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Pyrotinib and chrysin synergistically potentiate autophagy in HER2-positive breast cancer

Signal Transduction and Targeted Therapy 2024年第1期9卷 295-307页

作者： Xiaoxiao Liu xing Zhang Zhiying Shao Xiaorong Zhong Xin Ding Liang Wu Jie chen Ping He Yan cheng Kunrui Zhu Dan Zheng Jing Jing Ting Luo Institute for Breast Health Medicine Cancer CenterBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Department of Radiation Oncology Cancer CenterAffiliated Hospital of Xuzhou Medical UniversityJiangsu Center for the Collaboration and Innovation of Cancer BiotherapyCancer InstituteXuzhou Medical University221000 XuzhouChina Department of Orthopedics Trauma and Reconstructive SurgeryUniversity Hospital RWTH AachenAachen 52074Germany Cancer Institute Xuzhou Medical University221000 XuzhouJiangsuChina Division of Nephrology and Transplantation Department of Internal MedicineUniversity Medical Center Rotterdam Erasmus MCRotterdam 3015 GDThe Netherlands Institute for Breast Health Medicine Department of General SurgeryBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Institute for Breast Health Medicine West China HospitalSichuan University610041 ChengduSichuanChina

Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor *** that pyrotinib,a new HER2 inhibitor,has led to dramatic improvements in prognosis,the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired ***,identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing ***,we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive *** determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest,inhibit the proliferation of BT-474 and SK-BR-3 BC cells,and repress in vivo tumor growth in xenograft mice *** may be attributed to enhanced autophagy induced by endoplasmic reticulum ***,the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase(G6PD)degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16(ZBTB16)in tumorigenesis of ***,we identified that miR-16-5p was a potential upstream regulator of ZBTB16,and it showed a significant inverse correlation with *** of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive ***,these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.

关键词： HER2 synergistic Together

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Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

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Cancer Biology & Medicine 2024年第5期21卷 433-444页

作者： Shuzhen Lai Peijing Li Xiaohui Liu Guihong Liu Tieming Xie xing Zhang Xiaoxuan Wang Jing Huang Yiqiang Tang Zhigang Liu Guoping Shen Chaoming Li Fangxiao Lu Lei Wang Fagui Jiang Caixing Sun Yuanyuan chen Ming chen Department of Radiation Oncology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000China Department of Radiation Oncology Yuebei People’s Hospital Affiliated to the Medical College of Shantou UniversityShaoguan 512026China Chinese Academy of SciencesHangzhou 310022China Department of Radiation Oncology The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhou 311403China Department of Radiation Oncology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221004China Chinese Academy of SciencesHangzhou 310022China State Key Laboratory of Translational Medicine and Innovative Drug Development Jiangsu Simcere Diagnostics Co.LtdNanjing 210000China Department of Radiation Oncology The Affiliated Huai’an First People’s Hospital of Nanjing Medical UniversityHuai’an 223399China Department of Radiation Oncology Jiangxi Cancer Hospital of Nanchang UniversityNanchang 330029China Department of Radiotherapy Dongguan Institute of Clinical Cancer ResearchDongguan Key Laboratory of Precision Diagnosis and Treatment for TumorsAffiliated Dongguan HospitalSouthern Medical UniversityDongguan 523059China The Cancer Center The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 519000China Department of Radiation Oncology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of Oncology Maoming People’s HospitalMaoming 525000China Department of Radiation Oncology Kecheng District People’s HospitalQuzhou 324003China Chinese Academy of SciencesHangzhou 310022China Department of Radiation Oncology State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhou 510060China United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University&Chinese Academy of Sciences Ion Medical Technology Co. LtdGuangzhou 510060China

Objective:Glioblastomas are highly vascularized malignant *** determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed ***:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November *** underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/*** primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned *** median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant *** patients discontinued treatment due to ***1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter ***:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable ***1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

关键词： Glioblastoma anti-angiogenesis multi-kinase inhibitor anlotinib temozolomide progression-free survival

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Therapeutic effect of manual massage on early postpartum rectus abdominis separation and postpartum depression

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World Journal of Psychiatry 2024年第5期14卷 678-685页

作者： Yun chen Xiao-Yan Sun cheng Qian Xiao-xing Zhang Yin-Jian Zhou Hong-Yun Zhang Zhen-Wei Xie Department of Gynecology Women’s Hospital School of Medicine Zhejiang UniversityHangzhou 310006Zhejiang ProvinceChina Department of Obstetrics and Gynecology Huzhou Maternity and Child Health Care HospitalHuzhou 313000Zhejiang ProvinceChina Department of Surgery Huzhou Maternity and Child Health Care HospitalHuzhou 313000Zhejiang ProvinceChina Department of Obstetrics Huzhou Maternity and Child Health Care HospitalHuzhou 313000Zhejiang ProvinceChina Department of Ultrasound Women’s Hospital School of Medicine Zhejiang UniversityHangzhou 310006Zhejiang ProvinceChina

