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Metagenomic insights into microorganisms and antibiotic resistance genes of waste antibiotic fermentation residues along production,storage and treatment processes

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Journal of Environmental Sciences 2024年第2期136卷 45-55页

作者： Ziming Han Xiao Luan Haodi Feng Yanqin deng min Yang Yu Zhang State Key Laboratory of Environmental Aquatic Chemistry Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China National Engineering Research Center of Industrial Wastewater Detoxication and Resource Recovery Beijing 100085China Wuhan Agricultural Inspection Center Wuhan 430016China University of Chinese Academy of Sciences Beijing 100049China

Antibiotic fermentation residue(AFR)is nutrient-rich solid waste generated from fermentative antibiotic production process.It is demonstrated that AFR contains high-concentration of remaining antibiotics,and thus may promote antibiotic resistance development in receiving environment or feeding farmed animals.However,the dominate microorganisms and antibiotic resistance genes(ARGs)in AFRs have not been adequately explored,hampering understanding on the potential antibiotic resistance risk development caused by AFRs.Herein,seven kinds of representative AFRs along their production,storage,and treatment processes were collected,and multiple methods including amplicon sequencing,metagenomic sequencing,and bioinformatic approaches were adopted to explore the biological characteristics of AFRs.As expected,antibiotic fermentation producer was found as the predominant species in raw AFRs,which were collected at the outlet of fermentation tanks.However,except for producer species,more environment-derived species persisted in stored AFRs,which were temporarily stored at a semi-open space.Lactobacillus genus,classified as Firmicutes phylum and Bacilli class,became predominant bacterial taxa in stored AFRs,which might attribute to its tolerance to high concentration of antibiotics.Results from metagenomic sequencing together with assembly and binning approaches showed that these newly-colonizing species(e.g.,Lactobacillus genus)tended to carry ARGs conferring resistance to the remaining antibiotic.However,after thermal treatment,remaining antibiotic could be efficiently removed from AFRs,and microorganisms together with DNA could be strongly destroyed.In sum,the main risk from the AFRs was the remaining antibiotic,while environment-derived bacteria which tolerate extreme environment,survived in ARFs with high content antibiotics,and may carry ARGs.Thus,hydrothermal or other harmless treatment technologies are recommended to remove antibiotic content and inactivate bacteria before recycling of AFRs in pharmaceutical industry.

关键词： Pharmaceutical manufacturing Antibiotic mycelia residue Antibiotic resistance bacteria Thermal treatment Solid waste

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Regulation of AMPK activation by extracellular matrix stiffness in pancreatic cancer

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Genes & Diseases 2024年第3期11卷 338-350页

作者： Xin Xu Yuan Fang Somaira Nowsheen Ye-Xiong Li Zhenkun Lou min deng State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of General Surgery Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai 200080China Department of General Surgery Zhongshan HospitalFudan UniversityShanghai 200032China Department of Dermatology University of California San DiegoSan DiegoCA 92093USA Department of Oncology Mayo ClinicRochesterMN 55905USA

The adenosine monophosphate(AMP)-activated protein kinase(AMPK)sits at a cen-tral node in the regulation of energy metabolism and tumor progression.AMPK is best known to sense high cellular ADP or AMP levels,which indicate the depletion of energy stores.Previous studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic cancer.In this study,we report that AMPK is also highly sensitive to extracellular matrix(ECM)stiffness.We found that AMPK is activated in cells when cultured under low ECM stiffness conditions and is functionally required for the metabolic switch induced by ECM stiffness.This regulation of AMPK requires the Hippo kinases but not LKB1/CaMKKp.Hippo kinases directly phosphorylate AMPKa at Thr172 to activate AMPK at low ECM stiffness.Furthermore,we found AMPK activity is inhibited in patients with pancreatic ductal adenocarcinoma(PDAC)with high ECM stiffness and is associated with a poor survival outcome.The activation of Hippo kinases by ROCK inhibitor Y-27632 in combination with the mitochondrial inhibitor metformin synergistically activates AMPK and dramatically inhibits PDAC growth.Together,these findings establish a novel model for AMPK regulation by the mechanical properties of ECMs and provide a rationale for simultaneously targeting the ECM stiffness-Hippo kinases-AMPK signaling and low glucose-LKB1-AMPK signaling pathways as an effective therapeutic strategy against PDAC.

