OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-perf...OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon.The most common psychological issue in UC patients is varying degrees of depre-ssion,which affects the condition and quality of li...BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon.The most common psychological issue in UC patients is varying degrees of depre-ssion,which affects the condition and quality of life of UC patients and may lead to deterioration of the patient’s condition.UC drugs combined with anti-anxiety and antidepression drugs can alleviate symptoms of both depression and UC.Brain-derived neurotrophic factor(BDNF)precursor(proBDNF)/p75 neurotrophin receptor(p75NTR)/sortilin and BDNF/tropomyosin receptor kinase B(TrkB)signalling balance is essential for maintaining brain homeostasis and preventing the development of depressive behaviours.AIM To explore the mechanism by which Wuling powder regulates the proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of UC with depre-ssion.METHODS Depression was established in C57BL/6J mice via chronic restraint stress,and the UC model was induced with dextran sodium sulfate(DSS).In the treatment stage,mesalazine(MS)was the basic treatment,Wuling powder was the experimental treatment,and fluoxetine was the positive control drug for treating depression.Changes in intestinal mucosal inflammation,behaviour,and the proBDNFp75NTR/sortilin and BDNF/TrkB pathways were evaluated.RESULTS In the depression groups,Wuling powder decreased the immobility time,increased the distance travelled in the central zone and the total distance travelled,and restored balance in the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways.In the DSS and chronic restraint stress+DSS groups,immobility time increased,distance travelled in the central zone and total distance travelled decreased,activity of the proBDNF/p75NTR/sortilin pathway was upregulated,and activity of the BDNF/TrkB pathway was downregulated,indicating that mice with UC often have comorbid depression.Compared with those of MS alone,Wuling powder combined with MS further decreased the colon histopathological scores and the expression levels of tumor necrosis factor-alpha and interleukin-6 mRNAs.CONCLUSION This study confirmed that Wuling powder may play an antidepressant role by regulating the balance of the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways and further relieve intestinal inflammation in UC.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thio...BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.METHODS This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to 2022.Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab.We evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine withdrawal.RESULTS There were 62 UC participants with mean age of 43.4 years and 42%were females.All participants received vedolizumab as maintenance therapy with 67.7%withdrew thiopurine.Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies detected.Pa-tients with clinical remission had higher trough concentrations at week 48.In quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission.CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial.While thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remission.展开更多
BACKGROUND Bullous pemphigoid(BP)is an autoimmune blistering skin disorder.It is associated with other autoimmune disorders and the use of certain drugs.We describe a case of BP in a patient with ulcerative colitis(UC...BACKGROUND Bullous pemphigoid(BP)is an autoimmune blistering skin disorder.It is associated with other autoimmune disorders and the use of certain drugs.We describe a case of BP in a patient with ulcerative colitis(UC)treated with mesalamine.CASE SUMMARY A 38-year-old male patient with UC and a history of multiple flares was maintained on mesalamine with good clinical response.One year after starting mesalamine,he sought medical care following the onset of a severe itchy rash of several weeks’duration with a recent appearance of skin bullae.A biopsy of the skin revealed subepidermal blistering dermatitis with focal eosinophilic spongiosis.Direct immunofluorescence studies revealed linear IgG and C3 immune reactant deposits at the dermoepidermal junction,consistent with the diagnosis of BP.Prednisone therapy alleviated his symptoms.However,tapering prednisone led to re-eruption of the bullae.CONCLUSION BP should be considered when patients with UC develop skin manifestations.Although BP is not one of the extraintestinal manifestations of UC,there may be an association between these two conditions.Whether treatment with mesalamine or other therapeutic agents plays a role in the development of BP remains unclear.展开更多
Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to...Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to regulating the proliferation,differentiation,and migration of Th17 and Treg cells.Wdr63,a gene containing the WD repeat domain,participates in the structure and functional modulation of actin cytoskeleton.Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition.This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis.Methods We constructed Wdr63-/-mice,induced colitis in mice using dextran sulfate sodium salt,collected colon tissue for histopathological staining,collected mesenteric lymph nodes for flow cytometry analysis,and collected healthy mouse feces for microbial diversity detection.Results Compared with wild-type colitis mice,Wdr63-/-colitis mice had a more pronounced shortening of colonic tissue,higher scores on disease activity index and histological damage index,Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes,a lower level of anti-inflammatory cytokine IL-10,and a higher level of pro-inflammatory cytokine IL-17A.In addition,WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis.It maintains the balance of Bacteroidota and Firmicutes,promoting the formation of beneficial intestinal bacteria linked to immune inflammation.Conclusion Wdr63 deletion aggravates ulcerative colitis in mice,WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.展开更多
OBJECTIVE:To investigate the effect and mechanism of mild moxibustion on the non-neuronal cholinergic system(NNCS) in rats with ulcerative colitis(UC).METHODS:UC rat model was established by administering 4% dextran s...OBJECTIVE:To investigate the effect and mechanism of mild moxibustion on the non-neuronal cholinergic system(NNCS) in rats with ulcerative colitis(UC).METHODS:UC rat model was established by administering 4% dextran sulfate sodium.After 7 d,mild moxibustion,α7 nicotinic acetylcholine receptors(α7nAchRs) antagonist(α-bungarotoxin,α-BGT),vesicular acetylcholine transport inhibitor(vesamicol hydrochloride,VH) and organic cation transporters inhibitor(quinine,Qu) treatments were performed once daily for 7 d.Haematoxylin and eosin staining was used for morphological evaluation of colon tissues.Enzymelinked immunosorbent assay(ELISA) was used to measure the protein expressions of interleukin-1β(IL-1β) and choline acetyltransferase(ChAT) in colon tissue.Reverse transcription quantitative real-time polymerase chain reaction(RT-q PCR) was used to detect the mRNA expressions of IL-1β,carnosine acetyltransferase(CarAT),ChAT,and nuclear factor kappa-B p65 subunit(NF-κB p65) in colon tissue.Western blot was used to detect NF-κB p65 protein expression in colon tissue.Immunofluorescence was used to detect the expressions of neuronal acetylcholine(nAch) and non-neuronal acetylcholine(nnAch,released by NNCS) in colon tissue.RESULTS:Mild moxibustion inhibited colon inflammation and repaired mucosal damage to the colon in UC rats.Meanwhile,mild moxibustion could downregulate the expressions of IL-1β,NF-κB p65 protein and mRNA(P < 0.01),and upregulate the expressions of ChAT protein and CarAT mRNA(P < 0.05,P < 0.01).The α7nAChR antagonist α-BGT can reverse the protective effect of mild moxibustion on the UC and the inhibitory effect on the inflammatory factors.VH cannot affect the effect of mild moxibustion on the expressions of IL-1β and nnAch,while Qu can reverse the effect of mild moxibustion on the expression of IL-1β and nnAch.CONCLUSIONS:Mild moxibustion can inhibite colon inflammation in UC rats,which is closely related to the release of acetylcholine by NNCS and its mediated mechanism of cholinergic anti-inflammation pathway.展开更多
