BACKGROUND Ulcerative colitis(UC)is an idiopathic,chronic inflammatory bowel disease(IBD)most often located in the rectum,but may involve the entire colon.Extra intestinal manifestations(EIMs)occur with varying freque...BACKGROUND Ulcerative colitis(UC)is an idiopathic,chronic inflammatory bowel disease(IBD)most often located in the rectum,but may involve the entire colon.Extra intestinal manifestations(EIMs)occur with varying frequency depending on the affected organ.The most common ones are musculoskeletal EIMs,affecting up to 33%-40%of IBD patients.These include,among others,inflammatory back pain,tendinitis,plantar fasciitis and arthritis.Only a few case reports in literature discuss Achilles tendinitis.CASE SUMMARY This report describes a patient with UC and Achilles tendinitis in whom after many unsuccessful attempts of treatment with sulfasalazine,mesalazine,glucocorticosteroids,infliximab and tofacitinib,a complete UC remission and resolution of Achilles tendinitis were achieved with the use of dual biologic therapy(DBT)-ustekinumab and adalimumab(ADA).CONCLUSION This case mentions rare EIMs of UC and suggests that DBT may be an alternative for patient with ulcerative colitis and EIMs.展开更多
Inflammatory bowel disease,particularly ulcerative colitis(UC),poses significant treatment challenges due to its chronic nature and potential for severe complications.This editorial reviews a recent network meta-analy...Inflammatory bowel disease,particularly ulcerative colitis(UC),poses significant treatment challenges due to its chronic nature and potential for severe complications.This editorial reviews a recent network meta-analysis that evaluated the efficacy of and highlighted the superior outcomes achieved by combining each of five traditional Chinese medicine(TCM)formulations with mesalazine for the adjuvant treatment of UC.Clinical outcomes included enhanced mucosal healing,improved quality of life,and reduced recurrence rates.Additionally,the combination therapy resulted in a lower incidence of adverse reactions compared with mesalazine monotherapy.Despite these promising results,limitations such as variability in study quality and TCM dosage highlight the need for further highquality,large-sample,multicenter randomized controlled trials.This editorial underscores the potential of TCM in enhancing UC management and calls for more rigorous research to substantiate these findings and refine clinical guidelines.展开更多
BACKGROUND This was an observational, descriptive, and retrospective study from 2011 to 2020 from the Department of Informatics of the Brazilian Healthcare System database.AIM To describe the intestinal complications(...BACKGROUND This was an observational, descriptive, and retrospective study from 2011 to 2020 from the Department of Informatics of the Brazilian Healthcare System database.AIM To describe the intestinal complications(IC) of patients with ulcerative colitis(UC) who started conventional therapies in Brazil’s public Healthcare system.METHODS Patients ≥ 18 years of age who had at least one claim related to UC 10th revision of the International Statistical Classification of Diseases and Related Health Problems(ICD-10) code and at least 2 claims for conventional therapies were included. IC was defined as at least one claim of: UC-related hospitalization, procedures code for rectum or intestinal surgeries, and/or associated disease defined by ICD-10 codes(malignant neoplasia of colon, stenosis, hemorrhage, ulcer and other rectum or anus disease, megacolon, functional diarrhea volvulus, intussusception and erythema nodosum). Descriptive statistics, annual incidence, and incidence rate(IR) [per 100 patient-years(PY)] over the available follow-up period were calculated.RESULTS In total, 41229 UC patients were included(median age, 48 years;65% women) and the median(interquartile range) follow-up period was 3.3(1.8-5.3) years. Conventional therapy used during follow-up period included: mesalazine(87%), sulfasalazine(15%), azathioprine(16%) or methotrexate(1%) with a median duration of 1.9(0.8-4.0) years. Overall IR of IC was 3.2 cases per 100 PY. Among the IC claims, 54% were related to associated diseases, 20% to procedures and 26% to hospitalizations. The overall annual incidence of IC was 2.9%, 2.6% and 2.5% in the first, second and third year after the first claim for therapy(index date), respectively. Over the first 3 years, the annual IR of UC-related hospitalizations ranged from 0.8% to 1.1%;associated diseases from 0.9% to 1.2%-in which anus or rectum disease, and malignant neoplasia of colon were the most frequently reported;and procedure events from 0.6% to 0.7%, being intestinal resection and polyp removal the most frequent ones.CONCLUSION Study shows that UC patients under conventional therapy seem to present progression of disease developing some IC, which may have a negative impact on patients and the burden on the health system.展开更多
