ObjectiveTo investigate the effects and underlying mechanisms of polydatin in delaying the progression of colitis-associated colorectal cancer （CAC） by constructing an azoxymethane （AOM）/dextran sulfate sodium （DSS）-induced CAC mouse model and conducting in vitro experiments. MethodsFifty-four male C57BL/6J mice were randomly divided into normal， model， and polydatin groups （0.045 g·kg^-1）. The CAC mouse model was established using AOM/DSS， and samples were collected at 4， 7， and 10 weeks. Body weight change rate， disease activity index （DAI）， and tumor formation were assessed. Hematoxylin-eosin （HE） staining was used to observe pathological injury in intestinal tissues. Immunohistochemistry （IHC） was performed to detect zonula occludens-1 （ZO-1） expression in colonic tissues， and Western blot was used to detect the expression of E-cadherin， N-cadherin， and Vimentin in colonic epithelial cells. Real-time PCR was used to measure mRNA expression of interleukin-17A （IL-17A）， Wnt3a， β-catenin， T cell factor 1 （Tcf1）， E-cadherin， N-cadherin， and Vimentin in colonic tissues. Flow cytometry was used to analyze the proportion of CD8⁺T cells and the expression of exhaustion-related molecules in tumors. Human colon cancer DLD-1 cells were cultured in a polydatin-containing medium， and wound healing assays were performed to observe migration changes. Real-time PCR was used to detect mRNA expression of interleukin-17 receptor A （IL-17RA）， Wnt3a， β-catenin， Tcf1， E-cadherin， N-cadherin， and Vimentin in DLD-1 cells. ResultsCompared with the normal group， the model group at all three time points showed significantly decreased body weight change rate （P<0.01）， significantly shortened colon length （P<0.01）， and markedly increased DAI scores （P<0.01）. HE staining revealed significant inflammatory cell infiltration in the submucosa of the colon in the model group， accompanied by epithelial dysplasia. ZO-1 expression in colonic tissues was significantly reduced （P<0.01）. The mRNA expression of the pro-inflammatory factor IL-17A and key molecules of the Wnt/β-catenin pathway （Wnt3a， β-catenin， Tcf1） was significantly elevated （P<0.05）. The mRNA and protein expression of epithelial-mesenchymal transition （EMT） markers N-cadherin and Vimentin was significantly upregulated （P<0.05）， while E-cadherin expression was significantly downregulated （P<0.05）. The proportion of tumor-infiltrating CD8⁺T cells expressing immunosuppressive molecules （TIM-3， LAG-3， PD-1） was significantly increased （P<0.05）. Compared with the model group， the polydatin group showed significant improvement in body weight and DAI score （P<0.01）， as well as recovery of colon length and tissue injury. ZO-1 expression in colonic tissue was significantly increased （P<0.01）， while IL-17A， Wnt3a， β-catenin， Tcf1， N-cadherin， and Vimentin expression levels were significantly decreased （P<0.05）， and E-cadherin expression was significantly increased （P<0.01）. Tumor-infiltrating CD8⁺ T cells expressing immunosuppressive molecules were significantly reduced （P<0.05）. In vitro experiments showed that polydatin significantly inhibited migration of DLD-1 cells （P<0.01） and reversed the upregulation of IL-17RA， Wnt3a， β-catenin， N-cadherin， and Vimentin mRNA， as well as the downregulation of E-cadherin mRNA （P<0.05）. ConclusionPolydatin inhibits IL-17A secretion and IL-17RA expression， improves the immune microenvironment， blocks activation of the Wnt/β-catenin signaling pathway， suppresses EMT markers （N-cadherin and Vimentin）， and restores tight junction protein expression in intestinal epithelial cells， thereby delaying the progression from colitis to colorectal cancer in mice.