关键词： AMPKactivity Cellularmetabolic switch ECM stiffness Hippokinase signaling Pancreaticductal adenocarcinoma

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Field-based evidence for the enrichment of intrinsic antibiotic resistome stimulated by plant-derived fertilizer in agricultural soil

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Journal of Environmental Sciences 2024年第1期135卷 728-740页

作者： Shihai Liu Ziming Han Dong Zhu Xiao Luan Liujie deng Liping Dong min Yang Yu Zhang State Key Laboratory of Environmental Aquatic Chemistry Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China State Key Laboratory of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China State Environmental Protection Engineering Center for Harmless Treatment and Resource Utilization of Antibiotic Residues Khorgos 835007China University of Chinese Academy of Sciences Beijing 100049China

Animal manures have been demonstrated to enhance antibiotic resistance in agricultural soils.However,little is known about the effects of plant-derived fertilizer on soil antibiotic resistome.Herein,metagenomic sequencing was used to investigate the effects of a plantderived fertilizer processed from sugarcane and beet on soil antibiotic resistance genes(ARGs)in a soybean field along crop growth stages.ARG profiles in the soils amended by plant-derived fertilizer were compared with those in the soils amended by chicken manure.The abundance and diversity of total ARGs in the soils amended by plant-derived fertilizer were significantly(P<0.05)elevated at the sprout stage,to a level comparable to that in the manured soils.Whereas,unlike chicken manure mainly introducing manure-borne ARGs to soil,the plant-derived fertilizer was indicated to mainly enrich multidrug resistance genes in soil by nourishing indigenous bacteria.ARGs with abundances in amended soils significantly(P<0.05)higher than in unamended soils at the sprout stage of soybean were considered as enriched ARGs.Decrease in the abundance of the enriched ARGs was observed in both the amended soils from the sprout to the harvest.Network analysis further identified Proteobacteria and Bacteroidetes as the primary bacterial taxa involved in the temporal variation of the enriched ARGs in the soils amended by plant-derived fertilizer,while in manured soils were Firmicutes and Actinobacteria.As revealed by multivariate statistical analyses,variation of the enriched ARGs in the soils amended by plant-derived fertilizer was majorly attributed to the response of co-occurred bacteria to depleting nutrients,which was different from the failed establishment of manure-borne bacteria in the manured soils.Our study provided field-based evidence that plant-derived fertilizer stimulated the intrinsic antibiotic resistome,and proposed attention to the un-perceived risk since some clinically relevant ARGs originate and evolve from natural resistome.

关键词： Organic fertilizer Intrinsic antibiotic resistance Indigenous bacteria Metagenomic sequencing

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Functional assessment of cadherin as a shared mechanism for cross/dual resistance to Cry1Ac and Cry2Ab in Helicoverpa zea

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Journal of Integrative Agriculture 2024年第5期23卷 1604-1617页

作者： Jizhen Wei min Zhang Pin Li Zhongyuan deng Xinming Yin Shiheng An Xianchun Li State Key Laboratory of Wheat and Maize Crop Science/College of Plant Protection Henan Agricultural UniversityZhengzhou 450046China Department of Entomology and BIO5 Institute University of ArizonaTucsonAZ 85721USA School of Agricultural Sciences Zhengzhou UniversityZhengzhou 450001China

Helicoverpa zea is a major target pest of pyramided transgenic crops expressing Cry1,Cry2 and/or Vip3Aa proteins from Bacillus thuringiensis(Bt)in the United States.Laboratory-selected Cry1Ac/Cry2Ab cross resistance and fieldevolved practical dual resistance of H.zea to these two toxins have been widely reported.Whether the widespread Cry1Ac/Cy2Ab dual resistance of H.zea has resulted from the selection of one shared or two independent resistance mechanisms by pyramided Bt crops remains unclear.Cadherin is a well-confirmed receptor of Cry1Ac and a suggested receptor of Cry2Ab in at least three Lepidopteran species.To test whether cadherin may serve as one shared mechanism for the cross and dual resistance of H.zea to Cry1Ac and Cry2Ab,we cloned H.zea cadherin(HzCadherin)cDNA and studied its functional roles in the mode of action of Cry1Ac and Cry2Ab by gain-and lossof-function analyses.Heterologous expression of HzCadherin in H.zea midgut,H.zea fat body and Sf9 cells made all three of these cell lines more susceptible to activated Cry1Ac but not activated Cry2Ab,whereas silencing HzCadherin of H.zea midgut and fat body cells significantly reduced the susceptibility to Cry1Ac but not Cry2Ab.Likewise,suppressing HzCadherin with siRNA made H.zea larvae resistant to Cry1Ac.These results clearly demonstrate that HzCadherin is not a receptor for Cry2Ab,and thus it is unlikely to serve as one shared mechanism for the cross and dual resistance of H.zea to Cry1Ac and Cry2Ab.

