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Moxibustion improves experimental colitis in rats with crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor

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Journal of Integrative Medicine 2023年第2期21卷 194-204页

作者： Jia-cheng shen Qin Qi Dong Han Yuan Lu Rong Huang Yi Zhu Lin-shan Zhang Xiu-di Qin Fang Zhang Huan-gan Wu Hui-rong Liu Key Laboratory of Acupuncture and Immunological Effects Shanghai University of Traditional Chinese MedicineShanghai 200030China shanghai Research Institute of Acupuncture and Meridian Shanghai 200030China

Objective:This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn’s disease(CD)regulated by moxibustion through bile acid(BA)enterohepatic circulation and intestinal farnesoid X receptor(FXR).Methods:sprague-Dawley rats were randomly divided into control group,CD model group,mild moxibustion group and herb-partitioned moxibustion group.CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu(sT25)and Qihai(CV6).The changes in CD symptoms were rated according to the disease activity index score,the serum and colon tissues of rats were collected,and the pathological changes in colon tissues were observed via histopathology.Western blot,immunohistochemistry(IHC)and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway.Results:Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD,inhibited inflammation and repaired mucosal damage to the colon in CD rats.Meanwhile,moxibustion could improve the abnormal expression of BA in the colon,liver and serum,downregulate the expression of interferon-γand upregulate the expression of FXR mRNA,and inhibit Toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88)mRNA.The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression.Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR.Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65.In particular,herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon.Conclusion:Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA,activating colonic F

关键词： Crohn’s disease Moxibustion Bile acid Farnesoid X receptor Colitis Intestinal mucosal barrier

Joint Detection of serum Vitamin D,Body Mass Index,and Tumor Necrosis Factor Alpha for the Diagnosis of Crohn’s disease

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当代医学科学(英文) 2023年第3期43卷 496-504页

作者： Ying ZHENG Jing-hong LI shan-ying LIAO Yi-ming FU Yan-jun ZHANG Jun-long LIN Xin-bin CHEN Wei-hong sHA shi-xue DAI Wen-jun MA Department of Nutrition Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou510080China The second school of Clinical Medicine Southern Medical UniversityGuangzhou 510080China Department of Gastroenterology Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080China The First school of Clinical Medicine&Nanfang Hospital Southern Medical UniversityGuangzhou 510080China Department of Gastroenterology Guangdong Provincial Geriatrics InstituteNational Key Clinical SpecialtyGuangdong Provincial People's HospitalGuangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080China

Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(Ps under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.

关键词： Crohn’s disease vitamin D body mass index tumor necrosis factor alpha

Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn’s disease

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World Journal of stem Cells 2024年第3期16卷 257-266页

作者： Min Young Park Yong sik Yoon Jae Ha Park Jong Lyul Lee Chang sik Yu Division of Colon and Rectal surgery Department of SurgeryYonsei University College of MedicineSeoul 03722South Korea Division of Colon and Rectal surgery Department of SurgeryUniversity of Ulsan College of MedicineAsan Medical CenterSeoul 05505South Korea

BACKGROUND stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.However,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure.AIM This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and recurrence.METHODs The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled.Clinical data were compared according to anti-TNF therapy and CPF closure.REsULTs A total of 65 patients were included.The median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)patients.The closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).Clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for closure.The cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,respectively.CONCLUsION Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation.However,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy.Fistulous tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.

关键词： Crohn’s disease Anus Fistula stem cell transplantation Tumor necrosis factor-alpha inhibitors Infliximab

Acupuncture and Moxibustion Inhibited Intestinal Epithelial-Mesenchymal Transition in Patients with crohn's disease Induced by TGF-β1/smad3/snail Pathway:A Clinical Trial study

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Chinese Journal of Integrative Medicine 2022年第9期28卷 823-832页

作者： GUO sen ZHOU Jing ZHANG Liang BAO Chun-hui ZHAO Ji-meng GAO Yan-ling WU Pin WENG Zhijun sHI Yin Graduate school Shanghai University of Traditional Chinese MedicineShanghai201203China Department of Acupuncture and Moxibustion Shanghai Shanghai Traditional Chinese Medicine Integrated HospitalShanghai University of Traditional Chinese MedicineShanghai200082China Department of Acupuncture and Moxibustion Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese MedicineShanghai200437China Key Laboratory of Acupuncture and Immunological Effects Shanghai Research Institute of Acupuncture and MeridianShanghai200030China Outpatient Department Shanghai Research Institute of Acupuncture and MeridianShanghai200030China