ObjectiveTo clarify the repair effect of Mume Fructus on the intestinal mucosal epithelial barrier in the mouse model of inflammatory bowel disease （IBD） and explore the repair mechanism. MethodsThirty-six male C57BL/6 mice were randomly assigned into six groups： normal， model， low-， medium-， and high-dose （200， 400， and 800 mg·kg^-1） Mume Fructus， and sulfasalazine （300 mg·kg^-1）. Except the normal group， the rest groups had free access to 2% dextran sulfate sodium （DSS） solution for seven days to establish the IBD model， followed by a seven-day drug intervention. The body weight change and disease activity index （DAI） were recorded. After the last administration， spleen and colon tissue samples were collected to analyze the differences in colon length and spleen index. Hematoxylin-eosin staining was used to observe the morphology of the colon tissue. The level of diamine oxidase （DAO） in the serum was measured by the DAO assay kit. Immunohistochemistry was employed to determine the expression of tight junction proteins such as Claudin-1， Occludin， and zonula occludens-1 （ZO-1） in the colon tissue. Real-time PCR was performed to measure the mRNA levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the colon tissue. Finally， Western blot was employed to determine the protein levels of mitogen-activated protein kinase kinase （MEK）， extracellular signal-regulated kinase （ERK）， phosphorylated （p）-MEK， and phosphorylated ERK in the colon tissue. ResultsCompared with the normal group， the model group exhibited decreases in body weight and colon length （P<0.01）， increases in DAI， spleen index， and serum DAO level （P<0.01）， damaged colonic epithelium and goblet cells， and obvious infiltration of inflammatory cells. In addition， the model group exhibited higher positive expression of Claudin-1， Occludin， and ZO-1 （P<0.01）， higher mRNA levels of TNF-α and IL-1β （P<0.01）， and higher protein levels of p-MEK and p-ERK （P<0.05， P<0.01） than the normal group. However， sulfasalazine and three doses of Mume Fructus markedly decreased the body weight and DAI （P<0.05）， recovered the colon length and spleen index， alleviated colon tissue damage， lowered the level of DAO in the serum （P<0.01）， and down-regulated the mRNA levels of TNF-α and IL-1β （P<0.01） and the protein levels of p-MEK and p-ERK （P<0.05）. Sulfasalazine and low- and medium-dose Mume Fructus increased the positive expression of Occludin， Claudin-1， and ZO-1 （P<0.05， P<0.01）. Furthermore， high-dose Mume Fructus elevated the protein expression of Occludin （P<0.05）. ConclusionMume Fructus can restore the expression of intestinal epithelial tight junction proteins by inhibiting the phosphorylation of proteins in the MEK/ERK signaling pathway and down-regulating the levels of TNF-α and IL-1β， thus repairing the intestinal mucosal barrier in the mouse model of IBD.

ObjectiveTo explore the evolution of medication patterns and syndrome-herb associations of traditional Chinese medicine （TCM） in treating inflammatory bowel disease （IBD）， providing a theoretical foundation for precise syndrome differentiation and treatment in clinical practice. MethodsMedical case literature on TCM treatment of IBD from 1960 to 2024 was retrieved to establish a database. Frequency statistics， cluster analysis， change point detection， and association rule mining were employed to comprehensively analyze the syndrome distribution， therapeutic methods， medication patterns， and their temporal variations. ResultsA total of 685 medical cases were included. Common syndromes were dampness-heat （66.42%） and spleen deficiency （56.20%）. Primary therapeutic methods included heat clearing （63.65%）， spleen invigorating （47.45%）， and dampness draining （36.79%）. High-frequency herbs included Coptidis Rhizoma （354）， Paeoniae Radix Alba （303）， Aucklandiae Radix （292）， Codonopsis Radix （253）， and Glycyrrhizae Radix et Rhizoma （244）. Initial prescription clustering revealed three core therapeutic method combinations： heat clearing and detoxifying （represented by Baitouweng Tang）， spleen invigorating and Qi reinforcing （represented by Shenling Baizhusan）， and cold-heat regulation （represented by Wumeiwan combined with Shaoyao tang）. Temporal analysis identified 2008 as a key transition point in TCM treatment of IBD， with significantly increased usage frequency of heat-clearing and dampness-drying herbs such as Fraxini Cortex， Phellodendri Chinensis Cortex， Sophorae Flavescentis Radix， and Scutellariae Radix as well as hemostatic herbs such as carbonized Sanguisorbae Radix， Bletillae Rhizoma， Agrimoniae Herba， and Notoginseng Radix et Rhizoma. Follow-up efficacy analysis showed median improvement rates of 64.0% at the first follow-up， 76.0% at the second follow-up， and 78.7% at the third follow-up. Syndrome-drug association analysis revealed specific herb pairs with significant therapeutic advantages， including Notoginseng Radix et Rhizoma + Coicis Semen， Sanguisorbae Radix + Coptidis Rhizoma， and Codonopsis Radix + Aconii Lateralis Radix Praeparaia. ConclusionTCM medication patterns for treating IBD demonstrate distinct temporal evolution characteristics， with significantly increased usage frequency of herbs such as Fraxini Cortex， Notoginseng Radix et Rhizoma， and Agrimoniae Herba. Significant therapeutic method-herb associations and syndrome-herb association patterns exist， with the formation of specific herb pairs， providing evidence-based support for precise syndrome differentiation and treatment of IBD.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