BACKGROUND Rectus abdominis separation(DRA)affects pelvic stability and body *** studies have explored the effects of manual massage on early postpartum DRA and postpartum *** To analyze the curative effect of massage on early postpartum DRA and its impact on postpartum depression and thus its ability promote the overall psychosomatic rehabilitation of postpartum *** Data were retrospectively collected on 70 primiparous women with postpartum DRA who underwent rehabilitation at the Postpartum Rehabilitation Center of Huzhou Maternal and Child Health Hospital from October 2022 to September *** patients were divided into the Group S(35 cases,biomimetic electrical stimulation treatment)and Group L(35 cases,biomimetic electrical stimulation combined with manual massage treatment).Baseline data,the edinburgh postpartum depression scale(EPDS)score,and the visual analog scale(VAS)scores for rectus abdominis distance,waist circumference,and lower back pain before and after treatment were *** No significant differences were found in the baseline data,rectus abdominis distance,waist circumference,and VAS and EPDS scores between the two groups before treatment(P>0.05).After treatment,the distance between rectus abdominis and waist circumference in Group L were significantly smaller than those in Group S(P<0.05).Furthermore,lower back pain(VAS score)and the EPDS score in Group L were significantly lower than those in Group S(P<0.05).CONCLUSION Manual massage can significantly reduce early postpartum DRA,waist circumference,and back pain and improve the patient’s mental state and postpartum depression.

关键词： Manual massage Postpartum Rectus abdominis muscle separation Postpartum depression

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SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation

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Cancer Communications 2024年第3期44卷 384-407页

作者： Shiyu Zhang xing Jia Haojiang Dai xingxin Zhu Wenfeng Song Suchen Bian Hao Wu Shinuo chen Yangbo Tang Junran chen cheng Jin Mengqiao Zhou Haiyang Xie Shusen Zheng Penghong Song Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP.R.China National Health Commission Key Laboratory of Combined Multi-organ Transplantation HangzhouZhejiangP.R.China Key Laboratory of the Diagnosis and Treatment of Organ Transplantation Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic CancerChinese Academy of Medical SciencesHangzhouZhejiangP.R.China Key Laboratory of Organ Transplantation Research Center for Diagnosis and Treatment of Hepatobiliary DiseasesHangzhouZhejiangP.R.China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP.R.China

Background:Liver cancer is a malignancy with high morbidity and mortality *** family E member 2(SERPINE2)has been reported to play a key role in the metastasis of many *** this study,we aimed to investigate the potential mechanism of SERPINE2 in liver cancer ***:The Cancer Genome Atlas database(TCGA),including DNA methy-lation and transcriptome sequencing data,was utilized to identify the crucial oncogene associated with DNA methylation and cancer progression in liver *** from the TCGA and RNA sequencing for 94 pairs of liver cancer tissues were used to explore the correlation between SERPINE2 expression and clin-ical parameters of *** methylation sequencing was used to detect the DNA methylation levels in liver cancer tissues and *** sequencing,cytokine assays,immunoprecipitation(IP)and mass spectrometry(MS)assays,protein stability assays,and ubiquitination assays were performed to explore the regulatory mechanism of SERPINE2 in liver cancer ***-derived xenografts and tumor organoid models were established to determine the role of SERPINE2 in the treatment of liver cancer using ***:Based on the public database screening,SERPINE2 was identified as a tumor promoter regulated by DNA ***2 expression was significantly higher in liver cancer tissues and was associated with the dismal prognosis in patients with liver ***2 promoted liver cancer metas-tasis by enhancing cell pseudopodia formation,cell adhesion,cancer-associated fibroblast activation,extracellular matrix remodeling,and ***/MS assays confirmed that SERPINE2.activated epidermal growth factor receptor(EGFR)and its downstream signaling pathways by interacting with ***,SERPINE2 inhibited EGFR ubiquitination and maintained its protein stability by competing with the E3 ubiquitin ligase,***,EGFR was activated in liver cancer cells after sorafenib treatment,and SER

关键词： liver cancer metastasis DNA methylation SERPINE2 EGFR c-Cbl ubiquitination

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Artificial Intelligence and Network Pharmacology Reveal the Medication Rules of Professor Wang Yu-Ying in the Treatment of Climacteric Syndrome

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 180-190页

作者： Meng-Yuan Hu Tian-xing Yi Qi-Rui Liu Xin-Yu Zhang Ai-Ping chen Yu-Ying Wang Yi Lu School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijingChina

