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.

Objective To analyze the disease burden trend of non-rheumatic degenerative mitral valve disease (NR-DMVD) in China from 1990 to 2023 and compare it with global levels and those in the United States and India. Methods Based on the Global Burden of Disease (GBD) 2023 database, data on incidence, mortality, prevalence, and disability-adjusted life years (DALYs) for NR-DMVD were extracted. Joinpoint regression, decomposition analysis, and autoregressive integrated moving average model (ARIMA) were used to analyze trends, drivers, and project burden to 2040. Results In 2023, China's age-standardized DALY rate (2.56/100 000) and mortality rate (0.037/100 000) for NR-DMVD were significantly lower than those in the United States, India, and globally, while its age-standardized incidence rate (10.39/100 000) and prevalence rate (126.03/100 000) showed slow increases. From 1990 to 2023, the estimated annual percentage changes (EAPC) for China's age-standardized DALY rate and mortality rate were –2.11% [95%CI (–2.25%, –1.98%)] and –4.54% [95%CI (–4.92%, –4.16%)], respectively, while the incidence rate and prevalence rate continued to rise; India showed increasing trends in all burden indicators. Decomposition analysis indicated that population aging was the primary driver of the increase in DALYs and prevalence cases, while epidemiological improvement was the key factor that led to the reduction in the number of deaths. Joinpoint analysis showed that China's age-standardized DALY rate declined most rapidly between 2000 and 2013, while the age-standardized mortality rate decreased fastest between 2007 and 2013. ARIMA models projected that China's prevalence rate would continue to rise and mortality rate would continue to decline through 2040. Conclusion NR-DMVD in China exhibits a dual-track pattern of "declining mortality but rising prevalence", driven by population aging. A tiered prevention and control system focusing on the elderly and high-risk male groups is needed.

ObjectiveTo investigate the potential mechanisms of Zingiberis Rhizoma in treating inflammatory bowel disease （IBD） by integrating network pharmacology with in vitro and in vivo experiments. MethodsTraditional Chinese Medicine Systems Pharmacology Database And Analysis Platform （TCMSP）， Traditional Chinese Medicine Integrated Database （TCMID） Database were used to obtain the active component targets of Zingiberis Rhizoma. GeneCards was used to obtain the IBD targets. DAVID was used to perform Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses on core targets. Cytoscape 3.10.2 was used to establish the "active component-disease target-signaling pathway" interaction network. Mice were randomly assigned to control， model， and Zingiberis Rhizoma （400 mg·kg^-1） groups. An IBD model was induced via dextran sulfate sodium （DSS）. The colonic tissue was collected post-treatment to assess histology， expression of Ly6C⁺ monocytes/macrophages， and mRNA levels of Toll-like receptor 4 （TLR4）， and inflammatory cytokines. The effect of Zingiberis Rhizoma aqueous extract on RAW264.7 cell viability was evaluated. Furthermore， the effects of the extract at 100， 10， and 1 mg·L^-1 on LPS-induced differentiation of RAW264.7 cells into Ly6C^hi monocytes/macrophages， mRNA levels of TLR4 and inflammatory cytokines， and protein levels of factors in the TLR4/mitogen-activated protein kinase （MAPK） signaling pathway. ResultsA total of 241 targets were identified for Zingiberis Rhizoma and 6 787 for IBD， with 122 shared targets among Zingiberis Rhizoma， ulcerative colitis （UC）， and Crohn's disease （CD）. The enrichment analyses yielded 297 GO terms and 88 KEGG pathways. Associations were noted between Zingiberis Rhizoma's active component targets and IBD targets. In vivo experiments： Compared with the control group， the model group showed decreased body weight and disease activity index （DAI）（P<0.01）， shortened colon length， damaged mucosal epithelium with inflammatory cell infiltration， raised pathological scores （P<0.05）， increased Ly6C^hi and Ly6C^lo monocytes/macrophages （P<0.05）， and up-regulated mRNA levels of TLR4， TNF-α， IL-1β， and IL-6 （P<0.05） and protein levels of TLR4， phosphorylated extracellular signal-regulated protein kinase 1/2 （p-ERK1/2）， and phosphorylated p38 MAPK （p-p38 MAPK） （P<0.05）. Zingiberis Rhizoma intervention reversed these changes and reduced Ly6C^hi monocytes/macrophages （P<0.01）. In vitro experiments： compared with the control， LPS increased the proportion and number of Ly6C^hi monocytes/macrophages and mRNA levels of TLR4， TNF-α， IL-1β， and IL-6 （P<0.01） and enhanced the expression of TLR4， p-ERK1/2， and p-p38 MAPK （P<0.05）. Zingiberis Rhizoma reduced Ly6C^hi monocytes/macrophages （P<0.05）， down-regulated the mRNA levels of inflammatory cytokines （P<0.05）， and suppressed the TLR4/MAPK pathway （P<0.05）. ConclusionZingiberis Rhizoma alleviates IBD by suppressing the TLR4/ERK/p38 MAPK signaling pathway and reducing inflammatory cytokine levels in Ly6C^hi monocytes/macrophages.

