BACKGROUND Thalidomide is an effective treatment for refractory Crohn’s disease(CD).However,thalidomide-induced peripheral neuropathy(TiPN),which has a large individual variation,is a major cause of treatment failure...BACKGROUND Thalidomide is an effective treatment for refractory Crohn’s disease(CD).However,thalidomide-induced peripheral neuropathy(TiPN),which has a large individual variation,is a major cause of treatment failure.TiPN is rarely predictable and recognized,especially in CD.It is necessary to develop a risk model to predict TiPN occurrence.AIM To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic variables.METHODS A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the model.The National Cancer Institute Common Toxicity Criteria Sensory Scale(version 4.0)was used to assess TiPN.With 18 clinical features and 150 genetic variables,five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve(AUROC),area under the precision-recall curve(AUPRC),specificity,sensitivity(recall rate),precision,accuracy,and F1 score.RESULTS The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248[P=0.0004,odds ratio(OR):8.983,95%confidence interval(CI):2.497-30.90],dose(mg/d,P=0.002),brainderived neurotrophic factor(BDNF)rs2030324(P=0.001,OR:3.164,95%CI:1.561-6.434),BDNF rs6265(P=0.001,OR:3.150,95%CI:1.546-6.073)and BDNF rs11030104(P=0.001,OR:3.091,95%CI:1.525-5.960).In the training set,gradient boosting decision tree(GBDT),extremely random trees(ET),random forest,logistic regression and extreme gradient boosting(XGBoost)obtained AUROC values>0.90 and AUPRC>0.87.Among these models,XGBoost and GBDT obtained the first two highest AUROC(0.90 and 1),AUPRC(0.98 and 1),accuracy(0.96 and 0.98),precision(0.90 and 0.95),F1 score(0.95 and 0.98),specificity(0.94 and 0.97),and sensitivity(1).In the validation set,XGBoost algorithm exhibited the best predictive performance with the highest specificity(0.857),accuracy(0.818),AUPRC(0.86)and AUROC(0.89).ET and GBDT obtained the highest sensitivity(1)and F1 score(0.8).Overall,compared with other state-of-the-art classifiers such as ET,GBDT and RF,XGBoost algorithm not only showed a more stable performance,but also yielded higher ROC-AUC and PRC-AUC scores,demonstrating its high accuracy in prediction of TiPN occurrence.CONCLUSION The powerful XGBoost algorithm accurately predicts TiPN using 18 clinical features and 14 genetic variables.With the ability to identify high-risk patients using single nucleotide polymorphisms,it offers a feasible option for improving thalidomide efficacy in CD patients.展开更多
AIM: To investigate the population-based prevalence of fatty liver disease (FLD) and its risk factors in Guangdong Province,China. METHODS: A cross-sectional survey with multiple-stage stratified cluster and random sa...AIM: To investigate the population-based prevalence of fatty liver disease (FLD) and its risk factors in Guangdong Province,China. METHODS: A cross-sectional survey with multiple-stage stratified cluster and random sampling of inhabitants over 7-year-old was performed in 6 urban and rural areas of Guangdong Province,China. Questionnaires,designed by co-working of epidemiologists and hepatologists,included demographic characteristics,current medication use,medical history and health-relevant behaviors,i.e. alcohol consumption,smoking habits,dietary habits and physical activities. Anthropometric measurements,biochemical tests and abdominal ultrasonography were carried out. RESULTS: Among the 3543 subjects,609 (17.2%) were diagnosed having FLD (18.0% males,16.7% females,P > 0.05). Among them,the prevalence of confirmed alcoholic liver disease (ALD),suspected ALD and nonalcoholic fatty liver disease (NAFLD) were 0.4%,1.8%,and 15.0%,respectively. The prevalence rate (23.0%) was significantly higher in urban areas than (12.9%) in rural areas. After adjustment for age,gender and residency,the standardized prevalence of FLD in adults was 14.5%. Among them,confirmed ALD,suspected ALD and NAFLD were 0.5%,2.3%,and 11.7%,respectively,in adults and 1.3% (all NAFLD) in children at the age of 7-18 years. The overall prevalence of FLD increased with age in both genders to the peak of 27.4% in the group of subjects at the age of 60-70 years. The prevalence rate was significantly higher in men than in women under the age of 50 years (22.4% vs 7.1%,P < 0.001). However,the opposite phenomenon was found over the age of 50 years (20.6% vs 27.6%,P < 0.05). Multivariate and logistic regression analysis indicated that male gender,urban residency,low education,high blood pressure,body mass index,waist circumference,waist to hip ratio,serum triglyceride and glucose levels were the risk factors for FLD. CONCLUSION: FLD,especially NAFLD,is prevalent in South China. There are many risk factors for FLD.展开更多
AIM:To evaluate potential risk factors in the development of ulcerative colitis(UC) in China.METHODS:A total of 1308 patients with UC and 1308 age-matched and sex-matched controls were prospectively studied in China.T...AIM:To evaluate potential risk factors in the development of ulcerative colitis(UC) in China.METHODS:A total of 1308 patients with UC and 1308 age-matched and sex-matched controls were prospectively studied in China.The UC cases were collected from 17 hospitals in China from April 2007 to April 2010.Uniform questionnaires were designed to investigate risk factors including smoking,appendectomy,stress,socio-economic conditions,nonsteroidal antiinflammatory drugs(NSAIDs),oral contraceptives,diet,breastfeeding,infections and family sanitary conditions.Group comparisons by each factor were done using simple logistic regression analysis.Conditional logistic regression was used for multivariate analysis.RESULTS:By univariate analysis,the variables predictive of UC included feeling stress,light and heavy alcoholic drinking,spicy food,sugar consumption and infectious diarrhea,while heavy tea intake and tap water consumption were protective against UC.On multivariate analysis,the protective factor for UC was tap water consumption [odds ratios(OR) = 0.424,95%CI:0.302-0.594,P < 0.001];while the potential risk factors for UC were heavy sugar consumption(OR = 1.632,95%CI:1.156-2.305,P < 0.001),spicy food(light intake:OR = 3.329,95%CI:2.282-4.857,P < 0.001;heavy intake:OR = 3.979,95%CI:2.700-5.863,P < 0.001),and often feeling stress(OR = 1.981,95%CI:1.447-2.711,P < 0.001).Other factors,such as smoking habit,appendectomy,breastfeeding,a history of measles,rural or urban residence,education,oral contraceptives,and NSAID use have not been found to have a significant association with the development of UC in the present study.CONCLUSION:Our study showed tap water consumption was a protective factor for UC,while spicy food,heavy sugar consumption and often feeling stress were risk factors for UC in this Chinese population.展开更多
