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Deep eutectic solvent-driven self-assembly of metal mercaptide complexes with enzyme-mimicking activities for detection of uric acid through one-step cascade catalytic reaction

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Green Chemical Engineering 2024年第1期5卷 75-84页

作者： Jean Claude Munyemana jia Chen Xin li Yangxia Han Hao Tang Hongdeng Qiu CAS Key Laboratory of Chemistry of Northwestern plant Resources and Key Laboratory for Natural Medicine of Gansu province Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou730000China University of Chinese Academy of Sciences Chinese Academy of SciencesBeijing100039China Department of pharmacy Gansu Provincial HospitalLanzhou730000China

This work presents a generic strategy to create a series of metal mercaptides complexes via coordination selfassembly between transition metals(Mn,Cu,Co,Fe,and Ni)and cysteine(Cys)by forming the sulfur-metal *** strategy involves dissolving metal chlorides and Cys into deep eutectic solvents(DES),followed by the precipitation of metal mercaptides complexes(such as Cys-Mn)by adding water as an antisolvent,where DES serves as the solvent,shape directing,and capping agent,thereby preventing the formation of other metal ***,the prepared complexes possess both laccase and peroxidase-like properties,allowing the design of a technique for the detection of L-3,4-dihydroxyphenylalanine(L-DOpA)and uric acid,*** prepared Cys-Mn can linearly oxidize L-DOpA with its concentrations from 0.1 to 130μM and the detection limit was calculated to be 75.5 n ***,the Cys-Mn can mimic the activity of peroxidase towards oxidization of o-phenylenediamine at neutral p H,allowing single-step and one-pot cascade reactions for visual and fluorometric measurements of uric acid(UA)that could work in the range of 0.2-500μM UA with a detection limit of 0.06μM and 0.054μМ,*** assay was successful in detecting UA in serum and urine samples with relative standard deviation(RSD)ranging from 7.3%to 10.2%and 3.0%-8.5%respectively,suggesting that it may prove useful in medical diagnostic testing.

关键词： Metal-mercaptides Deep eutectic solvents Self-assembly peroxidase-mimic catalyst Uric acid detection

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： lifang Zhao Mingkai Zhang Qimeng li Xuemin Wang Jie Lu Ying Han Yanning Cai Department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric Medical Research Center BeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Radiology and Nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research Center for Geriatric Diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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Activation of cerebral Ras-related C3 botulinum toxin substrate(Rac) 1 promotes post-ischemic stroke functional recovery in aged mice

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Neural Regeneration Research 2024年第4期19卷 881-886页

作者： Fan Bu jia-Wei Min Md Abdur Razzaque Ahmad El Hamamy Anthony patrizz li Qi Akihiko Urayama Jun li Department of Neurology University of Texas Health Science Center Department of Neurology&psychology The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine

Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain *** is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following *** evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced *** studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke ***,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic *** found that as mice aged,Rac1 expression declined in the *** overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–*** was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by *** a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial ***,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after *** work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.

关键词： aging angiogenesis brain-derived neurotrophic factor(BDNF) cerebral ischemia cognitive recovery neurite pak1 Rac1 sensorimotor recovery

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Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome

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World Journal of Cardiology 2024年第7期16卷 422-435页

作者： Si-Qi li dong-Yu Min Jun-Wen jiang Xiao-Ying li Xu-Na Yang Wen-Bo Gu jia-Hui jiang li-Hao Chen Han Nan Ze-Yu Chen Second Department of Cardiology The Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110000Liaoning ProvinceChina

BACKGROUND Chronic heart failure is a complex clinical *** Chinese herbal compound preparation jianpi Huatan Quyu recipe has been used to treat chronic heart failure;however,the underlying molecular mechanism is still not *** To identify the effective active ingredients of jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart *** The effective active ingredients of eight herbs composing jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems pharmacology Database and Analysis *** target genes of chronic heart failure were searched in the Genecards *** target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drugdisease targets,which were then used to construct a key chemical componenttarget network using Cytoscape 3.7.2 *** protein-protein interaction network was constructed using the String *** Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape ***,our previously published relevant articles were searched to verify the results obtained via network *** A total of 227 effective active ingredients for jianpi Huatan Quyu recipe were identified,of which quercetin,kaempferol,7-methoxy-2-methyl isoflavone,formononetin,and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3,MApK3,AKT1,JUN,MApK1,Tp53,TNF,HSp90AA1,p65,MApK8,MApK14,IL6,EGFR,EDN1,FOS,and other *** pathways identified by KEGG enrichment analysis include pathways in cancer,IL-17 signaling pathway,pI3K-Akt signaling pathway,HIF-1 signaling pathway,calcium signaling pathway,cAMp signaling pathway,NF-kappaB signaling pathway,AMpK signaling pathway,*** studies on jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α,IL-6,MApK

