1.A denoising method for low-dose CT images based on MDC-DCRN model
Hongchi CHEN ; Ying ZHAI ; Qiuxia LI ; Fangzuo LI
Chinese Journal of Medical Physics 2025;42(9):1136-1146
Objective Low-dose CT(LDCT)images significantly affect clinical diagnosis due to the substantial presence of noise and artifacts.To address the challenges such as over-smoothing of images,loss of texture details,and the presence of residual noise artifacts,a deconvolution-convolution residual network integrating multi-scale dilated convolution(MDC-DCRN)is proposed for LDCT denoising.Methods The network employed deconvolution-convolution architecture to better preserve image details and integrated an MDC module to enhance the feature extraction capabilities at different scales.Moreover,the issue of excessive image smoothing was effectively mitigated by the composite loss function combining L1 loss and perceptual loss.Results The experimental results on the Mayo dataset demonstrated that MDC-DCRN outperformed 4 classic denoising methods,namely RED-CNN,EDCNN,WGAN-RAM,and CTformer.MDC-DCRN effectively eliminated noise and artifacts while recovering more texture detail information.Compared with LDCT images,the images processed by MDC-DCRN had an average increase of 13.64%in peak signal-to-noise ratio,an average increase of 4.57%in structural similarity index,and an average decrease of 37.40%in root mean square error.Conclusion The proposed MDC-DCRN model can effectively preserve details while reducing noise from low-dose scanning,offering a novel approach to clinical LDCT image denoising.
2.Prediction of cumulative live birth rate in in vitro fertilization using multi-model machine learning algorithms
Peng XING ; Hui LIANG ; Ying CHEN ; Ting LIU ; Jiawei ZHAI ; Bo YUAN ; Yingjun TIAN
Chinese Journal of Reproduction and Contraception 2025;45(4):358-364
Objective:To develop and validate machine learning models for predicting the cumulative live birth rate (CLBR) following in vitro fertilization (IVF) and to analyze key predictive features using SHAP values. Methods:This retrospective study included data from patients who underwent IVF-embryo transfer at the Department of Reproductive Medicine, Baoding Maternal and Child Health Hospital, between January 2017 and December 2022. Patients were categorized into two groups based on live birth outcome: the live birth group ( n=1 036) and the non-live birth group ( n=756). The dataset was randomly divided into a training set and a validation set in a ratio of 7∶3. Five algorithms were utilized for model development: logistic regression, random forest, extreme gradient boosting (XGBoost), support vector machine, and neural networks. Model performance was assessed using the area under the receiver operating characteristic (AUC) curve, F1 score, and calibration curves. Clinical decision curve analysis (DCA) was employed to evaluate the clinical utility of the models. SHAP values were used to interpret feature importance in the XGBoost model and enhance its explainability. Results:The XGBoost model demonstrated the best performance in predicting CLBR,with accuracy of 72.44%, AUC of 0.775, and F1 score of 0.654, accuracy and F1 score outperforming logistic regression (accuracy was 70.02%, F1 score was 0.585), random forest (accuracy was 71.69%, F1 score was 0.606), support vector machine (accuracy was 70.20%, F1 score was 0.607), and neural network (accuracy was 68.72%, F1 score was 0.560). The calibration curve of XGBoost closely aligned with the diagonal line, indicating that the predicted probabilities were very close to the actual outcomes, demonstrating good calibration. DCA indicated that the XGBoost model provided higher net benefits across a wide range of clinical decision thresholds. SHAP value analysis identified number of previous IVF failures, antral follicle count, anti-Müllerian hormone level, percentage of normal sperm morphology, and sperm DNA fragmentation index as key predictors of CLBR.Conclusion:The XGBoost model exhibits excellent predictive performance and calibration for CLBR, with SHAP values providing important insights into feature importance. This model has the potential to support the development of personalized treatment strategies in clinical practice. However, its generalizability needs to be validated using external datasets to ensure its applicability to diverse populations.
