1.Protective effect and mechanism of chikusetsu saponin Ⅳa on the kidney in diabetic nephropathy rats
Yongli WANG ; Hai CHEN ; Xiaofang TIAN ; Xuechun WANG ; Liying YUAN ; Dan LIU ; Zhongfa LI ; Yanfang MENG ; Xiuyong YANG
China Pharmacy 2026;37(7):908-913
OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a (chsⅣ) on renal function in diabetic nephropathy (DN) model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group (i.g. administration of normal saline, high-fat diet), chsⅣ low-dose and high-dose groups (i.g. administration of 90, 180 mg/kg chsⅣ, high-fat diet), with 12 rats in each group. Additionally, 10 normal rats were set as the control group (i.g. administration of normal saline, regular diet). From the 5th to the 12th week after streptozotocin injection, they were given intragastric administration of relevant drug or normal saline, once a day. After the last medication, the levels of fasting blood glucose, fasting insulin, blood urea nitrogen, serum creatinine and urine protein as well as the levels of reduced glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissues were measured. Additionally, the insulin resistance index was calculated. Hematoxylin-eosin, periodic acid-Schiff, and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group, the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved, with significant decreases in renal histological scores, mesangial expansion index, and glomerulosclerosis scores ( P <0.05); the levels of fasting blood glucose, fasting insulin, blood urea nitrogen, serum creatinine, urine protein and homeostasis model assessment for insulin resistance, as well as MDA content, the expression levels of Notch1, Notch intracellular domain, hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased ( P <0.05). The levels of GSH and SOD in renal tissue were significantly elevated ( P <0.05). Moreover, the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group ( P <0.05). CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity, attenuation of renal oxidative stress, and suppression of aberrant Notch signaling pathway activation.
2.Analysis of the Path to Improve the Efficiency of Medical Resource Allocation in Chinese Medicine Hospitals under the Perspective of fsQCA Configuration
Xueyun TIAN ; Zhixin WANG ; Yiru ZHOU ; Yan JIANG ; Liying ZHAO ; Jie ZHOU ; Zi YANG ; Xiaowei MAN
Chinese Hospital Management 2025;45(1):41-45
Objective To explore the optimisation path of medical resource allocation efficiency improvement in Traditional Chinese Medicine (TCM) hospitals under the synergistic effect of multiple factors,so as to provide powerful support for the balanced development of medical resources in TCM hospitals.Methods The comprehensive efficiency of resource allocation in TCM hospitals in 31 provinces (cities and districts) of China obtained by Data Envelopment Analysis was taken as the outcome variable,and with the help of Fuzzy-set Qualitative Comparative Analysis,it examined the configurations of efficient medical resource allocation,considering the following conditional variables:per capital Regional GDP,the proportion of fiscal allocation revenue to total income,the ratio of TCM practicing (assistant) physicians to all practicing (assistant) physicians,the average length of hospital stay for discharged patients,the number of total diagnosis and treatments per thousand population,and the number of hospital beds per thousand population.Results By analyzing the conditional patterns of efficient allocation of medical resources in TCM hospitals,three equivalent driving paths can be summarized,which are comprehensive service capacity,TCM advantage and hospitalization driving paths.Conclusion The overall level of medical resource allocation efficiency of TCM hospitals in China needs to be improved.In the future,efforts should be made to improve the comprehensive service capacity and operational efficiency of hospitals,give full play to the advantages of TCM,build a high-quality TCM talent team,reasonably shorten the average hospital stay,and improve the utilization efficiency of hospital beds.