AIM： To investigate the single nucleotide polymorphism （SNPs） distribution of NOD2/CARD15 （R702W, G908R）, OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease （IBD）. METHODS： A to...AIM： To investigate the single nucleotide polymorphism （SNPs） distribution of NOD2/CARD15 （R702W, G908R）, OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease （IBD）. METHODS： A total of 61 patients with Crohn＇s disease （CD）, 151 patients with ulcerative colitis （UC）, and 200 unrelated healthy controls were genotyped. Genotyping was performed by sequence specific primer polymerase chain reaction （PCR-SSP） or by restriction fragment length polymorphism （PCR-RFLP） analysis. RESULTS： Among the subjects in our study groups, including patients with CD, UC and healthy controls, none had OCTN and CARD15 variants and very rare IBD family history was found in our patients with the percentage of 0 （0/61 with CD） and 1.3% （2/151 with UC）. CONCLUSION： Our results indicate that although OCTN or CARD15 variation is associated with susceptibility to IBD in Western populations, these might be rare and may not be associated with susceptibility to IBD in Chinese patients.展开更多
AIM: To study the evolution of gastrointestinal symptoms and associated factors in Chinese patients with functional dyspepsia (FD).METHODS: From June 2008 to November 2009, a total of 1049 patients with FD (65.3% fema...AIM: To study the evolution of gastrointestinal symptoms and associated factors in Chinese patients with functional dyspepsia (FD).METHODS: From June 2008 to November 2009, a total of 1049 patients with FD (65.3% female, mean age 42.80 ± 11.64 years) who visited the departments of gastroenterology in Wuhan, Beijing, Shanghai, Guangzhou, and Xi’an, China were referred for this study. All of the patients fulfilled the Rome III criteria for FD. Baseline demographic data, dyspepsia symptoms, anxiety, depression, sleep disorder, and drug treatment were assessed using self-report questionnaires. Patients completed questionnaires at baseline and after 1, 3, 6 and 12 mo follow-up. Comparison of dyspepsia symptoms between baseline and after follow-up was explored using multivariate analysis of variance of repeated measuring. Multiple linear regression was done to examine factors associated with outcome, both longitudinally and horizontally.RESULTS: Nine hundred and forty-three patients (89.9% of the original population) completed all four follow-ups. The average duration of follow-up was 12.24 ± 0.59 mo. During 1-year follow-up, the mean dyspeptic symptom score (DSS) in FD patients showed a significant gradually reduced trend (P < 0.001), and similar differences were found for all individual symptoms (P < 0.001). Multiple linear regression analysis showed that sex (P < 0.001), anxiety (P = 0.018), sleep disorder at 1-year follow-up (P = 0.019), weight loss (P < 0.001), consulting a physician (P < 0.001), and prokinetic use during 1-year follow-up (P = 0.035) were horizontally associated with DSS at 1-year follow-up. No relationship was found longitudinally between DSS at 1-year follow-up and patient characteristics at baseline.CONCLUSION: Female sex, anxiety, and sleep disorder, weight loss, consulting a physician and prokinetic use during 1-year follow-up were associated with outcome of FD.展开更多
AIM:To investigate macrophage migration inhibitory factor(MIF) expression and its clinical relevance in gastric cancer,and effects of MIF knockdown on proliferation of gastric cancer cells. METHODS:Tissue microarray c...AIM:To investigate macrophage migration inhibitory factor(MIF) expression and its clinical relevance in gastric cancer,and effects of MIF knockdown on proliferation of gastric cancer cells. METHODS:Tissue microarray containing 117 samples of gastric cancer and adjacent non-cancer normal tissues was studied for MIF expression by immunohistochemistry(IHC) semiquantitatively,and the association of MIF expression with clinical parameters was analyzed. MIF expression in gastric cancer cell lines was detected by reverse transcriptionpolymerase chain reaction(RT-PCR) and Western blot. Two pairs of si RNA targeting the MIF gene(MIF si-1 and MIF si-2) and one pair of scrambled si RNA as a negative control(NC) were designed and chemically synthesized. All si RNAs were transiently transfected in AGS cells with OligofectamineTM to knock down the MIF expression,with the NC group and mock group(OligofectamineTM alone) as controls. At 24,48,and 72 h after transfection,MIF m RNA was analyzed by RTPCR,and MIF and proliferating cell nuclear antigen(PCNA) proteins were detected by Western blot.The proliferative rate of AGS cells was assessed by methylthiazolyl tetrazolium(MTT) assay and colony forming assay.RESULTS:The tissue microarray was informative for IHC staining,in which the MIF expression in gastric cancer tissues was higher than that in adjacent noncancer normal tissues(P < 0.001),and high level of MIF was related to poor tumor differentiation,advanced T stage,advanced tumor stage,lymph node metastasis,and poor patient survival(P < 0.05 for all). After si RNA transfection,MIF m RNA was measured by real-time PCR,and MIF protein and PCNA were assessed by Western blot analysis. We found that compared to the NC group and mock group,MIF expression was knocked down successfully in gastric cancer cells,and PCNA expression was downregulated with MIF knockdown as well. The cell counts and the doubling times were assayed by MTT 4 d after transfection,and colonies formed were assayed by colony forming assay 10 d after transfection; all these showed significant changes in gastric cancer cells transfected with specific si RNA compared with the control si RNA and mock groups(P < 0.001 for all).CONCLUSION:MIF could be of prognostic value in gastric cancer and might be a potential target for small-molecule therapy.展开更多