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 investigate the modulating effect of modified Wumeiwan （MWMW） on the ulcerative colitis （UC）-associated intestinal helper T cell 17 （Th17）/regulatory T cell （Treg） balance and intestinal flora by using a human flora-associated model of UC patients with dampness-heat obstruction syndrome， thus providing a new idea for the UC-related research and therapeutic strategies. MethodsThe 24 male C57BL/6J mice were randomized into normal control， model， and MWMW groups （n=8）. Model and MWMW groups were first treated with an antibiotic cocktail （vancomycin， 0.1 g·kg^-1； neomycin sulfate， 0.2 g·kg^-1； ampicillin， 0.2 g·kg^-1； metronidazole， 0.2 g·kg^-1） for 21 days. At the end of antibiotic treatment， the gavage of fecal microbiota suspension from UC patients with dampness-heat obstruction syndrome was started at a dose of 0.2 mL·d^-1 for 19 consecutive days， by which a human flora-associated model of UC was obtained. The MWMW group was administrated daily with MWMW liquid （12.5 g·kg^-1）， while the normal control and model groups were administrated by gavage with an equal amount of sterile water for 7 consecutive days. The symptoms of dampness-heat obstruction were observed. The colon length and spleen index were measured and calculated， and the proportions of Th17 and Treg cells were detected by flow assay. The intestinal flora was analyzed by 16S rRNA high-throughput sequencing. ResultsCompared with the normal control group， the model group showed shortened colon （P<0.05） and increased spleen index （P<0.01）. Compared with the model group， the MWMW group showed prolonged colon （P<0.01） and decreased spleen index （P<0.05）. After the intervention of MWMW， the Th17 proportion and Th17/Treg ratio in the colon decreased （P<0.01）， and the proportion of Treg cells increased （P<0.05）. The number of species and alpha and beta diversity of intestinal flora in mice were regulated by MWMW （P<0.05）. In terms of intestinal flora composition， MWMW increased the relative abundance of several phyla （Firmicutes， Proteobacteria， Fusobacteriota， Actinobacteriota， and Gemmatimonadota）， the genus Bacteroides， and two species （Bacteroides thetaiotaomicron and B. fragilis） in model mice. Moreover， Spearman's correlation analysis showed that the relative abundance of B. thetaiotaomicron and B. fragilis were negatively correlated with the Th17 level （P<0.05）. In addition， the above changes in intestinal flora caused the changes in microbial genes involved in 14 pathways， such as glycolysis， amino acid degradation， inorganic nutrient metabolism， biosynthesis of pyrimidine deoxyribonucleotides， antibiotic resistance， and degradation of polysaccharides. ConclusionsThe human flora-associated model successfully simulated the changes （marked by a decrease in the abundance of Bacteroides） of intestinal flora in UC patients with dampness-heat obstruction syndrome. MWMW can enrich the abundance of beneficial bacteria such as B. thetaiotaomicron and B. fragilis and promote the synergistic intestinal immune modulation with the metabolic functions centered on glycolysis， amino acid metabolism， and nucleotide synthesis through bacterial polysaccharide utilization sites to reduce the Th17/Treg ratio， thereby exerting a protective effect on UC.