3.Relationship between NLRP,NF-κB and Caspase-1 levels in peripheral blood mononuclear cells and pregnancy outcome in patients with recurrent spontaneous abortion and reproductive tract infection
Guoxi SHI ; Hongli NIU ; Hongwei ZHONG ; Nan WANG ; Junying ZHAI ; Ying WANG
Chinese Journal of Nosocomiology 2025;35(11):1665-1669
OBJECTIVE To analyze the levels of NOD like receptor thermal protein domain associated protein 3(NLRP3),nuclear factor κB(NF-κB)and Caspase-1 in peripheral blood mononuclear cells in patients with recur-rent spontaneous abortion(RSA)and reproductive tract infection(RTI),and the relationship between above inde-xes and pregnancy outcome.METHODS A total of 136 patients with RSA and RTI who were admitted to Nanyang First People's Hospital from Mar.2021 to Apr.2024 were selected as the study group,70 patients with RSA but without RTI during the same period were selected as the control group,and those patients with RSA and RTI who were pregnant again were divided into the continued pregnancy group and the abortion group based on their preg-nancy outcomes.The levels of NLRP,NF-κB and caspase-1 in peripheral blood mononuclear cells were compared between the study group and the control group,Multivariate logistic regression analysis was used to identify risk factors for adverse pregnancy outcomes in patients with RSA and RTI.Receiver's operating characteristic(ROC)curves were used to evaluate the value of NLRP,NF-κB,and Caspase-1 in peripheral blood mononuclear cells in predicting pregnancy outcomes of patients with RSA and RTI.RESULTS The levels of NLRP,NF-κB and caspase-1 in the study group were(1.93±0.49),(1.82±0.41)and(2.23±0.41)respectively,which were higher than those in the control group(P<0.05).The proportion of abortion in the study group was 39.79%,which was higher than that in the control group(P=0.036).Pre-pregnancy body mass index(BMI)and the levels of glycated hemoglobin,triacylglycerol,NLRP,NF-κB and Caspase-1 in the abortion group were higher than those in the continued pregnancy group.Multivariate logistic regression analysis showed that NLRP3(OR=4.721,95%CI:1.336-16.680,P=0.016),NF-κB(OR=4.669,95%CI:1.495-14.58,P=0.008),caspase-1(OR=4.358,95%CI:1.260-15.070,P=0.023)and pre-pregnancy BMI(OR=2.927,95%CI:1.280-6.693,P=0.011)were risk factors affecting pregnancy outcomes of patients with RSA and RTI(P<0.05).ROC curves indicated that the area under the curve(AUC)of NLRP,NF-κB and Caspase-1 for pregnancy outcome in patients with RSA combined with RTI was 0.846,0.885 and 0.938.CONCLUSION The NLRP,NF-κB and Caspase-1 in peripheral blood mononuclear cells is highly expressed in patients with RSA and RTI,and the high expression of the above indicators is closely related to the adverse pregnancy of patients,which can be used as a predictor of pregnancy outcomes in patients with RSA and RTI.
4.Construction and validation of a model for jointly predicting early pregnancy loss at 6 weeks of gestation after IVF-ET based on serum FGF-21,AMH,and NRP-1
Hongwei ZHANG ; Nan WANG ; Guoxi SHI ; Junying ZHAI ; Hongli NIU ; Ying WANG
The Journal of Practical Medicine 2025;41(22):3480-3489
Objective To investigate the predictive value of pre-transfer serum fibroblast growth factor 21(FGF-21),anti-Müllerian hormone(AMH),and neuropilin-1(NRP-1)for early pregnancy loss at 6 weeks following in vitro fertilization-embryo transfer(IVF-ET),and to establish an early predictive model based on serum biochemical markers.Methods This prospective study consecutively enrolled 322 women who achieved clinical pregnancy after IVF-ET at our center between September 2022 and September 2024.Participants were randomly divided into a modeling cohort(n=225)and a validation cohort(n=97)at a 7:3 ratio.According to ultrasound findings at 6 weeks of gestation,patients in the modeling cohort were classified into an early pregnancy loss group(n=59)and an ongoing pregnancy group(n=166).Baseline clinical characteristics and pre-transfer serum levels of FGF-21,AMH,and NRP-1 were collected.Multivariate logistic regression was applied to identify inde-pendent risk factors for early pregnancy loss and to construct a predictive model.Model discrimination,calibra-tion,and stability were evaluated using receiver operating characteristic(ROC)curves,the Hosmer-Lemeshow goodness-of-fit test,and bootstrap resampling in both cohorts.Results Univariate analysis revealed that the FSH/LH ratio,antral follicle count,and number of retrieved oocytes were significantly associated with early pregnancy loss(P<0.001).Compared with the ongoing pregnancy