Objective: The objective of this study was to explore the medication rules and academic ideas of Professor Wang Yu-Ying in the treatment of climacteric syndrome(CLS) and to predict new prescriptions. Materials and Methods: The characteristics of frequency, clustering, four properties, and five flavors were analyzed, and new prescriptions were predicted through an artificial intelligence(AI)-based method. The potential pathways of new prescriptions were explored through network pharmacology-based analysis. Results: The top 16 medicinals used by Professor Wang Yu-Ying in the treatment of CLS included Danggui, Longgu, Muli, Fuling, Chuanxiong, Gancao, Xiangfu, and Tusizi. The AI method was applied to predict the basic prescription for treating CLS: Danggui 15 g, Duanlonggu 30 g, Duanmuli 30 g, Fuling 28 g, Chuanxiong 10 g, Gancao 6 g, Xiangfu 12 g, Tusizi 14 g, etc., Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the pathogenesis of CLS might be related to the estrogen pathway, involving typical steroid responses. Conclusions: This study summarized Professor Wang's medication experience in the treatment of CLS based on the data mining of clinical diagnoses and treatment cases. The AI method was used to predict the new prescription of CLS treatment, which was found to be reasonable by network pharmacology studies on its multi-target and multi-pathway mechanisms.

关键词： Artificial intelligence climacteric syndrome medication rules network pharmacology Professor Wang Yu-Ying

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Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

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World Journal of Gastroenterology 2024年第10期30卷 1346-1357页

作者： Jing-Feng chen Zhuo-Qing Wu Hao-Shuang Liu Su Yan You-Xiang Wang Miao xing Xiao-Qin Song Su-Ying Ding Health Management Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Institute of Systems Engineering Dalian University of TechnologyDalian 116024Liaoning ProvinceChina College of Public Health Zhengzhou UniversityZhengzhou 450001Henan ProvinceChina School of Basic Medicine and Forensic Medicine Henan University of Science and TechnologyLuoyang 471003Henan ProvinceChina

BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD *** A cohort of 3553 participants followed for four consecutive health examinations over 4 years was *** incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were *** proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset *** A total of 83.13%of participants with MAFLD had normal ALT *** incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT *** with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,*** Most participants with MAFLD had normal ALT ***-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

关键词： Metabolic dysfunction-associated fatty liver disease High-normal alanine aminotransferase level Cumulative effect Cox proportional hazards regression Cohort study

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西方戏剧叙事学研究的发展与困境

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当代外国文学 2024年第2期45卷 129-136页

作者：陈星南京大学外国语学院英语系

戏剧因传统上被定义为“非叙事”体裁而长期未被纳入经典叙事理论体系,直到跨媒介叙事研究逐步推进,西方学者才开始建构戏剧叙事理论。然而,虽然就理论层面而言,这一尝试让叙事理论的基本素材库得到补充、理论术语定义得到完善,但从实... 详细信息

戏剧因传统上被定义为“非叙事”体裁而长期未被纳入经典叙事理论体系,直到跨媒介叙事研究逐步推进,西方学者才开始建构戏剧叙事理论。然而,虽然就理论层面而言,这一尝试让叙事理论的基本素材库得到补充、理论术语定义得到完善,但从实践层面来看,戏剧叙事学理论在脱离语境的文本结构细读分析上不及经典叙事学研究细腻,在结合社会历史语境的作品分析上又不及其他理论指导下的戏剧研究深入。从其现有成果看,戏剧叙事理论建构并未实现更深刻、全面的戏剧阐释。

关键词：戏剧叙事学理论

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Vertical two-dimensional WS_(2)flakes grown on flexible CNT film for excellent electrochemical performance

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Rare Metals 2024年第1期43卷 164-174页

作者： Qian Gong Jing-Yun Zou Ming Ren Si-Qi Zhu Yu-Rong Zhou Li-Ming Zhao Jian chen Yu-Long Wu Jiang-Tao Di Li-xing Kang Qing-Wen Li School of Nano-Tech and Nano-Bionics University of Science and Technology of ChinaHefei 230026China Key Laboratory of Multifunctional Nanomaterials and Smart Systems Division of Advanced MaterialsSuzhou Institute of Nano-Tech and Nano-BionicsChinese Academy of SciencesSuzhou 215123China Jiangsu Key Laboratory of Micro and Nano Heat Fluid Flow Technology and Energy Application School of Physical Science and TechnologySuzhou University of Science and TechnologySuzhou 215009China

Soft electrochemical actuators that can generate mechanical motions in response to electrical stimuli can be used as artificial muscles in microscale *** electrode materials are the key component of the electrochemical actuator because they limit the ion diffusion and accumulation processes and thus affect the deformation in fast response-time and potential engineering ***-dimensional materials,such as one-dimensional(1D)CNT and two-dimensional(2D)vertically stood WS_(2),are great electrode due to their good electrochemical stability and high surface-to-volume ratios,but show limited performances when being used on their own in the actuators because of low reconstruction or low conductivity.A combination of 1D CNT and 2D WS_(2)could form a heterojunction with both high electrochemical activity and great mechanical ***,by depositing highly disordered graphene nanosheets(HDGNs)on CNT films and then WS_(2)on the formed low-dimensional nanocarbon film,a hybrid WS_(2)/HDGN/CNT film was synthesized through a multistep CVD *** grown WS_(2)nanosheets were achieved by taking advantage of HDGNs which limits CNTs ***,the volume expansion caused by the transition from WO_(3)to WS-2.an force the vertical growth of WS_(2).This hybrid film shows excellent electrochemical properties,such as high specific capacitance and high rate *** actuators based on the WS_(2)/HDGN/CNT films show good actuating performance,including stability and reconfigurability.

