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BackgroundUC patients suffer more from colorectal cancer (CRC) than the general population, which increases with disease duration. Early colonoscopy is difficult because ulcerative colitis-associated colorectal cancer (UCAC) lesions are flat and multifocal. Our study aimed to identify promising UCAC biomarkers that are complementary endoscopy strategies in the early stages.MethodsThe datasets may be accessed from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The co-expressed modules of UC and CRC were determined via weighted co-expression network analysis (WGCNA). The biological mechanisms of the shared genes were exported for analysis using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. To identify protein interactions and hub genes, a protein-protein interaction network and CytoHubba analysis were conducted. To evaluate gene expression, external datasets and experimental validation of human colon tissues were utilized. The diagnostic value of core genes was examined through receiver operating characteristic (ROC) curves. Immune infiltration analysis was employed to investigate the associations between immune cell populations and hub genes.ResultsThree crucial modules were identified from the WGCNA of UC and CRC tissues, and 33 coexpressed genes that were predominantly enriched in the NF-κB pathway were identified. Two biomarkers (CXCL1 and BCL6) were identified via Cytoscape and validated in external datasets and human colon tissues. CRC patients expressed CXCL1 at the highest level, whereas UC and CRC patients showed higher levels than the controls. The UC cohort expressed BCL6 at the highest level, whereas the UC and CRC cohorts expressed it more highly than the controls. The hub genes exhibited significant diagnostic potential (ROC curve > 0.7). The immune infiltration results revealed a correlation among the hub genes and macrophages, neutrophils and B cells.ConclusionsThe findings of our research suggest that BCL6 and CXCL1 could serve as effective biomarkers for UCAC surveillance. Additionally, they demonstrated a robust correlation with immune cell populations within the CRC tumour microenvironment (TME). Our findings provide a valuable insight about diagnosis and therapy of UCAC.

Abstract Monitoring extent and severity is vital in the ulcerative colitis (UC) follow-up, however, current assessment is complex and low cost-effectiveness. We aimed to develop a routine blood-based clinical decision support tool, Jin’s model, to investigate the extent and severity of UC. The multicentre retrospective cohort study recruited 975 adult UC inpatients and sub-grouped into training, internal validation and external validation set. Model was developed by logistics regression for the extent via Montreal classification and for the severity via Mayo score, Truelove and Witts score (TWS), Mayo endoscopic score (MES) and Degree of Ulcerative colitis Burden of Luminal Inflammation (DUBLIN) score. In Montreal classification, left-sided and extensive versus proctitis model achieved area under the receiver operating characteristic curve (AUROC) of 0.78 and 0.81 retrospectively. For severity, Mayo score model, TWS model, MES model and DUBLIN score model achieved an AUROC of 0.81, 0.70, 0.74 and 0.70 retrospectively. The models also were evaluated with satisfactory calibration and clinical unity. Jin’s model was free with open access at http://jinmodel.com:3000/ . Jin’s model is a noninvasive, convenient, and efficient approach to assess the extent and severity of UC.

Researchers have shown that bone mesenchymal stem cells (BMSCs) can alleviate the progression of liver cirrhosis; however, it is unclear how exactly BMSCs function to cure liver disease. In this study, we used bioinformatics methods to assess differentially expressed genes (DEGs) in liver cirrhosis and found a significantly upregulated gene, Fstl1, in liver cirrhosis. In vivo and in vitro experiments showed that compared with those in the disease model group, the mRNA, and protein expression levels of Fstl1 were significantly reduced after BMSCs treatment, and the β-Catenin protein level was also significantly reduced after BMSCs treatment. Subsequently, we downregulated Fstl1 in activated hepatic stellate cells (HSCs) and found that Wnt and β-Catenin protein expression levels also decreased. Finally, we found that in BMSCs-treated activated HSCs, overexpression of Fstl1 reversed the inhibitory effect of BMSCs on the Wnt/β-Catenin signaling pathway to a certain extent. In summary, our results show that BMSCs can inhibit Wnt/β-Catenin signaling pathway activation by downregulating the protein expression level of Fstl1, thus alleviating cirrhosis. Therefore, targeted regulation of Fstl1 may provide a new therapeutic strategy for the progression of liver cirrhosis.

