Corrosion mechanism of magnesia-chromite refractories by ZnO-containing fayalite slags: Effect of funnel glass addition

An efficient approach for lead extraction from waste funnel glass through the lead smelting process has been proposed. To clarify the effect of funnel glass addition on the degradation of magnesia-chromite refractories by ZnO-containing fayalite slag, the corrosion behavior of magnesia-chromite refractories in lead smelting slags with different funnel glass additions from 0wt% to 40wt% was tested. Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS) was used to acquire the microstructural information of the worn refractory samples. Experimental results showed that the corrosion of magnesia-chromite refractory consisted predominantly of the dissolution of MgO into slag. ZnO and FeO reacted with periclase and chromite to form (Zn,Fe,Mg)O solid solution and (Zn,Fe,Mg)(Fe,Al,Cr)2O4 spinel, respectively. With the addition of funnel glass, the solubility of MgO increased whereas ZnO levels remained stable, thereby resulting in a reduced Mg content and an elevated Zn and Fe content in the (Zn,Fe,Mg)O solid solution and the (Zn,Fe,Mg)(Fe,Al,Cr)2O4 spinel. Considering the stability of the (Zn,Fe,Mg)O solid solution layer and the penetration depth of the slag, the optimal funnel glass addition for lead smelting was found to be 20wt%.

Investigation of Microstructure and Phase Composition of Chromic Oxide, AZS/Cr and High-alumina Refractories after Exposure of Basalt and Aluminaboronsilicate Glasses Melts

The microstructure and phase composition of high-alumina,chromic oxide,and AZS/Cr refractories containing 30%and 60%(by mass)Cr_(2)O_(3) after exposure to aluminaboronsilicate glasses and basalt melts depending on the type of melts and temperature have been studied.The mechanisms of refractory corrosion by the used melts and the factors contributing to the inhibition of corrosion development have been investigated by the method of petrographic analysis.On the basis of obtained results,the use of high-alumina,chromic oxide,and AZS/Cr refractories in the sections of glass furnace linings,experiencing the intensive impact of aluminaboronsilicate glasses and basalt melts,has been confirmed and scientifically substantiated.

Spark plasma sintering of tungsten-based WTaVCr refractory high entropy alloys for nuclear fusion applications

W-based WTaVCr refractory high entropy alloys (RHEA) may be novel and promising candidate materials for plasma facing components in the first wall and diverter in fusion reactors. This alloy has been developed by a powder metallurgy process combining mechanical alloying and spark plasma sintering (SPS). The SPSed samples contained two phases, in which the matrix is RHEA with a body-centered cubic structure, while the oxide phase was most likely Ta2VO6through a combined analysis of X-ray diffraction (XRD),energy-dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The higher oxygen affinity of Ta and V may explain the preferential formation of their oxide phases based on thermodynamic calculations. Electron backscatter diffraction (EBSD) revealed an average grain size of 6.2μm. WTaVCr RHEA showed a peak compressive strength of 2997 MPa at room temperature and much higher micro-and nano-hardness than W and other W-based RHEAs in the literature. Their high Rockwell hardness can be retained to at least 1000°C.

The 9^(th) International Symposium on Refractories

Organizedby The Chinese Society for Metals The Chinese Ceramic Society Sinosteel Luoyang Institute of Refractories Research Co.,Ltd.Sponsored by Refractories Committee of The Chinese Society for Metals Sinosteel Luonai Materials Technology Corporation Co-Sponsoredby State Key Laboratory of Advanced Refractories The State Key Laboratory of Refractories and Metallurgy Refractories Press Indian Refractory Makers Association The Federation for International Refractory Research and Education.

Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab:A case report

BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

Glaucoma drainage device implantation and cyclophotocoagulation in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty

AIM:To compare the surgical outcomes of glaucoma drainage device implantation(GDI)and trans-scleral neodymium:YAG cyclophotocoagulation(CPC)in the management of refractory glaucoma after Descemetstripping automated endothelial keratoplasty(DSAEK).METHODS:This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery(15 with GDI and 14 with CPC).The main outcome measures were intraocular pressure(IOP),glaucoma surgery success rate(defined as IOP of 6–21 mm Hg without additional anti-glaucoma operation),number of glaucoma medications,endothelial graft status,and best-corrected visual acuity(BCVA).RESULTS:The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries,both for the GDI and CPC groups.Both groups showed significant IOP reduction after glaucoma surgery.The GDI group presented a significantly higher success rate in IOP control than the CPC group(60%vs 21.4%,P=0.03).Both procedures significantly decreased the number of glaucoma medications(P=0.03).Forty percent and 57%of cases in the GDI and the CPC group,respectively,experienced endothelial graft failure during follow-up(P=0.36).Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group.CONCLUSION:Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK.GDI is preferable to CPC in refractory glaucoma cases after DSAEK,as it manifests a significantly higher success rate for IOP control,similar endothelial graft failure rate,and relatively preserves BCVA than CPC.

Sporadic gastrinoma with refractory benign esophageal stricture:A case report

BACKGROUND Gastrinoma is characterized by an excessive release of gastrin,leading to hypersecretion of gastric acid,subsequently resulting in recurrent peptic ulcers,chronic diarrhea,and even esophageal strictures.This case report aims to improve awareness and facilitate early diagnosis and treatment of gastrinoma by presenting a rare case of gastrinoma with refractory benign esophageal stricture(RBES).Additionally,it highlights the persistent challenges that gastroenterologists encounter in managing RBES.CASE SUMMARY This case demonstrates a patient with gastrinoma who developed RBES and complete esophageal obstruction despite management with maximal acid suppressive therapy,multiple endoscopic bougie dilations and endoscopic incisional therapy(EIT).CONCLUSION It is essential to diagnose gastrinoma as early as possible,as inadequately controlled acid secretion over an extended period increases the risk of developing severe esophageal strictures.In patients with esophageal strictures causing complete luminal obstruction,blind reopening EIT presents challenges and carries a high risk of perforation.

Intermittent melena and refractory anemia due to jejunal cavernous lymphangioma:A case report

BACKGROUND Lymphangiomas in the gastrointestinal tract are extremely rare in adults.As a benign lesion,small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive diagnosis.However,lymphangiomas can give rise to complications such as abdominal pain,bleeding,volvulus,and intussusception.Here,we report a case of jejunal cavernous lymphangioma that presented with intermittent melena and refractory anemia in a male adult.CASE SUMMARY A 66-year-old man presented with intermittent melena,fatigue and refractory anemia nine months prior.Esophagogastroduodenoscopy and colonoscopy were performed many times and revealed no apparent bleeding.Conservative management,including transfusion,hemostasis,gastric acid secretion inhibition and symptomatic treatment,was performed,but the lesions tended to recur shortly after surgery.Ultimately,the patient underwent capsule endoscopy,which revealed a more than 10 cm lesion accompanied by active bleeding.After singleballoon enteroscopy and biopsy,a diagnosis of jejunal cavernous lymphangioma was confirmed,and the patient underwent surgical resection.No complications or recurrences were observed postoperatively.CONCLUSION Jejunal cavernous lymphangioma should be considered a cause of obscure gastrointestinal bleeding.Capsule endoscopy and single-balloon enteroscopy can facilitate diagnosis.Surgical resection is an effective management method.

New therapeutic strategy with extracorporeal membrane oxygenation for refractory hepatopulmonary syndrome after liver transplant: A case report

BACKGROUND Due to the lack of published literature about treatment of refractory hepatopulmonary syndrome(HPS)after liver transplant(LT),this case adds information and experience on this issue along with a treatment with positive outcomes.HPS is a complication of end-stage liver disease,with a 10%-30%incidence in cirrhotic patients.LT can reverse the physiopathology of this process and restore normal oxygenation.However,in some cases,refractory hypoxemia persists,and extracorporeal membrane oxygenation(ECMO)can be used as a rescue therapy with good results.CASE SUMMARY A 59-year-old patient with alcohol-related liver cirrhosis and portal hypertension was included in the LT waiting list for HPS.He had good liver function(Model for End-Stage Liver Disease score 12,Child-Pugh class B7).He had pulmonary fibrosis and a mild restrictive respiratory pattern with a basal oxygen saturation of 82%.The macroaggregated albumin test result was>30.Spirometry demonstrated a forced expiratory volume in one second(FEV1)of 78%,forced vital capacity(FVC)of 74%,FEV1/FVC ratio of 81%,diffusion capacity for carbon monoxide of 42%,and carbon monoxide transfer coefficient of 57%.He required domiciliary oxygen at 2 L/min(16 h/d).The patient was admitted to the intensive care unit(ICU)and extubated in the first 24 h,needing high-flow therapy and non-invasive ventilation and inhaled nitric oxide afterwards.Reintubation was needed after 72 h.Due to the non-response to supportive therapies,installation of ECMO was decided with progressive recovery after 9 d.Extubation was possible on the tenth day,maintaining a high-flow nasal cannula and de-escalating to conventional oxygen therapy after 48 h.He was discharged from ICU on postoperative day(POD)20 with a 90%-92%oxygen saturation.Steroid recycling was needed twice for acute rejection.The patient was discharged from hospital on POD 27 with no symptoms,with an 89%-90%oxygen saturation.CONCLUSION Due to the favorable results observed,ECMO could become the central axis of treatment of HPS and refractory hypoxemia after LT.