AIM:To evaluate clinical response to initial corticosteroid(CS) treatment in Chinese ulcerative colitis patients(UC) and identify predictors of clinical response.METHODS:Four hundred and twenty-three UC patients who w...AIM:To evaluate clinical response to initial corticosteroid(CS) treatment in Chinese ulcerative colitis patients(UC) and identify predictors of clinical response.METHODS:Four hundred and twenty-three UC patients who were initially treated with oral or intravenous CS from 2007 to 2011 were retrospectively reviewed at eight inflammatory bowel disease centers in China,and 101 consecutive cases with one-year follow-up were analyzed further for clinical response and predictors.Short-term outcomes within one month were classified as primary response and primary non-response.Longterm outcomes within one year were classified as prolonged CS response,CS dependence and secondary non-response.CS refractoriness included primary and secondary non-response.Multivariate analyses were performed to identify predictors associated with clinical response.RESULTS:Within one month,95.0%and 5.0%of the cases were classified into primary response andnon-response,respectively.Within one year,41.6%of cases were assessed as prolonged CS response,while49.5%as CS dependence and 4.0%as secondary nonresponse.The rate of CS refractoriness was 8.9%,while the cumulative rate of surgery was 6.9%within one year.After multivariate analysis of all the variables,tenesmus was found to be a negative predictor of CS dependence(OR=0.336;95%CI:0.147-0.768;P=0.013)and weight loss as a predictor of CS refractoriness(OR=5.662;95%CI:1.111-28.857;P=0.040).After one-month treatment,sustained high Sutherland score(≥6)also predicted CS dependence(OR=2.347;95%CI:0.935-5.890;P=0.014).CONCLUSION:Tenesmus was a negative predictor of CS dependence,while weight loss and sustained high Sutherland score were strongly associated with poor CS response.展开更多
BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants signif...BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.展开更多
AIM To investigate the differences in family history of inflammatory bowel disease(IBD) and clinical outcomes among individuals with Crohn's disease(CD) residing in China and the United States.METHODS We performed...AIM To investigate the differences in family history of inflammatory bowel disease(IBD) and clinical outcomes among individuals with Crohn's disease(CD) residing in China and the United States.METHODS We performed a survey-based cross-sectional study of participants with CD recruited from China and the United States.We compared the prevalence of IBD family history and history of ileal involvement,CD-related surgeries and IBD medications in China and the United States,adjusting for potential confounders.RESULTS We recruited 49 participants from China and 145 from the United States.The prevalence of family history of IBD was significantly lower in China compared with the United States(China:4.1%,United States:39.3%).The three most commonly affected types of relatives were cousin,sibling,and parent in the United States compared with child and sibling in China.Ileal involvement(China:63.3%,United States:63.5%) and surgery for CD(China:51.0%,United States:49.7%) were nearly equivalent in the two countries.CONCLUSION The lower prevalence of familial clustering of IBD in China may suggest that the etiology of CD is less attributed to genetic background or a family-shared environment compared with the United States.Despite the potential difference in etiology,surgery and ileal involvement were similar in the two countries.Examining the changes in family history during the continuing rise in IBD may provide further insight into the etiology of CD.展开更多
Background and aim:This cross-sectional study investigated the prevalence and risk factors of high-risk human papilloma virus(HPV)infection,especially types 16 and 18,and cervical neoplasia in female Inflammatory bowe...Background and aim:This cross-sectional study investigated the prevalence and risk factors of high-risk human papilloma virus(HPV)infection,especially types 16 and 18,and cervical neoplasia in female Inflammatory bowel disease(IBD)patients.Methods:From July 2014 to January 2017,sexually active,female,Chinese IBD patients(21–60 years)and age-matched controls underwent cervical ThinPrep cytology testing(TCT)and high-risk HPV-DNA detection,and completed questionnaires about awareness of cervical cancer and HPV.Cervical dysplasia was categorized as cervical intraepithelial neoplasia(CIN)1,2 and 3.Results:Of 124 IBD patients(30 ulcerative colitis and 94 Crohn’s disease),17(13.7%)had high-risk HPV among whom 9(7.3%)had HPV 16/18 infection and 4(3.2%)had cervical CIN(3 CIN 3,1 CIN 1)by pathology.Among 372 controls,33(8.9%)had high-risk HPV and only 1(0.3%)had HPV 16 infection.Cervical TCT detected atypical squamous cells of unknown significance in one control;no control had CIN.The HPV 16/18 infection rate and CIN prevalence were significantly higher in IBD patients than controls(both P<0.001).The HPV-infection rate was higher in patients administered methotrexate[P=0.005,odds ratio(95%confidence interval)4.76(1.471–15.402)]or more than two immunosuppressants[P=0.013,odds ratio(95%confidence interval)3.64(1.255–10.562)].Thiopurine,steroid,infliximab and disease behavior/location were not associated with HPV infection.Only 29.3%of patients had undergone cervical-cancer screening.Awareness of HPV infection and HPVrelated cervical cancer was poor(28.2%).Conclusions:Female IBD patients are at increased risk of high-risk HPV infection and cervical neoplasia,which may be associated with immunosuppressants.Education and routine follow-up with HPV-DNA testing and TCT are recommended,especially in female Chinese IBD patients.展开更多