Objective:To explore whether acupuncture combined with moxibustion could inhibit epithelialmesenchymal transition in Crohn’s disease by affecting the transforming growth factorβ1(TGF-β1)/smad3/snail pathway.Methods:sixty-three patients with Crohn’s disease were randomly divided into an observation group(31 cases)receiving moxibustion at 43℃ combined with acupuncture,and a control group(32 cases)receiving moxibustion at 37℃combined with sham acupuncture using a random number table.Patients were treated for12 weeks.Crohn’s disease Activity Index(CDAI)was used to evaluate disease activity.Hematoxylin-eosin staining and transmission electron microscopy were utilized to observe the morphological and ultrastructural changes.Immunohistochemistry was used to detect the expression of transforming growth factorβ1(TGF-β1),TβR1,TβR2,smad3,snail,E-cadherin and fibronectin in intestinal mucosal tissues.Results:The decrease of the CDAI score,morphological and ultrastructural changes were more significant in observation group.The expression levels of TGF-β1,TβR2,smad3,and snail in the observation group were significantly lower than those before the treatment(Pssion levels of TGF-β1,TβR2,and snail in the observation group were significantly lower than those in the control group(all Pssion of fibronectin in the observation group was significantly decreased,and the expression of E-cadherin was significantly increased(all Psions:Moxibustion at 43℃combined with acupuncture may suppress TGF-β1/smad3/snail pathway-mediated epithelial-mesenchymal transition of intestinal epithelial cells in Crohn’s disease patients by inhibiting the expression levels of TGF-β1,TβR2,smad3,and snail.(Registration No.ChiCTR-IIR-16007751).

关键词： Crohn’s disease moxibustion acupuncture transforming growth factorβ1/smad3/snail pathway intestinal epithelial-mesenchymal transition

Pregnancy and Crohn’s disease:concerns and assurance of medical therapy

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Gastroenterology Report 2022年第1期10卷 171-177页

作者： Reezwana Chowdhury sunanda V.Kane Division of Gastroenterology and Hepatology Department of MedicineJohns Hopkins UniversityBaltimoreMDUSA Division of Gastroenterology and Hepatology Department of MedicineMayo ClinicRochesterMNUSA

Approximately 50%of patients with inflammatory bowel disease including both Crohn’s disease and ulcerative colitis are female with many being diagnosed and treated during their reproductive years.It is important for women to be in remission prior to and during pregnancy.There have been many advances in the treatment of inflammatory bowel disease,including new therapies.In this review,we summarize the currently approved medications for Crohn’s disease and their safety in pregnancy and postpartum.The totality of evidence suggests that the majority of therapies are low-risk before and during pregnancy,and should be continued to control maternal disease.

关键词： Crohn’s disease pregnancy teratogenicity inflammatory bowel disease lactation biologics anti-TNF

Pediatric stricturing crohn's disease

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World Journal of Gastroenterology 2024年第12期30卷 1651-1654页

作者： Alessandro Boscarelli Matteo Bramuzzo Department of Pediatric surgery and Urology Institute for Maternal and Child Health-IRCCS“Burlo Garofolo”Trieste 34137Italy Department of Gastrointestinal Endoscopy and Nutrition Institute for Maternal and Child Health-IRCCS"Burlo Garofolo"Trieste 34137Italy

Crohn’s disease(CD)is a chronic inflammatory disease of the digestive tract.The incidence of pediatric CD is increasing and is currently 2.5-11.4 per 100000 world-wide.Notably,approximately 25%of children with CD develop stricturing CD(sCD)that requires intervention.symptomatic stricturing diseases refractory to pharmacological management frequently require non-pharmacological interventions.Non-pharmacological therapeutic strategies include endoscopic balloon dilatation,stricturoplasty,and surgical resection of the strictured seg-ment.However,strictures tend to recur postoperatively regardless of treatment modality.The lifetime risk of surgery in patients with childhood sCD remains at 50%-90%.Thus,new and emerging strategies,advanced diagnostic tools,and minimally invasive approaches are under investigation to improve the outcomes and overall quality of life of pediatric patients with sCD.

