Development and validation of a novel criterion of histologic healing in ulcerative colitis defined by inflammatory cell enumeration in lamina propria mucosa:A multicenter retrospective cohort in China

Background:Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis(UC).Here,we developed a novel diagnostic criterion for assessing histological healing in UC patients.Methods:We conducted a retrospective cohort study in UC patients,whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022.We identified an inflammatory cell enumeration index(ICEI)for assessing histological healing based on the proportions of eosinophils,CD177^(+)neutrophils,and CD40L^(+)T cells in the colonic lamina propria under high power field(HPF),and the outcomes(risks of symptomatic relapses)of achieving histological remission vs.persistent histological inflammation using Kaplan-Meier curves.Intrareader reliability and inter-reader reliability were evaluated by each reader.The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness.The ICEI was further validated in a new cohort of UC patients from other nine university hospitals.Results:We developed an ICEI for clinical diagnosis of histological healing,i.e.,Y=1.701X_(1)+0.758X_(2)+1.347X_(3)-7.745(X_(1),X_(2),and X_(3)represent the proportions of CD177^(+)neutrophils,eosinophils,and CD40L^(+)T cells,respectively,in the colonic lamina propria under HPF).The receiver operating characteristics curve(ROC)analysis revealed that Y<-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve(AUC)was 0.942(95%confidence interval[CI]:0.905-0.979)with a sensitivity of 92.5%and a specificity of 83.6%(P<0.001).The intraclass correlation coefficient(ICC)for the intrareader reliability was 0.855(95%CI:0.781-0.909),and ICEI had good inter-reader reliability of 0.832(95%CI:0.748-0.894).During an 18-month follow-up,patients with histological healing had a substantially better outcome compared with those with unachieved histological healing(P<0.001)using ICEI.During a 12-month follow-up from other nine hospitals,patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing.Conclusions:ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy.Therefore,ICEI provides a promising,simplified approach to monitor histological healing and to predict the prognosis of UC.Registration:Chinese Clinical Trial Registry,No.ChiCTR2300077792.

The new insights of hyperbaric oxygen therapy:focus on inflammatory bowel disease

Inflammatory bowel diseases(IBD),with an increasing incidence,pose a significant health burden.Although there have been significant advances in the treatment of IBD,more progress is still needed.Hyperbaric oxygen therapy(HBOT)has been shown to treat a host of conditions such as carbon monoxide poisoning,decompression sickness,and gas gangrene.In the last few years,there has been an increase in research into the use of HBOT as an adjunct to conventional treatment for IBD.Related research has shown that HBOT may exert its therapeutic effects by decreasing oxidative stress,inhibiting mucosal inflammation,promoting ulcer healing,influencing gut microbes,and reducing the incidence of IBD complications.This paper aims to provide a comprehensive review of experimental and clinical trials exploring HBOT as a supplement to IBD treatment strategies.

Blockade of Syk modulates neutrophil immune-responses via the mTOR/RUBCNL-dependent autophagy pathway to alleviate intestinal inflammation in ulcerative colitis

Background:Ulcerative colitis(UC)is a progressive chronic inflammatory disorder.Neutrophils play a critical role in regulating in-testinal mucosal homeostasis in UC.Spleen tyrosine kinase(Syk)is involved in several inflammatory diseases.Here,we evaluated the effects and underlying mechanisms of Syk on neutrophil immune-responses in UC.Methods:Syk expression in the colonic tissues of patients with UC was determined using quantitative reverse transcription-polymerase chain reaction(qRT-PCR),western blotting,and immunohistochemistry.Colonic biopsies from patients with UC were obtained for single-cell RNA-sequencing.Neutrophils isolated from peripheral blood were pre-treated with R788(a Syk inhibitor)and gene differences were determined using RNA sequencing.Neutrophil functions were analyzed using qRT-PCR,flow cytometry,and Transwell assay.R788 was administered daily to mice with dextran sulfate sodium(DSS)-induced colitis to verify the effects of Syk on intestinal inflammation.Results:Syk expression was increased in inflamed mucosa and neutrophils of patients with UC and positively correlated with dis-ease activity.Pharmacological inhibition of Syk in neutrophils decreased the production of pro-inflammatory cytokines,chemokines,neutrophil extracellular traps,reactive oxygen species,and myeloperoxidase.Apoptosis and migration of neutrophils were sup-pressed by Syk blockade.Syk blockade ameliorated mucosal inflammation in DSS-induced murine colitis by inhibiting neutrophil-associated immune responses.Mechanistically,Syk regulated neutrophil immune-responses via the mammalian target of rapamycin kinase/rubicon-like autophagy enhancer-dependent autophagy pathway.Conclusions:Our findings indicate that Syk facilitates specific neutrophil functional responses to mucosal inflammation in UC,and its inhibition ameliorates mucosal inflammation in DSS-induced murine colitis,suggesting its potential as a novel therapeutic target for UC treatment.