Abstract Stool characteristics are of great value to assess diseases, but patients knew little. E-learning applied in health popularization and patient education is booming. In China, WeChat applets has advantages of abundant users, convenient access and low cost, which may be a great media in patient education on stool. This preliminary study aims to develop and evaluate a stool card WeChat applet. We collected stools images during 2020 to 2022 in the Department of Gastroenterology and Hepatology in the Second Affiliated Hospital of Harbin Medical University, constructed a stool card applet named the Doctor Friend Primary Screening Stool Card (DFPSSC) and evaluated it. Eligible participants were divided into the applet, traditional paper media and control group. We implement a series of tests to evaluate the effectiveness. 20 clinicians and participants using the DFPSSC completed a questionnaire to evaluate the usability. We developed the DFPSSC for an E-learning approach. Of 108 volunteers, 97 completed the DFPSSC learning. No significant pretest differences were found among the three groups (P = 0.303). Applet group had significantly higher posttest scores than pretest scores in intervention (P

Abstract Bone marrow mesenchymal stromal cells (BMSCs) have a protective effect against liver cirrhosis. Long noncoding RNAs (lncRNAs) play crucial roles in the progression of liver cirrhosis. Therefore, it is aimed to clarify the lncRNA Kcnq1ot1 involved protective mechanism of BMSCs in liver cirrhosis. This study found that BMSCs treatment attenuates CCl4‐induced liver cirrhosis in mice. Additionally, the expression of lncRNA Kcnq1ot1 is upregulated in human and mouse liver cirrhosis tissues, in addition to TGF‐β1‐treated LX2 cells and JS1 cells. The expression of Kcnq1ot1 in liver cirrhosis is reversed with BMSCs treatment. The knockdown of Kcnq1ot1 alleviated liver cirrhosis both in vivo and in vitro. Fluorescence in situ hybridization (FISH) confirms that Kcnq1ot1 is mainly distributed in the cytoplasm of JS1 cells. It is predicted that miR‐374‐3p can directly bind with lncRNA Kcnq1ot1 and Fstl1, which is verified via luciferase activity assay. The inhibition of miR‐374‐3p or the overexpression of Fstl1 can attenuate the effect of Kcnq1ot1 knockdown. In addition, the transcription factor Creb3l1 is upregulated during JS1 cells activation. Moreover, Creb3l1 can directly bind to the Kcnq1ot1 promoter and positively regulate its transcription. In conclusion, BMSCs alleviate liver cirrhosis by modulating the Creb3l1/lncRNA Kcnq1ot1/miR‐374‐3p/Fstl1 signaling pathway.

Background: Small intestinal ischemia-reperfusion (IR) injury is a common intestinal disease with high morbidity and mortality. Mesenchymal stem cells (MSCs) have been increasingly used in various intestinal diseases. This study aimed to evaluate the therapeutic effect of hair follicle MSCs (HFMSCs) on small intestinal IR injury.Methods: We divided Sprague–Dawley rats into three groups: the sham group, IR group and IR + HFMSCs group. A small intestinal IR injury rat model was established by clamping of the superior mesenteric artery (SMA) for 30 min and reperfusion for 2 h. HFMSCs were cultured in vitro and injected into the rats through the tail vein. Seven days after treatment, the intrinsic homing and differentiation characteristics of the HFMSCs were observed by immunofluorescence and immunohistochemical staining, and the paracrine mechanism of HFMSCs was assessed by Western blotting and enzyme-linked immunosorbent assay (ELISA).Results: A small intestinal IR injury model was successfully established. HFMSCs could home to damaged sites, express proliferating cell nuclear antigen (PCNA) and intestinal stem cell (ISC) markers, and promote small intestinal ISC marker expression. The expression levels of angiopoietin-1 (ANG1), vascular endothelial growth factor (VEGF) and insulin growth factor-1 (IGF1) in the IR + HFMSCs group were higher than those in the IR group. HFMSCs could prevent IR-induced apoptosis by increasing B-cell lymphoma-2 (Bcl-2) expression and decreasing Bcl-2 homologous antagonist/killer (Bax) expression. Oxidative stress level detection showed that the malondialdehyde (MDA) content was decreased, while the superoxide dismutase (SOD) content was increased in the IR + HFMSCs group compared to the IR group. An elevated diamine oxidase (DAO) level reflected the potential protective effect of HFMSCs on the intestinal mucosal barrier.Conclusion: HFMSCs are beneficial to alleviate small intestinal IR injury through intrinsic homing to the small intestine and by differentiating into ISCs, via a paracrine mechanism to promote angiogenesis, reduce apoptosis, regulate the oxidative stress response, and protect intestinal mucosal function potentially. Therefore, this study suggests that HFMSCs serve as a new option for the treatment of small intestinal IR injury.