BACKGROUND There is paucity of data on outcomes of acute severe ulcerative colitis(ASUC)in older adults(≥60 years of age).AIM To assess steroid non-response rates during the index admission for ASUC in older adults.S...BACKGROUND There is paucity of data on outcomes of acute severe ulcerative colitis(ASUC)in older adults(≥60 years of age).AIM To assess steroid non-response rates during the index admission for ASUC in older adults.Secondary outcomes were response to medical rescue therapy and colectomy rates;at index admission,3 and 12 mo.METHODS This retrospective multicentre cohort study included ASUC admissions who received intravenous steroids between January 2013 and July 2020 at two tertiary hospitals.Electronic medical records were reviewed to collect clinical,biochemical,and endoscopic data.A modified Poisson regression model was used for analysis.RESULTS Of 226 ASUC episodes,45(19.9%)occurred in patients≥60 years of age.Steroid non-response rates were comparable in older adults and patients<60 years of age[19(42.2%)vs 85(47%),P=0.618],crude risk ratio(RR)=0.89[95%confidence interval(CI):0.61-1.30],adjusted RR=0.99(0.44-2.21).Rates of response to medical rescue therapy in older adults was comparable to the younger cohort[76.5%vs 85.7%,P=0.46,crude RR=0.89(0.67-1.17)].Index admission colectomy[13.3%vs 10.5%,P=0.598,crude RR=1.27(0.53-2.99),adjusted RR=1.43(0.34-6.06)],colectomy at 3 mo[20%vs 16.6%,P=0.66,crude RR=1.18(0.61-2.3),adjusted RR=1.31(0.32-0.53)]and colectomy at 12 mo[20%vs 23.2%,P=0.682,crude RR=0.85(0.45-1.57),adjusted RR=1.21(0.29-4.97)],were similar between the two groups.CONCLUSION In older adults with ASUC,the steroid non-response rate,response to medical rescue therapy,and colectomy rate at index admission,3 and 12 mo is similar to patients less than 60 years of age.展开更多
Ulcerative colitis(UC)is a type of inflammatory bowel disease characterized by inflammation,ulcers and irritation of the mucosal lining.Oral drug delivery in UC encounters challenges because of multifaceted barriers.D...Ulcerative colitis(UC)is a type of inflammatory bowel disease characterized by inflammation,ulcers and irritation of the mucosal lining.Oral drug delivery in UC encounters challenges because of multifaceted barriers.Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes(Dexa-GP/ES/Pu NCs)have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota,and an underneath galactosylated-PLGA core(GP).The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C(MGL-2)surface receptor.Therefore,both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake.Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs.The nanocargoes were tested using in vitro,ex vivo techniques and dextran sodium sulfate(DSS)induced UC model.Prepared nanocargoes had desired physicochemical properties,drug release,cell uptake and cellular viability.Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2,and restoration of clinical,histopathological,biochemical indices,antioxidant balance,microbial alterations,FTIR spectra,and epithelial junctions’integrity.Thus,Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.展开更多
Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmenta...Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants(including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor(TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab(anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab(another anti-TNF-α agent), tofacitinib(a Janus kinase inhibitor), and vedolizumab and etrolizumab(integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC.展开更多
AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 ...AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5%(v/v) acetic acid.Twenty-four hours after exposed to acetic acid,rats were divided into three experimental groups:control group,attenuated Salmonella typhimurium Ty21a strain(SP) group and SP strain carrying human KGF gene(SPK) group,and they were separately administered orally with 10% NaHCO3,SP or SPK.Animals were sacrificed and colonic tissues were harvested respectively on day 3,5,7 and 10 after administration.Weights of rats,colonic weight/length ratio and stool score were evaluated.Histological changes of colonic tissues were examined by hematoxylin and eosin(HE) staining method.The expression of KGF,KGF receptor(KGFR) and TNF-α were measured either by enzyme-linked immunosorbent assay or Western blotting.Immunohistochemistry was used to detect the cellular localization of KGFR and Ki67.In addition,superoxide dismutase(SOD) activity and malondialdehyde(MDA) contents in the homogenate were measured.RESULTS:Body weight and colonic weight/length ratio were declined in SPK group compared with SP and control groups(body weight:272.78 ± 17.92 g vs 243.72 ± 14.02 g and 240.68 ± 12.63 g,P < 0.01;colonic weight/length ratio:115.76 ± 7.47 vs 150.32 ± 5.99 and 153.67 ± 5.50 mg/cm,P < 0.01).Moreover,pathological changes of damaged colon were improved in SPK group as well.After administration of SPK strain,KGF expression increased markedly from the 3rd d,and remained at a high level till the 10th d.Furthermore,KGFR expression and Ki67 expression elevated,whereas TNF-α expression was inhibited in SPK group.In the group administered with SPK,SOD activity increased significantly(d 5:26.18 ± 5.84 vs 18.12 ± 3.30 and 18.79 ± 4.74 U/mg,P < 0.01;d 7:35.48 ± 3.35 vs 22.57 ± 3.44 and 21.69 ± 3.94 U/mg,P < 0.01;d 10:46.10 ± 6.23 vs 25.35 ± 4.76 and 27.82 ± 6.42 U/mg,P < 0.01) and MDA contents decreased accordingly(d 7:7.40 ± 0.88 vs 9.81 ± 1.21 and 10.45 ± 1.40 nmol/mg,P < 0.01;d 10:4.36 ± 0.62 vs 8.41 ± 0.92 and 8.71 ± 1.27 nmol/mg,P < 0.01),compared with SP and control groups.CONCLUSION:KGF gene therapy mediated by attenuated Salmonella ameliorates ulcerative colitis induced by acetic acids,and it may be a safe and effective treatment for ulcerative colitis.展开更多
AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate imm...AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders"(n = 12) and "non-responders"(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, IL-1β, IL-6), immuno-regulatory(IL-10), Th1(IL-12, IFNγ) and Th2(IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.RESULTS Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy.展开更多
Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significan...Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis (UC) diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram (ECG) revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram (ECHO) revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries (< 3.5 mm). Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.展开更多