3.Establishment of animal models of rat abdominal wall with implantation of polypropylene mesh and mersi-lene tape and comparative study on their biomechanical properties and histocompatibility
Junlin GAO ; Guangjie YIN ; Chao MENG ; Chunlei XIU ; Liying HUANG ; Tian TIAN
The Journal of Practical Medicine 2025;41(10):1496-1501
Objective To establish animal models by implanting Gynemesh polypropylene mesh and Mersilene tape into the abdominal walls of rats,followed by conducting mechanical experiments and performing HE staining on abdominal wall tissues at 30 and 90 days post-implantation,respectively,in order to evaluate the biomechanical properties and histocompatibility of the two types of meshes.Methods The Gynemesh mesh and Mersilene tape were implanted into the abdominal wall of adult female rats(n=10)using W6977M polyester non-absorbable sutures and V-Loc absorbable sutures.The rats were randomly assigned to either a 30-day group or a 90-day group(n=5 per group)based on different experimental time points.Mechanical tests were conducted at these time points to evaluate the ultimate load required for avulsion of the meshes from the abdominal wall.Following the mechanical experiments,the tissues surrounding the meshes were harvested for hematoxylin and eosin(HE)staining.The inflammatory response,neovascularization,and fibroblast proliferation in the tissues were scored to compare the histocompatibility of the two types of meshes.Results(1)In the 30-day group,the ultimate load values were as follows:Gynemesh+6977(14.96±2.22)N,Gynemesh+V-Loc(12.73±1.11)N,Mersilene+6977(10.65±0.91)N,and Mersilene+V-Loc(8.70±1.18)N.No statistically significant difference was observed in the ultimate load between the Gynemesh+6977 and Gynemesh+V-Loc groups(P=0.12),whereas statistically significant differences were noted among the other groups(P<0.05).(2)In the 90-day group,the ultimate load values were as follows:Gynemesh+6977(18.97±0.59)N,Gynemesh+V-Loc(18.18±0.54)N,Mersilene+6977(13.87±0.67)N,and Mersilene+V-Loc(10.41±0.73)N.No statistically significant difference was observed in the ultimate load between the Gynemesh+6977 and Gynemesh+V-Loc groups(P=0.06),while statistically significant differences were noted among the other groups(P<0.05).(3)The ultimate load at 90 days for each group was significantly greater than that at 30 days,with statistically significant differences observed across all groups(P<0.05).(4)In the 30-day group,Gynemesh exhibited a lower inflammatory response compared to Mersilene tape(2.0±0.69 vs.3.10±0.71,P<0.05),with no statistically significant differences in neovascular-ization or fibroblast proliferation(2.37±0.61 vs.2.40±0.62,P=0.84;2.43±0.73 vs.2.63±0.67,P=0.27).In the 90-day group,Gynemesh demonstrated a lower inflammatory response score(1.10±0.66 vs.2.00±0.74,P<0.05),reduced fibroblast proliferation(2.87±0.68 vs.3.27±0.67,P<0.05),and no significant difference in neovascular proliferation(2.20±0.55 vs.2.13±0.68,P=0.68)compared to Mersilene tape.(5)The inflam-matory response for both mesh types was higher in the 30-day group compared to the 90-day group(Gynemesh group:2.0±0.69 vs.1.10±0.66,P<0.05;Mersilene group:3.13±0.73 vs.2.0±0.74,P<0.05).Additionally,the degree of fibroblast proliferation was lower in the 30-day group than in the 90-day group(Gynemesh group:2.43±0.73 vs.2.87±0.68,P<0.05;Mersilene group:2.63±0.67 vs.3.27±0.69,P<0.05).However,there was no statistically significant difference in neovascularization proliferation between the two groups(Gynemesh group:2.53±0.74 vs.2.47±0.74,P=0.81;Mersilene group:2.40±0.62 vs.2.13±0.68,P=0.12).Conclusion Compared with Mersilene tape,Gynemesh polypropylene mesh exhibits superior tensile strength and enhanced biocompatibility.
