BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithel...BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of U...Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of UC remain elusive. Currenttherapeutic approaches, including anti-inflammatory, immunosuppressiveand immunomodulating agents, are often limited in efficacy and frequently associatedwith adverse drug reactions. Therefore, there is an urgent need to developsafer and more effective treatment strategies to address the limitations of existingtherapies. Scutellaria baicalensis Georgi (HQ), a traditional Chinese medicinal herb,has been employed in the treatment of UC for over 2000 years. Recent studieshave demonstrated that HQ contains multiple active components capable oftreating UC through anti-inflammation, immune modulation, intestinal barrierprotection, antioxidant activity, and regulation of the gut microbiota. This paperreviews recent studies on the mechanism of action and clinical trials of HQ intreating UC based on relevant literature, with the aim of providing valuable insightsinto future treatment approaches.展开更多
We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t m...We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t merely alter“good”or“bad”bacteria but restores the gut microbiota’s holistic equilibrium.This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifidobacterium,rectifying the diseased,hypoxic environment,causing their aberrant overgrowth.This challenges the conventional probiotic paradigm and underscores a core TCM principle:Herbal formulas treat disease by restoring the body’s overall functional balance.Future research should focus on the interplay between herbal components,intestinal oxygen,and microbial metabolites to further unravel this sophisticated dialogue.展开更多
BACKGROUND Oral 5-aminosalicylic acid(5-ASA)has been a cornerstone treatment for mild to moderate ulcerative colitis(UC),traditionally used to maintain remission.With the rise of advanced therapies(biologics and small...BACKGROUND Oral 5-aminosalicylic acid(5-ASA)has been a cornerstone treatment for mild to moderate ulcerative colitis(UC),traditionally used to maintain remission.With the rise of advanced therapies(biologics and small molecules),the role of 5-ASA has come under renewed scrutiny.While earlier systematic reviews affirmed its efficacy compared to placebo,these did not account for the advent of advanced therapies.AIM To assess the efficacy and safety of oral 5-ASA in maintaining remission in quiescent UC,compared to placebo,alternative 5-ASA formulations,and advanced therapies,in the era of biologics and small molecules.METHODS It was systematically searched MEDLINE,EMBASE,and the Cochrane Library,alongside conference proceedings(European Crohn’s and Colitis Organisation,British Society of Gastroenterology),for randomized controlled trials published between 2003 and 2024 in English.Eligible studies involved oral 5-ASA therapies for quiescent UC with a minimum treatment duration of six months.Outcomes included failure to maintain remission,adverse events,and serious adverse events(SAEs).Data were analyzed using Cochrane methods,with GRADE assessing evidence certainty.RESULTS From 44 studies(9967 participants),5-ASA was superior to placebo in maintaining remission,with 37%of 5-ASA users relapsing at 6-12 months compared to 55%of placebo users[risk ratios(RR):0.68;95%CI:0.61-0.76;high-certainty evidence].SAEs were rare and comparable between groups(RR:0.60;95%CI:0.19-1.84;low-certainty evidence).Comparative analyses suggested 5-ASA remains a viable option alongside advanced therapies,with notable differences in cost and safety profiles.CONCLUSION 5-ASA remains effective and safe for maintaining remission in quiescent UC,even in the advanced therapy era.However,tailored approaches are needed to balance efficacy,safety,and cost in clinical practice.This study provides critical insights to guide therapeutic strategies and underscores the enduring relevance of 5-ASA.展开更多
BACKGROUND Despite advances in the treatment of ulcerative colitis(UC),some patients remain refractory to the currently available treatments.Dual biologic therapy(DBT)has emerged as a promising strategy for these pati...BACKGROUND Despite advances in the treatment of ulcerative colitis(UC),some patients remain refractory to the currently available treatments.Dual biologic therapy(DBT)has emerged as a promising strategy for these patients.CASE SUMMARY A patient with extensive UC presented with steroid dependence and contraindications(past medical history included breast cancer and previous myocardial infarction)to treatment with tumor necrosis factor and Janus kinase inhibitors.DBT ofα4β7 integrin antagonist(vedolizumab)and interleukin 23p19 inhibitor(mirikizumab)resulted in a sustained clinical and biochemical remission.No adverse events were recorded during the follow-up.CONCLUSION This case highlighted the challenge of managing refractory UC,especially in frail patients.展开更多