关键词： Bt crops cadherin Cry toxin receptor resistance mechanism

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Early monitoring values of oncogenic signalling molecules for hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2350-2361页

作者： min Yao Rong-Fei Fang Qun Xie min Xu Wen-Li Sai deng-Fu Yao Department of Immunology Medical School of Nantong University and Research Center of Clinical MedicineThe Affiliated Hospital of Nantong UniversityNantong 226001Jiangsu ProvinceChina Department of Gastroenterology The Affiliated Hospital of Nantong UniversityNantong 226001Jiangsu ProvinceChina Department of Infectious Diseases Haian People’s HospitalHaian 226600Jiangsu ProvinceChina Research Center of Clinical Medicine The Affiliated Hospital of Nantong UniversityNantong 226001Jiangsu ProvinceChina

The prevention and early diagnosis of liver cancer remains a global medical challenge.During the malignant transformation of hepatocytes,a variety of oncogenic cellular signalling molecules,such as novel high mobility group-Box 3,angiopoietin-2,Golgi protein 73,glypican-3,Wnt3a(a signalling molecule in the Wnt/β-catenin pathway),and secretory clusterin,can be expressed and secreted into the blood.These signalling molecules are derived from different signalling pathways and may not only participate in the malignant transformation of hepatocytes but also become early diagnostic indicators of hepatocarcinogenesis or specific targeted molecules for hepatocellular carcinoma therapy.This article reviews recent progress in the study of several signalling molecules as sensitive biomarkers for monitoring hepatocarcinogenesis.

关键词： Hepatocarcinogenesis Cell signals Specific biomarkers Early diagnosis

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Electronic structure and spin state regulation of vanadium nitride via a sulfur doping strategy toward flexible zinc-air batteries

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Journal of Energy Chemistry 2024年第2期89卷 239-249,I0007页

作者： Daijie deng Honghui Zhang Jianchun Wu Xing Tang min Ling Sihua Dong Li Xu Henan Li Huaming Li Institute for Energy Research Institute of Quantum and Sustainable TechnologySchool of Chemistry and Chemical EngineeringSchool of Materials Science and EngineeringJiangsu Province and Education Ministry Co-Sponsored Synergistic Innovation Center of Modern Agricultural EquipmentJiangsu UniversityZhenjiang 212013JiangsuChina Key Laboratory of Radio Frequency and Micro-Nano Electronics of Jiangsu Province Nanjing 210023JiangsuChina Zhenjiang Kangyuan Electrical Appliance Co. Ltd.Zhenjiang 212013JiangsuChina College of Chemical and Biological Engineering Zhejiang UniversityHangzhou 310027ZhejiangChina YTO Group Corporation Dongfanghong(Henan)Agricultural Service Technology Co. Ltd.Luoyang 471033HenanChina

Owing to the distinctive structural characteristics,vanadium nitride(VN)is highly regarded as a catalyst for oxygen reduction reaction(ORR)in zinc-air batteries(ZABs).However,VN exhibits limited intrinsic ORR activity due to the weak adsorption ability to O-containing species.Here,the S-doped VN anchored on N,S-doped multi-dimensional carbon(S-VN/Co/NS-MC)was constructed using the solvothermal and in-situ doping methods.Incorporating sulfur atoms into VN species alters the electron spin state of vanadium in the S-VN/Co/NS-MC for regulating the adsorption energy of vanadium sites to oxygen molecules.The introduced sulfur atoms polarize the V 3d_(z)^(2) electrons,shifting spin-down electrons closer to the Fermi level in the S-VN/Co/NS-MC.Consequently,the introduction of sulfur atoms into VN species enhances the adsorption energy of vanadium sites for oxygen molecules.The*OOH dissociation transitions from being unspontaneous on the VN surface to a spontaneous state on the S-doped VN surface.Then,the ORR barrier on the S-VN/Co/NS-MC surface is reduced.The S-VN/Co/NS-MC demonstrates a higher half-wave potential and limiting current density compared to the VN/Co/N-MC.The S-VN/Co/NS-MC-based liquid ZABs display a power density of 195.7 m W cm^(-2),a specific capacity of 815.7 m A h g^(-1),and a cycling stability exceeding 250 h.The S-VN/Co/NS-MC-based flexible ZABs are successfully employed to charge both a smart watch and a mobile phone.This approach holds promise for advancing the commercial utilization of VN-based catalysts in ZABs.