4.Correlation between thyroid autoimmunity and gestational diabetes mellitus in Chinese euthyroid women
Yue ZHAO ; Xiangyan RUAN ; Liying ZOU ; Jun MA ; Yuejiao WANG ; Xuanxuan TIAN ; Jing JIN
Journal of Capital Medical University 2025;46(4):626-631
Objective To explore the correlation between thyroid autoimmunity(TAI)and gestational diabetes mellitus(GDM)in Chinese euthyroid women.Methods A total of 508 euthyroid women were enrolled in the cross-sectional study,who performed their entire clinical/biological workup and oral glucose tolerance test(OGTT)from the department of Gynecology and Endocrinology of the Beijing Obstetrics and Gynecology Hospital,Capital Medical University from June 2023 to June 2024.At median 8(6-10)weeks of gestation,thyroid-stimulating hormone(TSH),free thyroxine(fT4),and thyroid peroxidase antibodies(TPOAb)were measured,baseline characteristics were recorded,and an OGTT was performed between 24 and 28 weeks of pregnancy.According to the OGTT results,they were divided into GDM group(n=169)and non GDM group(n=339).Thyroid parameters,the demographic and obstetric parameters,and the prevalence of TAI were compared with two groups.The factors associated with GDM were analyzed with multivariate Logistic regression analysis.Results The age,body mass index(BMI),and proportion of obese women before pregnancy in the GDM group were all significantly higher than those in the non-GDM group,with statistically significant differences(P<0.001).The proportion of pregnant women over 30 years old in the GDM group was significantly higher than that in the non-GDM group(59.17%vs 6.79%,χ2=168.667,P<0.001).The proportion of obese mothers(BMI≥28 kg/m2)before pregnancy in the GDM group was 24.26%,which was significantly higher than that in the non-GDM group(8.26%)(χ2=24.599,P<0.001).The incidence of TAI in the GDM group was 54.44%,while it was 15.93%in the non-GDM group.The difference between the two groups was statistically significant(χ2=81.659,P<0.001).The results of Logistic regression analysis showed that maternal age over 30 years and pre-pregnancy obesity increased the risk of GDM occurrence in TAI women by 6.08 times(OR=6.08,95%CI 3.61-10.25,P<.001).Conclusion Among early pregnancy women with normal thyroid function,as age increases during follow-up(especially over 30 years old),pre-pregnancy BMI increases(especially in obese individuals),and those with pre-pregnancy TAI,the risk of developing GDM during pregnancy significantly increases.It is necessary to explore preventive strategies for GDM in euthyroid TAI women,with a view to improving adverse pregnancy outcomes.
5.Establishment of animal models of rat abdominal wall with implantation of polypropylene mesh and mersi-lene tape and comparative study on their biomechanical properties and histocompatibility
Junlin GAO ; Guangjie YIN ; Chao MENG ; Chunlei XIU ; Liying HUANG ; Tian TIAN
The Journal of Practical Medicine 2025;41(10):1496-1501
Objective To establish animal models by implanting Gynemesh polypropylene mesh and Mersilene tape into the abdominal walls of rats,followed by conducting mechanical experiments and performing HE staining on abdominal wall tissues at 30 and 90 days post-implantation,respectively,in order to evaluate the biomechanical properties and histocompatibility of the two types of meshes.Methods The Gynemesh mesh and Mersilene tape were implanted into the abdominal wall of adult female rats(n=10)using W6977M polyester non-absorbable sutures and V-Loc absorbable sutures.The rats were randomly assigned to either a 30-day group or a 90-day group(n=5 per group)based on different experimental time points.Mechanical tests were conducted at these time points to evaluate the ultimate load required for avulsion of the meshes from the abdominal wall.Following the mechanical experiments,the tissues surrounding the meshes were harvested for hematoxylin and eosin(HE)staining.The inflammatory response,neovascularization,and fibroblast proliferation in the tissues were scored to compare the histocompatibility of the two types of meshes.Results(1)In the 30-day group,the ultimate load values were as follows:Gynemesh+6977(14.96±2.22)N,Gynemesh+V-Loc(12.73±1.11)N,Mersilene+6977(10.65±0.91)N,and Mersilene+V-Loc(8.70±1.18)N.No statistically significant difference was observed in the ultimate load between the Gynemesh+6977 and Gynemesh+V-Loc groups(P=0.12),whereas statistically significant differences were noted among the other groups(P<0.05).