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Perturbation of autophagy pathways in murine alveolar macrophage by 2D TMDCs is chalcogen-dependent

Journal of Environmental Sciences 2024年第1期135卷 97-107页

作者： Xiaofei Zhou Weitao jin Rui Zhang xuan Mao Jianbo Jia Hongyu Zhou College of Science&Technology Hebei Agricultural UniversityHuanghua 061100China Institute of Environmental Research at Greater Bay Area Key Laboratory for Water Quality and Conservation of the Pearl River DeltaMinistry of EducationGuangzhou UniversityGuangzhou 510006China

Increasing risks of incidental and occupational exposures to two-dimensional transition metal dichalcogenides(2D TMDCs)due to their broad application in various areas raised their public health concerns.While the composition-dependent cytotoxicity of 2D TMDCs has been well-recognized,how the outer chalcogenide atoms and inner transition metal atoms differentially contribute to their perturbation on cell homeostasis at non-lethal doses remains to be identified.In the present work,we compared the autophagy induction and related mechanisms in response to WS_(2),NbS_(2),WSe_(2)and Nb Se_(2)nanosheets exposures in MH-S murine alveolar macrophages.All these 2D TMDCs had comparable physicochemical properties,overall cytotoxicity and capability in triggering autophagy in MH-S cells,but showed outer chalcogen-dependent subcellular localization and activation of autophagy pathways.Specifically,WS_(2)and NbS_(2)nanosheets adhered on the cell surface and internalized in the lysosomes,and triggered m TOR-dependent activation of autophagy.Meanwhile,WSe_(2)and Nb Se_(2)nanosheets had extensive distribution in cytoplasm of MH-S cells and induced autophagy in an m TOR-independent manner.Furthermore,the 2D TMDCs-induced perturbation on autophagy aggravated the cytotoxicity of respirable benzo[a]pyrene.These findings provide a deeper insight into the potential health risk of environmental 2D TMDCs from the perspective of homeostasis perturbation.

关键词： Chalcogen group Autophagy pathway Cell function Endosomal escape Inhalation toxicity

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Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

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World Journal of Stem Cells 2024年第4期16卷 444-458页

作者： Cheng-jin Ai Ling-Juan Chen Li-xuan Guo Ya-Ping Wang Zi-Yi Zhao Department of Laboratory Medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Department of Ophthalmology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Central Laboratory Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Traditional Chinese Medicine Regulating Metabolic Diseases Key Laboratory of Sichuan Province Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

关键词： Leukemia stem cells Gossypol acetic acid Reactive oxygen species Mitochondrial dysfunction Interleukin 6/janus kinase 1/signal transducer and activator of transcription 3 signaling

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Preoperative prediction of perineural invasion of rectal cancer based on a magnetic resonance imaging radiomics model:A dual-center study

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World Journal of Gastroenterology 2024年第16期30卷 2233-2248页

作者： Yan Liu Bai-jin-Tao Sun Chuan Zhang Bing Li Xiao-xuan Yu Yong Du Department of Radiology The Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina Department of Radiology The Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina.duyong@***

BACKGROUND Perineural invasion(PNI)has been used as an important pathological indicator and independent prognostic factor for patients with rectal cancer(RC).Preoperative prediction of PNI status is helpful for individualized treatment of RC.Recently,several radiomics studies have been used to predict the PNI status in RC,demonstrating a good predictive effect,but the results lacked generalizability.The preoperative prediction of PNI status is still challenging and needs further study.AIM To establish and validate an optimal radiomics model for predicting PNI status preoperatively in RC patients.METHODS This retrospective study enrolled 244 postoperative patients with pathologically confirmed RC from two independent centers.The patients underwent preoperative high-resolution magnetic resonance imaging(MRI)between May 2019 and August 2022.Quantitative radiomics features were extracted and selected from oblique axial T2-weighted imaging(T2WI)and contrast-enhanced T1WI(T1CE)sequences.The radiomics signatures were constructed using logistic regression analysis and the predictive potential of various sequences was compared(T2WI,T1CE and T2WI+T1CE fusion sequences).A clinical-radiomics(CR)model was established by combining the radiomics features and clinical risk factors.The internal and external validation groups were used to validate the proposed models.The area under the receiver operating characteristic curve(AUC),DeLong test,net reclassification improvement(NRI),integrated discrimination improvement(IDI),calibration curve,and decision curve analysis(DCA)were used to evaluate the model performance.RESULTS Among the radiomics models,the T2WI+T1CE fusion sequences model showed the best predictive performance,in the training and internal validation groups,the AUCs of the fusion sequence model were 0.839[95%confidence interval(CI):0.757-0.921]and 0.787(95%CI:0.650-0.923),which were higher than those of the T2WI and T1CE sequence models.The CR model constructed by combining clinical risk factors had the best predictive

