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Addressing chemoresistance with a lipid gemcitabine nanotherapeutic strategy for effective treatment of pancreatic cancer

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Nano Research 2024年第9期17卷 8377-8388页

作者： Jiawei Hong Shiyun Xian Shusen Zheng Hangxiang Wang Donghai Jiang The First Affiliated Hospital NHC Key Laboratory of Combined Multi-Organ TransplantationCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesState Key Laboratory for Diagnosis and Treatment of Infectious DiseasesSchool of MedicineZhejiang UniversityHangzhou 310003China Jinan Microecological Biomedicine Shandong laboratory Jinan 250117China

Resistance to gemcitabine in pancreatic cancer poses a significant clinical *** investigation is warranted to assess whether nano-formulation strategy can be employed to enhance the sensitivity of resistant strains to gemcitabine *** this study,using gemcitabine-resistant pancreatic cancer cell lines,we examined the therapeutic potential of a gemcitabine nanodelivery platform and assessed the ability to overcome drug resistance against resistant *** of human equilibrative nucleoside transporter 1(hENT1)led to reduced cellular uptake of gemcitabine,resulting in chemoresistance in pancreatic *** nanoparticles circumvented the entry blockade caused by hENT1 silencing through *** entry via clathrin-mediated endocytosis increased intracellular gemcitabine accumulation in gemcitabine-resistant pancreatic cancer ***,gemcitabine nanoparticles are preferential in vivo delivery to tumor tissues,likely due to the enhanced permeability and retention *** comparison to free gemcitabine,gemcitabine nanoparticles demonstrate a more pronounced cytotoxic effect on gemcitabine-resistant pancreatic cancer cells,with favorable *** study improved the efficacy of gemcitabine through nanotechnology,providing a novel strategy to address gemcitabine-resistant pancreatic cancer.

关键词： pancreatic cancer gemcitabine resistance gemcitabine nanoparticle human equilibrative nucleoside transporter 1

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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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M2-type macrophage membrane-mediated delivery of Carvedilol nanocomplex for acute liver failure treatment and remodeling inflammatory microenvironment

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Nano Research 2024年第7期17卷 6362-6375页

作者： Mingge Shang Yaohui Zhang Junjie Qian Wenchao Wang Xizhi Yu Jiacheng Huang Lin Zhou Shusen Zheng Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China NHC key laboratory of combined multi-organ transplantation Key Laboratory of Organ TransplantationHangzhou 310003China 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 Sciences(2019RU019)Hangzhou 310003China State key laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesHangzhou 310003China Department of Thyroid Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College Hangzhou 310000China

Interactions of hepatic macrophages with local inflammatory microenvironment is the key factor promoting the development of acute liver failure(ALF).Hence,reprogramming pro-inflammatory M1 into anti-inflammatory M2 phenotype may offer a promising strategy for treating ALF by targeting *** group found Carvedilol possessed potential anti-inflammatory property previously,which had been scarcely reported in *** present a synergy strategy to induce macrophages into the phenotype M2-type anti-inflammatory macrophages with interleukin-4(IL-4)and IL-10 at *** Carvedilol is loaded on the macrophage membrane-camouflaged biomimetic nano-platform(termed as M2M@CNP)to evade reticuloendothelial system(RES)and afford Carvedilol delivery to the inflammatory environment with overproduced reactive oxygen species(ROS),further prolonging its circulation and *** released Carvedilol produced anti-inflammatory,antioxidant and anti-apoptosis effects,combining local M2-type cell membranes(M2-CM)inhibited pro-inflammatory cytokines and ROS levels,which in turn promoted and amplified M1 to M2 phenotype polarization *** study offers new insights into the rational design of biomimetic nanosystems for safe and effective ALF therapy to accelerate the clinical translation.

关键词： acute liver failure hepatic drug delivery M2 macrophage-camouflaged nanoplatform inflammatory microenvironment macrophage polarization

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A Single-Cell Landscape of Human Liver transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction

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Engineering 2024年第5期36卷 193-208页

作者： Xin Shao Zheng Wang Kai Wang Xiaoyan Lu Ping Zhang Rongfang Guo Jie Liao Penghui Yang Shusen Zheng Xiao Xu Xiaohui Fan Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China national key laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314103China Zhejiang University School of Medicine Hangzhou 310058China NHC key laboratory of combined multi-organ transplantation Hangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)Hospital Affiliated to Shulan International Medical CollegeZhejiang Shuren UniversityHangzhou 310000China Engineering Research Center of Innovative Anticancer Drugs Ministry of EducationHarbin 150023China

Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver *** notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical concern,exacerbating the current organ shortage and detrimentally affecting the prognosis of ***,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to ***,we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients,with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion *** of the 75231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells,granzyme B^(+)(GZMB^(+))granzyme K^(+)(GZMK^(+))natural killer cells,and S100 calcium binding protein A12^(+)(S100A12^(+))***,we verified this immune niche and its association with EAD occurrence in two independent *** findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level,thus,offering valuable insights into EAD onset.

