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.

Digital medical insurance governance， as an important component of digital transformation， improves the efficiency of medical insurance services while facing complex ethical challenges. Taking stakeholder theory as the analytical framework， this paper explored the generative mechanisms， manifestations， and countermeasures of ethical issues in digital medical insurance governance. This study uncovered that accelerated technological iteration and lagging ethical and legal norms， as well as interest conflicts among multiple participants in governance， constituted the major causes of ethical issues. These issues specifically manifested as data privacy leakage， unfair algorithmic decision-making， widening digital divide， ambiguous accountability， and other aspects. To address these issues， this paper put forward systematic countermeasures， such as establishing a dynamic ethical and legal regulatory system， balancing the demands of stakeholders， strengthening technological ethical governance， narrowing the digital divide， and enhancing accountability mechanisms. Through the implementation of multi-dimensional governance strategies， it aimed to balance technological innovation and ethical constraints， advance the inclusiveness， fairness， and sustainable development of digital medical insurance， and provide theoretical reference and practical references for improving China’s digital medical insurance governance system.

Objective:To investigate the status of allostatic load (AL) in patients with polycystic ovary syndrome (PCOS) and its influence on the clinical outcomes of in vitro fertilization-embryo transfer.Methods:This was a prospective study. By using convenient sampling method, 421 patients with PCOS (PCOS group) and 372 control infertility patients (control group) in the Reproductive Center of the First Affiliated Hospital of Anhui Medical University from April 2022 to January 2024 were investigated for basic information, physical examination, laboratory examination and follow-up of clinical outcomes. The total score of AL was calculated using 16 related indicators of cardiovascular system, metabolic system and immune system, and AL>3 was used as the judgment criteria for the high level AL group and the low level AL group. The differences in general data, embryo development and clinical outcomes between the groups were compared.Results:There were 222 cases (52.7%, 222/421) in PCOS low level AL group and 199 cases (47.3%, 199/421) in PCOS high level AL group. There were 214 patients (57.5%, 214/372) in the control low level AL group and 158 patients (42.5%, 158/372) in the control high level AL group. Embryo development outcomes: number of oocytes retrieved (median: 12, 12, 19, 14, respectively; P<0.001), number of two pronuclei (median: 8, 7, 11, 8, respectively; P<0.001), number of fertilization (median: 9, 9, 13, 10, respectively; P<0.001), number of metaphase of meiosis Ⅱ oocytes (median: 9, 8, 13, 10, respectively; P<0.001), number of transferable embryos (median: 5, 5, 7, 6, respectively; P<0.001), number of high-quality embryos (median: 4, 3, 6, 5, respectively; P<0.001), gonadotropin(Gn) starting dosage (median: 150, 200, 150, 200 U, respectively; P<0.001), total dosage of Gn (median: 1 800, 2 075, 1 575, 2 025 U, respectively; P<0.001), duration of Gn used (median: 10, 10, 10, 10 days, respectively; P=0.027) in the control low level AL group, control high level AL group, PCOS low level AL group and PCOS high level AL group were significantly different. Pairings between groups showed that number of oocytes retrieved, number of two pronuclei, number of fertilization, number of metaphase of meiosis Ⅱ oocytes and number of transferable embryos in PCOS high level AL group were lower than those in PCOS low level AL group (all P<0.05); Gn starting dosage and total dosage of Gn in PCOS low level AL group were lower than those in the other three groups (all P<0.05); duration of Gn used in PCOS high level AL group was higher than that PCOS low level AL group ( P<0.05). Clinical outcomes: the control low level AL group, control high level AL group, PCOS low level AL group and PCOS high level AL group underwent fresh transplantation [27.4% (57/208), 24.4% (38/156), 15.1% (32/212), 17.1% (33/193), respectively; P=0.006] and the proportion of transplanted day 5 embryos [82.7% (172/208), 77.6% (121/156), 91.0% (193/212), 86.5% (167/193), respectively; P=0.018] were statistically significant. There were no significant differences in fertilization rate, biochemical pregnancy rate, clinical pregnancy rate, multiple pregnancy rate and early abortion rate among the four groups (all P>0.05). Conclusion:The high level of AL in PCOS patients may affect the outcomes of embryo development, and more attention should be paid to AL in PCOS patients to reduce stress.

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 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.

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 develop and evaluate dietary and exercise intervention program for over-weight/obese patients with polycystic ovary syndrome(PCOS).Methods Seventy patients with over-weight/obese PCOS were prospectively selected as research subjects and divided into intervention group(n=35)and control group(n=35)according to random number table method.According to the completion of the intervention plan,29 cases were finally included in the intervention group and 28 cases in the control group.The control group was given conventional nursing intervention,while the intervention group was applied with the diet and exercise intervention program for overweight/obese patients with PCOS.Both groups were intervened for 3 months.The physical indicators,PCOS sign scores,natural pregnancy rate,degree of self-body image distress(Multidimensional Self-body Im-age Relationship Questionnaire-Appearance Subscale)and self-efficacy level(Self-efficacy Scale)before and after the intervention were compared between the two groups.The occurrence of adverse reactions during the intervention period between the two groups were compared.Results After 1 month and 3 months of intervention,the body mass index(BMI)and PC OS sign score of the pa-tients in the intervention group were significantly lower than those in the control group(P＜0.05).The natural conception rate of the intervention group was 34.48％(10/29),which was significantly higher than 10.71％(3/28)of the control group(P＜0.05).After 1 month and 3 months of inter-vention,the scores of the self-body image relationship-appearance subscale of the patients in the inter-vention group were significantly higher than those in the control group(P＜0.001).After 3 months of intervention,the score of the Self-efficacy Scale of patients in the intervention group was significantly higher than that in the control group(P＜0.001).During the intervention period,no adverse reac-tions caused by diet and exercise intervention occurred in either group.Conclusion Implementing a diet and exercise intervention program for overweight/obese patients with PCOS is beneficial for re-ducing patients' BMI,increasing the natural pregnancy rate,improving self-body image disorders,and enhancing self-efficacy.

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

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.