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Immunosenescence:molecular mechanisms and diseases

Signal Transduction and Targeted Therapy 2023年第6期8卷 2671-2686页

作者： Zaoqu Liu Qimeng Liang Yuqing Ren Chunguang Guo Xiaoyong Ge Libo Wang Quan Cheng Peng Luo Yi Zhang Xinwei Han department of interventional radiology The First Affiliated Hospital of Zhengzhou University450052ZhengzhouHenanChina interventional Institute of Zhengzhou university 450052ZhengzhouHenanChina interventional Treatment and Clinical Research Center of Henan Province 450052ZhengzhouHenanChina Nephrology hospital the First Affiliated Hospital of Zhengzhou UniversityZhengzhou University4500052HenanChina department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou University450052ZhengzhouHenanChina department of Endovascular Surgery The First Affiliated Hospital of Zhengzhou University450052ZhengzhouHenanChina department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou University450052ZhengzhouHenanChina department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaChina department of Oncology Zhujiang HospitalSouthern Medical UniversityGuangzhouChina Biotherapy Center and Cancer Center The First Affiliated Hospital of Zhengzhou University450052ZhengzhouChina

Infection susceptibility,poor vaccination efficacy,age-related disease onset,and neoplasms are linked to innate and adaptive immune dysfunction that accompanies aging(known as immunosenescence).During aging,organisms tend to develop a characteristic inflammatory state that expresses high levels of pro-inflammatory markers,termed *** chronic inflammation is a typical phenomenon linked to immunosenescence and it is considered the major risk factor for age-related *** involution,naïve/memory cell ratio imbalance,dysregulated metabolism,and epigenetic alterations are striking features of *** T-cell pools and chronic antigen stimulation mediate premature senescence of immune cells,and senescent immune cells develop a proinflammatory senescence-associated secretory phenotype that exacerbates *** the underlying molecular mechanisms remain to be addressed,it is well documented that senescent T cells and inflammaging might be major driving forces in *** counteractive measures will be discussed,including intervention of cellular senescence and metabolic-epigenetic axes to mitigate *** recent years,immunosenescence has attracted increasing attention for its role in tumor *** a result of the limited participation of elderly patients,the impact of immunosenescence on cancer immunotherapy is *** some surprising results from clinical trials and drugs,it is necessary to investigate the role of immunosenescence in cancer and other age-related diseases.

关键词： metabolism neoplasms alterations

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Inhibited experimental corneal neovascularization by neutralizing anti-SDF-1α antibody

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International Journal of Ophthalmology(English edition) 2012年第1期5卷 7-12页

作者： Gao-Qin Liu, Xue-Guang Zhang department of Ophthalmology the First Affiliated Hospital of Soochow University Suzhou 215006 Jiangsu Province China Jiangsu Institute of Clinic Immunology the First Affiliated Hospital of Soochow University Suzhou 215006 Jiangsu Province China

AIM: To explore the effect of SDF-1α on the development of experimental corneal neovascularization (CRNV).METHODS: CRNV was induced by alkali injury in mice. The expression of SDF-1α and CXCR4 in burned corneas was examined by Flow Cytometry. Neutralizing anti-mouse SDF-1α antibody was locally administrated after alkali injury and the formation of CRNV 2 weeks after injury was assessed by Immunohistochemistry. The expression of VEGF and C-Kit in burned corneas was detected by ***: The number of CRNV peaks at 2 weeks after alkali injury. Compared to control group, SDF-1α neutralizing antibody treatment significantly decreased the number of CRNV. RT-PCR confirmed that SDF-1α neutralizing antibody treatment resulted in decreased intracorneal VEGF and C-Kit ***: SDF-1α neutralizing antibody treated mice exhibited impaired experimental CRNV through down regulated VEGF and C-Kit expression.