Essential thrombocythemia is classified as a chronic myeloproliferative disorder characterized by the overproduction of platelets stemming from a megakaryocytic clone. The diagnosis primarily relies on bone marrow bio...Essential thrombocythemia is classified as a chronic myeloproliferative disorder characterized by the overproduction of platelets stemming from a megakaryocytic clone. The diagnosis primarily relies on bone marrow biopsy findings and the detection of the JAK2 V617F mutation, after the exclusion of secondary thrombocytosis due to conditions such as inflammation, hemolysis, infection, and iron deficiency. On the other hand, Ulcerative colitis represents an inflammatory disorder of the colon. The diagnosis of ulcerative colitis is established through clinical assessment, endoscopic examination, and histological criteria, without a discernible alternative etiology. The concomitant occurrence of these two conditions is infrequent. We present the case of an 85-year-old patient with a history of essential thrombocythemia who exhibited gastrointestinal symptoms characterized by alternating episodes of diarrhea and constipation. A subsequent colonoscopy accompanied by a biopsy revealed histological features consistent with ulcerative colitis. The patient was administered cytoreductive therapy in combination with mesalazine, resulting in favorable outcomes. Current literature addressing this association is limited, indicating the need for further investigative studies to elucidate the causal relationships between these two pathologies and to achieve improved therapeutic management strategies.展开更多
BACKGROUND Tofacitinib is an oral,selective Janus kinase inhibitor that is approved for the treatment of ulcerative colitis(UC).The 8-week induction protocol involves the administration of 10 mg twice daily(bid)with t...BACKGROUND Tofacitinib is an oral,selective Janus kinase inhibitor that is approved for the treatment of ulcerative colitis(UC).The 8-week induction protocol involves the administration of 10 mg twice daily(bid)with the possibility of extending the induction period to 16 weeks.The maintenance dose of tofacitinib is either 5 mg or 10 mg bid.AIM To assess predictors for clinical remission and drug persistence in patients with UC receiving the extended induction tofacitinib protocol.METHODS This was a real-world multicenter retrospective study in patients with moderateto-severe UC.Patients received physician-directed extended induction tofacitinib treatment.We collected clinical and demographic data at baseline and data regarding clinical,laboratory,and endoscopic evaluations,therapeutic modifications,and adverse events at the 52-week follow-up.Possible predictors for clinical remission at week 52 was the primary endpoint.Differences between patients receiving 5 mg bid vs 10 mg bid at week 52 and identification of predictors for treatment persistence were secondary endpoints.RESULTS Thirty-seven consecutive patients from 11 medical centers were included[51.4%males with median age 39(17-64)years].Twenty-eight patients continued treatment until week 52(75.7%)with 67.9%receiving 10 mg tofacitinib;all had prior history of biologic use.We observed that 57.1%of patients achieved clinical remission(66.7%in the 5 mg tofacitinib group and 52.6%in the 10 mg tofacitinib group,P=0.483).De-escalation to 5 mg tofacitinib was attempted in 17 patients with a success rate of 52.9%.Prior biologic use was significantly more frequent in patients treated with 10 mg tofacitinib.Active smoking was significantly associated with treatment discontinuation at week 52.We identified eight adverse events,and only one led to treatment discontinuation.CONCLUSION Our results supported the extended induction strategy with tofacitinib in selected patients with UC.Patients with prior failure of advanced therapies particularly benefitted,highlighting the importance of personalized maintenance regimens.展开更多
Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,de...Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,despite the lack of supporting evidence.This highlights the critical need for innovative research directions and methodologies to uncover the cause and develop a cure for this disease.By analyzing existing data from less than a dozen previously published studies,a novel,evidence-based pathogenesis was constructed,implicating colonic epithelial hydrogen peroxide as a causal factor in the development of this disease.This newly identified mechanism informed the creation of a ground-breaking class of therapeutics,known as reducing agents,which have demon-strated remarkable success in resolving colonic inflammation and restoring colonic health in patients with refractory ulcerative colitis.This paper outlines the timeline of these publications and reinterprets the findings within the context of contemporary biomedical science.展开更多
BACKGROUND Pyoderma gangrenosum(PG)is one of the most severe extra-intestinal manifest-ations of ulcerative colitis(UC).The treatment of refractory UC combined with PG is challenging,particularly for patients with sch...BACKGROUND Pyoderma gangrenosum(PG)is one of the most severe extra-intestinal manifest-ations of ulcerative colitis(UC).The treatment of refractory UC combined with PG is challenging,particularly for patients with schizophrenia(SCZ)with a long-term history of risperidone use,and there have been no successfully treated patients reported in the literature.CASE SUMMARY A 36-year-old woman attended the gastroenterological clinic due to intermittent symptoms of diarrhea and mucous bloody stools.Prior to the emergence of these symptoms,the patient had a history of SCZ for 3 years.She had been receiving long-term risperidone treatment and had stable mental symptoms.In April 2023,she was diagnosed with UC E3 moderate and began taking mesalazine 3 g/day.In March 2024,her intestinal symptoms recurred and approximately 2 months later,PG developed in both lower limbs.Previous treatments with adalimumab and steroids were ineffective for PG and UC,and simultaneously,the patient experienced headache,confusion,and severe sleep disturbances.After switching to upadacitinib(UPA)45 mg/day,PG lesions showed complete healing and fecal calprotectin was<10μg/g after 7 weeks of treatment.Following approximately 12 weeks of UPA therapy,colonoscopy indicated that the patient had achieved mucosal healing.No adverse events occurred during UPA induction and main-tenance therapy for 6 months with risperidone.CONCLUSION UPA treatment led to successful resolution of both intestinal and extra-intestinal manifestations in this patient with new-onset UC who had a history of SCZ.No adverse effects were observed with concurrent UPA and risperidone use.展开更多
BACKGROUND Mesalamine is the recommended first-line treatment for inducing and maintaining remission in mild-to-moderate ulcerative colitis(UC).However,adherence in real-world settings is frequently suboptimal.Encoura...BACKGROUND Mesalamine is the recommended first-line treatment for inducing and maintaining remission in mild-to-moderate ulcerative colitis(UC).However,adherence in real-world settings is frequently suboptimal.Encouraging collaborative patient-provider relationships may foster better adherence and patient outcomes.AIM To quantify the association between patient participation in treatment decisionmaking and adherence to oral mesalamine in UC.METHODS We conducted a 12-month,prospective,non-interventional cohort study at 113 gastroenterology practices in Germany.Eligible patients were aged≥18 years,had a confirmed UC diagnosis,had no prior mesalamine treatment,and provided informed consent.At the first visit,we collected data on demographics,clinical characteristics,patient preference for mesalamine formulation(tablets or granules),and disease knowledge.Self-reported adherence and disease activity were assessed at all visits.Correlation analyses and logistic regression were used to examine associations between adherence and various factors.RESULTS Of the 605 consecutively screened patients,520 were included in the study.The median age was 41 years(range:18-91),with a male-to-female ratio of 1.1:1.0.Approximately 75%of patients reported good adherence at each study visit.In correlation analyses,patient participation in treatment decision-making was significantly associated with better adherence across all visits(P=0.04).In the regression analysis at 12 months,this association was evident among patients who both preferred and received prolonged-release mesalamine granules(odds ratio=2.73,P=0.001).Patients reporting good adherence also experienced significant improvements in disease activity over 12 months(P<0.001).CONCLUSION Facilitating patient participation in treatment decisions and accommodating medication preferences may improve adherence to mesalamine.This may require additional effort but has the potential to improve long-term management of UC.展开更多