Of the diverse biological agents used for patients with ulcerative colitis, the anti-tumor necrosis factor-α agents infliximab and adalimumab have been used in large-scale clinical trials and are currently...Of the diverse biological agents used for patients with ulcerative colitis, the anti-tumor necrosis factor-α agents infliximab and adalimumab have been used in large-scale clinical trials and are currently widely used in the treatment of inflammatory bowel disease patients. Recent studies have indicated that golimumab, oral tofacitinib and vedolizumab reportedly achieved good clinical response and remission rates in ulcerative colitis patients. Thus, we believe that the detailed investigation of various studies on clinical trials may provide important information for the selection of appropriate biological agents, and therefore, we have extensively reviewed such trials in the present study.展开更多
The current ulcerative colitis (UC) treatment algorithm involves a step-up therapeutic strategy, mainly aiming at inducing and maintaining its clinical remission. Although this therapeutic strategy may seem to be co...The current ulcerative colitis (UC) treatment algorithm involves a step-up therapeutic strategy, mainly aiming at inducing and maintaining its clinical remission. Although this therapeutic strategy may seem to be cost-efficient and reduce the risk of side effects, recent trials and case reports have shown that top-down therapy using infliximab induces a rapid clinical response, enhances patient quality of life, promotes mucosal healing, reduces surgeries and indirect cost of treatment for patients with severe UC. Moreover, since long-term treatment with infliximab is safe and well tolerated, early aggressive top-down therapeutic strategy may be a more effective approach, at least in a subgroup of severe extensive UC patients.展开更多
AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn&...AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease (CD) and ulcerative colitis (UC).展开更多
For the optimal management of refractory ulcerative colitis(UC),secondary loss of response(LOR)and primary non-response to biologics is a critical issue.This article aimed to summarize the current literature on the us...For the optimal management of refractory ulcerative colitis(UC),secondary loss of response(LOR)and primary non-response to biologics is a critical issue.This article aimed to summarize the current literature on the use of cytapheresis(CAP)in patients with UC showing a poor response or LOR to biologics and discuss its advantages and limitations.Further,we summarized the efficacy of CAP in patients with UC showing insufficient response to thiopurines or immunomodulators(IM).Eight studies evaluated the efficacy of CAP in patients with UC with inadequate responses to thiopurines or IM.There were no significant differences in the rate of remission and steroid-free remission between patients exposed or not exposed to thiopurines or IM.Three studies evaluated the efficacy of CAP in patients with UC showing an insufficient response to biologic therapies.Mean remission rates of biologics exposed or unexposed patients were 29.4%and 44.2%,respectively.Fourteen studies evaluated the efficacy of CAP in combination with biologics in patients with inflammatory bowel disease showing a poor response or LOR to biologics.The rates of remission/response and steroid-free remission in patients with UC ranged 32%-69%(mean:48.0%,median:42.9%)and 9%-75%(mean:40.7%,median:38%),respectively.CAP had the same effectiveness for remission induction with or without prior failure on thiopurines or IM but showed little benefit in patients with UC refractory to biologics.Although heterogeneity existed in the efficacy of the combination therapy with CAP and biologics,these combination therapies induced clinical remission/response and steroid-free remission in more than 40%of patients with UC refractory to biologics on average.Given the excellent safety profile of CAP,this combination therapy can be an alternative therapeutic strategy for UC refractory to biologics.Extensive prospective studies are needed to understand the efficacy of combination therapy with CAP and biologics.展开更多
Novel coronavirus(SARS‑CoV‑2,SARS‑CoV‑2 for short)infection can cause a series of gastrointestinal damage.Related studies have reported that SARS‑CoV‑2 infection can lead to the occurrence and progression of ulcerativ...Novel coronavirus(SARS‑CoV‑2,SARS‑CoV‑2 for short)infection can cause a series of gastrointestinal damage.Related studies have reported that SARS‑CoV‑2 infection can lead to the occurrence and progression of ulcerative colitis,which may be related to the cytokine storm caused by SARS‑CoV‑2 infection.Recently,we have also paid attention to whether infection with SARS‑CoV‑2 will aggravate the condition of UC patients receiving biological immunotherapy and whether vaccination with SARS‑CoV‑2 is safe and effective for these patients.At present,the interaction mechanism between SARS‑CoV‑2,SARS‑CoV‑2 vaccine and ulcerative colitis is not fully understood,and more research is needed to further clarify the relationship.展开更多
