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
Celiac disease(CeD)is a chronic autoimmune disorder that is triggered by gluten in genetically susceptible individuals,and that is characterized by CeD-specific antibodies,HLA-DQ2 and/or HLA-DQ8 haplotypes,enteropathy...Celiac disease(CeD)is a chronic autoimmune disorder that is triggered by gluten in genetically susceptible individuals,and that is characterized by CeD-specific antibodies,HLA-DQ2 and/or HLA-DQ8 haplotypes,enteropathy and different clinical pictures related to many organs.Intestinal lymphoma may develop as a result of refractory CeD.If a patient diagnosed with CeD is symptomatic despite a strict gluten-free diet for at least 12 months,and does not improve with severe villous atrophy,refractory CeD can be considered present.The second of the two types of refractory CeD has abnormal monoclonal intraepithelial lymphocytes and can be considered as pre-lymphoma,and the next picture that will emerge is enteropathy-associated T-cell lymphoma.This manuscript addresses"CeD and malignancies"through a review of current literature and guidelines.展开更多
Background:To systematically evaluate the efficacy and safety of traditional Chinese medicine in the treatment of refractory gastroesophageal reflux.Methods:PubMed,The Cochrane Library,Embase,Web of Science,China Nati...Background:To systematically evaluate the efficacy and safety of traditional Chinese medicine in the treatment of refractory gastroesophageal reflux.Methods:PubMed,The Cochrane Library,Embase,Web of Science,China National Knowledge Infrastructure,Wanfang Database,China Science and Technology Journal Database and Chinese BioMedical Literature Database were searched for randomized controlled trials of traditional Chinese medicine in the treatment of refractory gastroesophageal reflux from database establishment time to December 2020.After two researchers independently screened the literature,extracted data and evaluated the bias risk included in the study,RevMan5.3 software was used for meta-analysis.Results:A total of 12 randomized controlled trials,were included,including 893 patients.The results of meta-analysis showed that the total effective rate of the treatment group(relative risk=1.28,95%confidence interval(CI)(1.19,1.38),P<0.00001),RGERDQ(refractory gastroesophageal reflux disease)score(mean difference(MD)=−3.35,95%CI(−4.13,−2.57),P<0.00001],acid reflux(acid in the stomach comes out of the mouth)[MD=−0.30,95%CI(−0.45,−0.15),P<0.00001],heartburn(the feeling that the heart is burned)(MD=−0.44,95%CI(−0.60,−0.29),P<0.00001,and retrosternal pain(MD=−0.27,95%CI(−0.44,−0.10),P<0.00001,belching(MD=−0.40,95%CI(−0.57,−0.24),P<0.00001],endoscopic mucosal score(MD=−0.62,95%CI(−0.78,−0.46),P<0.00001],the differences were statistically significant,and the effective rate of mucosal improvement under endoscopy was P=0.93>0.05,with no statistically significant difference.Conclusion:The current evidence shows that traditional Chinese medicine in the treatment of refractory gastroesophageal reflux disease is better than that of western medicine in the total effective rate,relieving acid reflux,heartburn,retrosternal pain and belching symptoms,but it is impossible to judge the improvement of mucosa under endoscope.Due to the limitations of the quality and quantity of included studies,more high-quality studies are needed to confirm the above conclusions.展开更多
Stem cell medicine is gaining momentum in the development of therapy for various end-stage diseases.The search for new seed cells and exploration of their application prospects are topics of interest in stem cell medi...Stem cell medicine is gaining momentum in the development of therapy for various end-stage diseases.The search for new seed cells and exploration of their application prospects are topics of interest in stem cell medicine.In recent years,vascular endothelial cells(VECs)have attracted wide attention from scholars.VECs,which form the inner lining of blood vessels,are critically involved in many physiological functions,including permeability,angiogenesis,blood pressure regulation,immunity,and pathological development,such as atherosclerosis and malignant tumors.VECs have significant therapeutic effects and broad application prospects in stem cell medicine for the treatment of various refractory diseases,including atherosclerosis,myocardial infarction,diabetic complications,hypertension,coronavirus disease 2019,and malignant tumors.On the one hand,VECs and their extracellular vesicles can be directly used for the treatment of these diseases.On the other hand,VECs can be used as therapeutic targets for some diseases.However,there are still some obstacles to the use of VECs in stem cell medicine.In this review,advances in the applications and challenges that come with the use of these cells are discussed.展开更多
Objective To evaluate the efficacy and safety of thalidomide(100 to 200 mg per day)in the treatment of adult refractory Crohn’s disease(CD).Methods From July 2008 to February 2013,29 refractory CD patients were enrol...Objective To evaluate the efficacy and safety of thalidomide(100 to 200 mg per day)in the treatment of adult refractory Crohn’s disease(CD).Methods From July 2008 to February 2013,29 refractory CD patients were enrolled in thalidomide(100 to 200 mg per day)cohort study.The clinical activity was evaluated by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.