关键词： Rectal cancer Perineural invasion Magnetic resonance imaging Radiomics Nomogram

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Microstructural Evolutions and Mechanical Properties of Energetic Al_(1) (TiZrNbTaMoCr)_(15) High-Entropy Alloys

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Acta Metallurgica Sinica(English Letters) 2024年第4期37卷 620-632页

作者： xuan-Hong Cai Zhen-Hua Wang Ben Niu jin-Feng Li Qing Wang Show authors Key Laboratory of Materials Modification By Laser Ion and Electron Beams(Ministry of Education)Engineering Research Center of High Entropy Alloy Materials(Liaoning Province)School of Materials Science and EngineeringDalian University of TechnologyDalian116024China Institute of Materials China Academy of Engineering PhysicsMianyang621908China

The present study focuses on investigating the microstructural evolutions and mechanical properties of energetic Al_(1)(TiZrNbTaMoCr)_(15) refractory high-entropy alloys with the different heat treatments at low Al content state. It is found that even with a reduction in the Al content, the strength of these alloys remains unaffected at room temperature and high temperature, while the plasticity improves significantly. In particular, the coherent BCC/B_(2) microstructure with needle-like B_(2) nanoprecipitates dispersed into the BCC matrix is formed in 873 K-aged Al_(1)Ti_(6)Zr_(2)Nb_(3)Ta_(3)Mo_(0.5)Cr_(0.5) alloy. Therefore, this alloy exhibits the highest compression yield strength (σ_(YS) = 1333 and 717 MPa) at room temperature and 1073 K, respectively. After 973 K-aged, the coherent BCC/B_(2) microstructure underwent destabilization, and the B_(2) phase transforms into the brittle Zr5Al3 phase which then coarsens and dominates the microstructure of S3-AlTa_(3) alloy after 1073 K-aged. Moreover, these current alloys exhibit exceptionally high theoretical exothermic enthalpy (ΔH), surpassing 11606 J·g^(−1), which highlights their significant potential as innovative high-performance energetic structural materials.

关键词： Refractory high-entropy alloy Coherent microstructure Mechanical property Exothermic enthalpy

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PPP1R14A is Associated with Immunotherapy Resistance in Head and Neck Squamous Cell Carcinoma Identified by Single-Cell and Bulk RNA-Sequencing

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Chinese Medical Sciences Journal 2024年第2期39卷 111-121页

作者： Jun-Jie Ma Lei Zhang jin Lu Hao-xuan Zhang Department of Clinical Medicine Bengbu Medical UniversityBengbu 233030AnhuiChina Department of General Surgery The Second Affiliated Hospital of Bengbu Medical UniversityBengbu 233030AnhuiChina Department of Human Anatomy Bengbu Medical UniversityBengbu 233030AnhuiChina Anhui Key Laboratory of Computational Medicine and Intelligent Health Bengbu Medical UniversityBengbu 233030AnhuiChina

Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.

关键词： PPP1R14A head and neck squamous cell carcinoma immunotherapy drug resistance

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Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 300-309页

作者： Qing Huang Jia-Wen Liu Hai-Bin Dong Zheng-Jie Wei jin-Zhe Liu Yu-Tang Ren xuan Jiang Bo Jiang Department of Gastroenterology Beijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 102218China

Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the int

关键词： Acute pancreatitis Mesenteric adipose tissue B lymphocyte Intestinal barrier Pyroptosis

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Lipase and photodecarboxylase coexpression: A potential strategy for alkane-based biodiesel production from natural triglycerides

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Chinese Journal of Chemical Engineering 2024年第3期67卷 238-246页