Surgical therapy for ulcerative colitis(UC) depends on the medical therapy administered for the patient's condition. UC is a benign disease. However, it has been reported that the rare cases of cancer in UC patien...Surgical therapy for ulcerative colitis(UC) depends on the medical therapy administered for the patient's condition. UC is a benign disease. However, it has been reported that the rare cases of cancer in UC patients are increasing, and such cases have a worse prognosis. Recently, surgical therapy has greatly changed, there has been quite an increase in the number of UC patients with high-grade dysplasia and/or cancer. These lesions are known as colitis-associated cancer(CAC). The relationship between inflammation and tumorigenesis is well-established, and in the last decade, a great deal of supporting evidence has been obtained from genetic, pharmacological, and epidemiological studies. Inflammatory bowel disease, especially UC, is an important risk factor for the development of colon cancer. We should determine the risk factors for UC patients with cancer based on a large body of data, and we should attempt to prevent the increase in the number of such patients using these newly identified risk factors in the near future. Actively introducing the surgical treatment in addition to medical treatment should be considered. Several physicians should analyze UC from their unique perspectives in order to establish new clinically relevant diagnostic and treatment methods in the future. This article discusses CAC, including its etiology, mechanism, diagnosis, and treatment in UC patients.展开更多
BACKGROUND Drug shortages are common yet their impact on patient care and their commercial ramifications has not been adequately researched.In Australia a shortage of balsalazide(2012-2013)necessitated substitution wi...BACKGROUND Drug shortages are common yet their impact on patient care and their commercial ramifications has not been adequately researched.In Australia a shortage of balsalazide(2012-2013)necessitated substitution with alternative 5-aminosalicylate(5-ASA)formulations for ulcerative colitis(UC).AIM To assess and compare the clinical and commercial sequelae of non-medical switching from balsalazide to another 5-ASA and/or return to balsalazide once supply resumed.METHODS A prospective cohort study of patients on balsalazide for mild-moderate UC was conducted where,strictly due to the national shortage(November 2012-January 2013),were switched to alternative 5-ASA and/or then returned to balsalazide once supply resumed.Clinical(Partial Mayo),endoscopic(Mayo score)activity,adverse effects(to alternative 5-ASA)and percentage market share(of continuous 5-ASA users)from baseline(i.e.,time of switching due to shortage)through to five years were assessed.RESULTS Of 31 patients switched due to the shortage,12(38.7%)resumed balsalazide immediately once supply resumed,8(25.8%)prompted by adverse effects to the alternative 5-ASA used.Three patients(9.7%)had documented symptomatic improvement,15(48.4%)were unchanged and 13(41.9%)had symptomatic worsening vs baseline(P<0.01),after switching to an alternative 5-ASA.At 3 and 5y post switch,overall 26/31(83.9%)and 23/31(74.2%)had remained continuously on any 5-ASA therapy respectively.Twelve(38.7%)and 11(35.5%)patients remained on balsalazide continuously at three and five years respectively after drug supply returned,equating to a loss of market share(within 5-ASA class)of 45.2%and 38.7%respectively.CONCLUSION This study of a balsalazide shortage in UC patients exemplifies the detrimental impact of a drug shortage on long term patient,disease and commercial outcomes.展开更多
Objective:To construct the miRNA-mRNA regulatory network,andidentify more reliable therapeutic targets and potential drugs in ulcerative colitis associated colorectal cancer.Methods:Two datasets were downloaded from t...Objective:To construct the miRNA-mRNA regulatory network,andidentify more reliable therapeutic targets and potential drugs in ulcerative colitis associated colorectal cancer.Methods:Two datasets were downloaded from the GEO,and the differently expressed analysis were conducted by R software limma package.Functional enrichment analysis was performed using R software.The targets of differently expressed miRNAs were predicted by FunRich software,and the miRNA-mRNA regulatory network was constructed by Cytoscape software.The cMAP and TCMSP databases were used to predict small molecule drugs and traditional Chinese medicine respectively.Results:A total of 79 differently expressed miRNAs and 8865 differently expressed mRNAs were identified.Then the miRNA-mRNA regulatory network was constructed.Among DE miRNAs in the network,hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p may be the most significant due to their large number of connecting nodes in ulcerative colitis associated colorectal cancer.The integrated differently genes were mainly concentrated in protein processing in endoplasmic reticulum,ferroptosis and other signalingpathways.In addition,10 kinds of small molecule drugs and 6 kinds of traditional Chinese medicine were screened as therapeutic agents for ulcerative colitis associated colorectal cancer.Conclusion:hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p can be used as therapeutic targets forulcerative colitis associated colorectal cancer.The pathogenesis of ulcerative colitis associated colorectal cancer may be related to the protein processing in endoplasmic reticulum/ferroptosis signaling pathway,and it is predicted that 10 kinds of small molecule drugs,such asIsoflupredone,and 4 traditional Chinese medicines,such as Baiqucai(Celandine),Guanhuangbai(Cortex phellodendri amurensis),Huangbai(Phellodendron amurense)and Bajiaolian(Dysosma Versipellis),can be used as therapeutic drugs forulcerative colitis associated colorectal cancer.展开更多