关键词： corneal neovascularization alkali injury chemokine

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Inhibitory effect of CCR3 signal on alkali-induced corneal neovascularization

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International Journal of Ophthalmology(English edition) 2012年第3期5卷 251-257页

作者： Wen-Juan Zhou, Pei-Rong Lu department of Ophthalmology the First Affiliated Hospital of Soochow University Suzhou 215006 Jiangsu Province China Jiangsu Institute of Clinic Immunology the First Affiliated Hospital of Soochow University Suzhou 215006 Jiangsu Province China

AIM: To investigate the effect of CC chemokine receptor 3 (CCR3) signal on corneal neovascularization (CRNV) induced by alkali burn and to explore its mechanism. METHODS: Specific pathogen-free male BALB/C mice (aged 6-8 weeks) were randomly divided into CCR3-antagonist treated group (experimental group) and control group. CRNV was induced by alkali burn in mice. The time kinetic CCR3 expression in injured corneas was examined by reverse transcription polymerase chain reaction (RT-PCR). CCR3-antagonist (SB-328437 at different concentration of 125 mu g/mL, 250 mu g/mL, and 500 mu g/mL) was locally administrated after alkali injury. The formation of CRNV was assessed by CD31 corneal whole mount staining at two weeks after injury. Monocyte chemotactic protein 1 (MCP-1), monocyte chemotactic protein 3 (MCP-3) expressions in the early phase after injury were quantified and compared by RT-PCR. Macrophage intracorneal accumulation in the early phase after injury was evaluated and compared by immunohistochemistry. RESULTS: Alkali injury induced the time kinetic intracorneal CCR3 expression. 500 mu g/mL of CCR3-antagonist treatment in the early phase but not the late phase resulted in significant impaired CRNV as compared to control group (P <0.05). CCR3-antagonist treatment in the early phase significantly reduced the intracorneal MCP-1 and MCP-3 enhancement compare to control group at day 2 and day 4 (P <0.05). Moreover, the number of intracorneal macrophage infiltration in the experimental group was reduced than those in control group at day 4 (P <0.05). CONCLUSION: CCR3 signal is involved in alkali-induced CRNV. CCR3-antagonist can inhibit alkali-induced CRNV by reducing the intracorneal MCP-1 and MCP-3 mRNA expression and the intracorneal macrophage infiltration.

关键词： corneal neovascularization CCR3 monocyte chemotactic protein 1 monocyte chemotactic protein 3 macrophage

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Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study

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World Journal of Gastroenterology 2020年第6期26卷 657-669页

作者： Zhe-Xuan Wang En-Xin Wang Wei Bai Dong-Dong Xia Wei Mu Jing Li Qiao-Yi Yang Ming Huang Guo-Hui Xu Jun-Hui Sun Hai-Liang Li Hui Zhao Jian-Bing Wu Shu-Fa Yang Jia-Ping Li Zi-Xiang Li Chun-Qing Zhang Xiao-Li Zhu Yan-Bo Zheng Qiu-He Wang Jing Li Jie Yuan Xiao-Mei Li Jing Niu Zhan-Xin Yin Jie-Lai Xia Dai-Ming Fan Guo-Hong Han China HCC-TACE Study Group department of Liver Disease and Digestive interventional radiology National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’an 710032Shaanxi ProvinceChina department of radiology the Southwest HospitalThird Military Medical UniversityChongqing 400037China department of Hepatobiliary Surgery the Second Affiliated Hospital of Third Military Medical UniversityChongqing 400037China department of Minimally Invasive International Therapy the Third Affiliated Hospital of Kunming UniversityTumor Hospital of Yunnan ProvinceKunming 650000Yunnan ProvinceChina department of interventional radiology Tumor Hospital of Sichuan ProvinceChengdu 610000Sichuan ProvinceChina department of Hepatobiliary and Pancreatic interventional Cancer the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvinceChina department of interventional radiology Henan Cancer Hospitalthe Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450008Henan ProvinceChina department of interventional radiology the Affiliated Hospital of Nantong UniversityNantong 226001Jiangsu ProvinceChina department of Oncology the Second Affiliated Hospital of Nanchang UniversityNanchang 330000Jiangxi ProvinceChina department of interventional radiology the Affiliated Tumor Hospital of Xinjiang Medical UniversityUrumqi 830001Xinjiang Uygur Autonomous RegionChina department of interventional radiology the First Affiliated Hospital of Sun Yatsen UniversityGuangzhou 510080Guangdong ProvinceChina department of interventional Medical Center the Affiliated Hospital of Qingdao UniversityQingdao 266000Shandong ProvinceChina department of Gastroenterology and Hepatology Shandong Province Hospital affiliated to Shandong UniversityJinan 250021Shandong ProvinceChina department of interventional radiology The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina department of interventional Radi