Background:Mesalazine preparations serve as first-line therapy for active mild-to-moderate ulcerative colitis(UC),however,not all patients respond to mesalazine.Patients with mesalazine-refractory UC often switch to c...Background:Mesalazine preparations serve as first-line therapy for active mild-to-moderate ulcerative colitis(UC),however,not all patients respond to mesalazine.Patients with mesalazine-refractory UC often switch to corticosteroids,immunological therapy,and biological agents,but their use is limited owing to their well-characterised side effects(e.g.osteoporosis and cushingoid feature).Therefore,there is an unmet medical need for novel treatments with a manageable safety profile for patients with mesalazine-refractory UC.New Wumei Pill is a novel and effective herbal prescription for the treatment of UC,and our preliminary study suggested that New Wumei Pill has a significant effect on patients with mesalazine-refractory UC.However,its effectiveness and safety has not been evaluated convincingly.Objectives:This trail aims to evaluate efficacy,safety and mechanisms of New Wumei Pill in the treatment of patients with mesalazine-refractory UC.Methods:This is a prospective,randomized,double-blind control trial,in which 72 patients with mesalazine-refractory mild-to-moderate UC will be randomized in a 1:1 ratio in the treatment and control group.Patients will be screened for eligibility at the outpatient and ward of the Department of Gastroenterology in Dongfang Hospital,Beijing University of Chinese Medicine.72 participants will undergo strict screening to meet the diagnostic criteria of mildly to moderately active UC,with modified Mayo score of 3-10 points.All patients will be administered by mesalazine enteric-coated tablets for 8 weeks,at the same time,the patients in treatment group will receive New Wumei Pill,while patients from control group will be administered by dummy New Wumei Pill.Results:The primary outcomes are clinical efficacy rate and clinical remission rate according to the modified Mayo score.The secondary outcomes are individual symptom score,TCM syndrome score,endoscopic response rate,mucosal healing rate,and quality of life scale score.Finally,biological samples from participants will be preserved to reveal the mechanisms of New Wumei Pill on UC.Conclusions:We hypothesize that the patients with mesalazine-refractory mild-to-moderate UC will benefit from New Wumei Pill.If successful,this trial will provide evidence of traditional Chinese medicine in the treatment of UC,and hold promises for novel options UC patients and policymakers.展开更多
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
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
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
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
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
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
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
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
基金Supported by National Natural Science Foundation of China,No.82374200Construction of Traditional Chinese Medicine Inheritance and Innovation Development Demonstration Pilot Projects in Pudong New Area-High-Level Research-Oriented Traditional Chinese Medicine Hospital Construction,No.YC-2023-0901.
文摘Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of UC remain elusive. Currenttherapeutic approaches, including anti-inflammatory, immunosuppressiveand immunomodulating agents, are often limited in efficacy and frequently associatedwith adverse drug reactions. Therefore, there is an urgent need to developsafer and more effective treatment strategies to address the limitations of existingtherapies. Scutellaria baicalensis Georgi (HQ), a traditional Chinese medicinal herb,has been employed in the treatment of UC for over 2000 years. Recent studieshave demonstrated that HQ contains multiple active components capable oftreating UC through anti-inflammation, immune modulation, intestinal barrierprotection, antioxidant activity, and regulation of the gut microbiota. This paperreviews recent studies on the mechanism of action and clinical trials of HQ intreating UC based on relevant literature, with the aim of providing valuable insightsinto future treatment approaches.
文摘We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t merely alter“good”or“bad”bacteria but restores the gut microbiota’s holistic equilibrium.This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifidobacterium,rectifying the diseased,hypoxic environment,causing their aberrant overgrowth.This challenges the conventional probiotic paradigm and underscores a core TCM principle:Herbal formulas treat disease by restoring the body’s overall functional balance.Future research should focus on the interplay between herbal components,intestinal oxygen,and microbial metabolites to further unravel this sophisticated dialogue.