group,women with early loss showed significantly elevated pre-transfer serum FGF-21 levels,whereas AMH and NRP-1 levels were markedly reduced(P<0.001).Multivariate logistic regression demonstrated that an FSH/LH ratio<1.8(OR=1.629,P=0.002)and higher FGF-21 levels(OR=1.338,P=0.002)were independent risk factors,while higher AMH(OR=0.741,P=0.010)and NRP-1 levels(OR=0.874,P=0.007)were protective.Stratified analysis indicated that among patients with FSH/LH≥1.8,FGF-21 levels were significantly higher and AMH and NRP-1 levels significantly lower(all P<0.001).Interaction analysis further suggested that the FSH/LH ratio significantly modified the associations between these biomarkers and pregnancy loss risk(P for interaction<0.05).Specifically,in the higher FSH/LH subgroup,the risk effect of FGF-21 was amplified,while the protective effects of AMH and NRP-1 were more pronounced.The combined predictive model achieved C-indices of 0.869(95%CI:0.826~0.926)in the modeling cohort and 0.835(95%CI:0.811~0.907)in the validation cohort.Its AUC for predicting early pregnancy loss was 0.934 in the modeling co-hort and 0.909 in the validation cohort,both significantly outperforming individual markers(AUCs:FGF-21=0.867,AMH=0.881,NRP-1=0.853;Z=2.024,1.831;P<0.001).Decision curve analysis showed that the model provided consistent net clinical benefit across threshold probabilities of 0.1~0.4,underscoring its clinical utility.Conclusions Elevated pre-transfer serum FGF-21 and reduced AMH and NRP-1 levels are strongly associ-ated with early pregnancy loss at 6 weeks after IVF-ET.The predictive model developed in this study demonstrates robust accuracy and stability,offering substantial clinical application value for early risk stratification.
5.Expression of serum microRNA-497 in patients with colorectal cancer and its diagnostic and prognostic values
Mei HUA ; Xiaolu ZHAI ; Chong TANG ; Ying CHEN ; Dian YIN
The Journal of Practical Medicine 2025;41(22):3579-3584
Objective To characterize the expression patterns of serum microRNA-497(miR-497)in patients with colorectal cancer(CRC)and to investigate its associations with clinicopathological characteristics,diagnostic performance,and long-term prognostic outcomes.Methods This study retrospectively analyzed data from 122 patients with CRC admitted to the hospital between March 2020 and March 2022(CRC group),and enrolled 100 healthy individuals undergoing routine physical examinations(healthy control group)for comparison.Serum samples were collected from all participants prior to any surgical intervention,and the expression levels of miR-497 in serum were quantified using real-time quantitative polymerase chain reaction(qRT-PCR).Simulta-neously,the levels of carcinoembryonic antigen(CEA)and carbohydrate antigen 199(CA199)were measured.To investigate the association between miR-497 expression and clinicopathological characteristics,we evaluated its diagnostic performance using receiver operating characteristic(ROC)curve analysis.Furthermore,Kaplan-Meier survival analysis and Cox proportional hazards regression models were employed to assess its impact on patient prognosis.Results Compared to healthy individuals,CRC patients exhibited significantly lower serum miR-497 expression levels(P<0.001).Notably,miR-497 expression was strongly correlated with TNM stage progression and lymph node metastasis(P<0.001),but showed no significant association with tumor location,patient sex,or age.Diagnostic evaluation using ROC curves demonstrated that miR-497 achieved an AUC of 0.845 for CRC detection,outperforming CEA(AUC=0.748)and CA19-9(AUC=0.702),with DeLong's test confirming the statistically significant differences(P<0.05).Kaplan-Meier survival analysis revealed a significantly higher 3-year DFS rate among patients with high miR-497 expression(84.06%)compared to those with low expression(64.58%),with median DFS not reached in the high-expression group versus 36 months in the low-expression group(P=0.015).Multivariate Cox regression analysis confirmed that reduced miR-497 expression(HR=1.923,95%CI:1.184~3.125),advanced TNM stage(HR=2.511,95%CI:1.421~4.437),and lymph node metastasis(HR=1.753,95%CI:1.151~2.664)were independently associated with poorer disease-free survival outcomes.Conclusions Serum miR-497 is downregulated in patients with CRC and is significantly associated with tumor progression and poor prognosis.It demonstrates high diagnostic accuracy and strong potential for prognostic evalua-tion,highlighting its promise as a biomarker for auxiliary diagnosis and outcome prediction in CRC.