BACKGROUND Epstein-Barr virus(EBV)infection of the intestinal mucosa is associated with surgical risk in ulcerative colitis(UC);however,the exact effect remains unclear.AIM To determine whether EBV infection can predi...BACKGROUND Epstein-Barr virus(EBV)infection of the intestinal mucosa is associated with surgical risk in ulcerative colitis(UC);however,the exact effect remains unclear.AIM To determine whether EBV infection can predict the need for colectomy and to develop a surgical risk predictive model.METHODS This was a single-center retrospective study of 153 patients with moderate-tosevere UC between September 2012 and May 2023.EBV-encoded small RNA(EBER)in situ hybridization and immunohistochemistry(IHC)were used for EBV testing and assessment.Cytomegalovirus(CMV)was detected by IHC.Logistic regression analysis was conducted to identify risk factors for colectomy and develop a predictive risk model.RESULTS EBER-positivity in the intestinal mucosa was present in 40.4%(19/47)and 4.7%(5/106)of patients in the surgery and non-surgery groups,respectively,with significant differences between the groups(P<0.01,odds ratio=13.707).The result of multivariate logistic regression revealed that age,EBV infection in the colonic mucosa,CMV infection in the colonic mucosa,and treatment with three or more immunosuppressive agents before admission were significant independent predictors of colectomy.A nomogram incorporating these variables demonstrated good discriminative ability,and exhibited good calibration and clinical utility.IHC showed that EBV-infected cells mainly included B and T lymphocytes in patients with high EBER concentrations.CONCLUSION EBV infection of the intestinal mucosa is a significant independent risk factor for colectomy in patients with moderate-to-severe UC.The nomogram model,which includes EBV infection,effectively predicts colectomy risk.展开更多
BACKGROUND Strictures in ulcerative colitis(UC)are relatively uncommon but are associated with increased risk of malignancy and complications.Until recently,fibrogenesis and strictures have remained largely unexplored...BACKGROUND Strictures in ulcerative colitis(UC)are relatively uncommon but are associated with increased risk of malignancy and complications.Until recently,fibrogenesis and strictures have remained largely unexplored in UC.AIM To investigate the incidence,long-term prognosis and risk factors of colorectal strictures in a large cohort of UC patients.METHODS A total of 938 hospitalized UC patients at Peking Union Medical College Hospital were included from 2014 to 2024.Stricture was defined as a fixed localized narrowing of the colorectal lumen.Risk factors for stricture formation were identified by multivariable Cox regression.Prognosis was analyzed using the Kaplan-Meier or Fine-Gray method.Sensitivity analysis excluded malignant strictures due to their distinct pathophysiology.RESULTS The overall incidence of stricture was 12.4%over a median follow-up of 8.70 years,with a 10-year cumulative probability of 11.3%.Malignancy occurred in 8.6%of stricture cases.UC patients with strictures were at higher risk for intestinal complications,surgery and malignancy(P<0.05).The 10-year cumulative probabilities of surgery and all-cause mortality were 37.6%and 1.6%,respectively.Age≥40 years at diagnosis[hazard ratio(HR)=2.197,95%confidence interval(CI):1.487-3.242]and extraintestinal manifestations(HR=2.072,95%CI:1.326-3.239)were associated with higher stricture risk,while the use of biological agents such as vedolizumab(HR=0.382,95%CI:0.203-0.720)was protective against strictures(P<0.05).Sensitivity analysis on benign strictures showed consistent findings,with similar risk factors and worse longterm outcomes.CONCLUSION UC patients with strictures had worse long-term prognostic outcomes.Earlier endoscopic surveillance and biologic treatment should be considered in patients≥40 years or those with extraintestinal manifestations.展开更多
Ulcerative colitis(UC)is a long-term inflammatory disorder that has evolved into a worldwide challenge.The development of new therapies against UC is imperative as all current therapies for UC are flawed in some way.T...Ulcerative colitis(UC)is a long-term inflammatory disorder that has evolved into a worldwide challenge.The development of new therapies against UC is imperative as all current therapies for UC are flawed in some way.Thus,the present study aimed to assess the palliative effects of Lactobacillus rhamnosus MP108 on UC in mice and to explore its potential mechanisms.The results showed that L.rhamnosus MP108 ameliorated the symptoms of UC,including preventing body weight loss,disease activity index(DAI)elevation,and colon shortening,and attenuated colonic pathological damage.L.rhamnosus MP108 dramatically increased the number of goblet cells,MUC2 level,and tight junction protein level in the colon and remarkably inhibited epithelial cell apoptosis,thereby strengthening the intestinal barrier.L.rhamnosus MP108 pronouncedly diminished pro-inflammatory cytokine levels and strikingly augmented anti-inflammatory cytokine levels,in turn suppressing inflammation.Furthermore,L.rhamnosus MP108 conspicuously boosted the proportion of short-chain fatty acids(SCFAs)producers in gut microbiota,contributing to increased levels of acetate and butyrate.Therefore,L.rhamnosus MP108 might alleviate UC via improving the intestinal barrier,inhibiting inflammation,and modulating intestinal microbiota.展开更多
Background:Baitouweng decoction is a classic prescription for treating chronic dysentery and mainly used to treat heat-toxic dysentery and is widely used in damp-heat ulcerative colitis(UC)in China.Methods:Meta-analys...Background:Baitouweng decoction is a classic prescription for treating chronic dysentery and mainly used to treat heat-toxic dysentery and is widely used in damp-heat ulcerative colitis(UC)in China.Methods:Meta-analysis and network pharmacology were used to examine the pharmacological properties of Baitouweng decoction in the treatment of UC.Additionally,the potential mechanisms of action were investigated.In the meta-analysis,studies were searched from databases up to March 2024.Data from the included studies were extracted.The results were quantified by calculating the standardized mean difference(SMD).Additionally,95%confidence intervals(CI)were used to assess the precision of the estimates.Results:It was found that 201 components of Baitouweng decoction,including Pulsatillae Radix(Baitouweng),Coptidis Rhizoma(Huanglian),Phellodendri Chinensis Cortex(Huangbo),Fraxini Cortex(Qinpi),and 106 intersecting targets of UC,were obtained from INPUT.PPI and enrichment analyses showed Baitouweng decoction might regulate inflammatory response to improve UC injury.Seventeen included studies were published between 2004 and 2024.The meta-analysis results suggested that Baitouweng decoction may help increase body weight,decrease DAI and CMDI,reduce colon length shortening associated with UC,lower the spleen index,and alleviate tissue damage in colitis.In addition,Baitouweng decoction could inhibit inflammatory response and repair intestinal barrier in UC model.The protective mechanism of Baitouweng decoction was consistent with the predicted targets of network pharmacology,which suggested the results were accurate.Conclusion:Baitouweng decoction could improve UC injury by regulating the inflammatory response,cell apoptosis,and body metabolism through the integration of network pharmacology and meta-analysis.Its protective mechanisms are related to anti-inflammation,regulation of intestinal flora,brain-gut peptides,and protection of the intestinal mucosal barrier,along with modulation of body metabolism,including SCFA,bile acids,and tryptophan metabolism.展开更多
BACKGROUND Endocytoscopy is an advanced imaging modality that provides real-time,ultrahigh magnification views of the intestinal mucosa.In ulcerative colitis(UC),the combined assessment of endoscopic and histological ...BACKGROUND Endocytoscopy is an advanced imaging modality that provides real-time,ultrahigh magnification views of the intestinal mucosa.In ulcerative colitis(UC),the combined assessment of endoscopic and histological remission is now becoming a standard practice.However,histological evaluation typically falls outside the scope of the endoscopist.By offering in vivo microscopic imaging,endocytoscopy has the potential to streamline workflow and enhance efficiency in assessing UC activity.AIM To evaluate the utility of real-time endocytoscopy in assessing endoscopic and histological disease activity in UC,and to validate endocytoscopic scoring systems.METHODS This study was conducted at Concord Hospital.Patients with UC who consented to undergo colonoscopy with endocytoscopy were enrolled.Data collected included patient demographics,clinical disease activity,Mayo endoscopic score(MES),and endocytoscopic features such as crypt architecture,intercrypt distance and cellular infiltration.Correlation between endocytoscopic findings were evaluated against MES and the Nancy histological index.Agreement and validation were assessed using the ErLangen Endocytoscopy in ColiTis(ELECT)score and the endocytoscopy score(ECSS),applying Kappa(κ)statistics and Spearman’s correlation coefficient(r).RESULTS A total of 61 colonic segments from 15 patients were assessed,with 187 analyzable endocytoscopic images.Endocytoscopy showed significant correlation with the MES using both the ECSS(κ=0.60,P<0.001;r=0.78,P<0.001)and ELECT(κ=0.88,P<0.001;r=0.81,P<0.001)scoring systems.Similarly,correlations with the Nancy histological index were significant for both ECSS(κ=0.47,P<0.001;r=0.69,P<0.001)and ELECT(κ=0.88,P<0.001;r=0.74,P<0.001).The ELECT score demonstrated superior diagnostic accuracy in identifying histological remission,with a sensitivity of 100%,specificity of 85%,and an area under the receiver operating characteristic curve of 0.90(95%confidence interval:0.78-1.00),compared to 68.3%,85%,and an area under the receiver operating characteristic curve of 0.88(95%confidence interval:0.75-1.00)for the ECSS.No serious adverse events occurred,except for transient urinary discoloration due to methylene blue excretion.CONCLUSION Endocytoscopy allows for real-time,simultaneous assessment of endoscopic and histological activity in UC and has been proven to be accurate,safe,and well-tolerated.Compared with the ECSS,the ELECT score showed superior concordance with histological findings.展开更多