文摘BACKGROUND Oral 5-aminosalicylic acid(5-ASA)has been a cornerstone treatment for mild to moderate ulcerative colitis(UC),traditionally used to maintain remission.With the rise of advanced therapies(biologics and small molecules),the role of 5-ASA has come under renewed scrutiny.While earlier systematic reviews affirmed its efficacy compared to placebo,these did not account for the advent of advanced therapies.AIM To assess the efficacy and safety of oral 5-ASA in maintaining remission in quiescent UC,compared to placebo,alternative 5-ASA formulations,and advanced therapies,in the era of biologics and small molecules.METHODS It was systematically searched MEDLINE,EMBASE,and the Cochrane Library,alongside conference proceedings(European Crohn’s and Colitis Organisation,British Society of Gastroenterology),for randomized controlled trials published between 2003 and 2024 in English.Eligible studies involved oral 5-ASA therapies for quiescent UC with a minimum treatment duration of six months.Outcomes included failure to maintain remission,adverse events,and serious adverse events(SAEs).Data were analyzed using Cochrane methods,with GRADE assessing evidence certainty.RESULTS From 44 studies(9967 participants),5-ASA was superior to placebo in maintaining remission,with 37%of 5-ASA users relapsing at 6-12 months compared to 55%of placebo users[risk ratios(RR):0.68;95%CI:0.61-0.76;high-certainty evidence].SAEs were rare and comparable between groups(RR:0.60;95%CI:0.19-1.84;low-certainty evidence).Comparative analyses suggested 5-ASA remains a viable option alongside advanced therapies,with notable differences in cost and safety profiles.CONCLUSION 5-ASA remains effective and safe for maintaining remission in quiescent UC,even in the advanced therapy era.However,tailored approaches are needed to balance efficacy,safety,and cost in clinical practice.This study provides critical insights to guide therapeutic strategies and underscores the enduring relevance of 5-ASA.
文摘BACKGROUND Despite advances in the treatment of ulcerative colitis(UC),some patients remain refractory to the currently available treatments.Dual biologic therapy(DBT)has emerged as a promising strategy for these patients.CASE SUMMARY A patient with extensive UC presented with steroid dependence and contraindications(past medical history included breast cancer and previous myocardial infarction)to treatment with tumor necrosis factor and Janus kinase inhibitors.DBT ofα4β7 integrin antagonist(vedolizumab)and interleukin 23p19 inhibitor(mirikizumab)resulted in a sustained clinical and biochemical remission.No adverse events were recorded during the follow-up.CONCLUSION This case highlighted the challenge of managing refractory UC,especially in frail patients.
基金supported by the Unveiling and Leading Projects of Beijing University of Chinese Medicine(No.2023-JYB-JBQN-014)the China Association of Chinese Medicine Young Talent Support Project(No.CACM-2022-QNRC2-A02).
文摘Background:Mesalazine preparations serve as first-line therapy for active mild-to-moderate ulcerative colitis(UC),however,not all patients respond to mesalazine.Patients with mesalazine-refractory UC often switch to corticosteroids,immunological therapy,and biological agents,but their use is limited owing to their well-characterised side effects(e.g.osteoporosis and cushingoid feature).Therefore,there is an unmet medical need for novel treatments with a manageable safety profile for patients with mesalazine-refractory UC.New Wumei Pill is a novel and effective herbal prescription for the treatment of UC,and our preliminary study suggested that New Wumei Pill has a significant effect on patients with mesalazine-refractory UC.However,its effectiveness and safety has not been evaluated convincingly.Objectives:This trail aims to evaluate efficacy,safety and mechanisms of New Wumei Pill in the treatment of patients with mesalazine-refractory UC.Methods:This is a prospective,randomized,double-blind control trial,in which 72 patients with mesalazine-refractory mild-to-moderate UC will be randomized in a 1:1 ratio in the treatment and control group.Patients will be screened for eligibility at the outpatient and ward of the Department of Gastroenterology in Dongfang Hospital,Beijing University of Chinese Medicine.72 participants will undergo strict screening to meet the diagnostic criteria of mildly to moderately active UC,with modified Mayo score of 3-10 points.All patients will be administered by mesalazine enteric-coated tablets for 8 weeks,at the same time,the patients in treatment group will receive New Wumei Pill,while patients from control group will be administered by dummy New Wumei Pill.Results:The primary outcomes are clinical efficacy rate and clinical remission rate according to the modified Mayo score.The secondary outcomes are individual symptom score,TCM syndrome score,endoscopic response rate,mucosal healing rate,and quality of life scale score.Finally,biological samples from participants will be preserved to reveal the mechanisms of New Wumei Pill on UC.Conclusions:We hypothesize that the patients with mesalazine-refractory mild-to-moderate UC will benefit from New Wumei Pill.If successful,this trial will provide evidence of traditional Chinese medicine in the treatment of UC,and hold promises for novel options UC patients and policymakers.
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.
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.
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(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.