(2)In the 90-day group,the ultimate load values were as follows:Gynemesh+6977(18.97±0.59)N,Gynemesh+V-Loc(18.18±0.54)N,Mersilene+6977(13.87±0.67)N,and Mersilene+V-Loc(10.41±0.73)N.No statistically significant difference was observed in the ultimate load between the Gynemesh+6977 and Gynemesh+V-Loc groups(P=0.06),while statistically significant differences were noted among the other groups(P<0.05).(3)The ultimate load at 90 days for each group was significantly greater than that at 30 days,with statistically significant differences observed across all groups(P<0.05).(4)In the 30-day group,Gynemesh exhibited a lower inflammatory response compared to Mersilene tape(2.0±0.69 vs.3.10±0.71,P<0.05),with no statistically significant differences in neovascular-ization or fibroblast proliferation(2.37±0.61 vs.2.40±0.62,P=0.84;2.43±0.73 vs.2.63±0.67,P=0.27).In the 90-day group,Gynemesh demonstrated a lower inflammatory response score(1.10±0.66 vs.2.00±0.74,P<0.05),reduced fibroblast proliferation(2.87±0.68 vs.3.27±0.67,P<0.05),and no significant difference in neovascular proliferation(2.20±0.55 vs.2.13±0.68,P=0.68)compared to Mersilene tape.(5)The inflam-matory response for both mesh types was higher in the 30-day group compared to the 90-day group(Gynemesh group:2.0±0.69 vs.1.10±0.66,P<0.05;Mersilene group:3.13±0.73 vs.2.0±0.74,P<0.05).Additionally,the degree of fibroblast proliferation was lower in the 30-day group than in the 90-day group(Gynemesh group:2.43±0.73 vs.2.87±0.68,P<0.05;Mersilene group:2.63±0.67 vs.3.27±0.69,P<0.05).However,there was no statistically significant difference in neovascularization proliferation between the two groups(Gynemesh group:2.53±0.74 vs.2.47±0.74,P=0.81;Mersilene group:2.40±0.62 vs.2.13±0.68,P=0.12).Conclusion Compared with Mersilene tape,Gynemesh polypropylene mesh exhibits superior tensile strength and enhanced biocompatibility.
6.Analysis of the Path to Improve the Efficiency of Medical Resource Allocation in Chinese Medicine Hospitals under the Perspective of fsQCA Configuration
Xueyun TIAN ; Zhixin WANG ; Yiru ZHOU ; Yan JIANG ; Liying ZHAO ; Jie ZHOU ; Zi YANG ; Xiaowei MAN
Chinese Hospital Management 2025;45(1):41-45
Objective To explore the optimisation path of medical resource allocation efficiency improvement in Traditional Chinese Medicine (TCM) hospitals under the synergistic effect of multiple factors,so as to provide powerful support for the balanced development of medical resources in TCM hospitals.Methods The comprehensive efficiency of resource allocation in TCM hospitals in 31 provinces (cities and districts) of China obtained by Data Envelopment Analysis was taken as the outcome variable,and with the help of Fuzzy-set Qualitative Comparative Analysis,it examined the configurations of efficient medical resource allocation,considering the following conditional variables:per capital Regional GDP,the proportion of fiscal allocation revenue to total income,the ratio of TCM practicing (assistant) physicians to all practicing (assistant) physicians,the average length of hospital stay for discharged patients,the number of total diagnosis and treatments per thousand population,and the number of hospital beds per thousand population.Results By analyzing the conditional patterns of efficient allocation of medical resources in TCM hospitals,three equivalent driving paths can be summarized,which are comprehensive service capacity,TCM advantage and hospitalization driving paths.Conclusion The overall level of medical resource allocation efficiency of TCM hospitals in China needs to be improved.In the future,efforts should be made to improve the comprehensive service capacity and operational efficiency of hospitals,give full play to the advantages of TCM,build a high-quality TCM talent team,reasonably shorten the average hospital stay,and improve the utilization efficiency of hospital beds.