关键词： jianpi Huatan Quyu recipe Traditional Chinese medicine Chronic heart failure Data mining Network pharmacology Bioinformatics Spleen Qi deficiency syndrome

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Establishment of predictive models and determinants of preoperative gastric retention in endoscopic retrograde cholangiopancreatography

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2574-2582页

作者： Ying jia Hao-Jun Wu Tang li jia-Bin liu ling Fang Zi-Ming liu Department of Thyroid Surgery West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Division of Biliary Tract Surgery Department of General SurgeryWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Division of General Surgery West China Hospital-Chengdu Shangjin NanfuWest China HospitalChengdu 611730Sichuan ProvinceChina

BACKGROUND Study on influencing factors of gastric retention before endoscopic retrograde cholangiopancreatography(ERCp)background:With the wide application of ERCp,the risk of preoperative gastric retention affects the smooth progress of the *** study found that female,biliary and pancreatic malignant tumor,digestive tract obstruction and other factors are closely related to gastric retention,so the establishment of predictive model is very important to reduce the risk of *** A retrospective analysis was conducted on 190 patients admitted to our hospital for ERCp preparation between January 2020 and February *** baseline clinical data were collected using an electronic medical record *** were randomly matched in a 1:4 ratio with data from 190 patients during the same period to establish a validation group(n=38)and a modeling group(n=152).patients in the modeling group were divided into the gastric retention group(n=52)and non-gastric retention group(n=100)based on whether gastric retention occurred *** data of patients in the validation group and identify factors influencing preoperative gastric retention in ERCp patients.A predictive model for preoperative gastric retention in ERCp patients was constructed,and calibration curves were used for *** receiver operating characteristic(ROC)curve was analyzed to evaluate the predictive value of the *** We found no statistically significant difference in general data between the validation group and modeling group(p>0.05).The comparison of age,body mass index,hypertension,and diabetes between the two groups showed no statistically significant difference(p>0.05).However,we noted statistically significant differences in gender,primary disease,jaundice,opioid use,and gastrointestinal obstruction between the two groups(pprimary disease,jaundice,opioid use,and gastrointestina

关键词： Cholangiopancreatography Gastric retention Influencing factors predictive model Endoscope

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Work-function-induced interfacial electron redistribution of MoO_(2)/WO_(2) heterostructures for high-efficiency electrocatalytic hydrogen evolution reaction

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Rare Metals 2024年第2期43卷 489-499页

作者： Tong-Fei li Jing li Lu-ping Zhang jia-Wei Ke Meng-Xing Fan li-Fang Zhang Cheng-Wei Deng Yi Sun Tao Qian Cheng-lin Yan School of Chemistry and Chemical Engineering Nantong UniversityNantong226019China jiangsu Key Laboratory of New power Batteries Jiangsu Collaborative Innovation Centre of Biomedical Functional MaterialsSchool of Chemistry and Materials ScienceNanjing Normal UniversityNanjing210023China Aerospace Hydrogen Energy Technology(Shanghai)Co.Ltd. Shanghai201800China Key Laboratory of Core Technology of High Specific Energy Battery and Key Materials for petroleum and Chemical Industry College of EnergySoochow UniversitySuzhou215006China light Industry Institute of Electrochemical power Sources Suzhou215006China

The engineering of the electronic configurations of active sites,together with the production of more accessible active sites through heterostructure design,has been established as a forceful methodology for boosting water electrolysis ***,a facile approach is developed to fabricate well-dispersed MoO_(2) and WO_(2) nanoparticles with abundant heterointerfaces entrapped in N,p-doped carbon nanofibers(referred to as MoO_(2)/WO_(2)@N,p-CNFs hereafter)as hydrogen evolution reaction(HER)electrocatalysts in alkaline and acidic *** spectroscopic analyses and theoretical findings manifest that the heterointerface formed by the work function modulation of MoO_(2)/WO_(2) triggers the spontaneous electron redistribution from MoO_(2)to WO_(2) and a built-in electric field,which is essential to promote water adsorption,optimize the H-intermediate adsorption energy,result in the enhanced charge transfer efficiency,and ultimately increase the intrinsic HER ***,the intimate confinement of MoO_(2)/WO_(2) heterostructures in the porous carbon substrate can restrain the active sites from unfavorable coarsening and detachment,thus ensuring facilitated HER kinetics and outstanding structural *** a result,MoO_(2)/WO_(2)@N,p-CNFs exhibit superior catalytic HER performance in acidic and basic solutions,requiring 118 and 95 mV overpotentials to achieve 10 mA·cm^(−2),respectively,surpassing a number of reported non-noble metal-based *** work provides guidelines for the rational design and construction of special metallic heterocomponents with optimized interfacial electronic structure for various electrochemical technologies.