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.

Objective To analyze the dynamic change in placental growth factor(PLGF)level in patients with preeclampsia(PE)and its role in predicting pregnancy outcomes.Methods A retrospective cohort study was conducted on 198 PE patients admitted to Department of Obstetrics of Tianjin Beichen Hospital from January 2021 to January 2024.Among them,151 cases were identified as non-severe PE and 47 cases as severe PE.During the same period,another 100 healthy pregnant women were included in the department and served as the control group.According to the final pregnancy status of the PE patients,they were divided into an adverse outcome group(88 cases)and a good outcome group(110 cases).Locally Weighted Scatterplot Smoothing(LOWESS)was used to analyze the relationship between vascular endothelial function indicators and PLGF level.Logistic regression was employed to identify the influencing factors for adverse pregnancy outcomes.Receiver operating characteristic(ROC)curve was plotted to evaluate the value of PLGF level for predicting adverse pregnancy outcomes in patients with non-severe PE and severe PE.Results The PLGF level was in a peak shape at different gestational weeks,relatively low at 28～29+6 weeks of gestation,gradually increasing with the increment of gestational weeks,reaching a peak at 30～31+6 weeks of gestation,and then gradually decreased(P<0.05).The PLGF level was gradually reduced in the control group,non-severe PE group,and severe PE group in turn(P<0.05).LOWESS analysis showed that the PLGF level exhibited certain nonlinear relationship with soluble fms-like tyrosine kinase receptor 1(sFlt-1),vascular endothelial growth factor(VEGF),nitric oxide(NO),thrombomodulin(TM),thromboxane A2(TXA2),and Von Willebrand factor(VwF).The results of logistic regression analysis indicated that after gradually eliminating collinearity confounding factors and adjusting for each covariate,there was still an independent correlation between the PLGF level at 28～29+6 gestational weeks and pregnancy outcome(OR=0.593,95%CI:0.583～0.778,P<0.001).After converting the PLGF level into a binary variable,there was an independent correlation between high PLGF level and pregnancy outcome(OR=0.773,95%CI:0.671～0.885,P<0.001).Compared with the quintile with the lowest PLGF(Q1),as the PLGF level gradually increased(Q2 to Q5),the correlation effect values were(OR=0.765,95%CI:0.639～0.837,P=0.092),(OR=0.752,95%CI:0.624～0.818,P=0.056),(OR=0.696,95%CI:0.615～0.813,P=0.027),and(OR=0.642,95%CI:0.591～0.733,P<0.001),and the trend test was statistically significant(Ptrend<0.001).ROC curve analysis revealed that the area under the ROC curve(AUC)of serum PLGF level at 28-29+6 gestational weeks in predicting adverse pregnancy outcomes in non-severe PE patients was 0.830(95%CI:0.635～0.917),the optimal critical threshold was 75.47 ng/L,the sensitivity was 88.37%,the specificity was 71.30%,the positive predictive value was 55.07%,and the negative predictive value was 93.90%.Its AUC value of the level for the prediction in patients with severe PE was 0.874(95%CI:0.677～0.923),the optimal critical threshold was 38.53 ng/L,the sensitivity was 88.89%,the specificity was 50.00%,the positive predictive value was 97.56%,and the negative predictive value was 16.67%.Conclusion At 28～29+6 gestational weeks,PLGF has an independent correlation with pregnancy outcomes and shows a good predictive performance for adverse pregnancy outcomes in patients with non-severe PE and severe PE.