6.The efficacy of Adalimumab in treatment of pediatric noninfectious uveitis and the factors influencing the efficacy
Chunbo ZHANG ; Ying CHEN ; Hui MIN ; Xiaorong XUE ; Yuyao ZHAI ; Rong ZENG
Chinese Journal of Ocular Fundus Diseases 2025;41(7):520-526
Objective:To investigate the clinical efficacy and factors influencing treatment of pediatric noninfectious uveitis with Adalimumab (ADA).Methods:A retrospective clinical study. A total of 86 pediatric patients with non-infectious uveitis, diagnosed and treated with ADA at Department of Uveitis Specialist of Xi'an People's Hospital (Xi' an Fourth Hospital) from January 1, 2021 to December 31, 2023, were included in this study. The age of all patients was ≤16 years. Among them, 55 (63.95%, 55/86) patients received ADA combined with one immunosuppressive agent, 28 (32.56%, 28/86) patients received ADA combined with ≥2 immunosuppressive agents, and 3 (3.49%, 3/86) patients received ADA alone without any immunosuppressive agents. All patients underwent best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. The thickness of the retinal nerve fiber layer (RNFL) in the macular region was measured using an OCT device. The cumulative treatment effectiveness rate at 12 months post-treatment was evaluated using the Kaplan-Meier survival analysis. Multivariate analysis was performed using the Cox proportional hazards regression model, and the optimal predictive model was selected based on the Bayesian information criterion. The association between different treatment regimens and various clinical outcomes was assessed.Results:Among the 86 pediatric patients, 42 were male and 44 were female, with a mean age of (10.47±3.23) years. The distribution of uveitis types was as follows: anterior uveitis in 37 cases, intermediate uveitis in 15 cases, posterior uveitis in 10 cases, and panuveitis in 24 cases. Anterior chamber cells (ACC), keratic precipitates, and synechiae were present in 66, 55, and 38 cases, respectively. The cumulative treatment effectiveness at 12 months was 85.1% [95% confidence interval ( CI) 71.9-92.2], with a median time to treatment effectiveness of 3 months. Compared with baseline, after 6 months of treatment, the BCVA, RNFL thickness ( Z=?6.323, ?8.017), and the grading of ACC and vitreous haze ( χ2= ?6.917, ?5.027) showed significant improvement, with statistically significant differences ( P<0.05). Multivariate analysis revealed that ACC (hazard ratio=22.31, 95% CI 2.43-204.68) and anterior uveitis (hazard ratio=3.88, 95% CI 2.03-7.42) were significantly associated with treatment effectiveness ( P<0.05). Patients with ACC had a median time to treatment effectiveness of 2 months, with a 12-month cumulative treatment effectiveness of 95.5% (95% CI 86.3-98.5). Patients with anterior uveitis had a median time to treatment effectiveness of 2 months, with a 12-month cumulative treatment effectiveness of 97.3% (95% CI 81.3-99.6). Patients without anterior uveitis had a median time to treatment effectiveness of 5 months, with a 12-month cumulative treatment effectiveness of 76.7% (95% CI 54.1-88.2). The cumulative recurrence risk at 12 months was 15.6% (95% CI 6.2-24.1). Conclusion:ADA is safe and effective in treating pediatric non-infectious uveitis, and ACC and anterior uveitis are associated with response rate.
7.Dose-adjusted plasma concentrations of valproic acid between different valproate formulations in patients with mental disorders
Jing DING ; Ying CHEN ; Xiaohua CUI ; Zhuocheng MENG ; Suo ZHANG ; Jiao HE ; Yuanyuan ZHAI
Chinese Journal of Neuromedicine 2025;24(11):1125-1133
Objective:To explore differences in dose-adjusted plasma concentrations of valproic acid between different valproate formulations in patients with mental disorders based on therapeutic drug monitoring data.Methods:A retrospective analysis was performed; clinical data, including demographic characteristics, therapeutic drug monitoring results, comorbidities, medication details (daily valproic acid dose, concomitant medications), and liver and kidney function indicators, were collected from 633 patients with bipolar disorder or schizophrenia who were hospitalized at Xi'an Mental Health Center and received different valproates from January 2024 to June 2024 (98 patients receiving sodium valproate and 535 receiving magnesium valproate). Clinical data between a sodium valproate group and a magnesium valproate group were compared. Multivariate linear regression was used to identify independent influencing factors for dose-adjusted plasma concentration of valproic acid. Valproic acid daily doses, and plasma concentrations and dose-adjusted plasma concentrations of valproic acid were compared between the two groups, with subgroup analyses conducted by gender and age categories.Results:A total of 658 measurements of plasma valproic acid concentration were obtained in 633 patients, including 104 measurements in the sodium valproate group and 554 in the magnesium valproate group. Significant differences in proportions of comorbidities