like FOS,LT A,PTGS2,MAP2K3.Immunoblotting experiments at the protein level also confirmed the impact of KZL204 on the expression of apoptotic proteins,including the upregulation of Bax,cleaved Caspase-3 protein,and the downregulation ofAKT,Bcl-2,Caspase-3,and Caspase-8 protein expression.In summary,KZL204 significantly inhibits the growth and metastasis of drug-resistant glioblastoma and induces apoptosis and cell cycle arrest by regulating the PI3K-AKT and apoptosis-related signaling pathways,demonstrating its potential as a candidate drug against drug-resistant glioma.

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