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Background: Crohn's disease (CD) is a chronic disease that may have an adverse impact on health-related quality of life (HRQoL). This study aimed to describe the HRQoL of CD patients and assess correlating factors using the EQ-5D-5L in China.Methods: We recruited CD patients at Shanghai Renji Hospital from October 2018 to May 2019. The data collected included demographic and clinical information, medical expenditures, and EQ-5D-5L questionnaire responses. The chi-square test or Fisher's exact test was applied to analyse the proportion of patients in subgroups at each level. After the selection of correlating variables by univariate analysis, multivariate regression analyses were used to explore the correlating factors of HRQoL in CD patients.Results: A total of 202 CD inpatients with a mean disease duration of 3.3 years were enrolled in the study. A total of 71.8% of patients were males, and 49.5% of patients were aged between 30 and 49 years. The average EQ-5D-5L utility score was 0.85, with a standard deviation (SD) of 0.12. Males, ileum lesions, remission status, and lower expenditure predicted higher EQ-5D-5L scores. In each EQ-5D-5L dimension, the proportion of patients differed significantly by gender, disease activity and location subgroup. In the multivariate regression models, being in an active CD state and using antibiotics had significantly adverse impacts on HRQoL (p < 0.05).Conclusions: CD may have a significant negative impact on HRQoL in Chinese CD patients. Being in an active phase of the disease and using antibiotics were identified as affecting HRQoL. [ABSTRACT FROM AUTHOR]

Background and Aims: Deregulation of RNA N6-methyladenosine (m 6 A) modification in intestinal epithelial cells (IECs) influences intestinal immune cells and leads to intestinal inflammation. We studied the function of fat mass-and obesity-associated protein (FTO), one of the m 6 A demethylases, in patients with ulcerative colitis (UC)., Methods: We analysed colon tissues of Fto flox/flox ; Villin-cre mice and their Fto flox/flox littermates with dextran sulfate sodium (DSS) using real-time PCR and 16s rRNA sequencing. RNA and methylated RNA immunoprecipitation sequencing were used to analyse immunocytes and IECs. Macrophages were treated with conditioned medium of FTO-knockdown MODE-K cells or sphingosine-1-phosphate (S1P) and analysed for gene expression. Liquid chromatograph mass spectrometry identified C 16 -ceramide., Results: FTO downregulation was identified in our in-house cohort and external cohorts of UC patients. Dysbiosis of gut microbiota, increased infiltration of proinflammatory macrophages, and enhanced differentiation of Th17 cells were observed in Fto flox/flox ;Villin-cre mice under DSS treatment. FTO deficiency resulted in an increase in m 6 A modification and a decrease in mRNA stability of CerS6, the gene encoding ceramide synthetase, leading to the downregulation of CerS6 and the accumulation of S1P in IECs. Subsequentially, the secretion of S1P by IECs triggered proinflammatory macrophages to secrete serum amyloid A protein 1/3, ultimately inducing Th17 cell differentiation. In addition, through bioinformatic analysis and experimental validation, we identified UC patients with lower FTO expression might respond better to vedolizumab treatment., Conclusions: FTO downregulation promoted UC by decreasing CerS6 expression, leading to increased S1P accumulation in IECs and aggravating colitis via m 6 A-dependent mechanisms. Lower FTO expression in UC patients may enhance their response to vedolizumab treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Up to 40 per cent of people with active inflammatory bowel disease (IBD) also suffer from mood disorders such as anxiety and depression. Notwithstanding, the fundamental biological pathways driving depression in IBD remain unknown., Methods: We identified 33 core genes that drive depression in IBD patients and performed consensus molecular subtyping with the NMF algorithm in IBD. The CIBERSORT were employed to quantify the immune cells. Metabolic signature was characterized using the "IOBR" R package. The scoring system (D. score) based on PCA. Pre-clinical models are constructed using DSS., Results: Using transcriptome data from the GEO database of 630 IBD patients, we performed a thorough analysis of the correlation between IBD and depression in this research. Firstly, the samples were separated into two different molecular subtypes (D. cluster1 and D. cluster2) based on their biological signatures. Moreover, the immunological and metabolic differences between them were evaluated, and we discovered that D. cluster2 most closely resembled IBD patients concomitant with depression. We also developed a scoring system to assess the IBD-related depression and predict clinical response to anti-TNF- therapy, with a higher D. score suggesting more inflammation and worse reaction to biological therapies. Ultimately, we also identified through animal experiments an antidepressant, paroxetine, has the added benefit of lowering intestinal inflammation by controlling microorganisms in the digestive tract., Conclusions: This study highlights that IBD patients with or without depression show significant variations and antidepressant paroxetine may help reduce intestinal inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ning, Wang, Xuan, Ma, Yan, Gao, Tong, Cui, Chen, Li, Hong and Wang.)