This letter addresses Pravda's innovative review,which proposes hydrogen pe-roxide as the primary pathogenic factor in ulcerative colitis(UC).Although the author presents intriguing mechanistic insights and report...This letter addresses Pravda's innovative review,which proposes hydrogen pe-roxide as the primary pathogenic factor in ulcerative colitis(UC).Although the author presents intriguing mechanistic insights and reports encouraging clinical outcomes with reducing agents,several methodological and clinical considera-tions require discussion.We examine three key aspects:The selective evidence synthesis approach;the need for rigorous clinical validation of proposed thera-pies;and the integration of this novel hypothesis with established inflammatory bowel disease pathogenesis.Given the complexity of UC,future therapeutic ad-vances may require collaborative approaches that integrate redox-based mecha-nisms into existing evidence-based frameworks rather than replacing current paradigms.展开更多
The prevalence of ulcerative colitis(UC)is increasing annually,while current non-targeted drugs for UC have limited effectiveness,easily relapsed,and serious side effects.Herein,curcumin(Cur)-loaded nanoparticle with ...The prevalence of ulcerative colitis(UC)is increasing annually,while current non-targeted drugs for UC have limited effectiveness,easily relapsed,and serious side effects.Herein,curcumin(Cur)-loaded nanoparticle with conlon-targeted property based on Mesona chinensis polysaccharides(MCP)was developed for the synergistic and targeted improvement of UC.Results show that MCP-zein nanoparticles(ZmNPs)have good encapsulation of Cur,targeted delivery of Cur to the colon,and prolonged its retention time.In vivo safety assessments have shown that ZmNPs have good safety and biocompatibility.As expected,Cur-ZmNPs effectively alleviated the symptoms of Dextran sulfate sodium(DSS)-induced UC by decreasing colonic inflammation by inhibiting the TLR4/MAPK pathway,regulating the levels of oxidative stress and immune homeostasis of UC mice.Oral administration of Cur-ZmNPs can reduce apoptosis of intestinal epithelial cells,alleviate colonic mucosal damage and repair intestinal barrier function.Cur-ZmNPs also had a positive effect on improving gut microbiota disorders and promoting the production of SCFAs.This study provides a novel strategy for synergistic alleviation of UC by MCP-based NPs loaded with food bioactives.展开更多
BACKGROUND Ultrasound(US)can be a valuable tool for assessing arthritis associated with inflammatory bowel disease(IBD),especially in cases of psoriatic disease.The clinical case reviewed in this article addresses an ...BACKGROUND Ultrasound(US)can be a valuable tool for assessing arthritis associated with inflammatory bowel disease(IBD),especially in cases of psoriatic disease.The clinical case reviewed in this article addresses an exploratory finding that evaluates the effects of immunobiological treatments on dactylitis and IBD with the use of US techniques.CASE SUMMARY A 40-year-old Caucasian woman with psoriatic arthritis(PsA)and ulcerative colitis(UC)reported experiencing finger pain,knee arthritis,and bloody diarrhea.She showed a high Disease Activity index for PsA score and a severe Mayo score.She began treatment with adalimumab.Over the course of six months,the 18 MHz US procedure was performed on her joints and a 3.5 MHz US on her intestines.The joint US indicated dactylitis and swelling in her finger joints,while the intestinal US revealed 6.6 mm swelling in the sigmoid colon,increased abdominal fat,and high Doppler signal.Her fecal calprotectin level was 5984 mg/kg,and a colonoscopy showed that UC extended to the hepatic flexure,along with mild narrowing of the transverse colon.After six months treatment,all parameters showed improvement,including a remission of the Mayo score,better colonoscopy results,and Limberg score of 0.CONCLUSION More research is needed to find out the importance of using US in patients with PsA and UC as this could improve treatment strategies.展开更多
BACKGROUND Ulcerative colitis(UC)is a complex inflammatory bowel disease,and its etiology and pathogenesis remain incompletely elucidated.AIM To analyze the effects of Saccharomyces boulardii in combination with sulfa...BACKGROUND Ulcerative colitis(UC)is a complex inflammatory bowel disease,and its etiology and pathogenesis remain incompletely elucidated.AIM To analyze the effects of Saccharomyces boulardii in combination with sulfasalazine on intestinal microbiota and intestinal barrier function in patients with UC.METHODS A retrospective analysis of clinical data from 127 UC patients admitted to our hospital between January 2021 and January 2023 was conducted.All patients met complete inclusion and exclusion criteria.Based on the treatment interventions received,they were divided into a control group(n=63)and an observation group(n=64).Both groups of patients received routine treatment upon admission.The control group received sulfasalazine in addition to routine interventions,while the observation group received a combination of Saccharomyces boulardii on the basis of the control group’s treatment.The clinical efficacy,improvement in symptoms,modified Baron endoscopic scores,quality of life“inflammatory bowel disease questionnaire(IBDQ)”,levels of intestinal microbial indicators(such as Lactobacillus,Bifidobacterium,Enterococcus,and Escherichia coli),intestinal mucosal barrier function indicators[diamine oxidase(DAO),lipopolysaccharide(LPS),D-lactic acid(D-LA)],and adverse reaction occurrences were compared between the two groups.RESULTS(1)Clinical efficacy:The total effective rate in the control group was 79.37%,while in the observation group,it was 93.75%,significantly higher than that of the control group(P<0.05);(2)Improvement in symptoms:The observation group showed significantly lower relief time for abdominal pain,diarrhea,rectal bleeding,fever symptoms,and mucosal healing time compared to the control group(P<0.05);(3)Baron endoscopic scores and IBDQ scores:Before treatment,there was no significant difference in Baron endoscopic scores and IBDQ scores between the two groups(P>0.05).However,after treatment,the observation group showed significantly lower Baron endoscopic scores and higher IBDQ scores compared to the control group(P<0.05);(4)Levels of intestinal microbial indicators:Before treatment,there was no significant difference in the levels of Lactobacillus,Bifidobacterium,Enterococcus,and Escherichia coli between the two groups(P>0.05).After treatment,the levels of Lactobacillus and Bifidobacterium in the observation group were significantly higher than those in the control group,while the levels of Enterococcus and Escherichia coli were significantly lower than those in the control group(P<0.05);(5)Levels of intestinal mucosal barrier function indicators:Before treatment,there was no significant difference in the levels of DAO,LPS,and D-LA between the two groups(P>0.05).However,after treatment,the levels of DAO,LPS,and D-LA in the observation group were significantly lower than those in the control group(P<0.05);and(6)Occurrence of adverse reactions:The incidence of adverse reactions in the control group was 9.52%,while in the observation group,it was 10.94%.There was no significant difference in the occurrence of adverse reactions between the two groups(P>0.05).CONCLUSION The application of Saccharomyces boulardii in combination with sulfasalazine in UC patients demonstrates significant effectiveness.Compared to sole sulfasalazine intervention,the combined application of Saccharomyces boulardii further promotes the relief of relevant symptoms in patients,alleviates intestinal mucosal inflammation,and improves the quality of life.Its action may be related to rectifying the imbalance in intestinal microbiota and improving intestinal mucosal barrier function.Moreover,the combined use of Saccharomyces boulardii does not increase the risk of adverse reactions in patients,indicating a higher level of medication safety and advocating for its clinical promotion and application.展开更多