AIM To observe the therapeutic effect ofmoxibustion on ulcerative colitis and itsinfluence on the colonic mucosal morphology.METHODS Forty-six patients with ulcerativecolitis were randomly divided into themoxibustion ...AIM To observe the therapeutic effect ofmoxibustion on ulcerative colitis and itsinfluence on the colonic mucosal morphology.METHODS Forty-six patients with ulcerativecolitis were randomly divided into themoxibustion with herbal medicine underneathgroup and the western medicine group.Thirtypatients were treated with the abovemoxibustion and 16 patients with Salicylayefapyridine(SASP).The colonic mucosa of 13patients in the moxibustion group was observedby colonoscopy before and after the treatment.Mucin was also analyzed by H.E and AB-PASstaining.RESULTS Seventeen patients were clinicallycured,12 were improved and 1 unchanged in themoxibustion group.In the control group,5patients were clinically cured,7 improved and 4unchanged.Thirteen patients with active UCwere taken as the subjects for histopathologicanalysis in this study.The colonic mucosallesions were remarkably improved and thecharacteristic of the mucin also changed.Inmost sections,the chronic inflammation ofmucosa was geatly ameliorated(P【0.01).Theinflammatory cell infiltratation much decreased and neutrophils,disapeared in most sections(P【0.001).The goblet cells significantlyincreased(P【0.001);crypt paracrypt abscessor mucosal ulceration was seen(P【0.001).CONCLUSION The rate of cure of ulcerative colitis by moxibustion with herbal medicine beneath is superior to that by SASP. This sort of moxibustion can effectively improve the colonic mucosal lesions and restore the proportion of mucoprotein to near normal.展开更多
文摘BACKGROUND Ulcerative colitis(UC)is an idiopathic,chronic inflammatory bowel disease(IBD)most often located in the rectum,but may involve the entire colon.Extra intestinal manifestations(EIMs)occur with varying frequency depending on the affected organ.The most common ones are musculoskeletal EIMs,affecting up to 33%-40%of IBD patients.These include,among others,inflammatory back pain,tendinitis,plantar fasciitis and arthritis.Only a few case reports in literature discuss Achilles tendinitis.CASE SUMMARY This report describes a patient with UC and Achilles tendinitis in whom after many unsuccessful attempts of treatment with sulfasalazine,mesalazine,glucocorticosteroids,infliximab and tofacitinib,a complete UC remission and resolution of Achilles tendinitis were achieved with the use of dual biologic therapy(DBT)-ustekinumab and adalimumab(ADA).CONCLUSION This case mentions rare EIMs of UC and suggests that DBT may be an alternative for patient with ulcerative colitis and EIMs.
文摘Inflammatory bowel disease,particularly ulcerative colitis(UC),poses significant treatment challenges due to its chronic nature and potential for severe complications.This editorial reviews a recent network meta-analysis that evaluated the efficacy of and highlighted the superior outcomes achieved by combining each of five traditional Chinese medicine(TCM)formulations with mesalazine for the adjuvant treatment of UC.Clinical outcomes included enhanced mucosal healing,improved quality of life,and reduced recurrence rates.Additionally,the combination therapy resulted in a lower incidence of adverse reactions compared with mesalazine monotherapy.Despite these promising results,limitations such as variability in study quality and TCM dosage highlight the need for further highquality,large-sample,multicenter randomized controlled trials.This editorial underscores the potential of TCM in enhancing UC management and calls for more rigorous research to substantiate these findings and refine clinical guidelines.
文摘BACKGROUND This was an observational, descriptive, and retrospective study from 2011 to 2020 from the Department of Informatics of the Brazilian Healthcare System database.AIM To describe the intestinal complications(IC) of patients with ulcerative colitis(UC) who started conventional therapies in Brazil’s public Healthcare system.METHODS Patients ≥ 18 years of age who had at least one claim related to UC 10th revision of the International Statistical Classification of Diseases and Related Health Problems(ICD-10) code and at least 2 claims for conventional therapies were included. IC was defined as at least one claim of: UC-related hospitalization, procedures code for rectum or intestinal surgeries, and/or associated disease defined by ICD-10 codes(malignant neoplasia of colon, stenosis, hemorrhage, ulcer and other rectum or anus disease, megacolon, functional diarrhea volvulus, intussusception and erythema nodosum). Descriptive statistics, annual incidence, and incidence rate(IR) [per 100 patient-years(PY)] over the available follow-up period were calculated.RESULTS In total, 41229 UC patients were included(median age, 48 years;65% women) and the median(interquartile range) follow-up period was 3.3(1.8-5.3) years. Conventional therapy used during follow-up period included: mesalazine(87%), sulfasalazine(15%), azathioprine(16%) or methotrexate(1%) with a median duration of 1.9(0.8-4.0) years. Overall IR of IC was 3.2 cases per 100 PY. Among the IC claims, 54% were related to associated diseases, 20% to procedures and 26% to hospitalizations. The overall annual incidence of IC was 2.9%, 2.6% and 2.5% in the first, second and third year after the first claim for therapy(index date), respectively. Over the first 3 years, the annual IR of UC-related hospitalizations ranged from 0.8% to 1.1%;associated diseases from 0.9% to 1.2%-in which anus or rectum disease, and malignant neoplasia of colon were the most frequently reported;and procedure events from 0.6% to 0.7%, being intestinal resection and polyp removal the most frequent ones.CONCLUSION Study shows that UC patients under conventional therapy seem to present progression of disease developing some IC, which may have a negative impact on patients and the burden on the health system.