关键词： Human liver transplantation Early allograft dysfunction Pathogenic immune niche Single-cell analysis Cell-cell communication

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Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

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Cancer Biology & Medicine 2024年第4期21卷 347-362页

作者： Jian Chen Zhe Yang Fengqiang Gao Zhisheng Zhou Junli Chen Di Lu Kai Wang Meihua Sui Zhengxin Wang Wenzhi Guo Guoyue Lyu Haizhi Qi Jinzhen Cai Jiayin Yang Shusen Zheng Xiao Xu Zhejiang University School of Medicine Hangzhou 310030China Institute of organ transplantation Zhejiang UniversityHangzhou 310030China Department of Hepatobiliary and Pancreatic Surgery Shulan Hospital of HangzhouHangzhou 310006China national Center for healthcare Quality Management in Liver Transplant Hangzhou 310003China Department of General Surgery Huashan HospitalFudan UniversityShanghai 200040China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Hepatobiliary and Pancreatic Surgery The First Hospital of Jilin UniversityChangchun 130021China Department of Liver transplantation Second Xiangya HospitalCentral South UniversityChangsha 410008China Department of organ transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266003China Department of Liver Surgery and Liver transplantation Center West China HospitalSichuan UniversityChengdu 610044China NHC key laboratory of combined multi-organ transplantation Hangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be *** study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with ***:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were *** associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further ***:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male *** analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(Porgan allocation.

关键词： Sex liver transplantation hepatocellular carcinoma outcome recipient donor

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Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 83-90页

作者： Zhikun LIU Yichao WU Abid Ali KHAN Lun LU Jianguo WANG Jun CHEN Ningyang JIA Shusen ZHENG Xiao XU key laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou310006China Zhejiang University School of Medicine Hangzhou310058China Department of Radiology Easter Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai200438China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou310003China NHC key laboratory of combined multi-organ transplantation Hangzhou310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou310022China

Hepatocellular carcinoma(HCC)is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide(Forner et al.,2018;He et al.,2023).Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle(SM)mass that may be age-related or the result of malnutrition in cancer patients(Cruz-Jentoft and Sayer,2019).Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival(Voron et al.,2015;van Vugt et al.,2016).

关键词： cancer patients

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combined Effect of Outdoor Time and Other Modifiable Factors on Myopia Incidence Among Children and Adolescents—9 PLADs,China,2020

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China CDC weekly 2024年第9期6卷 151-156,I0001,I0002页

作者： Panliang Zhong Yunfei Liu Ning Ma Jiajia Dang Di Shi Shan Cai Ziyue Chen Yanhui Dong Peijin Hu Jun Ma Patrick W.C Lau Randall S.Stafford Yi Song Institute of Child and Adolescent health School of Public HealthPeking UniversityNational Health Commission Key Laboratory of Reproductive HealthBeijingChina Department of Sport Physical Education&HealthHong Kong Baptist UniversityKowloon TongHong Kong Special Administrative RegionChina Department of Medicine Stanford Prevention Research CenterStanford University School of MedicineStanfordCAUnited States

Summary What is already known about this topic?Myopia has been identified as a significant emerging challenge and policy priority among children and adolescents in China by the Ministry of Education and seven other *** research has been conducted to investigate the collective impact of outdoor time and other modifiable factors on the incidence of myopia.

关键词： Incidence collective policy

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Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles

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Military Medical Research 2024年第1期11卷 1-18页

作者： Zi-Sen Zhang Yi-Yan Liu Shuang-Shuang He Dai-Qin Bao Hong-Chen Wang Jie Zhang Xiao-Yong Peng Jia-Tao Zang Yu Zhu Yue Wu Qing-Hui Li Tao Li Liang-Ming Liu State key laboratory of Trauma Burns and Combined InjuryDepartment of Shock and TransfusionResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China

Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon *** hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and *** We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)*** a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive *** pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic *** effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also *** CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(Ptransplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin *** Pericytes are protective a

关键词： Pericyte Vascular reactivity Vascular permeability Cx43 Microvesicle

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Correlation between combined Urinary Metal Exposure and Grip Strength under Three Statistical Models:A Cross-sectional Study in Rural Guangxi