Autophagy has been associated with tumor progression, prognosis, and treatment response. However, an autophagy-related model and their clinical significance have not yet been fully elucidated. In the present study, through the integrative analysis of bulk RNA sequencing and single-cell RNA sequencing, an autophagy-related risk model was identified. The model was capable of distinguishing the worse prognosis of patients with gastric cancer (GC), which was validated in TCGA and two independent Gene Expression Omnibus cohorts utilizing the survival analysis, and was also independent of other clinical covariates evaluated by multivariable Cox regression. The clinical value of this model was further assessed using a receiver operating characteristic (ROC) and nomogram analysis. Investigation of single-cell RNA sequencing uncovered that this model might act as an indicator of the dysfunctional characteristics of T cells in the high-risk group. Moreover, the high-risk group exhibited the lower expression of immune checkpoint markers ( PDCD1 and CTLA4 ) than the low-risk group, which indicated the potential predictive power to the current immunotherapy response in patients with GC. In conclusion, this autophagy-associated risk model may be a useful tool for prognostic evaluation and will facilitate the potential application of this model as an indicator of the predictive immune checkpoint biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tong, Zhang, Zhu, Hui, Wang, Wu, Tang, Chen and Tian.)

Background: Epithelial-Mesenchymal Transition (EMT) is a major process in the initiation of tumor metastasis, where cancer cells lose sessile epithelial potential and gain mesenchymal phenotype. Large-scale cell identity shifts are often orchestrated on an epigenetic level and the interplay between epigenetic factors and EMT progression was still largely unknown. In this study, we tried to identify candidate epigenetic factors that involved in EMT progression., Methods: Colorectal cancer (CRC) cells were transfected with an arrayed shRNA library targeting 384 genes involved in epigenetic modification. Candidate genes were identified by real-time PCR. Western blot, RNA-seq and gene set enrichment analysis were conducted to confirm the suppressive role of ALKBH4 in EMT. The clinical relevance of ALKBH4 in CRC was investigated in two independent Renji Cohorts and a microarray dataset (GSE21510) from GEO database. In vitro transwell assay and in vivo metastatic tumor model were performed to explore the biological function of ALKBH4 in the metastasis of CRC. Co-IP (Co-Immunoprecipitation) and ChIP (Chromatin Immunoprecipitation) assays were employed to uncover the mechanism., Results: We screened for candidate epigenetic factors that affected EMT process and identified ALKBH4 as a candidate EMT suppressor gene, which was significantly downregulated in CRC patients. Decreased level of ALKBH4 was associated with metastasis and predicted poor prognosis of CRC patients. Follow-up functional experiments illustrated overexpression of ALKBH4 inhibited the invasion ability of CRC cells in vitro , as well as their metastatic capability in vivo . Mechanistically, CO-IP and ChIP assays indicated that ALKBH4 competitively bound WDR5 (a key component of histone methyltransferase complex) and decreased H3K4me3 histone modification on the target genes including MIR21 ., Conclusions: This study illustrated that ALKBH4 may function as a novel metastasis suppressor of CRC, and inhibits H3K4me3 modification through binding WDR5 during EMT., (Copyright © 2020 Shen, Yan, Tong, Shi, Ren, Zhang, Zhang, Cao, Yan, Ma, Zhu, Tian, Fang, Chen, Ji, Hong and Xuan.)