关键词： S-doped VN Electronic structures Spin state regulation Oxygen reduction reaction Zinc-air batteries

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A machine learning model for diagnosing acute pulmonary embolism and comparison with Wells score,revised Geneva score,and Years algorithm

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Chinese Medical Journal 2024年第6期137卷 676-682页

作者： Linfeng Xi Han Kang Mei deng Wenqing Xu Feiya Xu Qian Gao Wanmu Xie Rongguo Zhang min Liu Zhenguo Zhai Chen Wang Capital Medical University Beijing 100069China National Center for Respiratory Medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Pulmonary and Critical Care MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Institute of Advanced Research Infervision Medical Technology Co.Ltd.Beijing 100025China Department of Radiology China-Japan Friendship HospitalBeijing 100029China Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730China Department of Radiology Peking University China-Japan Friendship School of Clinical MedicineBeijing 100191China

Background:Acute pulmonary embolism(APE)is a fatal cardiovascular disease,yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs.A simple,objective technique will help clinicians make a quick and precise diagnosis.In population studies,machine learning(ML)plays a critical role in characterizing cardiovascular risks,predicting outcomes,and identifying biomarkers.This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.Methods:This is a single-center retrospective study.Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets.A total of 8 ML models,including random forest(RF),Naïve Bayes,decision tree,K-nearest neighbors,logistic regression,multi-layer perceptron,support vector machine,and gradient boosting decision tree were developed based on the training set to diagnose APE.Thereafter,the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies,including the Wells score,revised Geneva score,and Years algorithm.Eventually,the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic(ROC)analysis.Results:The ML models were constructed using eight clinical features,including D-dimer,cardiac troponin T(cTNT),arterial oxygen saturation,heart rate,chest pain,lower limb pain,hemoptysis,and chronic heart failure.Among eight ML models,the RF model achieved the best performance with the highest area under the curve(AUC)(AUC=0.774).Compared to the current clinical assessment strategies,the RF model outperformed the Wells score(P=0.030)and was not inferior to any other clinical probability assessment strategy.The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726.Conclusions:Based on RF algorithm,a novel prediction model was finally constructed for APE diagnosis.When compared to the current clinica

关键词： Acute pulmonary embolism Machine learning Wells score Revised Geneva score Years algorithm

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Individualized Traditional Chinese Medicine treatment vs antibiotics for recurrent urinary tract infections: a multicenter, randomized controlled study

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Journal of Traditional Chinese Medicine 2024年第3期44卷 524-529页

作者： GU Xiangchen QIU Meisi XIE Lin CHEN min deng Yueyi ZHANG Changming JIAN Guihua WANG Chen WANG Yi Department of Nephrology Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine Department of Nephrology Rizhao Hospital of Traditional Chinese Medicine Department of Nephrology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Department of Nephrology Shanghai Municipal Traditional Chinese Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Department of Nephrology the Sixth People's Hospital Affiliated Shanghai Jiaotong University Department of Nephrology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

OBJECTIVE: To systematically assess the effects of individualized Chinese medicines on recurrent urinary tract infections(rUTIs).METHODS: This study recruited 230 adult female patients in the remission phase of rUTIs from five hospitals in China. The patients were randomly allocated to two groups: an individualized Chinese medicine group(n = 114) and a control group(n = 116). Patients in the Chinese medicine group received individualized Chinese herbs, which were evaluated for syndrome differentiation.Patients in the control group received antibiotic treatment combined with a Chinese medicine placebo. The duration of treatment was three courses of four weeks each, with a three-month subsequent follow-up. UTI recurrence rate,Traditional Chinese Medicine(TCM) syndrome scores,36-item Short Form Survey(SF-36) score, and urine secretory immunoglobulin A(SIgA) were measured and analyzed before and after treatment in each group. RESULTS: Patients from the Chinese medicine group exhibited significant decreases in both short-and longterm UTI recurrence rates compared with the control group(P < 0.05). The changes in TCM syndrome scores between the Chinese medicine and control groups were significant(P < 0.05). The changes in the average SF-36 quality-of-life scores in the Chinese medicine group were also significantly higher than those in the control group after treatment(P < 0.05). The Chinese medicine group also demonstrated a significant increase in urine SIg A expression. CONCLUSION: Taken together, compared to the oftenused long-term antimicrobial prophylaxis during the remission stage of r UTIs, treating patients with an individualized Chinese medicine decoction by syndrome differentiation could effectively reduce the recurrence rate, improve the patients' TCM syndrome scores and quality of life, and enhance immunity, which in turn helps to prevent antibiotic resistance.