基金the Guangdong Provincial Basic and Applied Basic Research Project:Mechanistic Study on the Regulation of Inflammatory Microenvironment and Improvement of Ulcerative Colitis by Lingnan Traditional Medicine Ficus Pandurata Hance through Wilms'Tumor 1-associating Protein-Mediated RNA Methyltransferase Promoting Toll Like Receptor 4 m6A Modification(2023A1515011699)the Zhongshan Medical Research Project:Mechanistic Study on the Action of Xiahuo Pingwei San in the Treatment of Ulcerative Colitis(2022A020446)。
文摘OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon.The most common psychological issue in UC patients is varying degrees of depre-ssion,which affects the condition and quality of life of UC patients and may lead to deterioration of the patient’s condition.UC drugs combined with anti-anxiety and antidepression drugs can alleviate symptoms of both depression and UC.Brain-derived neurotrophic factor(BDNF)precursor(proBDNF)/p75 neurotrophin receptor(p75NTR)/sortilin and BDNF/tropomyosin receptor kinase B(TrkB)signalling balance is essential for maintaining brain homeostasis and preventing the development of depressive behaviours.AIM To explore the mechanism by which Wuling powder regulates the proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of UC with depre-ssion.METHODS Depression was established in C57BL/6J mice via chronic restraint stress,and the UC model was induced with dextran sodium sulfate(DSS).In the treatment stage,mesalazine(MS)was the basic treatment,Wuling powder was the experimental treatment,and fluoxetine was the positive control drug for treating depression.Changes in intestinal mucosal inflammation,behaviour,and the proBDNFp75NTR/sortilin and BDNF/TrkB pathways were evaluated.RESULTS In the depression groups,Wuling powder decreased the immobility time,increased the distance travelled in the central zone and the total distance travelled,and restored balance in the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways.In the DSS and chronic restraint stress+DSS groups,immobility time increased,distance travelled in the central zone and total distance travelled decreased,activity of the proBDNF/p75NTR/sortilin pathway was upregulated,and activity of the BDNF/TrkB pathway was downregulated,indicating that mice with UC often have comorbid depression.Compared with those of MS alone,Wuling powder combined with MS further decreased the colon histopathological scores and the expression levels of tumor necrosis factor-alpha and interleukin-6 mRNAs.CONCLUSION This study confirmed that Wuling powder may play an antidepressant role by regulating the balance of the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways and further relieve intestinal inflammation in UC.
基金Supported by Takeda Australia,No.IISR-2016-101883.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.METHODS This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to 2022.Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab.We evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine withdrawal.RESULTS There were 62 UC participants with mean age of 43.4 years and 42%were females.All participants received vedolizumab as maintenance therapy with 67.7%withdrew thiopurine.Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies detected.Pa-tients with clinical remission had higher trough concentrations at week 48.In quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission.CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial.While thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remission.
文摘BACKGROUND Bullous pemphigoid(BP)is an autoimmune blistering skin disorder.It is associated with other autoimmune disorders and the use of certain drugs.We describe a case of BP in a patient with ulcerative colitis(UC)treated with mesalamine.CASE SUMMARY A 38-year-old male patient with UC and a history of multiple flares was maintained on mesalamine with good clinical response.One year after starting mesalamine,he sought medical care following the onset of a severe itchy rash of several weeks’duration with a recent appearance of skin bullae.A biopsy of the skin revealed subepidermal blistering dermatitis with focal eosinophilic spongiosis.Direct immunofluorescence studies revealed linear IgG and C3 immune reactant deposits at the dermoepidermal junction,consistent with the diagnosis of BP.Prednisone therapy alleviated his symptoms.However,tapering prednisone led to re-eruption of the bullae.CONCLUSION BP should be considered when patients with UC develop skin manifestations.Although BP is not one of the extraintestinal manifestations of UC,there may be an association between these two conditions.Whether treatment with mesalamine or other therapeutic agents plays a role in the development of BP remains unclear.
文摘Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to regulating the proliferation,differentiation,and migration of Th17 and Treg cells.Wdr63,a gene containing the WD repeat domain,participates in the structure and functional modulation of actin cytoskeleton.Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition.This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis.Methods We constructed Wdr63-/-mice,induced colitis in mice using dextran sulfate sodium salt,collected colon tissue for histopathological staining,collected mesenteric lymph nodes for flow cytometry analysis,and collected healthy mouse feces for microbial diversity detection.Results Compared with wild-type colitis mice,Wdr63-/-colitis mice had a more pronounced shortening of colonic tissue,higher scores on disease activity index and histological damage index,Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes,a lower level of anti-inflammatory cytokine IL-10,and a higher level of pro-inflammatory cytokine IL-17A.In addition,WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis.It maintains the balance of Bacteroidota and Firmicutes,promoting the formation of beneficial intestinal bacteria linked to immune inflammation.Conclusion Wdr63 deletion aggravates ulcerative colitis in mice,WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.
基金National Natural Science Foundation of China:Study for the Mechanism of Moxibustion in Ulcerative Colitis based on the α7 Nicotinic Acetylcholine Receptor Mediated Cholinergic Antiinflammatory Pathway (No.82205293)National Natural Science Foundation of China:Study of the Central Nervous System Regulatory Mechanism of Moxibustion Repair of Ulcerative Colitis Gut Vascular Barrier Based on Ubiquitin Specific Peptidase 14 Deubiquitination (No.82274641)+3 种基金National Natural Science Foundation of China:Moxibustion Regulates P300-mediated Histone H3K27 Acetylation Modification in the Treatment of Crohn's Disease (No.82205262)National Natural Science Foundation of China:Study on the Protective Mechanism of Moxibustion on Intestinal Mucosal Barrier in Ulcerative Colitis based on GABAergic System (No.82105012)Shanghai Sailing Program:to Study the Protective Effect of Moxibustion on Intestinal Mucosal Barrier in Crohn's Disease Based on Histone H3 Acetylation Modification (No.22YF1444100)State Administration of Traditional Chinese Medicine High-level Key Discipline Construction Project (No.zyyzdxk-2023068)。
文摘OBJECTIVE:To investigate the effect and mechanism of mild moxibustion on the non-neuronal cholinergic system(NNCS) in rats with ulcerative colitis(UC).METHODS:UC rat model was established by administering 4% dextran sulfate sodium.After 7 d,mild moxibustion,α7 nicotinic acetylcholine receptors(α7nAchRs) antagonist(α-bungarotoxin,α-BGT),vesicular acetylcholine transport inhibitor(vesamicol hydrochloride,VH) and organic cation transporters inhibitor(quinine,Qu) treatments were performed once daily for 7 d.Haematoxylin and eosin staining was used for morphological evaluation of colon tissues.Enzymelinked immunosorbent assay(ELISA) was used to measure the protein expressions of interleukin-1β(IL-1β) and choline acetyltransferase(ChAT) in colon tissue.Reverse transcription quantitative real-time polymerase chain reaction(RT-q PCR) was used to detect the mRNA expressions of IL-1β,carnosine acetyltransferase(CarAT),ChAT,and nuclear factor kappa-B p65 subunit(NF-κB p65) in colon tissue.Western blot was used to detect NF-κB p65 protein expression in colon tissue.Immunofluorescence was used to detect the expressions of neuronal acetylcholine(nAch) and non-neuronal acetylcholine(nnAch,released by NNCS) in colon tissue.RESULTS:Mild moxibustion inhibited colon inflammation and repaired mucosal damage to the colon in UC rats.Meanwhile,mild moxibustion could downregulate the expressions of IL-1β,NF-κB p65 protein and mRNA(P < 0.01),and upregulate the expressions of ChAT protein and CarAT mRNA(P < 0.05,P < 0.01).The α7nAChR antagonist α-BGT can reverse the protective effect of mild moxibustion on the UC and the inhibitory effect on the inflammatory factors.VH cannot affect the effect of mild moxibustion on the expressions of IL-1β and nnAch,while Qu can reverse the effect of mild moxibustion on the expression of IL-1β and nnAch.CONCLUSIONS:Mild moxibustion can inhibite colon inflammation in UC rats,which is closely related to the release of acetylcholine by NNCS and its mediated mechanism of cholinergic anti-inflammation pathway.