Background Thalidomide is applied in therapy for refractory Crohn’s disease(CD)in adults,but systematic and rigorous clinical evidence is scant.The aim was to provide theoretical references for the efficacy of thalid...Background Thalidomide is applied in therapy for refractory Crohn’s disease(CD)in adults,but systematic and rigorous clinical evidence is scant.The aim was to provide theoretical references for the efficacy of thalidomide in the therapy for refractory CD in adults.Methods A double-center,double-blind,placebo-controlled,randomized clinical trial of refractory CD in adults in two inflammatory bowel disease centers in China.In the double-blind trial,patients were randomly assigned to 100mg of thalidomide or placebo daily for 8 weeks.The primary outcome was considered as the clinical remission rate calculated based on the Crohn’s disease activity index at the eighth week following thalidomide or placebo treatment.In open label,nonresponse to placebo was additionally treated with 8 weeks of thalidomide;all responders were continuously treated with thalidomide until the 48th week.Results Twenty-five patients were randomly assigned to each group.At the eighth week,the clinical remission rate in the thalidomide group was significantly higher than that in the placebo group(68.0%[17/25]vs 16.0%[4/25];relative risk,4.2;95%confidence interval,1.8–10.9,P<0.001).After a 48-week follow-up,the continuous treatment rate of thalidomide was 46.3%(19/41).Adverse events during the whole process were reported in 58.5%of patients,mainly involving drowsiness,rash,and peripheral neuropathy that were mild and tolerable.Conclusion Thalidomide can be used in the induction and maintenance therapy of refractory CD in adults.And it could be one of the treatment options for refractory CD.展开更多
Background and aims:Mucosal healing is regarded as a clinical endpoint of Crohn’s disease(CD),and transmural healing is correlated to the concept of deep remission.Current therapies to induce mucosal and transmural h...Background and aims:Mucosal healing is regarded as a clinical endpoint of Crohn’s disease(CD),and transmural healing is correlated to the concept of deep remission.Current therapies to induce mucosal and transmural healing in CD are not satisfactory.Exclusive enteral nutrition(EEN)is underestimated therapy and its value has not been fully evaluated.Our aim was to investigate the efficacy of oral EEN for inducing mucosal and transmural healing in CD patients.Methods:This was a prospective,single-center,open-label study including diagnosed CD children and adults conducted between January 2015 and December 2016 in the Sixth Affiliated Hospital of Sun Yat-sen University.All patients were treated with oral EEN and underwent paired assessment at baseline and completion using C-reaction protein,erythrocyte sedimentation rate,platelets,hemoglobin,body mass index,CD activity index,simple endoscopic score for CD and bowel sonography.Azathioprine was combined to prevent relapse.Results:In this prospective observational study,29 CD patients with an average age of 28.9 years were identified.After oral EEN treatment,23 patients(79%)achieved complete mucosal healing,and the mean time to reach mucosal healing was 123 days(ranged from 50 to 212 days).Although only five patients(17%)achieved transmural healing,a significant reduction was observed in bowel-wall thickness(9.4163.06 vs 4.9761.76mm,P<0.001)and a significant improvement was observed in complications(including fistulas,abscess,ascites,stricture)assessed by bowel sonography(all P<0.05).Conclusions:Oral EEN therapy is highly effective for inducing mucosal healing in CD patients.Both CD patients at active stage and those at clinical remission show excellent clinical response to oral EEN.展开更多
Background:This study sought to evaluate the risk factors for the development of colitis-associated neoplasia(CAN)in Chinese patients with inflammatory bowel disease(IBD).Methods:IBD patients who developed CAN between...Background:This study sought to evaluate the risk factors for the development of colitis-associated neoplasia(CAN)in Chinese patients with inflammatory bowel disease(IBD).Methods:IBD patients who developed CAN between 1999 and 2016 were identified from eight medical centers.In addition to initial pathology evaluation,a CAN diagnosis was confirmed by two expert pathologists.Patients with CAN(n=29)were compared with non-CAN controls(n=87).Matching was performed for gender and IBD type with a ratio of three controls to one subject.Results:Of the 29 patients with CAN,8(27.6%)had colorectal cancer(CRC),20(69.0%)had a final diagnosis of low-grade dysplasia and 1(3.4%)had high-grade dysplasia.Multivariate analysis revealed that an older age at the time of IBD diagnosis and a longer IBD duration were independent risk factors for the development of CAN,with odds ratios of 1.09[95%confidence interval(CI):1.04–1.14,P<0.001]and 1.14(95%CI:1.03–1.27,P=0.013),respectively.Comparison between IBD patients with CRC and those with dysplasia indicated that the former were older at the time of IBD diagnosis(P=0.012)and had longer IBD durations(P=0.019).Conclusions:Older age at the time of IBD diagnosis and longer IBD duration were found to be associated with the development of CAN in IBD patients.展开更多
基金National Natural Science Foundation of China,No.81973398,No.81730103,No.81573507 and No.82020108031The National Key Research and Development Program,No.2017YFC0909300 and No.2016YFC0905001+5 种基金Guangdong Provincial Key Laboratory of Construction Foundation,No.2017B030314030 and No.2020B1212060034Science and Technology Program of Guangzhou,No.201607020031National Engineering and Technology Research Center for New Drug Druggability Evaluation(Seed Program of Guangdong Province),No.2017B090903004The 111 Project,No.B16047China Postdoctoral Science Foundation,No.2019M66324,No.2020M683140 and No.2020M683139Natural Science Foundation of Guangdong Province,No.2022A1515012549 and No.2023A1515012667.