BACKGROUND The treatment outcome of transarterial chemoembolization(TACE)in unresectable hepatocellular carcinoma(HCC)varies greatly due to the clinical heterogeneity of the ***,several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE(re-TACE).AIM To investigate the correlations between prognostic systems and radiological response,compare the predictive abilities,and integrate them in sequence for outcome *** This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May *** Hepatoma Arterial-embolization Prognostic(HAP)score system and its modified versions(mHAP,mHAP2 and mHAP3),as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival(OS)prediction for first *** same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART(assessment for re-treatment with TACE)and ABCR(alpha-fetoprotein,Barcelona Clinic Liver Cancer,Child-Pugh and Response)systems for post re-TACE survival(PRTS).RESULTS All the prognostic systems were correlated with radiological response achieved by first TACE,and the six-and-twelve criteria exhibited the highest correlation(Spearman R=0.39,P=0.026)and consistency(Kappa=0.14,P=0.019),with optimal performance by area under the receiver operating characteristic curve of 0.71[95%confidence interval(CI):0.68-0.74].With regard to the prediction of OS,the mHAP3 system identified patients with a favorable outcome with the highest concordance(C)-index of 0.60(95%CI:0.57-0.62)and the best area under the receiver operating characteristic curve at any time point during follow-up;whereas,PRTS was well-predicted by the ABCR system with a C-index of 0.61(95%CI:0.59-0.63),rather than ***,combining the mHAP3 and ABCR systems identified candidates suitable for TA

关键词： Transarterial chemoembolization Hepatocellular carcinoma Prognostic system Radiological response Overall survival Predictive ability

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Therapeutic Characterization of ^(131)I-Labeled Humanized Anti-B7-H3 Antibodies for Radioimmunotherapy for Glioblastoma

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Engineering 2023年第11期30卷 190-202页

作者： Fengqing Fu Meng Zheng Shandong Zhao Yan Wang Minzhou Huang Hanqing Chen Ziyi Huang Kaijie Zhang Liyan Miao Xueguang Zhang Jiangsu Institute of Clinical Immunology the First Affiliated Hospital of Soochow UniversitySuzhou 215000China State Key Laboratory of Radiation Medicine and Protection Soochow UniversitySuzhou 215123China department of Clinical Pharmacology the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Suzhou Bright Scistar Antibody Biotech.Co. Ltd.Suzhou 215152China Institute for Interdisciplinary Drug Research and Translational Sciences College of Pharmaceutical SciencesSoochow UniversitySuzhou 215123China department of Hematology the First Affiliated Hospital of Soochow UniversitySuzhou 215000China