and concomitant use of olanzapine, quetiapine and clozapine were observed between the sodium valproate group and magnesium valproate group ( P<0.05). After adjusting for age, gender, body mass index, comorbidities, concomitant medications, and liver and kidney function indicators, the type of valproates remained an independent influencing factor for dose-adjusted plasma concentration of valproic acid (adjusted unstandardized B coefficient=13.814, 95% CI: 8.090-19.540, P<0.001). Daily dose in the sodium valproate group (1.0[1.0, 1.0] g/d) was significantly higher than that in the magnesium valproate group (0.5[0.5, 1.0] g/d), and dose-adjusted plasma concentration of valproic acid in the magnesium valproate group (93.00 [75.60, 117.40] [μg/mL]/[g·d]) was statistically higher than that in the sodium valproate group (78.55 [57.90, 90.00][μg/mL]/[g·d], P<0.05). Subgroup analysis revealed that, among patients stratified by genders and ages (<40 years vs. ≥40 years), the daily dose in the sodium valproate group was significantly higher than that in the magnesium valproate group, while the dose-adjusted plasma concentration of valproic acid in the magnesium valproate group was significantly higher than that in the sodium valproate group ( P<0.05). Conclusion:Significant differences in dose-adjusted plasma concentrations of valproic acid are observed among different valproate formulations for the treatment of mental disorders; therefore, therapeutic drug monitoring should be performed in patients when switching valproates to facilitate precise individualized dosage adjustment.
8.Clinicopathological features and surgery-related outcomes of duodenal adenocarcinoma: a multicenter retrospective study
Qifeng XIAO ; Xin WU ; Chunhui YUAN ; Zongting GU ; Xiaolong TANG ; Fanbin MENG ; Dong WANG ; Ren LANG ; Gang ZHAI ; Xiaodong TIAN ; Yu ZHANG ; Enhong ZHAO ; Xiaodong ZHAO ; Feng CAO ; Jingyong XU ; Ying XING ; Jishu WEI ; Shanmiao GOU ; Chengfeng WANG ; Jianwei ZHANG
Chinese Journal of Oncology 2025;47(10):1026-1038
Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P>0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P<0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.
9.The relationship between tumor necrosis factor alpha inducible protein 8 family members 2,cell prolifera-tion nuclear antigen expression levels,and clinical pathological parameters and prognosis in endometrial cancer tissue
Yiyang ZHAI ; Yunyi MA ; Junying ZHAI ; Hongli NIU ; Ying WANG
The Journal of Practical Medicine 2025;41(3):379-384
Objective To analyze the expression levels of TIPE2 and Ki67 in endometrial carcinoma(EC)and their relationship with clinicopathological parameters and prognosis.Methods Tissue samples and clinical data of 96 patients with EC who underwent surgical resection,120 patients who underwent total hysterec-tomy due to uterine fibroids and 120 patients who underwent total hysterectomy or curettage admitted to our hospital from February 2020 to February 2022 were retrospectively collected as the research objects,which were divided into the EC group,the normal endometrial group and the atypical hyperplasia endometrial group,respectively.All 3 groups were followed up until March 28,2023.Immunohistochemistry was used to detect the expression levels of TIPE2 and Ki67 in tissue samples of the three groups,and to analyze the relationship between the levels of TIPE2 and Ki67 and clinicopathological parameters and prognosis.Receiver operating characteristic curve(ROC)was used to analyze its diagnostic value for poor prognosis.Results The expression levels of TIPE2 and Ki67 in cancer tissues of the EC group were higher than those of the normal endometrial group and the atypical hyperplasia endometrial group,and those of the atypical hyperplasia endometrial group were higher than those of the normal endometrial group(P<0.05).The expression levels of TIPE2 and Ki67 in EC tissues were higher in patients with FIGO stage Ⅲ,lymph node metastasis,postmenopausal status,and ER and PR negative than patients with stageⅡ,no lymph node metastasis,premenopausal status,and ER and PR positive(P<0.05).Moreover,the expres-sion level of Ki67 in EC tissues was higher in p53 positive patients than in p53 negative patients(P<0.05),and there was a positive correlation between the both expression levels of TIPE2 and Ki67 in EC tissues(r=0.569,P<0.05).Compared with the poor prognosis group,the expression levels of TIPE2 and Ki67 in EC tissues in the good prognosis group were downregulated(P<0.05),and the AUC value of the combined detection of TIPE2 and Ki67 expression levels was 0.905,which was significantly higher than that of the single detection(P<0.05),sensitivity was 86.67%and specificity was 87.88%,and the predictive value was higher.Conclusion TIPE2 and Ki67 were highly expressed in EC tissues,and there was a positive correlation between the two,and their high expressions were related to clinicopathological features,and their combined detection had high predictive value for poor prognosis of EC.