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.

Objective To analyze the abnormal individual dose monitoring results in 206 medical institutions in a selected region in 2024, and to propose improvement measures. Methods Individuals with monitoring results exceeding the investigation level were subjected to high-dose investigation, and the results were statistically analyzed. Results In 2024, the individual dose monitoring of 206 medical institutions in a selected region showed 1.04% abnormal results. The proportions of abnormal results from primary, secondary, and tertiary medical institutions were 12.22%, 3.33%, and 84.45%, respectively. In analysis of the causes of abnormal results, 52.53% of the cases were due to personal dosimeters left in the radiation workplace, and 20.20% were due to the confusion in wearing personal dosimeters inside and outside the lead apron. In analysis of the occupational distribution of the radiation workers with abnormal monitoring results, interventional radiology and diagnostic radiology accounted for 73.34% and 24.44%, respectively. Statistical analysis of the dose range showed that doses in the ranges of 1.25-2.0 mSv and 2.0-5.0 mSv accounted for 42.22% and 33.33%, respectively. In the report of abnormal monitoring results, the proportions of reporting notional dose and reporting measured results accounted for 88.89% and 11.11%, respectively. Among institutions with consecutive abnormal results, primary, secondary, and tertiary medical institutions accounted for 15.39%, 7.69%, and 76.92%, respectively. Conclusion The level of the hospital, occupational type, the perceived importance of the hospital to the management of radiation protection, and the perceived importance and compliance of the radiation workers with the individual dose monitoring are potential causes of abnormal results. It is recommended that employers should enhance radiation protection training for their radiation workers to ensure proper wearing and storage of dosimeters, and progressively improve the standardization and effectiveness of individual dose monitoring practice.

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 construct the animal model,and to study the expression and clinical signifi-cance of YKL-40 in the progress of chronic renal failure complicating cardiac dysfunction.Methods C57BL/6N mice were chosen as the experimental subjects and divided into the blank control(BC)group,renal failure(RF)group,heart failure(HF)group and renal combined heart failure group.The renal failure model was constructed by adenine perfusion.The heart failure model was constructed by subcutaneous injection of isopro-terenol.The renal failure and heart failure group model was established by adenine perfusion combined with subcutaneous injection of isoproterenol.The validity of constructed models was evaluated by creatinine(SCr),urea nitrogen(BUN)and BNP levels,renal ultrasound and ultrasonic cardiogram examination results.The levels of C-reactive protein(CRP)and YKL-40 were detected by ELISA,and the YKL-40 mRNA expression level in kidney and heart tissues was measure by RT-qPCR.The Image J software was used to calculate the collagen fiber area of the Masson staining results.Results Except the blank control group,the mice weights in the other 3 groups were decreased,and the differences were statistically significant(P＜0.05).SCr,BUN,average renal cross sectional area,average renal volume and renal CVF in the renal failure group and renal combined heart failure group were higher than those in the blank control group and heart failure group(P＜0.05).The levels of LVEF,LVCO,LVSV,LVFS,LVPWd and LVPWs in the heart failure group and renal combined heart failure group were lower than those in the blank control group and renal failure group(P＜0.05).LVEF and LVFS in the renal combined heart failure group were higher than those in the heart failure group(P＜0.05).Compared with the blank control group,the serum CRP and YKL-40 levels in the other three groups were higher(P＜0.05);the CRP and YKL-40 levels in the renal combined heart failure group were higher than those in the renal failure group and heart failure group(P＜0.05).In the myocardial tis-sues,the YKL-40 mRNA expression level in the heart failure group and renal combined heart failure group was higher than those in the blank control group and renal failure group(P＜0.05).YKL-40 had the correla-tion with CRP(r=0.88,P＜0.05).Serum YKL-40 had the correlation with renal tissue YKL-40 gene expres-sion(r=0.77,P＜0.05),and had the correlation with the renal tissue CVF(r=0.89,P＜0.05).Conclusion YKL-40 has the influencing effect on renal failure complicating heart dysfunction,and could serve as the biomarker to mo-nitor the renal insufficiency complicating heart function abnormality.