B7 homolog 3(B7-H3)has attracted much attention in glioblastoma(GBM)radioimmunotherapy(RIT)due to its abnormally high expression on tumor *** this study,we report that two specific humanized anti-human B7-H3 antibodies(hu4G4 and hu4H12)derived from mouse anti-human B7-H3 antibodies that were generated by computer-aided design and exclusively recognize membrane expression of B7-H3 by human glioma cells,Hu4G4 and hu4H12 were radiolabeled with^(89)Zr for RIT antibody ***-positron emission tomography(PET)imaging,biodistribution and pharmacokinetic(PK)analyses of^(89)Zr-labeled antibodies were performed in U87-xenografted models.^(125)I labelling of the antibodies for single-photon emission computed tomography(SPECT)imaging was also used to investigate the biological behavior of the antibodies in *** rthermore,the pharmacodynamic(PD)of the^(131)Ilabeled antibodies were evaluated in U87-xenografted mice and GL261 Red-FLuc-B7-H3 in situ glioma tumor ***-PET imaging and biodistribution analysis with a gamma counter showed that^(89)Zr-deferoxamine(DFO)-hu4G4 had higher tumor targeting performance with lower liver uptake than^(89)Zr-DFO-(hu4H12,immunoglobulin G(IgG)).The biodistribution results of^(125)I-SPECT imaging were similar to those of^(89)Zr-PET imaging,though the biodistribution in long bone joints and the thyroid *** PD analysis results indicated that^(131)I-hu4G4 had an excellent therapeutic effect and high safety with no apparent ***,^(131)I-hu4G4 improved the tumor vasculature in tissues with higher expression of collagen typeⅣand platelet-derived growth factor receptorβ(PDGFR-β)compared with control treatment,as determined by immunofluorescence(IF),which contributed to inhibiting tumor *** together,our data indicate that hu4G4 exhibits good tumor targeting and specificity,achieves low nonspecific concentrations in normal tissues,and has acceptable PK characteristics.^(131)I-hu4G4 also exerts effect

关键词： B7-H3 Radioimmunotherapy Glioblastoma Pharmacokinetics Pharmacodynamics

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Piezo1-targeted aerosol inhalation nanoparticles for acute lung injury

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Journal of Materials Science & Technology 2023年第10期141卷 21-31页

作者： Xinxin Liu Xuwei Ling Jiachen He Xingzhi Liu Lin Wang Huiling Liu Chang Liu Yi Wang Xiao Lin Chunhua Ling Qin Shi department of Respiratory Medicine the First Affiliated Hospital of Soochow UniversitySuzhou 215031China department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Gannan Medical University/Gannan Branch of National Clinical Research Center for GeriatricsGanzhou 341000China department of Orthopedics the First Affiliated Hospital of Soochow UniversityOrthopedic Institute of Soochow UniversitySuzhou 215031China School of Nano-Tech and Nano-Bionics University of Science and Technology of ChinaSuzhou 215123China university of Science and Technology of China Hefei 230026China National Clinical Research Center for Hematologic Diseases the First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215031China

Inhaled drug-containing nanocarriers have been well applied as an important strategy in pulmonary *** lung injury(ALI)is characterized by abnormal lung tension and complex pathogenesis,with high mortality because of the limitations of targeted ***,in the present study,we first identified that the mechanosensitive ion channel Piezo1 participated in the ALI-associated processes induced by lipopolysaccharide(LPS)in vitro and in ***,chitosan-stabilized bovine serum albu-min nanoparticles(NCs)emulsified with the Piezo1 inhibitor GsMTx4(NC-GsMTx4)were generated and exhibited excellent biocompatibility and biological *** aerosol inhalation,NC-GsMTx4 im-proved lung injury and inhibited cell apoptosis in LPS-stressed ALI mice and alleviated pulmonary fibrosis during the later stage of ***,GsMTx4 could regulate inflammation and apoptosis in lung epithelial cells via NF-κB and ERK1/2 *** summary,our findings provide new insights into the pathological mechanisms of Piezo1 in ALI progression,and nebulized inhalation of NC-GsMTx4 offers a prospective platform for targeting Piezo1 to treat ALI efficiently and conveniently.