10.Mechanism of Shaoyaotang in Modulating MDSCs-related Immunosuppressive Microenvironment in Prevention and Treatment of Colitis-associated Carcinogenesis
Xue CHEN ; Chenglei WANG ; Bingwei YANG ; Haoyu ZHAI ; Ying WU ; Weidong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):10-19
ObjectiveTo explore the mechanism of Shaoyaotang in the prevention and treatment of colitis-associated carcinogenesis (CAC) based on myeloid-derived suppressor cells (MDSCs)-related immunosuppressive microenvironment. MethodsA total of 140 six-week-old SPF FVB male mice were randomly divided into seven groups: Blank group, Shaoyaotang without model group (7.12 g·kg-1), model group, sulfasalazine group (0.52 g·kg-1), Shaoyaotang low-dose group (3.56 g·kg-1), Shaoyaotang medium-dose group (7.12 g·kg-1) and Shaoyaotang high-dose group (14.24 g·kg-1), with 20 mice in each group. The blank control group and the Shaoyaotang without model group received a single intraperitoneal injection of physiological saline (10 mg·kg-1), while the other five groups were given a single intraperitoneal injection of azoxymethane (AOM) (10 mg·kg-1). After 1 week, the mice were given drinking water containing 2% dextran sulfate sodium (DSS) for 1 week, followed by normal drinking water for 2 weeks. This cycle was repeated three times over a total period of 14 weeks to establish the CAC mouse model. Each group was administered gavage once daily for 2 weeks starting on the 14th day of the experiment, followed by three times a week until the end of the experiment. The body weight of the mice was recorded weekly. Mice were sacrificed on the 28th and 98th days of the experiment. After dissection, the colon length, colon weight, spleen weight, tumor size, and tumor number were measured. Hematoxylin and eosin (HE) staining was used to assess the pathological morphology of colon tumor tissue. Flow cytometry was used to detect MDSCs, regulatory T cells (Tregs), CD4+ T cells, CD8+ T cells, and the CD4+/CD8+ T cell ratio in the spleen. Immunohistochemistry was used to detect the expression levels of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated nuclear factor-κB (p-NF-κB), and hypoxia-inducible factor 1α (HIF-1α) in the colon tissue. ResultsOn day 14, compared with the blank group, the body weight of the model group was significantly reduced (P<0.01), reaching its lowest point on day 28 (23.39 ± 0.95 ) g. On days 28 and 98, compared with the blank group, the colon length in the model group was significantly shortened (P<0.01), the colon index significantly increased (P<0.01), the spleen index significantly increased (P<0.01), and the tumor load significantly increased (P<0.01). HE staining showed that in the model group, tumor cells, a large number of inflammatory cell infiltrates, goblet cell disappearance, and crypt loss were observed. In each dose group of Shaoyaotang, the damage to the colonic mucosa, inflammatory cell infiltration, and crypt structure destruction were alleviated. Compared with the model group, the body weight of mice in each dose group of Shaoyaotang increased. On day 98, the colon length was significantly increased (P<0.01), the colon index significantly decreased (P<0.01), the spleen index significantly decreased (P<0.01), and the tumor burden significantly decreased (P<0.01) in each Shaoyaotang dose group. On days 28 and 98, MDSCs and Tregs in the spleen of the medium- and high-dose Shaoyaotang groups were significantly reduced (P<0.01), while CD4+ T cells and the CD4+/CD8+ T cell ratio were significantly increased (P<0.01). The proportion of CD8+ T cells in the spleen and the expression levels of PD-1 and PD-L1 in the colon tissues of mice in each Shaoyaotang dose group were significantly increased to varying degrees (P<0.05, P<0.01). On days 28 and 98, the expression of p-AMPK-positive cells in the colon tissue of the medium- and high-dose Shaoyaotang groups was significantly increased (P<0.01), while the expression of p-NF-κB and HIF-1α was significantly reduced (P<0.01). ConclusionShaoyaotang can regulate MDSC recruitment and modulate the immune function of T lymphocyte subsets to inhibit the occurrence and development of AOM/DSS-induced CAC in mice. The mechanism may be related to the activation of the AMPK/NF-κB/HIF-1α pathway.

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