Manufacture of Industrial Refractory Crucibles Based on Clays from Burkina Faso

In Burkina Faso, one of the three largest gold producers in West Africa, foundry activity is often paralyzed when basic equipment such as crucibles and cups are not available or should be imported. However, previous studies have shown the availability of kaolinite-rich clay resources that could be used for the local manufacture of silico-aluminous ceramic crucibles. This work allowed to manufacture industrial ceramic crucibles with local clays and then they were tested in foundry industry. The materials were manufactured from three (03) raw materials including two clays (SAB and ROU) and sand. The chemical and mineral analysis has shown that the raw materials are suitable for the formulation of refractory materials. The results of characterization of the materials formulated showed that the properties of use are appreciable. The porosity of the materials is relatively low (23 - 28 vol%) with a diametral compressive strength between 0.61 and 1.34 MPa. Crucibles sintered at 1250˚C with a stay of 2 hours have a mechanical strength capable of supporting the weight of the ores contained. These crucibles have a refractoriness under load (T0.5) above 1141˚C and resist chemical attacks. Tests were carried out in the industry at 1100˚C, and the results were satisfactory.

Microwave-assisted Synthesis of Al_(4)SiC_(4) and Its Effect on Properties of MgO-C Refractories

Al_(4)SiC_(4) was synthesized from Al powder, silicon carbide, and graphite by microwave sintering, and characterized by XRD and SEM. Then the synthesized material was added to the magnesia carbon refractory brick to study its effect on the oxidation resistance, apparent porosity, bulk density, elastic modulus, and modulus of rupture. It is found that Al_(4)SiC_(4) can be synthesized by microwave sintering at 1 300 ℃ and the addition of Al_(4)SiC_(4)-containing material as an antioxidant can enhance the oxidation resistance of the magnesia carbon refractory brick.

Identification of the key genes and mechanisms associated with transcatheter arterial chemoembolisation refractoriness in hepatocellular carcinoma

BACKGROUND Transcatheter arterial embolisation(TACE)is the primary treatment for intermediate-stage hepatocellular carcinoma(HCC)patients while some HCC cases have shown resistance to TACE.AIM To investigate the key genes and potential mechanisms correlated with TACE refractoriness in HCC.METHODS The microarray datasets of TACE-treated HCC tissues,HCC and non-HCC tissues were collected by searching multiple public databases.The respective differentially expressed genes(DEGs)were attained via limma R package.Weighted gene co-expression network analysis was employed for identifying the significant modules related to TACE non-response.TACE refractoriness-related genes were obtained by intersecting up-regulated TACE-associated and HCC-associated DEGs together with the genes in significant modules related to TACE nonresponse.The key genes expression in the above two pairs of samples was compared respectively via Wilcoxon tests and standard mean differences model.The prognostic value of the key genes was evaluated by Kaplan-Meier curve.Multivariate analysis was utilised to investigate the independent prognostic factor in key genes.Single-cell RNA(scRNA)sequencing analysis was conducted to explore the cell types in HCC.TACE refractoriness-related genes activity was calculated via AUCell packages.The CellChat R package was used for the investigation of the cell–cell communication between the identified cell types.RESULTS HCC tissues of TACE non-responders(n=66)and TACE responders(n=81),HCC(n=3941)and non-HCC(n=3443)tissues were obtained.The five key genes,DLG associated protein 5(DLGAP5),Kinesin family member 20A(KIF20A),Assembly factor for spindle microtubules(ASPM),Kinesin family member 11(KIF11)and TPX2 microtubule nucleation factor(TPX2)in TACE refractoriness-related genes,were identified.The five key genes were all up-regulated in the TACE non-responders group and the HCC group.High expression of the five key genes predicted poor prognosis in HCC.Among the key genes,TPX2 was an independent prognostic factor.Four cell types,hepatocytes,embryonic stem cells,T cells and B cells,were identified in the HCC tissues.The TACE refractoriness-related genes expressed primarily in hepatocytes and embryonic stem cells.Hepatocytes,as the providers of ligands,had the strongest interaction with embryonic stem cells that provided receptors.CONCLUSION Five key genes(DLGAP5,KIF20A,ASPM,KIF11 and TPX2)were identified as promoting refractory TACE.Hepatocytes and embryonic stem cells were likely to boost TACE refractoriness.