关键词： Acute lung injury Piezo1 Nanoparticle carrier NF-κB ERK1/2 GsMTx4

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Inhibition of viability of human retinal microvascular endothelial cells by vialinin A under high glucose condition

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1809-1815页

作者： Zhi-Gang Chen Gao-Qin Liu Wei-Ming Liu Pei-Rong Lu department of Ophthalmology the First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Jiangsu Clinical Immunology Institute the First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina

AIM:To investigate the effects of vialinin A on viability of human retinal endothelial cells(HRECs)under high glucose condition and its potential ***:The HRECs were divided into four groups:normal glucose control group(NG,5 mmol/L D-glucose),high glucose group(HG,30 mmol/L D-glucose),HG+1μmol/L vialinin A group,and HG+5μmol/L vialinin A *** cell viabilities were measured with cell counting kit-8(CCK-8)assay for proliferation,with scratch assay for migration,and tube formation,for evaluation of the impact of vialinin A on cellular ***-time PCR and Western blotting were used to determine the expression level of vascular endothelial growth factor(VEGF).RESULTS:The proliferative capacity and migration of HRECs was reduced by 5μmol/L vialinin A in high glucose environment(both P<0.05).Vialinin A also inhibited highglucose-induced tube formation of *** expression level of VEGF and PI3K in HRECs was also significantly decreased by vialinin A(P<0.05).CONCLUSION:Vialinin A inhibits the cell viability of *** may serve as a potential target for anti-angiogenic therapy.

关键词： vialinin A vascular endothelial growth factor human retinal endothelial cells cell viability

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Time trends and gender disparities of Chinese cataract burden and their predictions

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International Journal of Ophthalmology(English edition) 2023年第9期16卷 1527-1534页

作者： Tian-Hong Wu Bo Jiang Wei-Ming Liu Jian-Qing Li Zi-Yue Song Pei-Rong Lu department of Ophthalmology the First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina

AIM:To evaluate the trends and changes in the number and rates of disability-adjusted life years(DALYs)and prevalence of cataract in China between 1990 and 2019,and to predict the trends of cataract burden from 2020 to ***:The Global Burden of Diseases(GBD)database was employed to collect the data on DALYs and the prevalence of cataract in China,which was distinguished by age and sex during the past three decades from 1990 to 2019,and then changes in the number and rates of cataract from 2020 to 2030 were *** data were analyzed by the R program(version 4.2.2)and GraphPad Prism 9.0 statistics ***:The number of DALYs of cataract increased from 449322.84 in 1990 to 1087987.61 in 2019,number of cataract cases increased from 5607600.94 in 1990 to 18142568.96 in *** age-standardized DALY rates(ASDR)generally increased slightly[estimated annual percentage change(EAPC=0.1;95%CI:-0.24 to 0.45)],age-standardized prevalence rates(ASPR)also increased(EAPC=0.88;95%CI:0.6 to 1.15).Cataract burden increased with age and female *** the causes of cataract,air pollution was the most important,followed by smoking,high fasting plasma glucose,and high body mass index(BMI).The burden of cataract is predicted to grow persistently from 2020 to 2030,the number of DALYs and prevalence for cataract will rise to 2336431 and 43698620 respectively by 2030,the ASDR is predicted to be 85/100000 and ASPR will be 1586/100000 in 2030,females will still be at greater risk of suffering from cataract than ***:The burden of cataract in China kept rising from 1990 to *** age and female gender are risk factors for *** pollution,smoking,high fasting plasma glucose,and high BMI are associated with *** burden of cataract in China will gradually increase from 2020 to 2030,the elderly women in particular need *** results may be of help for providing reference strategies to reduce cataract burden in the near future

关键词： cataract disease burden tendency prediction

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Influence of lens position as detected by an anterior segment analysis system on postoperative refraction in cataract surgery

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International Journal of Ophthalmology(English edition) 2021年第7期14卷 1006-1012页

作者： Jia-Ju Zhang Jian-Qing Li Chen Li Yi-Hong Cao Pei-Rong Lu department of Ophthalmology the First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina