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Biomedical and Environmental Sciences 2024年第1期37卷 3-18页

作者： LIANG Yu Jian RONG Jia Hui WANG Xue Xiu CAI Jian Sheng QIN Li Dong LIU Qiu Mei TANG Xu MO Xiao Ting WEI Yan Fei LIN Yin Xia HUANG Shen Xiang LUO Ting Yu GOU Ruo Yu CAO Jie Jing HUANG Chu Wu LU Yu Fu QIN Jian ZHANG Zhi Yong Department of Environmental and Occupational health School of Public HealthGuangxi Medical UniversityNanning 530021GuangxiChina key laboratory of Tumor Immunology and Microenvironmental Regulation Guilin Medical UniversityGuilin 541199GuangxiChina Department of Environmental health and Occupational Medicine School of Public HealthGuilin Medical UniversityGuilin 541199GuangxiChina Guangxi Colleges and Universities key laboratory of Prevention and Control of Highly Prevalent Diseases Guangxi Medical UniversityNanning 530021GuangxiChina Guangxi key laboratory of Environment and health Research Guangxi Medical UniversityNanning 530021GuangxiChina key laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education Guangxi Medical UniversityNanning 530021GuangxiChina Guangxi health commission key laboratory of Entire Lifecycle health and Care Guilin Medical UniversityGuilin 541199GuangxiChina

Objective This study aimed to investigate the potential relationship between urinary metals copper(Cu),arsenic(As),strontium(Sr),barium(Ba),iron(Fe),lead(Pb)and manganese(Mn)and grip *** We used linear regression models,quantile g-computation and Bayesian kernel machine regression(BKMR)to assess the relationship between metals and grip *** In the multimetal linear regression,Cu(β=−2.119),As(β=−1.318),Sr(β=−2.480),Ba(β=0.781),Fe(β=1.130)and Mn(β=−0.404)were significantly correlated with grip strength(Pcombined exposure to metal mixtures is negatively associated with grip ***,Sr and As were negatively correlated with grip strength levels,and there were potential interactions between As and Mn and between Cu and Mn.

关键词： Urinary metals Handgrip strength Quantile g-computation Bayesian kernel machine regression

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Bioinspired mineral-in-shell nanoarchitectonics:Functional empowerment of mineral precursors for guiding intradentinal mineralization

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Nano Research 2024年第5期17卷 4338-4349页

作者： Xiaoran Zheng Yang Liu Mingjing Li Yuyan Li Wanshan Gao Rongmin Qiu Jiaqi Xing Jiaojiao Yang Yantao Chen Xinyuan Xu Mingming Ding Jun Luo Jianshu Li College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065China College of Stomatology Hospital of Stomatology Guangxi Medical UniversityGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and ReconstructionGuangxi Clinical Research Center for Craniofacial DeformityGuangxi Key Laboratory of Oral and Maxillofacial Surgery Disease TreatmentGuangxi Health Commission Key Laboratory of Prevention and Treatment for Oral Infectious DiseasesNanning 530021China State key laboratory of Oral Diseases West China Hospital of StomatologySichuan UniversityChengdu 610041China Shenzhen key laboratory of Environmental Chemistry and Ecological Remediation College of Chemistry and Environmental EngineeringShenzhen UniversityShenzhen 518060China Med-X Center for Material Sichuan UniversityChengdu 610041China

Effective mineralization of biological structures poses a significant challenge in hard tissue engineering as it necessitates overcoming geometric complexities and multistep biomineralization *** this regard,we propose“mineral-in-shell nanoarchitectonics”,inspired by the nanostructure of matrix vesicles,which can influence multiple mineralization *** nanostructural design empowers mineral precursors with tailorable properties through encapsulating amorphous calcium phosphate within a multifunctional tannic acid(TA)and silk fibroin(SF)*** bioinspired nanosystem facilitates efficient recruitment of mineral precursors throughout the dentin structures,followed by large-scale intradentinal mineralization both in vitro and in vivo,which provides persistent protection against external *** simulations combined with experimental studies attribute the success of intradentinal mineralization to the TA-SF nanoshell,which exhibits a strong affinity for the dentin structure,stabilizing amorphous precursors and thereby facilitating concomitant mineral ***,this bioinspired mineral-in-shell nanoarchitectonics shows a promising prospect for hard tissue repair and serves as a blueprint for next-generation biomineralization-associated materials.

关键词： mineral-in-shell nanohybrids self-assembly biomineralization dentinal tubule occlusion dental hypersensitivity

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