文摘Essential thrombocythemia is classified as a chronic myeloproliferative disorder characterized by the overproduction of platelets stemming from a megakaryocytic clone. The diagnosis primarily relies on bone marrow biopsy findings and the detection of the JAK2 V617F mutation, after the exclusion of secondary thrombocytosis due to conditions such as inflammation, hemolysis, infection, and iron deficiency. On the other hand, Ulcerative colitis represents an inflammatory disorder of the colon. The diagnosis of ulcerative colitis is established through clinical assessment, endoscopic examination, and histological criteria, without a discernible alternative etiology. The concomitant occurrence of these two conditions is infrequent. We present the case of an 85-year-old patient with a history of essential thrombocythemia who exhibited gastrointestinal symptoms characterized by alternating episodes of diarrhea and constipation. A subsequent colonoscopy accompanied by a biopsy revealed histological features consistent with ulcerative colitis. The patient was administered cytoreductive therapy in combination with mesalazine, resulting in favorable outcomes. Current literature addressing this association is limited, indicating the need for further investigative studies to elucidate the causal relationships between these two pathologies and to achieve improved therapeutic management strategies.
文摘BACKGROUND Tofacitinib is an oral,selective Janus kinase inhibitor that is approved for the treatment of ulcerative colitis(UC).The 8-week induction protocol involves the administration of 10 mg twice daily(bid)with the possibility of extending the induction period to 16 weeks.The maintenance dose of tofacitinib is either 5 mg or 10 mg bid.AIM To assess predictors for clinical remission and drug persistence in patients with UC receiving the extended induction tofacitinib protocol.METHODS This was a real-world multicenter retrospective study in patients with moderateto-severe UC.Patients received physician-directed extended induction tofacitinib treatment.We collected clinical and demographic data at baseline and data regarding clinical,laboratory,and endoscopic evaluations,therapeutic modifications,and adverse events at the 52-week follow-up.Possible predictors for clinical remission at week 52 was the primary endpoint.Differences between patients receiving 5 mg bid vs 10 mg bid at week 52 and identification of predictors for treatment persistence were secondary endpoints.RESULTS Thirty-seven consecutive patients from 11 medical centers were included[51.4%males with median age 39(17-64)years].Twenty-eight patients continued treatment until week 52(75.7%)with 67.9%receiving 10 mg tofacitinib;all had prior history of biologic use.We observed that 57.1%of patients achieved clinical remission(66.7%in the 5 mg tofacitinib group and 52.6%in the 10 mg tofacitinib group,P=0.483).De-escalation to 5 mg tofacitinib was attempted in 17 patients with a success rate of 52.9%.Prior biologic use was significantly more frequent in patients treated with 10 mg tofacitinib.Active smoking was significantly associated with treatment discontinuation at week 52.We identified eight adverse events,and only one led to treatment discontinuation.CONCLUSION Our results supported the extended induction strategy with tofacitinib in selected patients with UC.Patients with prior failure of advanced therapies particularly benefitted,highlighting the importance of personalized maintenance regimens.
文摘Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,despite the lack of supporting evidence.This highlights the critical need for innovative research directions and methodologies to uncover the cause and develop a cure for this disease.By analyzing existing data from less than a dozen previously published studies,a novel,evidence-based pathogenesis was constructed,implicating colonic epithelial hydrogen peroxide as a causal factor in the development of this disease.This newly identified mechanism informed the creation of a ground-breaking class of therapeutics,known as reducing agents,which have demon-strated remarkable success in resolving colonic inflammation and restoring colonic health in patients with refractory ulcerative colitis.This paper outlines the timeline of these publications and reinterprets the findings within the context of contemporary biomedical science.
文摘BACKGROUND Pyoderma gangrenosum(PG)is one of the most severe extra-intestinal manifest-ations of ulcerative colitis(UC).The treatment of refractory UC combined with PG is challenging,particularly for patients with schizophrenia(SCZ)with a long-term history of risperidone use,and there have been no successfully treated patients reported in the literature.CASE SUMMARY A 36-year-old woman attended the gastroenterological clinic due to intermittent symptoms of diarrhea and mucous bloody stools.Prior to the emergence of these symptoms,the patient had a history of SCZ for 3 years.She had been receiving long-term risperidone treatment and had stable mental symptoms.In April 2023,she was diagnosed with UC E3 moderate and began taking mesalazine 3 g/day.In March 2024,her intestinal symptoms recurred and approximately 2 months later,PG developed in both lower limbs.Previous treatments with adalimumab and steroids were ineffective for PG and UC,and simultaneously,the patient experienced headache,confusion,and severe sleep disturbances.After switching to upadacitinib(UPA)45 mg/day,PG lesions showed complete healing and fecal calprotectin was<10μg/g after 7 weeks of treatment.Following approximately 12 weeks of UPA therapy,colonoscopy indicated that the patient had achieved mucosal healing.No adverse events occurred during UPA induction and main-tenance therapy for 6 months with risperidone.CONCLUSION UPA treatment led to successful resolution of both intestinal and extra-intestinal manifestations in this patient with new-onset UC who had a history of SCZ.No adverse effects were observed with concurrent UPA and risperidone use.
文摘BACKGROUND Mesalamine is the recommended first-line treatment for inducing and maintaining remission in mild-to-moderate ulcerative colitis(UC).However,adherence in real-world settings is frequently suboptimal.Encouraging collaborative patient-provider relationships may foster better adherence and patient outcomes.AIM To quantify the association between patient participation in treatment decisionmaking and adherence to oral mesalamine in UC.METHODS We conducted a 12-month,prospective,non-interventional cohort study at 113 gastroenterology practices in Germany.Eligible patients were aged≥18 years,had a confirmed UC diagnosis,had no prior mesalamine treatment,and provided informed consent.At the first visit,we collected data on demographics,clinical characteristics,patient preference for mesalamine formulation(tablets or granules),and disease knowledge.Self-reported adherence and disease activity were assessed at all visits.Correlation analyses and logistic regression were used to examine associations between adherence and various factors.RESULTS Of the 605 consecutively screened patients,520 were included in the study.The median age was 41 years(range:18-91),with a male-to-female ratio of 1.1:1.0.Approximately 75%of patients reported good adherence at each study visit.In correlation analyses,patient participation in treatment decision-making was significantly associated with better adherence across all visits(P=0.04).In the regression analysis at 12 months,this association was evident among patients who both preferred and received prolonged-release mesalamine granules(odds ratio=2.73,P=0.001).Patients reporting good adherence also experienced significant improvements in disease activity over 12 months(P<0.001).CONCLUSION Facilitating patient participation in treatment decisions and accommodating medication preferences may improve adherence to mesalamine.This may require additional effort but has the potential to improve long-term management of UC.
基金Supported by General Hospital Integrated Guidance Project of Shanghai Municipal Health Commission and Municipal Administration of Traditional Chinese Medicine(Phase I),No.ZXXT-202210"Science and Technology Innovation Action Plan"Medical Innovation Research Project of Shanghai Municipal Science and Technology Commission,No.22Y11907900.