AIM:To predict postoperative intraocular lens(IOL)position using the Sirius anterior segment analysis system and investigate the effect of lens position and IOL type on postoperative ***:A total of 97 patients(102 eyes)were enrolled in the final *** anterior segment biometry measurement was performed preoperatively with Sirius and *** results of predicted lens position(PLP)and IOL power were automatically calculated by the software used by the *** lens position(ELP)was measured manually using Sirius 3 mo ***'s correlation analysis and linear regression analysis were used to determine the correlation of lens position to other ***:PLP and ELP were positively correlated to axial length(AL;r=0.42,P<0.0001 and r=0.49,P<0.0001,respectively).There was a weak correlation between the peLP(ELP-PLP)and the prediction error of spherical refraction(peSR;r=0.34,P<0.0001).The peLP of Softec HD IOL differed statistically from those of both the TECNIS ZCB00 and Sensor AR40E *** linear regression was used to obtain the prediction formula:ELP=0.66+0.63×[aqueous depth(AQD)+0.6 LT](r=0.61,P<0.0001),and a new variable(AQD+0.6 LT)was found to have the strongest correlation with ***:The Sirius anterior segment analysis system is helpful to predict ELP,which reduces postoperative refraction error.

关键词： lens position anterior segment analysis system postoperative refraction intraocular lens

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Clinical-radiomics predictors to identify the suitability of transarterial chemoembolization treatment in intermediate-stage hepatocellular carcinoma:A multicenter study

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Hepatobiliary & Pancreatic Diseases International 2023年第6期22卷 594-604页

作者： Dan-Dan Wang Jin-Feng Zhang Lin-Han Zhang Meng Niu Hui-Jie Jiang Fu-Cang Jia Shi-Ting Feng department of radiology the Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China Shenzhen Institute of Advanced Technology Chinese Academy of SciencesShenzhen 518055China department of Breast Surgery Harbin Medical University Cancer HospitalHarbin 150081China department of PET/CT the First Affiliated Hospital of Harbin Medical UniversityHarbin 150007China department of interventional Therapy the First Affiliated Hospital of China Medical UniversityShenyang 110001China department of radiology the First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China

Background: Although transarterial chemoembolization(TACE) is the first-line therapy for intermediatestage hepatocellular carcinoma(HCC), it is not suitable for all patients. This study aimed to determine how to select patients who are not suitable for TACE as the first treatment choice. Methods: A total of 243 intermediate-stage HCC patients treated with TACE at three centers were retrospectively enrolled, of which 171 were used for model training and 72 for testing. Radiomics features were screened using the Spearman correlation analysis and the least absolute shrinkage and selection operator(LASSO) algorithm. Subsequently, a radiomics model was established using extreme gradient boosting(XGBoost) with 5-fold cross-validation. The Shapley additive explanations(SHAP) method was used to visualize the radiomics model. A clinical model was constructed using univariate and multivariate logistic regression. The combined model comprising the radiomics signature and clinical factors was then established. This model’s performance was evaluated by discrimination, calibration, and clinical application. Generalization ability was evaluated by the testing cohort. Finally, the model was used to analyze overall and progression-free survival of different groups. Results: A third of the patients(81/243) were unsuitable for TACE treatment. The combined model had a high degree of accuracy as it identified TACE-unsuitable cases, at a sensitivity, specificity, and area under the receiver operating characteristic curve(AUC) of 0.759, 0.885, 0.906 [95% confidence interval(CI): 0.859-0.953] in the training cohort and 0.826, 0.776, and 0.894(95% CI: 0.815-0.972) in the testing cohort, respectively. Conclusions: The high degree of accuracy of our clinical-radiomics model makes it clinically useful in identifying intermediate-stage HCC patients who are unsuitable for TACE treatment.

关键词： Transarterial chemoembolization Hepatocellular carcinoma Radiomics Machine learning Prediction

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