文摘BACKGROUND There is paucity of data on outcomes of acute severe ulcerative colitis(ASUC)in older adults(≥60 years of age).AIM To assess steroid non-response rates during the index admission for ASUC in older adults.Secondary outcomes were response to medical rescue therapy and colectomy rates;at index admission,3 and 12 mo.METHODS This retrospective multicentre cohort study included ASUC admissions who received intravenous steroids between January 2013 and July 2020 at two tertiary hospitals.Electronic medical records were reviewed to collect clinical,biochemical,and endoscopic data.A modified Poisson regression model was used for analysis.RESULTS Of 226 ASUC episodes,45(19.9%)occurred in patients≥60 years of age.Steroid non-response rates were comparable in older adults and patients<60 years of age[19(42.2%)vs 85(47%),P=0.618],crude risk ratio(RR)=0.89[95%confidence interval(CI):0.61-1.30],adjusted RR=0.99(0.44-2.21).Rates of response to medical rescue therapy in older adults was comparable to the younger cohort[76.5%vs 85.7%,P=0.46,crude RR=0.89(0.67-1.17)].Index admission colectomy[13.3%vs 10.5%,P=0.598,crude RR=1.27(0.53-2.99),adjusted RR=1.43(0.34-6.06)],colectomy at 3 mo[20%vs 16.6%,P=0.66,crude RR=1.18(0.61-2.3),adjusted RR=1.31(0.32-0.53)]and colectomy at 12 mo[20%vs 23.2%,P=0.682,crude RR=0.85(0.45-1.57),adjusted RR=1.21(0.29-4.97)],were similar between the two groups.CONCLUSION In older adults with ASUC,the steroid non-response rate,response to medical rescue therapy,and colectomy rate at index admission,3 and 12 mo is similar to patients less than 60 years of age.
基金the Higher Education Commission of Pakistan for the provision of HEC Indigenous scholarship (PIN No. 315-12214-2BS3-132) for the research workthe provision of grant under HEC NRPU project No. 9272/Federal/NRPU/R&D/HEC/2017
文摘Ulcerative colitis(UC)is a type of inflammatory bowel disease characterized by inflammation,ulcers and irritation of the mucosal lining.Oral drug delivery in UC encounters challenges because of multifaceted barriers.Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes(Dexa-GP/ES/Pu NCs)have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota,and an underneath galactosylated-PLGA core(GP).The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C(MGL-2)surface receptor.Therefore,both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake.Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs.The nanocargoes were tested using in vitro,ex vivo techniques and dextran sodium sulfate(DSS)induced UC model.Prepared nanocargoes had desired physicochemical properties,drug release,cell uptake and cellular viability.Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2,and restoration of clinical,histopathological,biochemical indices,antioxidant balance,microbial alterations,FTIR spectra,and epithelial junctions’integrity.Thus,Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.
文摘Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants(including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor(TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab(anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab(another anti-TNF-α agent), tofacitinib(a Janus kinase inhibitor), and vedolizumab and etrolizumab(integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC.
基金Supported by Postdoctoral Science Foundation of China,No.20060390192,200801243research grant from Science and Technology Department of Gansu Province,China,No.0708NKCA128
文摘AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5%(v/v) acetic acid.Twenty-four hours after exposed to acetic acid,rats were divided into three experimental groups:control group,attenuated Salmonella typhimurium Ty21a strain(SP) group and SP strain carrying human KGF gene(SPK) group,and they were separately administered orally with 10% NaHCO3,SP or SPK.Animals were sacrificed and colonic tissues were harvested respectively on day 3,5,7 and 10 after administration.Weights of rats,colonic weight/length ratio and stool score were evaluated.Histological changes of colonic tissues were examined by hematoxylin and eosin(HE) staining method.The expression of KGF,KGF receptor(KGFR) and TNF-α were measured either by enzyme-linked immunosorbent assay or Western blotting.Immunohistochemistry was used to detect the cellular localization of KGFR and Ki67.In addition,superoxide dismutase(SOD) activity and malondialdehyde(MDA) contents in the homogenate were measured.RESULTS:Body weight and colonic weight/length ratio were declined in SPK group compared with SP and control groups(body weight:272.78 ± 17.92 g vs 243.72 ± 14.02 g and 240.68 ± 12.63 g,P < 0.01;colonic weight/length ratio:115.76 ± 7.47 vs 150.32 ± 5.99 and 153.67 ± 5.50 mg/cm,P < 0.01).Moreover,pathological changes of damaged colon were improved in SPK group as well.After administration of SPK strain,KGF expression increased markedly from the 3rd d,and remained at a high level till the 10th d.Furthermore,KGFR expression and Ki67 expression elevated,whereas TNF-α expression was inhibited in SPK group.In the group administered with SPK,SOD activity increased significantly(d 5:26.18 ± 5.84 vs 18.12 ± 3.30 and 18.79 ± 4.74 U/mg,P < 0.01;d 7:35.48 ± 3.35 vs 22.57 ± 3.44 and 21.69 ± 3.94 U/mg,P < 0.01;d 10:46.10 ± 6.23 vs 25.35 ± 4.76 and 27.82 ± 6.42 U/mg,P < 0.01) and MDA contents decreased accordingly(d 7:7.40 ± 0.88 vs 9.81 ± 1.21 and 10.45 ± 1.40 nmol/mg,P < 0.01;d 10:4.36 ± 0.62 vs 8.41 ± 0.92 and 8.71 ± 1.27 nmol/mg,P < 0.01),compared with SP and control groups.CONCLUSION:KGF gene therapy mediated by attenuated Salmonella ameliorates ulcerative colitis induced by acetic acids,and it may be a safe and effective treatment for ulcerative colitis.
文摘AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders"(n = 12) and "non-responders"(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, IL-1β, IL-6), immuno-regulatory(IL-10), Th1(IL-12, IFNγ) and Th2(IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.RESULTS Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy.