7.A cross-sectional study of the characteristics of patients with pneumoconiosis complicated with chronic obstructive pulmonary disease
Yao CHEN ; Pingping SONG ; Yani WEI ; Liying TIAN ; Hua ZHANG ; Yongjian YAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(1):32-37
Objective:To analyze the characteristics of patients with pneumoconiosis complicated with chronic obstructive pulmonary disease (COPD), and to explore the comorbidity of pneumoconiosis and COPD and its influencing factors.Methods:From October to December 2022, 255 pneumoconiosis patients admitted to an occupational disease prevention and control hospital from January 2018 to December 2021 were selected as the study subjects. According to whether the pneumoconiosis patients were complicated with COPD or not, they were divided into pneumoconiosis and COPD comorbidity group and pneumoconiosis group. The general condition and dust exposure of the two groups of patients were analyzed, and the relationship between different types and different periods of pneumoconiosis and COPD comorbidity was analyzed by multivariate logistic regression.Results:A total of 255 subjects were collected, including 64 patients with comorbidity of pneumoconiosis and COPD, and the comorbidity rate was 25.1%. There were 186 males (72.9%) and 69 females (27.1%), ranging in age from 35 to 90 (63.79±11.79) years, and working age from 1 to 45 (20.31±10.57) years. The comorbidity of pneumoconiosis and COPD increased with the increase of working age (χ 2trend=8.19, P=0.004), and the comorbidity rate for COPD with working age of more than 30 years was 37.7% (23/61). The comorbidity rate of pneumoconiosis and COPD also increased with the increase of the stage of pneumoconiosis (χ 2trend=13.14, P<0.001), and the comorbidity rate of pneumoconiosis and COPD in the stage Ⅲ was as high as 44.0% (11/25). The cumulative dust exposure was negatively correlated with forced expiratory volume in one second/forced vital capacity (FEV 1/FVC), and the linear regression equation y=-0.04 x+78.4. Multivariate logistic regression analysis showed that the length of services ≥30 years ( OR=3.30, 95% CI: 1.15-9.52) and stageⅡ ( OR=3.05, 95% CI: 1.03-9.04) were the risk factors for comorbidity between pneumoconiosis and COPD ( P<0.05) . Conclusion:The comorbidity rate of pneumoconiosis and COPD is high. Working age, pneumoconiosis stage and cumulative dust exposure are the main influencing factors of pneumoconiosis and COPD comorbidity, so more attention should be paid to the comorbidity of pneumoconiosis and COPD.
8.Screening and preliminary study of PIK3CG as a potential biomarker in polycystic ovary syndrome
Liying HUANG ; Lining LI ; Xiao QIN ; Shaohua LING ; Chun TIAN ; Yanlan LING ; Rong CHEN ; Li QIN
Chongqing Medicine 2025;54(8):1771-1780
Objective To explore the genes related to the pathogenesis of polycystic ovary syndrome(PCOS)through bioinformatics methods and verify them in ovarian granulosa cells,providing a reference for screening potential molecular markers of PCOS.Methods The GSE34526 and GSE137684 datasets were re-spectively used as the training set and validation set.The inflammation-related genes potentially associated with the onset of PCOS were explored through differential expression analysis and weighted gene co-expres-sion network analysis.Subsequently,their predictive value was verified through the receiver operating charac-teristic(ROC)curve.Thirty patients with PCOS(the PCOS group)and 27 patients without PCOS(the con-trol group)who were treated in Affiliated Hospital of Youjiang Medical University for Nationalities were se-lected as the research objects.RT-qPCR was applied to verify the expression level of core genes in granular cells.Spearman correlation and multiple linear regression were used to analyze the correlation between the ex-pression level of core genes and various clinical parameters,and the ROC curve was used to analyze the diag-nostic efficacy of the expression level of core genes for PCOS.Finally,the protein expression level of core genes was verified on animal models.Results A total of 1 888 differentially expressed genes,89 module-relat-ed genes and 366 inflammatory response-related genes were identified.The core gene phosphatidylinositol-4,5-diphosphate 3-kinase catalytic subunit γ(PIK3CG)was ultimately obtained by taking co-expressed genes and verifying with the ROC curve.RT-qPCR results showed that the expression level of PIK3CG in granulosa cells of the PCOS group was higher than that of the control group(P<0.05).Spearman correlation analysis showed that the expression level of PIK3CG was positively correlated with BMI,testosterone(T),fasting in-sulin(FINS),and insulin resistance index(HOMA-IR,P<0.05).Multivariate linear regression analysis showed that FINS,HOMA-IR and BMI were increased with the increasing of PIK3CG expression level(P<0.05).ROC curve analysis showed that the area under the curve for diagnosing PCOS patients with PIK3CG mRNA expression levels in granulosa cells was 0.659 3.The immunohistochemical results showed that the ex-pression of PIK3CG protein in the ovarian tissues of mice in the PCOS group was significantly increased.Con-clusion PIK3CG may be potentially associated with the pathogenesis of PCOS.