关键词： stricturing Crohn’s disease Pediatrics Insights Future perspectives

Early proactive monitoring of DNA-thioguanine in patients with Crohn’s disease predicts thiopurine-induced late leucopenia in NUDT15/TPMT normal metabolizers

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World Journal of Gastroenterology 2024年第12期30卷 1751-1763页

作者： Ting Yang Kang Chao Xia Zhu Xue-Ding Wang sumyuet Chan Yan-Ping Guan Jing Mao Pan Li shao-Xing Guan Wen Xie Xiang Gao Min Huang school of Pharmaceutical sciences Sun Yat-sen UniversityGuangzhou 510006Guangdong ProvinceChina Institute of Clinical Pharmacology Sun Yat-sen UniversityGuangzhou 510006Guangdong ProvinceChina Department of Gastroenterology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655Guangdong ProvinceChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080Guangdong ProvinceChina Center for Pharmacogenetics and Department of Pharmaceutical sciences University of PittsburghPittsburghPA 15261United States

BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODs Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte counts.REsULTs Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUsION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.

关键词： Thiopurine-induced late leucopenia DNA-thioguanine 6-thioguanine nucleotide Proactive therapeutic drug monitoring Crohn’s disease

Predicting short-term major postoperative complications in intestinal resection for Crohn’s disease:A machine learning-based study

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World Journal of Gastrointestinal surgery 2024年第3期16卷 717-730页

作者： Fang-Tao Wang Yin Lin Xiao-Qi Yuan Ren-Yuan Gao Xiao-Cai Wu Wei-Wei Xu Tian-Qi Wu Kai Xia Yi-Ran Jiao Lu Yin Chun-Qiu Chen Diagnostic and Treatment Center for Refractory diseases of Abdomen surgery Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China

BACKGROUND Due to the complexity and numerous comorbidities associated with Crohn’s disease(CD),the incidence of postoperative complications is high,significantly impacting the recovery and prognosis of patients.Consequently,additional stu-dies are required to precisely predict short-term major complications following intestinal resection(IR),aiding surgical decision-making and optimizing patient care.AIM To construct novel models based on machine learning(ML)to predict short-term major postoperative complications in patients with CD following IR.METHODs A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022.The study participants were randomly allocated to either a training cohort or a validation cohort.The logistic regression and random forest(RF)were applied to construct models in the training cohort,with model discrimination evaluated using the area under the curves(AUC).The validation cohort assessed the performance of the constructed models.REsULTs Out of the 259 patients encompassed in the study,5.0%encountered major postoperative complications(Clavien-Dindo≥III)within 30 d following IR for CD.The AUC for the logistic model was 0.916,significantly lower than the AUC of 0.965 for the RF model.The logistic model incorporated a preoperative CD activity index(CDAI)of≥220,a diminished preoperative serum albumin level,conversion to laparotomy surgery,and an extended operation time.A nomogram for the logistic model was plotted.Except for the surgical approach,the other three variables ranked among the top four important variables in the novel ML model.CONCLUsION Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complic-ations in patients with CD,with the RF model showing more superiority.A preoperative CDAI of≥220,a di-minished preoperative serum albumin level,and an extended operation time might be the most crucial variables.The findings of this study can assist clinicians in

关键词： Crohn’s disease Postoperative complications Nomogram Random forest Intestinal resection

Interventional inflammatory bowel disease:endoscopic therapy of complications of Crohn’s disease

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Gastroenterology Report 2022年第1期10卷 145-154页

作者： Bo shen Center for Inflammatory Bowel disease Columbia University Irving Medical Center/New York-Presbyterian HospitalNew YorkNYUSA

Endoscopic therapy for inflammatory bowel diseases(IBD)or IBD surgery-associated complications or namely interventional IBD has become the main treatment modality for Crohn’s disease,bridging medical and surgical treatments.Currently,the main applications of interventional IBD are(i)strictures;(ii)fistulas and abscesses;(iii)bleeding lesions,bezoars,foreign bodies,and polyps;(iv)post-operative complications such as acute and chronic anastomotic leaks;and(v)colitis-associated neoplasia.The endoscopic treatment modalities include balloon dilation,stricturotomy,strictureplasty,fistulotomy,incision and drainage(of fistula and abscess),sinusotomy,septectomy,banding ligation,clipping,polypectomy,endoscopic mucosal resection,and endoscopic submucosal dissection.The field of interventional IBD is evolving with a better understanding of the underlying disease process,advances in endoscopic technology,and interest and proper training of next-generation IBD interventionalists.

关键词： Crohn’s disease complication balloon dilation endoscopy fistula fistulotomy sinusotomy stricture strictureplasty stricturotomy therapy