文摘BACKGROUND Thalidomide is an effective treatment for refractory Crohn’s disease(CD).However,thalidomide-induced peripheral neuropathy(TiPN),which has a large individual variation,is a major cause of treatment failure.TiPN is rarely predictable and recognized,especially in CD.It is necessary to develop a risk model to predict TiPN occurrence.AIM To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic variables.METHODS A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the model.The National Cancer Institute Common Toxicity Criteria Sensory Scale(version 4.0)was used to assess TiPN.With 18 clinical features and 150 genetic variables,five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve(AUROC),area under the precision-recall curve(AUPRC),specificity,sensitivity(recall rate),precision,accuracy,and F1 score.RESULTS The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248[P=0.0004,odds ratio(OR):8.983,95%confidence interval(CI):2.497-30.90],dose(mg/d,P=0.002),brainderived neurotrophic factor(BDNF)rs2030324(P=0.001,OR:3.164,95%CI:1.561-6.434),BDNF rs6265(P=0.001,OR:3.150,95%CI:1.546-6.073)and BDNF rs11030104(P=0.001,OR:3.091,95%CI:1.525-5.960).In the training set,gradient boosting decision tree(GBDT),extremely random trees(ET),random forest,logistic regression and extreme gradient boosting(XGBoost)obtained AUROC values>0.90 and AUPRC>0.87.Among these models,XGBoost and GBDT obtained the first two highest AUROC(0.90 and 1),AUPRC(0.98 and 1),accuracy(0.96 and 0.98),precision(0.90 and 0.95),F1 score(0.95 and 0.98),specificity(0.94 and 0.97),and sensitivity(1).In the validation set,XGBoost algorithm exhibited the best predictive performance with the highest specificity(0.857),accuracy(0.818),AUPRC(0.86)and AUROC(0.89).ET and GBDT obtained the highest sensitivity(1)and F1 score(0.8).Overall,compared with other state-of-the-art classifiers such as ET,GBDT and RF,XGBoost algorithm not only showed a more stable performance,but also yielded higher ROC-AUC and PRC-AUC scores,demonstrating its high accuracy in prediction of TiPN occurrence.CONCLUSION The powerful XGBoost algorithm accurately predicts TiPN using 18 clinical features and 14 genetic variables.With the ability to identify high-risk patients using single nucleotide polymorphisms,it offers a feasible option for improving thalidomide efficacy in CD patients.
基金Supported by a Grant from Guangzhou Health Bureau Project, No. 2004-Z001
文摘AIM: To investigate the population-based prevalence of fatty liver disease (FLD) and its risk factors in Guangdong Province,China. METHODS: A cross-sectional survey with multiple-stage stratified cluster and random sampling of inhabitants over 7-year-old was performed in 6 urban and rural areas of Guangdong Province,China. Questionnaires,designed by co-working of epidemiologists and hepatologists,included demographic characteristics,current medication use,medical history and health-relevant behaviors,i.e. alcohol consumption,smoking habits,dietary habits and physical activities. Anthropometric measurements,biochemical tests and abdominal ultrasonography were carried out. RESULTS: Among the 3543 subjects,609 (17.2%) were diagnosed having FLD (18.0% males,16.7% females,P > 0.05). Among them,the prevalence of confirmed alcoholic liver disease (ALD),suspected ALD and nonalcoholic fatty liver disease (NAFLD) were 0.4%,1.8%,and 15.0%,respectively. The prevalence rate (23.0%) was significantly higher in urban areas than (12.9%) in rural areas. After adjustment for age,gender and residency,the standardized prevalence of FLD in adults was 14.5%. Among them,confirmed ALD,suspected ALD and NAFLD were 0.5%,2.3%,and 11.7%,respectively,in adults and 1.3% (all NAFLD) in children at the age of 7-18 years. The overall prevalence of FLD increased with age in both genders to the peak of 27.4% in the group of subjects at the age of 60-70 years. The prevalence rate was significantly higher in men than in women under the age of 50 years (22.4% vs 7.1%,P < 0.001). However,the opposite phenomenon was found over the age of 50 years (20.6% vs 27.6%,P < 0.05). Multivariate and logistic regression analysis indicated that male gender,urban residency,low education,high blood pressure,body mass index,waist circumference,waist to hip ratio,serum triglyceride and glucose levels were the risk factors for FLD. CONCLUSION: FLD,especially NAFLD,is prevalent in South China. There are many risk factors for FLD.