文摘Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis (UC) diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram (ECG) revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram (ECHO) revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries (< 3.5 mm). Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.
基金Supported by Grants from Wonkwang University in 2013
文摘Of the diverse biological agents used for patients with ulcerative colitis, the anti-tumor necrosis factor-α agents infliximab and adalimumab have been used in large-scale clinical trials and are currently widely used in the treatment of inflammatory bowel disease patients. Recent studies have indicated that golimumab, oral tofacitinib and vedolizumab reportedly achieved good clinical response and remission rates in ulcerative colitis patients. Thus, we believe that the detailed investigation of various studies on clinical trials may provide important information for the selection of appropriate biological agents, and therefore, we have extensively reviewed such trials in the present study.
文摘The current ulcerative colitis (UC) treatment algorithm involves a step-up therapeutic strategy, mainly aiming at inducing and maintaining its clinical remission. Although this therapeutic strategy may seem to be cost-efficient and reduce the risk of side effects, recent trials and case reports have shown that top-down therapy using infliximab induces a rapid clinical response, enhances patient quality of life, promotes mucosal healing, reduces surgeries and indirect cost of treatment for patients with severe UC. Moreover, since long-term treatment with infliximab is safe and well tolerated, early aggressive top-down therapeutic strategy may be a more effective approach, at least in a subgroup of severe extensive UC patients.
基金Supported by TAMOP-4.2.2.A-11/1/KONV-2012-0035,TA-MOP-4.2.2-A-11/1/KONV-2012-0052 TAMOP-4.2.2.A-11/1/KONV-2012-0073OTKA Research Proposal PD 105948(PI:Klaudia Farkas)
文摘AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease (CD) and ulcerative colitis (UC).
文摘For the optimal management of refractory ulcerative colitis(UC),secondary loss of response(LOR)and primary non-response to biologics is a critical issue.This article aimed to summarize the current literature on the use of cytapheresis(CAP)in patients with UC showing a poor response or LOR to biologics and discuss its advantages and limitations.Further,we summarized the efficacy of CAP in patients with UC showing insufficient response to thiopurines or immunomodulators(IM).Eight studies evaluated the efficacy of CAP in patients with UC with inadequate responses to thiopurines or IM.There were no significant differences in the rate of remission and steroid-free remission between patients exposed or not exposed to thiopurines or IM.Three studies evaluated the efficacy of CAP in patients with UC showing an insufficient response to biologic therapies.Mean remission rates of biologics exposed or unexposed patients were 29.4%and 44.2%,respectively.Fourteen studies evaluated the efficacy of CAP in combination with biologics in patients with inflammatory bowel disease showing a poor response or LOR to biologics.The rates of remission/response and steroid-free remission in patients with UC ranged 32%-69%(mean:48.0%,median:42.9%)and 9%-75%(mean:40.7%,median:38%),respectively.CAP had the same effectiveness for remission induction with or without prior failure on thiopurines or IM but showed little benefit in patients with UC refractory to biologics.Although heterogeneity existed in the efficacy of the combination therapy with CAP and biologics,these combination therapies induced clinical remission/response and steroid-free remission in more than 40%of patients with UC refractory to biologics on average.Given the excellent safety profile of CAP,this combination therapy can be an alternative therapeutic strategy for UC refractory to biologics.Extensive prospective studies are needed to understand the efficacy of combination therapy with CAP and biologics.
基金In‑Hospital Fund Project of No.940 Hospital(NO.20yjky020)General Research Fund Project of Huoshenshan Hospital(NO.HSS‑217)Gansu Provincial Science and Technology Department Social Development Department Clinical Medicine Research Center Project(NO.21JR7RA017)。
文摘Novel coronavirus(SARS‑CoV‑2,SARS‑CoV‑2 for short)infection can cause a series of gastrointestinal damage.Related studies have reported that SARS‑CoV‑2 infection can lead to the occurrence and progression of ulcerative colitis,which may be related to the cytokine storm caused by SARS‑CoV‑2 infection.Recently,we have also paid attention to whether infection with SARS‑CoV‑2 will aggravate the condition of UC patients receiving biological immunotherapy and whether vaccination with SARS‑CoV‑2 is safe and effective for these patients.At present,the interaction mechanism between SARS‑CoV‑2,SARS‑CoV‑2 vaccine and ulcerative colitis is not fully understood,and more research is needed to further clarify the relationship.
文摘Surgical therapy for ulcerative colitis(UC) depends on the medical therapy administered for the patient's condition. UC is a benign disease. However, it has been reported that the rare cases of cancer in UC patients are increasing, and such cases have a worse prognosis. Recently, surgical therapy has greatly changed, there has been quite an increase in the number of UC patients with high-grade dysplasia and/or cancer. These lesions are known as colitis-associated cancer(CAC). The relationship between inflammation and tumorigenesis is well-established, and in the last decade, a great deal of supporting evidence has been obtained from genetic, pharmacological, and epidemiological studies. Inflammatory bowel disease, especially UC, is an important risk factor for the development of colon cancer. We should determine the risk factors for UC patients with cancer based on a large body of data, and we should attempt to prevent the increase in the number of such patients using these newly identified risk factors in the near future. Actively introducing the surgical treatment in addition to medical treatment should be considered. Several physicians should analyze UC from their unique perspectives in order to establish new clinically relevant diagnostic and treatment methods in the future. This article discusses CAC, including its etiology, mechanism, diagnosis, and treatment in UC patients.