文摘BACKGROUND Epstein-Barr virus(EBV)infection of the intestinal mucosa is associated with surgical risk in ulcerative colitis(UC);however,the exact effect remains unclear.AIM To determine whether EBV infection can predict the need for colectomy and to develop a surgical risk predictive model.METHODS This was a single-center retrospective study of 153 patients with moderate-tosevere UC between September 2012 and May 2023.EBV-encoded small RNA(EBER)in situ hybridization and immunohistochemistry(IHC)were used for EBV testing and assessment.Cytomegalovirus(CMV)was detected by IHC.Logistic regression analysis was conducted to identify risk factors for colectomy and develop a predictive risk model.RESULTS EBER-positivity in the intestinal mucosa was present in 40.4%(19/47)and 4.7%(5/106)of patients in the surgery and non-surgery groups,respectively,with significant differences between the groups(P<0.01,odds ratio=13.707).The result of multivariate logistic regression revealed that age,EBV infection in the colonic mucosa,CMV infection in the colonic mucosa,and treatment with three or more immunosuppressive agents before admission were significant independent predictors of colectomy.A nomogram incorporating these variables demonstrated good discriminative ability,and exhibited good calibration and clinical utility.IHC showed that EBV-infected cells mainly included B and T lymphocytes in patients with high EBER concentrations.CONCLUSION EBV infection of the intestinal mucosa is a significant independent risk factor for colectomy in patients with moderate-to-severe UC.The nomogram model,which includes EBV infection,effectively predicts colectomy risk.
基金Supported by the National Natural Science Foundation of China,No.82270567the Central High-Level Hospital Clinical Research Project of Peking Union Medical College Hospital,No.2022-PUMCH-B-022 and No.2022-PUMCH-C-055.
文摘BACKGROUND Strictures in ulcerative colitis(UC)are relatively uncommon but are associated with increased risk of malignancy and complications.Until recently,fibrogenesis and strictures have remained largely unexplored in UC.AIM To investigate the incidence,long-term prognosis and risk factors of colorectal strictures in a large cohort of UC patients.METHODS A total of 938 hospitalized UC patients at Peking Union Medical College Hospital were included from 2014 to 2024.Stricture was defined as a fixed localized narrowing of the colorectal lumen.Risk factors for stricture formation were identified by multivariable Cox regression.Prognosis was analyzed using the Kaplan-Meier or Fine-Gray method.Sensitivity analysis excluded malignant strictures due to their distinct pathophysiology.RESULTS The overall incidence of stricture was 12.4%over a median follow-up of 8.70 years,with a 10-year cumulative probability of 11.3%.Malignancy occurred in 8.6%of stricture cases.UC patients with strictures were at higher risk for intestinal complications,surgery and malignancy(P<0.05).The 10-year cumulative probabilities of surgery and all-cause mortality were 37.6%and 1.6%,respectively.Age≥40 years at diagnosis[hazard ratio(HR)=2.197,95%confidence interval(CI):1.487-3.242]and extraintestinal manifestations(HR=2.072,95%CI:1.326-3.239)were associated with higher stricture risk,while the use of biological agents such as vedolizumab(HR=0.382,95%CI:0.203-0.720)was protective against strictures(P<0.05).Sensitivity analysis on benign strictures showed consistent findings,with similar risk factors and worse longterm outcomes.CONCLUSION UC patients with strictures had worse long-term prognostic outcomes.Earlier endoscopic surveillance and biologic treatment should be considered in patients≥40 years or those with extraintestinal manifestations.
基金supported by the National Natural Science Foundation of China(32021005)111 Project(BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Ulcerative colitis(UC)is a long-term inflammatory disorder that has evolved into a worldwide challenge.The development of new therapies against UC is imperative as all current therapies for UC are flawed in some way.Thus,the present study aimed to assess the palliative effects of Lactobacillus rhamnosus MP108 on UC in mice and to explore its potential mechanisms.The results showed that L.rhamnosus MP108 ameliorated the symptoms of UC,including preventing body weight loss,disease activity index(DAI)elevation,and colon shortening,and attenuated colonic pathological damage.L.rhamnosus MP108 dramatically increased the number of goblet cells,MUC2 level,and tight junction protein level in the colon and remarkably inhibited epithelial cell apoptosis,thereby strengthening the intestinal barrier.L.rhamnosus MP108 pronouncedly diminished pro-inflammatory cytokine levels and strikingly augmented anti-inflammatory cytokine levels,in turn suppressing inflammation.Furthermore,L.rhamnosus MP108 conspicuously boosted the proportion of short-chain fatty acids(SCFAs)producers in gut microbiota,contributing to increased levels of acetate and butyrate.Therefore,L.rhamnosus MP108 might alleviate UC via improving the intestinal barrier,inhibiting inflammation,and modulating intestinal microbiota.
基金supported by the National Natural Science Foundation of China(No.82405237,82373835,82173781)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515110768,2019A1515010806)+3 种基金Foshan Science and Technology Bureau’s self funded project(No.2320001007283)Key Field Projects(Intelligent Manufacturing)of General Universities in Guangdong Province(No.2020ZDZX2057)the Scientific Research Projects(Characteristic Innovation)of General Universities in Guangdong Province(No.2019KTSCX195)Guangdong Provincial Medical Research Foundation(No.A2022061).
文摘Background:Baitouweng decoction is a classic prescription for treating chronic dysentery and mainly used to treat heat-toxic dysentery and is widely used in damp-heat ulcerative colitis(UC)in China.Methods:Meta-analysis and network pharmacology were used to examine the pharmacological properties of Baitouweng decoction in the treatment of UC.Additionally,the potential mechanisms of action were investigated.In the meta-analysis,studies were searched from databases up to March 2024.Data from the included studies were extracted.The results were quantified by calculating the standardized mean difference(SMD).Additionally,95%confidence intervals(CI)were used to assess the precision of the estimates.Results:It was found that 201 components of Baitouweng decoction,including Pulsatillae Radix(Baitouweng),Coptidis Rhizoma(Huanglian),Phellodendri Chinensis Cortex(Huangbo),Fraxini Cortex(Qinpi),and 106 intersecting targets of UC,were obtained from INPUT.PPI and enrichment analyses showed Baitouweng decoction might regulate inflammatory response to improve UC injury.Seventeen included studies were published between 2004 and 2024.The meta-analysis results suggested that Baitouweng decoction may help increase body weight,decrease DAI and CMDI,reduce colon length shortening associated with UC,lower the spleen index,and alleviate tissue damage in colitis.In addition,Baitouweng decoction could inhibit inflammatory response and repair intestinal barrier in UC model.The protective mechanism of Baitouweng decoction was consistent with the predicted targets of network pharmacology,which suggested the results were accurate.Conclusion:Baitouweng decoction could improve UC injury by regulating the inflammatory response,cell apoptosis,and body metabolism through the integration of network pharmacology and meta-analysis.Its protective mechanisms are related to anti-inflammation,regulation of intestinal flora,brain-gut peptides,and protection of the intestinal mucosal barrier,along with modulation of body metabolism,including SCFA,bile acids,and tryptophan metabolism.
基金the Sydney Local Health District Human Research Ethics Committee,No.2023/ETH01690.