关键词： Electrospinning MoO_(2)/WO_(2) heterostructure Work function Hydrogen evolution reaction

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A Dynamic Covalent Bonding-based Nanoplatform for Intracellular Co-Delivery of protein Drugs and Chemotherapeutics with Enhanced Anti-Cancer Effect

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Chinese Journal of polymer Science 2024年第5期42卷 559-569,I0005页

作者： Sai-Nan liu jia-Hui Meng li-Yun Cui Hua Chen lin-Qi Shi Ru-jiang Ma Key Laboratory of Functional polymer Materials of Ministry of Education Institute of Polymer ChemistryTianjin Key Laboratory of Functional Polymer MaterialsState Key Laboratory of Medicinal Chemical BiologyFrontiers Science Center for New Organic MatterCollege of ChemistryNankai UniversityTianjin300071China Haihe Laboratory of Sustainable Chemical Transformations Tianjin300192China

Efficient intracellular delivery of protein drugs is critical for protein *** combination of protein drugs with chemotherapeutics represents a promising strategy in enhancing anti-cancer ***,co-delivery systems for efficient delivery of these two kinds of drugs are still lacking because of their different ***,we show a well-designed delivery system based on dynamic covalent bond for efficient intracellular co-delivery of ribonuclease A(RNase A)and doxorubicin(DOX).Two polymers,pEG-b-p(Asp-co-AspDA)and pAE-b-p(Asp-co-AsppBA),and two 2-acetylphenylboronic acid(2-ApBA)-functionalized drugs,2-ApBA-RNase A and 2-ApBA-DOX,self-assemble into mixed-shell nanoparticles(RNase A/DOX@MNps)via dynamic phenylboronic acid(pBA)-catechol bond between pBA and dopamine(DA)*** pBA-catechol bond endows the nanoparticles with high stability and excellent stimulus-responsive drug release *** the slight acidic environment at tumor tissue,RNase A/DOX@MNps are positively charged,promoting their *** cellular uptake into endosome,further protonation of pAE chains leads to the rupture of endosomes because of the proton sponge effect and the cleavage of pBA-catechol bond promotes the release of two *** cytoplasm,the high level of GSH removed the modification of 2-ApBA on *** restored RNase A and DOX show a synergistic and enhanced antic-cancer *** system may be a promising platform for intracellular co-delivery of protein drugs and chemotherapeutics.

关键词： Drug co-delivery Combination therapy Dynamic covalent bond

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Targeting colorectal cancer with Herba patriniae and Coix seed:Network pharmacology,molecular docking,and in vitro validation

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3539-3558页

作者： Cheng-Lei Wang Bing-Wei Yang Xin-Yan Wang Xue Chen Wei-dong li Hao-Yu Zhai Ying Wu Mu-YaoCui jia-He Wu Qing-Hui Meng Nan Zhang Department of Oncology Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing 100053China The First Clinical Medical College Shaanxi University of Chinese MedicineXianyang 712046Shaanxi ProvinceChina Department of Scientific Research Management Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing 100053China School of Clinical Medicine Qinghai University Xining 810000Qinghai ProvinceChina School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China

BACKGROUND Herba patriniae and Coix seed(HC)constitute a widely utilized drug combination in the clinical management of colorectal cancer(CRC)that is known for its diuretic,anti-inflammatory,and swelling-reducing *** its efficacy has been demonstrated in a clinical setting,the active compounds and their mechanisms of action in CRC treatment remain to be fully *** To identify the active,CRC-targeting components of HC and to elucidate the mechanisms of action *** Active HC components were identified and screened using *** for each component were ***-related targets were obtained from human gene *** targets between HC and CRC were identified.A“drug-ingredient-target”network was created to identify the core components and targets *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were conducted to elucidate the key pathways *** docking between core targets and key components was *** vitro experiments validated core *** Nineteen active components of HC were identified,with acacetin as the primary active *** predictive analysis identified 454 targets of the active compounds in *** mapping with 2685 CRC-related targets yielded 171 intervention targets,including 30 core *** and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase(pI3K)/Akt signaling *** docking showed that acacetin exhibited an optimal interaction with AKT1,identifying pI3K,AKT,and p53 as key genes likely targeted by HC during CRC *** inhibited HT-29 cell proliferation and migration,as well as promoted apoptosis,in *** blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-pI3K,p-Akt,and survivin,which likely contributed to CRC *** Acacetin,the principal active compound in the HC pair,inhibited the proliferati