作者： Yong-Yi Zeng Xin-Yi Xu jin-xuan Xie Wen-Li Chen Lan Liu Xin-Jian Yin Bi-Shuang Chen School of Marine Sciences Sun Yat-Sen UniversityZhuhai 519080China Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) Zhuhai 519080China

Alkane-based biodiesel is considered the next generation of biodiesel owing to its potential environmental benefits and the fact that it exhibits much higher specific caloric values than traditional biodiesel.However,the formidable obstacle impeding the commercialization of this cutting-edge fuel alternative lies in the cost associated with its production.In this study,an engineered strain Escherichia coli(E.coli)showcasing harmonized coexpression of a lipase(from Thermomyces lanuginosus lipase,TLL)and a fatty acid photodecarboxylase(from Chlorella variabilis,CvFAP)was first constructed to transform triglycerides into alkanes.The potential of E.coli BL21(DE3)/pRSFDuet-1-TLL-CvFAP for alkane synthesis was evaluated with tripalmitin as a model substrate under various process conditions.Following a comprehensive examination of the reaction parameters,the scope of the biotransformation was expanded to‘real’substrates(vegetable oils).The results showed that bioderived oils can be transformed into alkanes with high yields(0.80-10.20 mmol·L^(-1))under mild conditions(35℃,pH 8.0,and 36 h)and blue light illumination.The selected processes were performed on an increased lab scale(up to 100 ml)with up to 24.77 mmol·L^(-1) tripalmitin,leading to a yield of 18.89 mmol·L^(-1) pentadecane.With the employment of a method for efficiently producing alkanes under mild conditions and a simple procedure to isolate alkanes from the reaction system,the utilization of sustainable biomass as a fundamental feedstock emerges as the primary solution to lower the cost of alkane-based biodiesel.Thus,this study proposes a readily implementable and highly effective approach for alkane-based biodiesel production.

关键词： Alkane-based biodiesel Renewable biomass Co-overexpression Lipase Photodecarboxylase

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Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 554-570页

作者： Yin-xuan Pei Chen-Guang Su Zheng Liao Wei-Wei Li Zi-Xiang Wang jin-Long Liu Department of Hepatobiliary Surgery The Affiliated Hospital of Chengde Medical UniversityChengde 067000Hebei ProvinceChina

BACKGROUND For resectable hepatocellular carcinoma(HCC),radical hepatectomy is commonly used as a curative treatment.However,postoperative recurrence significantly diminishes the overall survival(OS)of HCC patients,especially with microva-scular invasion(MVI)as an independent high-risk factor for recurrence.While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients,the specific role of adju-vant therapies in those with MVI remains unclear.AIM To conduct a network meta-analysis(NMA)to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen.METHODS A systematic literature search was conducted on PubMed,EMBASE,and Web of Science until April 6,2023.Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included.Hazard ratios(HRs)with 95%confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA.RESULTS Fourteen eligible trials(2268 patients)reporting five different therapies were included.In terms of reducing the risk of recurrence,radiotherapy(RT)[HR=0.34(0.23,0.5);surface under the cumulative ranking curve(SUCRA)=97.7%]was found to be the most effective adjuvant therapy,followed by hepatic artery infusion chemotherapy[HR=0.52(0.35,0.76);SUCRA=65.1%].Regarding OS improvement,RT[HR:0.35(0.2,0.61);SUCRA=93.1%]demonstrated the highest effectiveness,followed by sorafenib[HR=0.48(0.32,0.69);SUCRA=70.9%].INTRODUCTION Hepatocellular carcinoma(HCC)is the sixth most common malignant tumor in the world and ranks third in terms of worldwide malignant tumor mortality rates in 2020[1].Curative treatments for HCC include ablation,radical hepatectomy,and liver transplantation.However,ablation is suitable only for early-stage HCC patients,who represent a small percentage of the overall HCC population.Although liver transplantation serves as the optimal treatment for HCC patients,the scarcity of donor or

关键词： Hepatocellular carcinoma Adjuvant therapy Network meta-analysis Transarterial chemoembolization Hepatic artery infusion chemotherapy Radiotherapy Sorafenib

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Automatic velocity picking based on optimal key points tracking algorithm

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Petroleum Science 2024年第2期21卷 903-917页