9.Correlation between thyroid autoimmunity and gestational diabetes mellitus in Chinese euthyroid women
Yue ZHAO ; Xiangyan RUAN ; Liying ZOU ; Jun MA ; Yuejiao WANG ; Xuanxuan TIAN ; Jing JIN
Journal of Capital Medical University 2025;46(4):626-631
Objective To explore the correlation between thyroid autoimmunity(TAI)and gestational diabetes mellitus(GDM)in Chinese euthyroid women.Methods A total of 508 euthyroid women were enrolled in the cross-sectional study,who performed their entire clinical/biological workup and oral glucose tolerance test(OGTT)from the department of Gynecology and Endocrinology of the Beijing Obstetrics and Gynecology Hospital,Capital Medical University from June 2023 to June 2024.At median 8(6-10)weeks of gestation,thyroid-stimulating hormone(TSH),free thyroxine(fT4),and thyroid peroxidase antibodies(TPOAb)were measured,baseline characteristics were recorded,and an OGTT was performed between 24 and 28 weeks of pregnancy.According to the OGTT results,they were divided into GDM group(n=169)and non GDM group(n=339).Thyroid parameters,the demographic and obstetric parameters,and the prevalence of TAI were compared with two groups.The factors associated with GDM were analyzed with multivariate Logistic regression analysis.Results The age,body mass index(BMI),and proportion of obese women before pregnancy in the GDM group were all significantly higher than those in the non-GDM group,with statistically significant differences(P<0.001).The proportion of pregnant women over 30 years old in the GDM group was significantly higher than that in the non-GDM group(59.17%vs 6.79%,χ2=168.667,P<0.001).The proportion of obese mothers(BMI≥28 kg/m2)before pregnancy in the GDM group was 24.26%,which was significantly higher than that in the non-GDM group(8.26%)(χ2=24.599,P<0.001).The incidence of TAI in the GDM group was 54.44%,while it was 15.93%in the non-GDM group.The difference between the two groups was statistically significant(χ2=81.659,P<0.001).The results of Logistic regression analysis showed that maternal age over 30 years and pre-pregnancy obesity increased the risk of GDM occurrence in TAI women by 6.08 times(OR=6.08,95%CI 3.61-10.25,P<.001).Conclusion Among early pregnancy women with normal thyroid function,as age increases during follow-up(especially over 30 years old),pre-pregnancy BMI increases(especially in obese individuals),and those with pre-pregnancy TAI,the risk of developing GDM during pregnancy significantly increases.It is necessary to explore preventive strategies for GDM in euthyroid TAI women,with a view to improving adverse pregnancy outcomes.
10.Targeting the JAK2-STAT3-UCHL3-ENO1 axis suppresses glycolysis and enhances the sensitivity to 5-FU chemotherapy in TP53-mutant colorectal cancer.
Haisong XIN ; Zitong ZHAO ; Shichao GUO ; Ruoxi TIAN ; Liying MA ; Yang YANG ; Lianmei ZHAO ; Guanglin WANG ; Baokun LI ; Xuhua HU ; Yongmei SONG ; Guiying WANG
Acta Pharmaceutica Sinica B 2025;15(5):2529-2544
Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

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