关键词： Colorectal cancer Baijiangcao(Herba patriniae) Yiyiren(Coix seed) Acacetin proliferation Migration Apoptosis Network pharmacology

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paleoenvironment of marine-continental transitional shales in the lower permian Shanxi formation,southeastern Ordos Basin,China

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Energy Geoscience 2024年第3期5卷 221-233页

作者： jia Tan Yuqiang jiang Xingtao li Chunhai Ji Yifan Gu Zhanlei Wang School of Geoscience and Technology Southwest Petroleum UniversityChengdu610500China The Unconventional Reservoir Evaluation Department PetroChina Key Laboratory of Unconventional Oil and Gas ResourcesChengdu610500China project Department of Tight Oil and Gas Exploration and Development PetroChina Southwest Oil&Gas Field CompanyChengdu610056China petroChina Coalbed Methane Company Beijing100028China Shale Gas Research Institute PetroChina Southwest Oil&Gasfield CompanyChengdu610051China

The paleoenvironment of shales can be reconstructed to some extent using the combinations or concentrations of elements that correlate strongly with environmental *** this study,we analyzed rare earth elements(REEs),major elements,and trace elements in the marine-continental transitional shales(transitional shales for short)of the Shan 2^(3)submember of the Shanxi Formation in the southeastern Ordos *** purpose is to deduce the paleoenvironmental conditions of the shales,encompassing paleoredox,paleoclimate,paleoproductivity,and *** Shan 2^(3)submember comprises four sections,namely Shan 2^(3)-1,Shan 2^(3)-2,Shan 2^(3)-3,and Shan 2^(3)-*** Ba/Al,p/Al,and Cu/Al ratios,along with biogenic barium(Babio),indicate that the paleoproductivity of the submember peaked during the Shan 2^(3)-1 deposition and exhibited a downtrend upward in other *** in the Uau and the Ni/Co,V/Cr,U/Th,and V/Sc ratios suggest that suboxic conditions prevailed during the Shan 2^(3)-1 deposition,with the oxidation level gradually increasing from Shan 2^(3)-1 to Shan 2^(3)-4.C-value and the Sr/Cu ***/Rb cross-plot indicate a warm and arid paleoclimate during the Shan 2^(3)-1 deposition,which transitioned to cooler,drier conditions during the deposition of other *** sensitive to paleoclimate,such as the K/Rb and Th/U ratios,along with the ICV,pIA,and Chemical Index of Alteration(CIA),highlight elevated weathering from Shan 2^(3)-2 to Shan 2^(3)-4,with Shan 2^(3)-1 exhibiting the weakest weathering during its *** suggested by the REE data,the Zr/Sc ***/Sr cross-plot,provenance discriminant functions,and the cross-plots of Hf ***/Th,Th ***-Co,and∑REE ***/Yb,the sedimentary provenance for the transitional shales of the Shan 2^(3)submember is of multiple origins,with significant contributions from the Upper Continental Crust(UCC).Discriminant diagrams,including those of Th-Co-Zr/10,Th-Sc-Zr/10,La-Th-Sc,and K_(2)O/Na_(2)O

关键词： Transitional shale paleoenvironment Elemental geochemistry Upper permian Shan 2^(3)submember Ordos basin

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prognostic value of circulating tumor cells combined with neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 372-385页

作者： jia-li Chen Lu Guo Zhen-Ying Wu Kun He Han li Chi Yang Yun-Wei Han Department of Oncology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of Ophthalmology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Clinical Research Institute The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of plastic Surgery Meguiar's Medical Beauty HospitalChengdu 610000Sichuan ProvinceChina

BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in *** Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the Department of Oncology,the Affiliated Hospital of Southwest Medical University,Sichuan,China,from 2021 to *** optimal cutoff values for CTC programmed death-ligand 1(pD-L1)(+)>1 or CTC pD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile *** were categorized into three groups based on CTC pD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was *** patients with high CTC pD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-pFS)and median overall survival(mOS)than those with low levels of CTC pD-L1(+)or NLR(ppatients in the CTC-NLR(2)group showed a significant decrease in mpFS and *** regression analysis revealed that alpha-fetoprotein(AFp),CTC pD-L1(+),and CTC-NLR were independent predictors of *** time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFp and CTC pD-L1(+).CONCLUSION HCC patients with high CTC pD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low ***-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.

关键词： Circulating tumor cells Neutrophil–lymphocyte ratio Hepatocellular carcinoma prognosis Survival Marker

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