Effect of ZrC Modified Graphite on Structure and Properties of Low-carbon Al_(2)O_(3)-C Refractories

To address the issues of reduced performance and shortened lifespan during the low-carbonizating process of Al_(2)O_(3)-C refractories,nano-crystalline ZrC modified graphite was prepared using Zr powder and flake graphite as raw materials,with NaCl and NaF mixed salt serving as the medium.The flake graphite was gradually replaced by ZrC modified graphite in the preparation of Al_(2)O_(3)-C refractories,and its impact on the material’s structure and properties was investigated.The results indicate that,compared to samples with only flake graphite,the introduction of 1 mass%to 5 mass%nano-crystalline ZrC modified graphite can significantly enhance the mechanical performance of low-carbon Al_(2)O_(3)-C refractories.When 5 mass%ZrC modified graphite is added,the mechanical properties of the samples are optimal,with the cold modulus of rupture and elastic modulus reaching 22.5 MPa and 65.0 GPa,respectively.

Effects of Al_(2)O_(3)-SiO_(2) Raw Material Types on Properties of Anorthite Based Insulation Refractories

To optimize their Al_(2)O_(3)-SiO_(2) raw materials,anorthite based insulation refractories were prepared by the in-situ sintering process combined with the foaming method after sintering at 1350℃for 3 h,using green and pollution-free kaolin,kyanite,andalusite and sillimanite as Al_(2)O_(3)-SiO_(2) raw materials,respectively,and industrial CaCO_(3) as the CaO source.Effects of Al_(2)O_(3)-SiO_(2) raw material types on the physical properties,phase composition and microstructure were investigated.The results are as follows.All samples prepared by different Al_(2)O_(3)-SiO_(2) raw materials have hexagonal flake anorthite and a small amount of mullite and corundum.Their bulk density and thermal conductivity decrease in the order of using kaolin,andalusite,kyanite and sillimanite as the Al_(2)O_(3)-SiO_(2) raw material,but their apparent porosity increases.Moreover,in the sample with kaolin,the bonding between anorthite crystals on the pore walls is closer than that of the other samples,which is conducive to increasing the cold crushing strength.The bonding between anorthite crystals on pore walls gradually decreases in the order of using kyanite,andalusite and sillimanite as the Al_(2)O_(3)-SiO_(2) raw material,thus their cold crushing strength decreases accordingly.In comprehensive consideration,the properties of the sample from kyanite are the optimal.Its apparent porosity,thermal conductivity and cold crushing strength are 84.6%,0.141 W·m^(-1)·K^(-1) and 1.89 MPa,respectively.

Sample Preparation for Monolithic Refractories Part 1:Refractory Castables

1 Scope This standard specifies the definition and test methods of flowability of dense and insulating refractory castables, and moulding equipment, moulding methods, curing and drying conditions of castables samples.