基金Supported by A Grant from Chinese Medical Association Re-search Special Funds,No. 07040490057 (to Professor Ou-yang Q)
文摘AIM:To evaluate potential risk factors in the development of ulcerative colitis(UC) in China.METHODS:A total of 1308 patients with UC and 1308 age-matched and sex-matched controls were prospectively studied in China.The UC cases were collected from 17 hospitals in China from April 2007 to April 2010.Uniform questionnaires were designed to investigate risk factors including smoking,appendectomy,stress,socio-economic conditions,nonsteroidal antiinflammatory drugs(NSAIDs),oral contraceptives,diet,breastfeeding,infections and family sanitary conditions.Group comparisons by each factor were done using simple logistic regression analysis.Conditional logistic regression was used for multivariate analysis.RESULTS:By univariate analysis,the variables predictive of UC included feeling stress,light and heavy alcoholic drinking,spicy food,sugar consumption and infectious diarrhea,while heavy tea intake and tap water consumption were protective against UC.On multivariate analysis,the protective factor for UC was tap water consumption [odds ratios(OR) = 0.424,95%CI:0.302-0.594,P < 0.001];while the potential risk factors for UC were heavy sugar consumption(OR = 1.632,95%CI:1.156-2.305,P < 0.001),spicy food(light intake:OR = 3.329,95%CI:2.282-4.857,P < 0.001;heavy intake:OR = 3.979,95%CI:2.700-5.863,P < 0.001),and often feeling stress(OR = 1.981,95%CI:1.447-2.711,P < 0.001).Other factors,such as smoking habit,appendectomy,breastfeeding,a history of measles,rural or urban residence,education,oral contraceptives,and NSAID use have not been found to have a significant association with the development of UC in the present study.CONCLUSION:Our study showed tap water consumption was a protective factor for UC,while spicy food,heavy sugar consumption and often feeling stress were risk factors for UC in this Chinese population.
基金Doctoral Natural Science Fund of Guangdong Province, China, No. 04300361
文摘AIM： To investigate the single nucleotide polymorphism （SNPs） distribution of NOD2/CARD15 （R702W, G908R）, OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease （IBD）. METHODS： A total of 61 patients with Crohn＇s disease （CD）, 151 patients with ulcerative colitis （UC）, and 200 unrelated healthy controls were genotyped. Genotyping was performed by sequence specific primer polymerase chain reaction （PCR-SSP） or by restriction fragment length polymorphism （PCR-RFLP） analysis. RESULTS： Among the subjects in our study groups, including patients with CD, UC and healthy controls, none had OCTN and CARD15 variants and very rare IBD family history was found in our patients with the percentage of 0 （0/61 with CD） and 1.3% （2/151 with UC）. CONCLUSION： Our results indicate that although OCTN or CARD15 variation is associated with susceptibility to IBD in Western populations, these might be rare and may not be associated with susceptibility to IBD in Chinese patients.
基金Supported by Project of the National Key Technologies R and D Program in the 11th Five-Year PlanNo.2007BAI04B01partially supported by Xi’an-Janssen Pharmaceutical Ltd
文摘AIM: To study the evolution of gastrointestinal symptoms and associated factors in Chinese patients with functional dyspepsia (FD).METHODS: From June 2008 to November 2009, a total of 1049 patients with FD (65.3% female, mean age 42.80 ± 11.64 years) who visited the departments of gastroenterology in Wuhan, Beijing, Shanghai, Guangzhou, and Xi’an, China were referred for this study. All of the patients fulfilled the Rome III criteria for FD. Baseline demographic data, dyspepsia symptoms, anxiety, depression, sleep disorder, and drug treatment were assessed using self-report questionnaires. Patients completed questionnaires at baseline and after 1, 3, 6 and 12 mo follow-up. Comparison of dyspepsia symptoms between baseline and after follow-up was explored using multivariate analysis of variance of repeated measuring. Multiple linear regression was done to examine factors associated with outcome, both longitudinally and horizontally.RESULTS: Nine hundred and forty-three patients (89.9% of the original population) completed all four follow-ups. The average duration of follow-up was 12.24 ± 0.59 mo. During 1-year follow-up, the mean dyspeptic symptom score (DSS) in FD patients showed a significant gradually reduced trend (P < 0.001), and similar differences were found for all individual symptoms (P < 0.001). Multiple linear regression analysis showed that sex (P < 0.001), anxiety (P = 0.018), sleep disorder at 1-year follow-up (P = 0.019), weight loss (P < 0.001), consulting a physician (P < 0.001), and prokinetic use during 1-year follow-up (P = 0.035) were horizontally associated with DSS at 1-year follow-up. No relationship was found longitudinally between DSS at 1-year follow-up and patient characteristics at baseline.CONCLUSION: Female sex, anxiety, and sleep disorder, weight loss, consulting a physician and prokinetic use during 1-year follow-up were associated with outcome of FD.
基金Supported by Grants from the National Natural Science Foundation of China,No.81072044the Guangdong Natural Science Foundation,No.S2011010004653
文摘AIM:To investigate macrophage migration inhibitory factor(MIF) expression and its clinical relevance in gastric cancer,and effects of MIF knockdown on proliferation of gastric cancer cells. METHODS:Tissue microarray containing 117 samples of gastric cancer and adjacent non-cancer normal tissues was studied for MIF expression by immunohistochemistry(IHC) semiquantitatively,and the association of MIF expression with clinical parameters was analyzed. MIF expression in gastric cancer cell lines was detected by reverse transcriptionpolymerase chain reaction(RT-PCR) and Western blot. Two pairs of si RNA targeting the MIF gene(MIF si-1 and MIF si-2) and one pair of scrambled si RNA as a negative control(NC) were designed and chemically synthesized. All si RNAs were transiently transfected in AGS cells with OligofectamineTM to knock down the MIF expression,with the NC group and mock group(OligofectamineTM alone) as controls. At 24,48,and 72 h after transfection,MIF m RNA was analyzed by RTPCR,and MIF and proliferating cell nuclear antigen(PCNA) proteins were detected by Western blot.The proliferative rate of AGS cells was assessed by methylthiazolyl tetrazolium(MTT) assay and colony forming assay.RESULTS:The tissue microarray was informative for IHC staining,in which the MIF expression in gastric cancer tissues was higher than that in adjacent noncancer normal tissues(P < 0.001),and high level of MIF was related to poor tumor differentiation,advanced T stage,advanced tumor stage,lymph node metastasis,and poor patient survival(P < 0.05 for all). After si RNA transfection,MIF m RNA was measured by real-time PCR,and MIF protein and PCNA were assessed by Western blot analysis. We found that compared to the NC group and mock group,MIF expression was knocked down successfully in gastric cancer cells,and PCNA expression was downregulated with MIF knockdown as well. The cell counts and the doubling times were assayed by MTT 4 d after transfection,and colonies formed were assayed by colony forming assay 10 d after transfection; all these showed significant changes in gastric cancer cells transfected with specific si RNA compared with the control si RNA and mock groups(P < 0.001 for all).CONCLUSION:MIF could be of prognostic value in gastric cancer and might be a potential target for small-molecule therapy.