关键词： CNT Graphene Vertically growth WS_(2) Electrochemical actuators

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Insight into structural degradation of NCMs under extreme fast charging process

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Rare Metals 2024年第1期43卷 41-50页

作者： Yu Tang xing-Yu Wang Jin-Can Ren Bo-Wen chen Zhi-Yong Huang Wei Wang Ya-Lan Huang Bing-Hao Zhang Si Lan Zhang-Long He Qi Liu Hao He Department of Physics City University of Hong KongHong Kong 999077China Shenzhen Research Institute City University of Hong KongShenzhen 518057China College of Materials Science and Engineering Changsha University of Science&TechnologyChangsha 410114China

Lithium-ion batteries(LIBs)with extreme fast charging(XFC)capability are considered an effective way to alleviate range anxiety for electric vehicle(EV)*** to the high ionic and electronic conductivity of LiNi_(x)Co_(y)Mn_zO_(2)(x+y+z=1,NCM)cathodes,the inevitable Li plating of graphite in NCM|graphite cell is usually identified as a key bottleneck for XFC ***,the capacity decay mechanism of cathode materials under XFC has not been fully *** this work,three typical NCM cathode materials with different Ni fractions were chosen and their electrochemical performances under XFC associated with structural evolution were investigated.A faster capacity decay of NCMs under XFC conditions is observed,especially for Ni-rich ***-situ X-ray diffraction(XRD)reveals that the multiple caxis parameters appear at the high-voltage regions in Nirich NCMs,which is probably triggered by the larger obstruction of Li(de)***,NCMs with moderate Ni fraction also present a similar trend under XFC *** phenomenon is more detrimental to the structural and morphological stability,resulting in a faster capacity decay than that under low current *** work provides new insight into the degradation mechanism of NCMs under XFC conditions,which can promote the development of NCM cathode materials with XFC capability.

关键词： Lithium-ion batteries Ni fraction Extreme fast charging Structural evolution

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Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients

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Current Medical Science 2024年第4期44卷 771-788页

作者： Hong-xiang HUANG Pei-yuan ZHONG Ping LI Su-juan PENG Xin-jing DING Xiang-lian CAI Jin-hong chen Xie ZHUI Zhi-hui LUI xing-yu TAO Yang-yang LIU Li chen Department of Oncology The First Affiliated Hospital of Nanchang UniversityNanchang330006China Jiangxi Institute of Respiratory Disease The First Affiliated Hospital of Nanchang UniversityNanchang330006China Department of Oncology Jiangxi Provincial People’s HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchang330006China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Nanchang UniversityNanchang330006China

Objective The activities and products of carbohydrate metabolism are involved in key processes of ***,its relationship with hepatocellular carcinoma(HCC)is *** The cancer genome atlas(TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public *** expressed genes(DEGs)between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes(CRGs)to obtain differentially expressed CRGs(DE-CRGs).Then,univariate Cox and least absolute shrinkage and selection operator(LASSO)analyses were applied to identify risk model genes,and HCC samples were divided into high/low-risk groups according to the median risk ***,gene set enrichment analysis(GSEA)was performed on the risk model *** sensitivity of the risk model to immunotherapy and chemotherapy was also *** A total of 8 risk model genes,namely,G6PD,PFKFB4,ACAT1,ALDH2.aCYP1,OGDHL,ACADS,and TKTL1,were ***,the risk score,cancer status,age,and pathologic T stage were strongly associated with the prognosis of HCC *** the stromal score and immune score had significant negative/positive correlations with the risk score,reflecting the important role of the risk model in immunotherapy ***,the stromal and immune scores had significant negative/positive correlations with risk scores,reflecting the important role of the risk model in immunotherapy ***,we found that high-/low-risk patients were more sensitive to 102 drugs,suggesting that the risk model exhibited sensitivity to chemotherapy *** results of the experiments in HCC tissue samples validated the expression of the risk model *** Through bioinformatic analysis,we constructed a carbohydrate metabolism-related risk model for HCC,contributing to the prognosis prediction and treatment of HCC patients.

关键词： hepatocellular carcinoma carbohydrate metabolism the cancer genome atlas bioinformatics

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