文摘Celiac disease(CeD)is a chronic autoimmune disorder that is triggered by gluten in genetically susceptible individuals,and that is characterized by CeD-specific antibodies,HLA-DQ2 and/or HLA-DQ8 haplotypes,enteropathy and different clinical pictures related to many organs.Intestinal lymphoma may develop as a result of refractory CeD.If a patient diagnosed with CeD is symptomatic despite a strict gluten-free diet for at least 12 months,and does not improve with severe villous atrophy,refractory CeD can be considered present.The second of the two types of refractory CeD has abnormal monoclonal intraepithelial lymphocytes and can be considered as pre-lymphoma,and the next picture that will emerge is enteropathy-associated T-cell lymphoma.This manuscript addresses"CeD and malignancies"through a review of current literature and guidelines.
文摘Background:To systematically evaluate the efficacy and safety of traditional Chinese medicine in the treatment of refractory gastroesophageal reflux.Methods:PubMed,The Cochrane Library,Embase,Web of Science,China National Knowledge Infrastructure,Wanfang Database,China Science and Technology Journal Database and Chinese BioMedical Literature Database were searched for randomized controlled trials of traditional Chinese medicine in the treatment of refractory gastroesophageal reflux from database establishment time to December 2020.After two researchers independently screened the literature,extracted data and evaluated the bias risk included in the study,RevMan5.3 software was used for meta-analysis.Results:A total of 12 randomized controlled trials,were included,including 893 patients.The results of meta-analysis showed that the total effective rate of the treatment group(relative risk=1.28,95%confidence interval(CI)(1.19,1.38),P<0.00001),RGERDQ(refractory gastroesophageal reflux disease)score(mean difference(MD)=−3.35,95%CI(−4.13,−2.57),P<0.00001],acid reflux(acid in the stomach comes out of the mouth)[MD=−0.30,95%CI(−0.45,−0.15),P<0.00001],heartburn(the feeling that the heart is burned)(MD=−0.44,95%CI(−0.60,−0.29),P<0.00001,and retrosternal pain(MD=−0.27,95%CI(−0.44,−0.10),P<0.00001,belching(MD=−0.40,95%CI(−0.57,−0.24),P<0.00001],endoscopic mucosal score(MD=−0.62,95%CI(−0.78,−0.46),P<0.00001],the differences were statistically significant,and the effective rate of mucosal improvement under endoscopy was P=0.93>0.05,with no statistically significant difference.Conclusion:The current evidence shows that traditional Chinese medicine in the treatment of refractory gastroesophageal reflux disease is better than that of western medicine in the total effective rate,relieving acid reflux,heartburn,retrosternal pain and belching symptoms,but it is impossible to judge the improvement of mucosa under endoscope.Due to the limitations of the quality and quantity of included studies,more high-quality studies are needed to confirm the above conclusions.
基金the National Natural Science Foundation of China,No.81670951.
文摘Stem cell medicine is gaining momentum in the development of therapy for various end-stage diseases.The search for new seed cells and exploration of their application prospects are topics of interest in stem cell medicine.In recent years,vascular endothelial cells(VECs)have attracted wide attention from scholars.VECs,which form the inner lining of blood vessels,are critically involved in many physiological functions,including permeability,angiogenesis,blood pressure regulation,immunity,and pathological development,such as atherosclerosis and malignant tumors.VECs have significant therapeutic effects and broad application prospects in stem cell medicine for the treatment of various refractory diseases,including atherosclerosis,myocardial infarction,diabetic complications,hypertension,coronavirus disease 2019,and malignant tumors.On the one hand,VECs and their extracellular vesicles can be directly used for the treatment of these diseases.On the other hand,VECs can be used as therapeutic targets for some diseases.However,there are still some obstacles to the use of VECs in stem cell medicine.In this review,advances in the applications and challenges that come with the use of these cells are discussed.
文摘Objective To evaluate the efficacy and safety of thalidomide(100 to 200 mg per day)in the treatment of adult refractory Crohn’s disease(CD).Methods From July 2008 to February 2013,29 refractory CD patients were enrolled in thalidomide(100 to 200 mg per day)cohort study.The clinical activity was evaluated by