基金Supported by Grants from the Ministry of Public Health,No.201002020Hubei Provincial Outstanding Medical Academic Leader Program(2013)
文摘AIM:To evaluate clinical response to initial corticosteroid(CS) treatment in Chinese ulcerative colitis patients(UC) and identify predictors of clinical response.METHODS:Four hundred and twenty-three UC patients who were initially treated with oral or intravenous CS from 2007 to 2011 were retrospectively reviewed at eight inflammatory bowel disease centers in China,and 101 consecutive cases with one-year follow-up were analyzed further for clinical response and predictors.Short-term outcomes within one month were classified as primary response and primary non-response.Longterm outcomes within one year were classified as prolonged CS response,CS dependence and secondary non-response.CS refractoriness included primary and secondary non-response.Multivariate analyses were performed to identify predictors associated with clinical response.RESULTS:Within one month,95.0%and 5.0%of the cases were classified into primary response andnon-response,respectively.Within one year,41.6%of cases were assessed as prolonged CS response,while49.5%as CS dependence and 4.0%as secondary nonresponse.The rate of CS refractoriness was 8.9%,while the cumulative rate of surgery was 6.9%within one year.After multivariate analysis of all the variables,tenesmus was found to be a negative predictor of CS dependence(OR=0.336;95%CI:0.147-0.768;P=0.013)and weight loss as a predictor of CS refractoriness(OR=5.662;95%CI:1.111-28.857;P=0.040).After one-month treatment,sustained high Sutherland score(≥6)also predicted CS dependence(OR=2.347;95%CI:0.935-5.890;P=0.014).CONCLUSION:Tenesmus was a negative predictor of CS dependence,while weight loss and sustained high Sutherland score were strongly associated with poor CS response.
基金Supported by the National Natural Science Foundation of China,No.81573507,No.81473283,No.81173131,and No.81320108027Guangdong Provincial Key Laboratory Construction Foundation,No.2017B030314030+1 种基金The National Key Research and Development Program,No.2016YFC0905003the 111 Project,No.B16047
文摘BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.
基金Supported by (in part)Johns Hopkins Institute for Clinical and Translational Research,No.UL1TR001079
文摘AIM To investigate the differences in family history of inflammatory bowel disease(IBD) and clinical outcomes among individuals with Crohn's disease(CD) residing in China and the United States.METHODS We performed a survey-based cross-sectional study of participants with CD recruited from China and the United States.We compared the prevalence of IBD family history and history of ileal involvement,CD-related surgeries and IBD medications in China and the United States,adjusting for potential confounders.RESULTS We recruited 49 participants from China and 145 from the United States.The prevalence of family history of IBD was significantly lower in China compared with the United States(China:4.1%,United States:39.3%).The three most commonly affected types of relatives were cousin,sibling,and parent in the United States compared with child and sibling in China.Ileal involvement(China:63.3%,United States:63.5%) and surgery for CD(China:51.0%,United States:49.7%) were nearly equivalent in the two countries.CONCLUSION The lower prevalence of familial clustering of IBD in China may suggest that the etiology of CD is less attributed to genetic background or a family-shared environment compared with the United States.Despite the potential difference in etiology,surgery and ileal involvement were similar in the two countries.Examining the changes in family history during the continuing rise in IBD may provide further insight into the etiology of CD.
基金This work was supported by National Key Clinical Discipline,the National Nature Science Fund of China(No.81370498)the Science and Technology Planning Project of Guangdong Province,China(No.2012B091100455)+1 种基金the Science and Technology Project of Tianhe District,Guangdong Province,China(No.201404KW018)the Medical Scientific and Technical Foundation of Guangdong Province(A2016322).
文摘Background and aim:This cross-sectional study investigated the prevalence and risk factors of high-risk human papilloma virus(HPV)infection,especially types 16 and 18,and cervical neoplasia in female Inflammatory bowel disease(IBD)patients.Methods:From July 2014 to January 2017,sexually active,female,Chinese IBD patients(21–60 years)and age-matched controls underwent cervical ThinPrep cytology testing(TCT)and high-risk HPV-DNA detection,and completed questionnaires about awareness of cervical cancer and HPV.Cervical dysplasia was categorized as cervical intraepithelial neoplasia(CIN)1,2 and 3.Results:Of 124 IBD patients(30 ulcerative colitis and 94 Crohn’s disease),17(13.7%)had high-risk HPV among whom 9(7.3%)had HPV 16/18 infection and 4(3.2%)had cervical CIN(3 CIN 3,1 CIN 1)by pathology.Among 372 controls,33(8.9%)had high-risk HPV and only 1(0.3%)had HPV 16 infection.Cervical TCT detected atypical squamous cells of unknown significance in one control;no control had CIN.The HPV 16/18 infection rate and CIN prevalence were significantly higher in IBD patients than controls(both P<0.001).The HPV-infection rate was higher in patients administered methotrexate[P=0.005,odds ratio(95%confidence interval)4.76(1.471–15.402)]or more than two immunosuppressants[P=0.013,odds ratio(95%confidence interval)3.64(1.255–10.562)].Thiopurine,steroid,infliximab and disease behavior/location were not associated with HPV infection.Only 29.3%of patients had undergone cervical-cancer screening.Awareness of HPV infection and HPVrelated cervical cancer was poor(28.2%).Conclusions:Female IBD patients are at increased risk of high-risk HPV infection and cervical neoplasia,which may be associated with immunosuppressants.Education and routine follow-up with HPV-DNA testing and TCT are recommended,especially in female Chinese IBD patients.