Objective To establish the characteristic atlas of Shexiang Jiegu Capsule and determine the contents of seven active components （hydroxysafflor Yellow A, paeoniflorin, ferulic acid, naringin, ligustilide, catechin, epicatechin）. Methods Octadecyl silane bonded silica gel was used as the filling agent, the mobile phase was composed of methanol-0.05% phosphoric acid by gradient elution, the detection wavelength was 245 nm, flow rate was 1.0 ml/min, column temperature was 30℃. The similarity of the fifteen batches of sample was evaluated in line with the TCM Chromatographic Fingerprint （2012 edition）, and the contents of seven active components were determined. Results The HPLC fingerprint of Shexiang Jiegu Capsules was established. The similarity of fingerprint between fifteen batches of samples and control fingerprint was between 0.893 and 0.992. The results of methodological investigation for the determination of seven active components in fifteen batches of samples all met the requirements. Conclusion The established characteristic atlas of Shexiang Jiegu Capsules had high specificity and good repeatability, which could provide scientific basis for quality control of Shexiang Jiegu Capsules.

Childhood tumors pose a significant threat to the health of children.Compared with adult tumors,childhood tumors have unique biological characteristics and clinical outcomes.These tumors affect the growth and development and quality of life of children and increase the burden on families and society.This article summarizes the research updates on the epidemiological characteristics,risk factors,detec-tion methods,and treatment strategies of childhood tumors.Owing to differences in medical and public health systems across regions with a varying socio-demographic index(SDI),childhood tumors tend to have a relatively high incidence in high SDI regions and relatively high mor-tality in low SDI regions.Meanwhile,the rapid development of genomics and immunology has provided important technical support for pre-cision medicine in childhood tumors.This article provides a comprehensive review from the perspective of graded prevention,providing sci-entifically valid theoretical references and practical directions to improve the prevention and control system of childhood tumors.

Objective:To explore the current status of self-management behavior in patients with inflammatory bowel disease and to construct a structural equation model to explore the mediating role of health literacy between discharge readiness and self-management behavior.Methods:From March to September 2023, 310 hospitalized patients with inflammatory bowel disease in the Tenth People ′s Hospital Affiliated to Tongji University were selected as the research subjects by the convenience sampling method. A cross-sectional survey was conducted using the general information questionnaire, the Health Literacy Management Scale, the Discharge Readiness Scale, and the Self-management Behavior Scale. Results:Eventually, 303 valid questionnaires were retrieved. Among the 303 patients, there were 190 males and 113 females, with an average age of (35.63 ± 16.41) years old. The total score of health literacy of patients with inflammatory bowel disease was (94.35 ± 10.78) points, indicating a health literacy compliance rate of 74.3%(225/303). The total score of discharge readiness was (79.52 ± 9.16) points, and the total score of self-management behavior was (135.22 ± 17.36) points. In patients with inflammatory bowel disease, the discharge readiness was positively correlated with the total score of health literacy ( r=0.748, P<0.01), the discharge readiness was positively correlated with the total score of self-management behavior ( r=0.821, P< 0.01), and the health literacy was positively correlated with the total score of self-management behavior ( r=0.767, P<0.01). Health literacy may serve as a mediating variable, partially explaining the relationship between discharge readiness and self-management behavior in patients with inflammatory bowel disease. The mediating effect accounted for 47.5% of the total effect. Conclusions:Discharge readiness not only positively impacts self-management behavior among patients with inflammatory bowel disease but also indirectly influences this behavior through health literacy. It is essential for clinical healthcare professionals to prioritize the assessment of discharge readiness and health literacy among these patients. By improving discharge readiness and enhancing health literacy, clinical healthcare professionals can effectively support patients with inflammatory bowel disease in their self-management efforts.