文摘BACKGROUND Endocytoscopy is an advanced imaging modality that provides real-time,ultrahigh magnification views of the intestinal mucosa.In ulcerative colitis(UC),the combined assessment of endoscopic and histological remission is now becoming a standard practice.However,histological evaluation typically falls outside the scope of the endoscopist.By offering in vivo microscopic imaging,endocytoscopy has the potential to streamline workflow and enhance efficiency in assessing UC activity.AIM To evaluate the utility of real-time endocytoscopy in assessing endoscopic and histological disease activity in UC,and to validate endocytoscopic scoring systems.METHODS This study was conducted at Concord Hospital.Patients with UC who consented to undergo colonoscopy with endocytoscopy were enrolled.Data collected included patient demographics,clinical disease activity,Mayo endoscopic score(MES),and endocytoscopic features such as crypt architecture,intercrypt distance and cellular infiltration.Correlation between endocytoscopic findings were evaluated against MES and the Nancy histological index.Agreement and validation were assessed using the ErLangen Endocytoscopy in ColiTis(ELECT)score and the endocytoscopy score(ECSS),applying Kappa(κ)statistics and Spearman’s correlation coefficient(r).RESULTS A total of 61 colonic segments from 15 patients were assessed,with 187 analyzable endocytoscopic images.Endocytoscopy showed significant correlation with the MES using both the ECSS(κ=0.60,P<0.001;r=0.78,P<0.001)and ELECT(κ=0.88,P<0.001;r=0.81,P<0.001)scoring systems.Similarly,correlations with the Nancy histological index were significant for both ECSS(κ=0.47,P<0.001;r=0.69,P<0.001)and ELECT(κ=0.88,P<0.001;r=0.74,P<0.001).The ELECT score demonstrated superior diagnostic accuracy in identifying histological remission,with a sensitivity of 100%,specificity of 85%,and an area under the receiver operating characteristic curve of 0.90(95%confidence interval:0.78-1.00),compared to 68.3%,85%,and an area under the receiver operating characteristic curve of 0.88(95%confidence interval:0.75-1.00)for the ECSS.No serious adverse events occurred,except for transient urinary discoloration due to methylene blue excretion.CONCLUSION Endocytoscopy allows for real-time,simultaneous assessment of endoscopic and histological activity in UC and has been proven to be accurate,safe,and well-tolerated.Compared with the ECSS,the ELECT score showed superior concordance with histological findings.
文摘This letter addresses Pravda's innovative review,which proposes hydrogen pe-roxide as the primary pathogenic factor in ulcerative colitis(UC).Although the author presents intriguing mechanistic insights and reports encouraging clinical outcomes with reducing agents,several methodological and clinical considera-tions require discussion.We examine three key aspects:The selective evidence synthesis approach;the need for rigorous clinical validation of proposed thera-pies;and the integration of this novel hypothesis with established inflammatory bowel disease pathogenesis.Given the complexity of UC,future therapeutic ad-vances may require collaborative approaches that integrate redox-based mecha-nisms into existing evidence-based frameworks rather than replacing current paradigms.
基金supported by the National Key Research and Development Program of China(2023YFF1104001)Natural Science Foundation of Jiangxi Province,China(20232BCD44003).
文摘The prevalence of ulcerative colitis(UC)is increasing annually,while current non-targeted drugs for UC have limited effectiveness,easily relapsed,and serious side effects.Herein,curcumin(Cur)-loaded nanoparticle with conlon-targeted property based on Mesona chinensis polysaccharides(MCP)was developed for the synergistic and targeted improvement of UC.Results show that MCP-zein nanoparticles(ZmNPs)have good encapsulation of Cur,targeted delivery of Cur to the colon,and prolonged its retention time.In vivo safety assessments have shown that ZmNPs have good safety and biocompatibility.As expected,Cur-ZmNPs effectively alleviated the symptoms of Dextran sulfate sodium(DSS)-induced UC by decreasing colonic inflammation by inhibiting the TLR4/MAPK pathway,regulating the levels of oxidative stress and immune homeostasis of UC mice.Oral administration of Cur-ZmNPs can reduce apoptosis of intestinal epithelial cells,alleviate colonic mucosal damage and repair intestinal barrier function.Cur-ZmNPs also had a positive effect on improving gut microbiota disorders and promoting the production of SCFAs.This study provides a novel strategy for synergistic alleviation of UC by MCP-based NPs loaded with food bioactives.
文摘BACKGROUND Ultrasound(US)can be a valuable tool for assessing arthritis associated with inflammatory bowel disease(IBD),especially in cases of psoriatic disease.The clinical case reviewed in this article addresses an exploratory finding that evaluates the effects of immunobiological treatments on dactylitis and IBD with the use of US techniques.CASE SUMMARY A 40-year-old Caucasian woman with psoriatic arthritis(PsA)and ulcerative colitis(UC)reported experiencing finger pain,knee arthritis,and bloody diarrhea.She showed a high Disease Activity index for PsA score and a severe Mayo score.She began treatment with adalimumab.Over the course of six months,the 18 MHz US procedure was performed on her joints and a 3.5 MHz US on her intestines.The joint US indicated dactylitis and swelling in her finger joints,while the intestinal US revealed 6.6 mm swelling in the sigmoid colon,increased abdominal fat,and high Doppler signal.Her fecal calprotectin level was 5984 mg/kg,and a colonoscopy showed that UC extended to the hepatic flexure,along with mild narrowing of the transverse colon.After six months treatment,all parameters showed improvement,including a remission of the Mayo score,better colonoscopy results,and Limberg score of 0.CONCLUSION More research is needed to find out the importance of using US in patients with PsA and UC as this could improve treatment strategies.
文摘BACKGROUND Ulcerative colitis(UC)is a complex inflammatory bowel disease,and its etiology and pathogenesis remain incompletely elucidated.AIM To analyze the effects of Saccharomyces boulardii in combination with sulfasalazine on intestinal microbiota and intestinal barrier function in patients with UC.METHODS A retrospective analysis of clinical data from 127 UC patients admitted to our hospital between January 2021 and January 2023 was conducted.All patients met complete inclusion and exclusion criteria.Based on the treatment interventions received,they were divided into a control group(n=63)and an observation group(n=64).Both groups of patients received routine treatment upon admission.The control group received sulfasalazine in addition to routine interventions,while the observation group received a combination of Saccharomyces boulardii on the basis of the control group’s treatment.The clinical efficacy,improvement in symptoms,modified Baron endoscopic scores,quality of life“inflammatory bowel disease questionnaire(IBDQ)”,levels of intestinal microbial indicators(such as Lactobacillus,Bifidobacterium,Enterococcus,and Escherichia coli),intestinal mucosal barrier function indicators[diamine oxidase(DAO),lipopolysaccharide(LPS),D-lactic acid(D-LA)],and adverse reaction occurrences were compared between the two groups.RESULTS(1)Clinical efficacy:The total effective rate in the control group was 79.37%,while in the observation group,it was 93.75%,significantly higher than that of the control group(P<0.05);(2)Improvement in symptoms:The observation group showed significantly lower relief time for abdominal pain,diarrhea,rectal bleeding,fever symptoms,and mucosal healing time compared to the control group(P<0.05);(3)Baron endoscopic scores and IBDQ scores:Before treatment,there was no significant difference in Baron endoscopic scores and IBDQ scores between the two groups(P>0.05).However,after treatment,the observation group showed significantly lower Baron endoscopic scores and higher IBDQ scores compared to the control group(P<0.05);(4)Levels of intestinal microbial indicators:Before treatment,there was no significant difference in the levels of Lactobacillus,Bifidobacterium,Enterococcus,and Escherichia coli between the two groups(P>0.05).After treatment,the levels of Lactobacillus and Bifidobacterium in the observation group were significantly higher than those in the control group,while the levels of Enterococcus and Escherichia coli were significantly lower than those in the control group(P<0.05);(5)Levels of intestinal mucosal barrier function indicators:Before treatment,there was no significant difference in the levels of DAO,LPS,and D-LA between the two groups(P>0.05).However,after treatment,the levels of DAO,LPS,and D-LA in the observation group were significantly lower than those in the control group(P<0.05);and(6)Occurrence of adverse reactions:The incidence of adverse reactions in the control group was 9.52%,while in the observation group,it was 10.94%.There was no significant difference in the occurrence of adverse reactions between the two groups(P>0.05).CONCLUSION The application of Saccharomyces boulardii in combination with sulfasalazine in UC patients demonstrates significant effectiveness.Compared to sole sulfasalazine intervention,the combined application of Saccharomyces boulardii further promotes the relief of relevant symptoms in patients,alleviates intestinal mucosal inflammation,and improves the quality of life.Its action may be related to rectifying the imbalance in intestinal microbiota and improving intestinal mucosal barrier function.Moreover,the combined use of Saccharomyces boulardii does not increase the risk of adverse reactions in patients,indicating a higher level of medication safety and advocating for its clinical promotion and application.