基金supported by Academician Jie-shou Li Intestinal Barrier Special Research Fund[grant number LJS-201908C].
文摘Background Thalidomide is applied in therapy for refractory Crohn’s disease(CD)in adults,but systematic and rigorous clinical evidence is scant.The aim was to provide theoretical references for the efficacy of thalidomide in the therapy for refractory CD in adults.Methods A double-center,double-blind,placebo-controlled,randomized clinical trial of refractory CD in adults in two inflammatory bowel disease centers in China.In the double-blind trial,patients were randomly assigned to 100mg of thalidomide or placebo daily for 8 weeks.The primary outcome was considered as the clinical remission rate calculated based on the Crohn’s disease activity index at the eighth week following thalidomide or placebo treatment.In open label,nonresponse to placebo was additionally treated with 8 weeks of thalidomide;all responders were continuously treated with thalidomide until the 48th week.Results Twenty-five patients were randomly assigned to each group.At the eighth week,the clinical remission rate in the thalidomide group was significantly higher than that in the placebo group(68.0%[17/25]vs 16.0%[4/25];relative risk,4.2;95%confidence interval,1.8–10.9,P<0.001).After a 48-week follow-up,the continuous treatment rate of thalidomide was 46.3%(19/41).Adverse events during the whole process were reported in 58.5%of patients,mainly involving drowsiness,rash,and peripheral neuropathy that were mild and tolerable.Conclusion Thalidomide can be used in the induction and maintenance therapy of refractory CD in adults.And it could be one of the treatment options for refractory CD.
基金supported by the National Natural Science Foundation of China(81470795)the Science and Technology Planning Project of Guangdong Province,China(2013B022000035).
文摘Background and aims:Mucosal healing is regarded as a clinical endpoint of Crohn’s disease(CD),and transmural healing is correlated to the concept of deep remission.Current therapies to induce mucosal and transmural healing in CD are not satisfactory.Exclusive enteral nutrition(EEN)is underestimated therapy and its value has not been fully evaluated.Our aim was to investigate the efficacy of oral EEN for inducing mucosal and transmural healing in CD patients.Methods:This was a prospective,single-center,open-label study including diagnosed CD children and adults conducted between January 2015 and December 2016 in the Sixth Affiliated Hospital of Sun Yat-sen University.All patients were treated with oral EEN and underwent paired assessment at baseline and completion using C-reaction protein,erythrocyte sedimentation rate,platelets,hemoglobin,body mass index,CD activity index,simple endoscopic score for CD and bowel sonography.Azathioprine was combined to prevent relapse.Results:In this prospective observational study,29 CD patients with an average age of 28.9 years were identified.After oral EEN treatment,23 patients(79%)achieved complete mucosal healing,and the mean time to reach mucosal healing was 123 days(ranged from 50 to 212 days).Although only five patients(17%)achieved transmural healing,a significant reduction was observed in bowel-wall thickness(9.4163.06 vs 4.9761.76mm,P<0.001)and a significant improvement was observed in complications(including fistulas,abscess,ascites,stricture)assessed by bowel sonography(all P<0.05).Conclusions:Oral EEN therapy is highly effective for inducing mucosal healing in CD patients.Both CD patients at active stage and those at clinical remission show excellent clinical response to oral EEN.
基金This work was supported by National Key Clinical Discipline,National Natural Science Foundation of China(No.81870383)Guangdong Natural Science Foundation(No.2017A030313785)+1 种基金Science and Technology Planning Project of Guangzhou City(No.201804010014)Science and Technology Planning Project of Guangdong Province(No.2015B020229001).
文摘Background:This study sought to evaluate the risk factors for the development of colitis-associated neoplasia(CAN)in Chinese patients with inflammatory bowel disease(IBD).Methods:IBD patients who developed CAN between 1999 and 2016 were identified from eight medical centers.In addition to initial pathology evaluation,a CAN diagnosis was confirmed by two expert pathologists.Patients with CAN(n=29)were compared with non-CAN controls(n=87).Matching was performed for gender and IBD type with a ratio of three controls to one subject.Results:Of the 29 patients with CAN,8(27.6%)had colorectal cancer(CRC),20(69.0%)had a final diagnosis of low-grade dysplasia and 1(3.4%)had high-grade dysplasia.Multivariate analysis revealed that an older age at the time of IBD diagnosis and a longer IBD duration were independent risk factors for the development of CAN,with odds ratios of 1.09[95%confidence interval(CI):1.04–1.14,P<0.001]and 1.14(95%CI:1.03–1.27,P=0.013),respectively.Comparison between IBD patients with CRC and those with dysplasia indicated that the former were older at the time of IBD diagnosis(P=0.012)and had longer IBD durations(P=0.019).Conclusions:Older age at the time of IBD diagnosis and longer IBD duration were found to be associated with the development of CAN in IBD patients.