Third-line and rescue therapy for refractory Helicobacter pylori infection: A systematic review

BACKGROUND Due to increasing resistance rates of Helicobacter pylori(H.pylori)to different antibiotics,failures in eradication therapies are becoming more frequent.Even though eradication criteria and treatment algorithms for first-line and second-line therapy against H.pylori infection are well-established,there is no clear recommendation for third-line and rescue therapy in refractory H.pylori infection.AIM To perform a systematic review evaluating the efficacy and safety of rescue therapies against refractory H.pylori infection.METHODS A systematic search of available rescue treatments for refractory H.pylori infection was conducted on the National Library of Medicine’s PubMed search platform based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Randomized or non-randomized clinical trials and observational studies evaluating the effectiveness of H.pylori infection rescue therapies were included.RESULTS Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy,and 21 of these were selected for analysis of mean eradication rate as third-line treatment.For rifabutin-,sitafloxacin-,levofloxacin-,or metronidazole-based triple-therapy as third-line treatment,mean eradication rates of 81.6%and 84.4%,79.4%and 81.5%,55.7%and 60.6%,and 62.0%and 63.0%were found in intention-to-treat(ITT)and per-protocol(PP)analysis,respectively.For third-line quadruple therapy,mean eradication rates of 69.2%and 72.1%were found for bismuth quadruple therapy(BQT),88.9%and 90.9%for bismuth quadruple therapy,three-in-one,Pylera®(BQT-Pylera),and 61.3%and 64.2%for non-BQT)in ITT and PP analysis,respectively.For rifabutin-,sitafloxacin-,levofloxacin-,or metronidazole-based triple therapy as rescue therapy,mean eradication rates of 75.4%and 78.8%,79.4 and 81.5%,55.7%and 60.6%,and 62.0%and 63.0%were found in ITT and PP analysis,respectively.For quadruple therapy as rescue treatment,mean eradication rates of 76.7%and 79.2%for BQT,84.9%and 87.8%for BQT-Pylera,and 61.3%and 64.2%for non-BQT were found in ITT and PP analysis,respectively.For susceptibility-guided therapy,mean eradication rates as third-line and rescue treatment were 75.0%in ITT and 79.2%in PP analysis.CONCLUSION We recommend sitafloxacin-based triple therapy containing vonoprazan in regions with low macrolide resistance profile.In regions with known resistance to macrolides or unavailability of bismuth,rifabutin-based triple therapy is recommended.

Successful treatment of patients with refractory idiopathic membranous nephropathy with low-dose Rituximab:A single-center experience

BACKGROUND The recognition of idiopathic membranous nephropathy(IMN)as an autoimmune disease has paved the way for the use of B-cell-depleting agents,such as Rituximab(RTX),which is now a first-line drug for treating IMN with proven safety and efficacy.Nevertheless,the usage of RTX for the treatment of refractory IMN remains controversial and challenging.AIM To evaluate the efficacy and safety of a new low-dose RTX regimen for the treatment of patients with refractory IMN.METHODS A retrospective study was performed on refractory IMN patients that accepted a low-dose RTX regimen(RTX,200 mg,once a month for five months)in the Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences’Department of Nephrology from October 2019 to December 2021.To assess the clinical and immune remission data,we performed a 24 h urinary protein quantification(UTP)test and measured the serum albumin(ALB)and serum creatinine(SCr)levels,phospholipase A2 receptor(PLA2R)antibody titer,and CD19+B-cell count every three months.RESULTS A total of nine refractory IMN patients were analyzed.During follow-up conducted twelve months later,the results from the 24 h UTP decreased from baseline[8.14±6.05 g/d to 1.24±1.34 g/d(P<0.05)]and the ALB levels increased from baseline[28.06±8.42 g/L to 40.93±5.85 g/L(P<0.01)].Notably,after administering RTX for six months,the SCr decreased from 78.13±16.49μmol/L to 109.67±40.87μmol/L(P<0.05).All of the nine patients were positive for serum anti-PLA2R at the beginning,and four patients had normal anti-PLA2R titer levels at six months.The level of CD19+B-cells decreased to 0 at three months,and CD19+B-cell count remained at 0 up until six months of follow-up.CONCLUSION Our low-dose RTX regimen appears to be a promising treatment strategy for refractory IMN.

Chinese Standards on Refractories Dimensions of Refractory Bricks-Part 1:Specification for General Bricks

1 Scope This standard specifies the terms, definition, di-mension series, size designation representation, dimen-sion standard representation, brick dimension, and di- mension characteristics of general refractory bricks.

Comparison and development of machine learning for thalidomideinduced peripheral neuropathy prediction of refractory Crohn’s disease in Chinese population

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.