关键词： Chinese traditional immunoglobulin A, secretory medicine quality of life randomized controlled trial syndrome differentiation urinary tract infections

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Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors

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World Journal of Gastroenterology 2024年第11期30卷 1533-1544页

作者： Li-min Yang Hong-Juan Wang Shan-Lin Li Guan-Hua Gan Wen-Wen deng Yong-Sheng Chang Lian-Feng Zhang Department of Gastroenterology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Gastroenterology Zhoukou Central Hospital of Henan ProvinceZhoukou 466000Henan ProvinceChina Department of Gastroenterology The First Affiliated Hospital of Xinxiang Medical CollegeXinxiang 453000Henan ProvinceChina

BACKGROUND Patients with liver cancer complicated by portal hypertension present complex challenges in treatment.AIM To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition.METHODS Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group(n=50)and a control group(n=50)according to the treatment regimen.The research group received radiofrequency ablation(RFA)in combination with sorafenib,and the control group only received RFA.The short-term efficacy of both the research and control groups was observed.Liver function and portal hypertension were compared before and after treatment.Alpha-fetoprotein(AFP),glypican-3(GPC-3),and AFP-L3 levels were compared between the two groups prior to and after treatment.The occurrence of adverse reactions in both groups was observed.The 3-year survival rate was compared between the two groups.Basic data were compared between the survival and non-surviving groups.To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension,multivariate logistic regression analysis was employed.RESULTS When comparing the two groups,the research group's total effective rate(82.00%)was significantly greater than that of the control group(56.00%;Pminotransferase and aspartate aminotransferase levels increased,and portal vein pressure decreased in both groups.The degree of improvement for every index was substantially greater in the research group than in the control group(P<0.05).Following treatment,the AFP,GPC-3,and AFP-L3 levels in both groups decreased,with the research group having significantly lower levels than the control group(P<0.05).The incidence of diarrhea,rash,nausea and vomiting,and fatigue in the research group was significantly greater than that in the control group(P<0.05).The 1-

关键词： Radiofrequency ablation Sorafenib Liver cancer Portal hypertension Efficacy Prognosis analysis

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Correlation between serum markers and transjugular intrahepatic portosystemic shunt prognosis in patients with cirrhotic ascites

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 481-490页

作者： Xiao-Gang Hu Xiao-Xian Yang Jun Lu Gang Li Jian-Ji Dai Jia-min Wang Yi deng Rui Feng Department of Interventional Radiology The Affiliated Jinhua HospitalZhejiang University School of MedicineJinhua 321000Zhejiang ProvinceChina Medical College Jinhua PolytechnicJinhua 321017Zhejiang ProvinceChina Department of Interventional Medicine Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou 310000Zhejiang ProvinceChina

BACKGROUND Individuals with refractory ascites in the context of liver cirrhosis typically face an adverse prognosis.The transjugular intrahepatic portosystemic shunt(TIPS)is an efficacious intervention,but there is a lack of reliable tools for postoperative pro-gnosis assessment.Previously utilized clinical biochemical markers,such as the serum albumin concentration(Alb),sodium(Na+)concentration,and serum creatinine(Scr),have limited predictive value.Therefore,the quest for novel,specific biomarkers to evaluate the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites holds significant practical importance.A retrospective analysis was conducted on 75 patients with liver cirrhosis and refractory ascites who underwent TIPS at our institution from August 2019 to August 2021.These patients were followed up regularly for two years,and the death toll was meticulously documented.The patients were allocated into a survival group(n=45 patients)or a deceased group(n=30 patients)based on their prognosis status.The clinical data of the two groups were collected,and Child-Pugh scores and MELD scores were calculated for analysis.Spearman correlation analysis was carried out to evaluate the correlation of prognosis with Child-Pugh grade,MELD score,and Cys C level.Additionally,a multiple-factor analysis utilizing the Cox proportional hazard model was used to identify independent risk factors affecting the post-TIPS prognosis of patients with liver cirrhosis and refractory ascites.The receiver operating characteristic curve(ROC)ascertained the predictive value of the Cys C concen-tration,Child-Pugh grade,and MELD score for the prognosis of liver cirrhosis with refractory ascites in post-TIPS patients.RESULTS During a 2-year follow-up period,among 75 patients with liver cirrhosis and refractory ascites who underwent TIPS treatment,30 patients(40.00%)passed away.The deceased cohort exhibited heightened aspartate aminotrans-ferase,alanine aminotransferase,total bilirubin,Scr,prothrombin time,Cys C,internationa

关键词： Liver cirrhosis Refractory ascites Transjugular intrahepatic portosystemic shunt Cystatin C

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