作者： Yong-Hao Wang Wen-Kai Lu Song-Bai jin Yang Li Yu-xuan Li Xiao-Feng Gu The Institute for Artificial Intelligence(THUAI) Tsinghua UniversityBeijing100084China State Key Laboratory of Intelligent Technology and Systems Tsinghua UniversityBeijing100084China Beijing National Research Center for Information Science and Technology(BNRist) Beijing100084China The Department of Automation Tsinghua UniversityBeijing100084China

Picking velocities from semblances manually is laborious and necessitates experience. Although various methods for automatic velocity picking have been developed, there remains a challenge in efficiently incorporating information from nearby gathers to ensure picked velocity aligns with seismic horizons while also improving picking accuracy. The conventional method of velocity picking from a semblance volume is computationally demanding, highlighting a need for a more efficient strategy. In this study, we introduce a novel method for automatic velocity picking based on multi-object tracking. This dynamic tracking process across different semblance panels can integrate information from nearby gathers effectively while maintaining computational efficiency. First, we employ accelerated density clustering on the velocity spectrum to discern cluster centers without the requirement for prior knowledge regarding the number of clusters. These cluster centers embody the maximum likelihood velocities of the main subsurface structures. Second, our proposed method tracks key points within the semblance volume. Kalman filter is adopted to adjust the tracking process, followed by interpolation on these tracked points to construct the final velocity model. Our synthetic data example demonstrates that our proposed algorithm can effectively rectify the picking errors of the clustering algorithm. We further compare the performances of the clustering method(CM), the proposed tracking method(TM), and the variational method(VM) on a field dataset from the Gulf of Mexico. The results attest that our method offers superior accuracy than CM, achieves comparable accuracy with VM, and benefits from a reduced computational cost.

关键词： Velocity picking Multi-object tracking Density clustering Kalman filter

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UPLC-Q-TOF/MS-Based Serum Metabolomics Reveals Potential Anti-tumor Mechanism of Banxia Xiexin Decoction in Colorectal Cancer Mice

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Chinese Journal of Integrative Medicine 2024年第7期30卷 623-632页

作者： YUE Yin-zi LI Ming-xuan WANG Xiao-hui QIN Yuan-yuan WANG Ya-hui TAN jin-hua SU Lian-lin YAN Shuai Department of General Surgery Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine School of Pharmacy Nanjing University of Chinese Medicine Department of General Surgery Bayinguoleng Mongolian Autonomous Prefecture People's Hospital Department of Pharmacy Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine Department of Anorectal Surgery Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine

Objective: To clarify the potential mechanism of Banxia Xiexin Decoction(BXD) on colorectal cancer(CRC) from the perspective of metabolomics. Methods: Forty male C57BL/6 mice were randomly divided into normal control(NC), azoxymethane/dextran sulfate sodium(AOM/DSS) model, low-dose BXD(L-BXD), high-dose BXD(H-BXD) and mesalamine(MS) groups according to a random number table, 8 mice in each group. Colorectal cancer model was induced by AOM/DSS. BXD was administered daily at doses of 3.915(L-BXD) and 15.66 g/kg(H-BXD) by gavage for consecutive 21 days, and 100 mg/kg MS was used as positive control. Following the entire modeling cycle, colon length of mice was measured and quantity of colorectal tumors were counted. The spleen and thymus index were determined by calculating the spleen/thymus weight to body weight. Inflammatory cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry(UPLC-Q/TOF-MS), respectively. Results: Notably, BXD supplementation protected against weight loss, mitigated tumor formation, and diminished histologic damage in mice treated with AOM/DSS(P<0.05 or P<0.01). Moreover, BXD suppressed expression of serum inflammatory enzymes, and improved the spleen and thymus index(P<0.05). Compared with the normal group, 102 kinds of differential metabolites were screened in the AOM/DSS group, including 48 potential biomarkers, involving 18 main metabolic pathways. Totally 18 potential biomarkers related to CRC were identified, and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, nitrogen metabolism and so on. Conclusion: BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation, protecting organism immunity ability, and regulating amino acid metabolism.

关键词： colorectal cancer metabolomics ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry azoxymethane dextran sulfate sodium Banxia Xiexin Decoction Chinese medicine

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