文摘BACKGROUND Drug shortages are common yet their impact on patient care and their commercial ramifications has not been adequately researched.In Australia a shortage of balsalazide(2012-2013)necessitated substitution with alternative 5-aminosalicylate(5-ASA)formulations for ulcerative colitis(UC).AIM To assess and compare the clinical and commercial sequelae of non-medical switching from balsalazide to another 5-ASA and/or return to balsalazide once supply resumed.METHODS A prospective cohort study of patients on balsalazide for mild-moderate UC was conducted where,strictly due to the national shortage(November 2012-January 2013),were switched to alternative 5-ASA and/or then returned to balsalazide once supply resumed.Clinical(Partial Mayo),endoscopic(Mayo score)activity,adverse effects(to alternative 5-ASA)and percentage market share(of continuous 5-ASA users)from baseline(i.e.,time of switching due to shortage)through to five years were assessed.RESULTS Of 31 patients switched due to the shortage,12(38.7%)resumed balsalazide immediately once supply resumed,8(25.8%)prompted by adverse effects to the alternative 5-ASA used.Three patients(9.7%)had documented symptomatic improvement,15(48.4%)were unchanged and 13(41.9%)had symptomatic worsening vs baseline(P<0.01),after switching to an alternative 5-ASA.At 3 and 5y post switch,overall 26/31(83.9%)and 23/31(74.2%)had remained continuously on any 5-ASA therapy respectively.Twelve(38.7%)and 11(35.5%)patients remained on balsalazide continuously at three and five years respectively after drug supply returned,equating to a loss of market share(within 5-ASA class)of 45.2%and 38.7%respectively.CONCLUSION This study of a balsalazide shortage in UC patients exemplifies the detrimental impact of a drug shortage on long term patient,disease and commercial outcomes.
文摘Objective:To construct the miRNA-mRNA regulatory network,andidentify more reliable therapeutic targets and potential drugs in ulcerative colitis associated colorectal cancer.Methods:Two datasets were downloaded from the GEO,and the differently expressed analysis were conducted by R software limma package.Functional enrichment analysis was performed using R software.The targets of differently expressed miRNAs were predicted by FunRich software,and the miRNA-mRNA regulatory network was constructed by Cytoscape software.The cMAP and TCMSP databases were used to predict small molecule drugs and traditional Chinese medicine respectively.Results:A total of 79 differently expressed miRNAs and 8865 differently expressed mRNAs were identified.Then the miRNA-mRNA regulatory network was constructed.Among DE miRNAs in the network,hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p may be the most significant due to their large number of connecting nodes in ulcerative colitis associated colorectal cancer.The integrated differently genes were mainly concentrated in protein processing in endoplasmic reticulum,ferroptosis and other signalingpathways.In addition,10 kinds of small molecule drugs and 6 kinds of traditional Chinese medicine were screened as therapeutic agents for ulcerative colitis associated colorectal cancer.Conclusion:hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p can be used as therapeutic targets forulcerative colitis associated colorectal cancer.The pathogenesis of ulcerative colitis associated colorectal cancer may be related to the protein processing in endoplasmic reticulum/ferroptosis signaling pathway,and it is predicted that 10 kinds of small molecule drugs,such asIsoflupredone,and 4 traditional Chinese medicines,such as Baiqucai(Celandine),Guanhuangbai(Cortex phellodendri amurensis),Huangbai(Phellodendron amurense)and Bajiaolian(Dysosma Versipellis),can be used as therapeutic drugs forulcerative colitis associated colorectal cancer.
基金the National Science Foudation of China,No.39670899.39970922
文摘AIM To observe the therapeutic effect ofmoxibustion on ulcerative colitis and itsinfluence on the colonic mucosal morphology.METHODS Forty-six patients with ulcerativecolitis were randomly divided into themoxibustion with herbal medicine underneathgroup and the western medicine group.Thirtypatients were treated with the abovemoxibustion and 16 patients with Salicylayefapyridine(SASP).The colonic mucosa of 13patients in the moxibustion group was observedby colonoscopy before and after the treatment.Mucin was also analyzed by H.E and AB-PASstaining.RESULTS Seventeen patients were clinicallycured,12 were improved and 1 unchanged in themoxibustion group.In the control group,5patients were clinically cured,7 improved and 4unchanged.Thirteen patients with active UCwere taken as the subjects for histopathologicanalysis in this study.The colonic mucosallesions were remarkably improved and thecharacteristic of the mucin also changed.Inmost sections,the chronic inflammation ofmucosa was geatly ameliorated(P【0.01).Theinflammatory cell infiltratation much decreased and neutrophils,disapeared in most sections(P【0.001).The goblet cells significantlyincreased(P【0.001);crypt paracrypt abscessor mucosal ulceration was seen(P【0.001).CONCLUSION The rate of cure of ulcerative colitis by moxibustion with herbal medicine beneath is superior to that by SASP. This sort of moxibustion can effectively improve the colonic mucosal lesions and restore the proportion of mucoprotein to near normal.