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Science China Life Sciences 2025年第1期 297-299页

作者： Junbin Zhou Rongli Wei Guanghan Fan Zhengxing Lian Xuanyu Zhang Linsong Tang Zhetuo Qi haiyang xie Shusen Zheng Qiang Wei Xiao Xu Department of Hepatobiliary and Pancreatic Surgery People's Hospital of LishuiAffiliated Lishui Hospital of Wenzhou Medical UniversityThe First Affiliated Hospital of Lishui University NHFPC Key Laboratory of Combined Multi-Organ Transplantation Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryHangzhou First People's Hospital Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of Medicine Department of Urology The Second Affiliated HospitalZhejiang University School of Medicine Department of Hepatobiliary and Pancreatic Surgery Department of Liver TransplantationShulan (Hangzhou) Hospital Hangzhou Medical College Zhejiang University School of Medicine

Dear Editor, Liver transplantation(LT) is the only curative therapy for patients with endstage liver disease(He et al., 2023; Ling et al., 2022). Post-transplant hypertriglyceridemia(PTHT), which has an incidence of up to 32.8% in 6 months after LT, is one of the major post-transplant complications(Toshima et al., 2020).

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Isolating the cDNA fragment inhibiting nontargeted mutagenesis in vero cell by antisense technology

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Chinese Science Bulletin 1999年第6期44卷 533-537页

作者： Wenwei Hu Yingnian Yu Xingruo Chen Tao Song haiyang xie Zhejiang Med Univ Dept Pathophysiol Hangzhou 310031 Peoples R China

Among the expressed sequence tags (ESTs) which were isolated from genetically instable monkey kidney vero cells induced by N-methyI-N’-nitro-N-nitrosoguanidine (MNNG), a fragment 9 was isolated. When the expression of fragment 9 was blocked through transcripting antisense RNA, MNNGinduced nontargeted mutation frequency enhanced significantly compared with control ( P < 0.05). The result showed that the relevant gene of fragment 9 might participate in maintaining cellular genetic stability and be involved in inhibition of nontargeted mutagenesis.

关键词： antisense RNA mutation nontargeted genetic instability.

Stereotactic body radiation therapy versus radiofrequency ablation in patients with small hepatocellular carcinoma:a systematic review and meta-analysis

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Hepatobiliary Surgery and Nutrition 2021年第5期10卷 623-630,I0008页

作者： Jiawei Hong Linping Cao haiyang xie Yuanxing Liu Jun Yu Shusen Zheng Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryFirst Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Key Lab of Combined Multi-Organ Transplantation Ministry of Public HealthHangzhouChina The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Zhejiang UniversityHangzhouChina

Background:This study aimed to compare the clinical outcomes and toxicity between small hepatocellular carcinoma(HCC)patients treated with stereotactic body radiation therapy(SBRT)and those treated with radiofrequency ablation(RFA).Methods:We searched databases for relevant clinical *** primary outcomes of interest were overall survival(OS)at 1 and 2 years,freedom from local progression(FFLP)rate at 2 years,and ***:Five cohorts from 5 retrospective studies and 4,814 patients with HCC were *** OS at 2 years was significantly lower for SBRT than for RFA[odds ratio(OR):0.63;95%confidence interval(CI):0.51-0.79;P<0.0001],but the pooled FFLP rate at 2 years was higher for SBRT than for RFA(OR:1.66;95%CI:1.05-2.61;P=0.03).In addition,there was no significant difference in the local and liver toxicities of the two *** contradictory conclusion between the OS and FFLP outcome may be attributed to the difference in radiological dose and location,but there were no uniform criteria to illustrate the radiological dose and location in the included ***:SBRT had a higher local control ratio but poorer prognosis than RFA in patients with small *** local toxicity was comparable in both *** trials should be designed with uniform standards for SBRT and RFA treatments.

关键词： Hepatocellular carcinoma(HCC) stereotactic body radiation therapy(SBRT) radiofrequency ablation(RFA) meta-analysis

Long noncoding RNA HOTTIP expression predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation

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Hepatobiliary Surgery and Nutrition 2018年第6期7卷 429-439页

作者： Liming Wu Zhe Yang Jie Zhang haiyang xie Lin Zhou Shusen Zheng Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China Innovation Center for Diagnosis and Treatment of Infectious Diseases Hangzhou 310003China Jingning National Hospital of the First Affiliated Hospital School of MedicineZhejiang UniversityHangzhou 310003China Department of Hepatobiliary Surgery First Hospital of JiaxingJiaxing UniversityJiaxing 314000China

Background:The long noncoding RNA HOTTIP has recently been described as a biomarker of poor prognosis in patients with hepatocellular carcinoma(HCC).Methods:In the present study,we evaluated the clinical significance of HOTTIP expression in predicting the rate of tumor recurrence in HCC patients after liver transplantation(LT).We examined the expression pattern and single nucleotide polymorphism(SNP)genotype of HOTTIP in HCC samples from 155 patients underwent LT,and its correlation with clinical parameters and patient prognosis was *** was suppressed using siRNA to explore the role HOTTIP plays in tumor ***:The expression level of HOTTIP in cancer tissues was higher than in adjacent noncancerous *** analyses revealed that HOTTIP expression was an independent prognostic factor for tumor recurrence and lower overall survival times in HCC patients after *** who beyond the Milan criteria and exhibit decreased HOTTIP expression experienced longer recurrence-free survival and overall *** rs2071265 is associated with an earlier recurrence in HCC ***,the suppression of HOTTIP in liver cancer cell lines reduced cell invasion rates and increased ***:In summary,the high expression level of HOTTIP in HCC could serve as a candidate biomarker for predicting poor prognosis in HCC patients underwent liver transplant ***,HOTTIP might be a potential therapeutic target.

关键词： Hepatocellular carcinoma(HCC) liver transplantation HOTTIP long noncoding RNA HOTTIP

Structural shifts in the intestinal microbiota of rats treated with cyclosporine A after orthotropic liver transplantation

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Frontiers of Medicine 2019年第4期13卷 451-460页

作者： Junjun Jia Xinyao Tian Jianwen Jiang Zhigang Ren Haifeng Lu Ning He haiyang xie Lin Zhou Shusen Zheng Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China Key Laboratory of Combined Multi-Organ Transplantation Ministry of Public Health Collaborative Innovation Center for Diagnosis and Treatment ofInfectious Diseases the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

Understanding the effect of immunosuppressive agents on intestinal microbiota is important to reduce the mortality and morbidity from orthotopic liver transplantation (OLT). We investigated the relationship between the commonly used immunosuppressive agent cyclosporine A (CSA) and the intestinal microbial variation in an OLT model. The rat samples were divided as follows:(1) N group (normal control);(2) I group (isograft LT, Brown Norway [BN] rat to BN);(3) R group (allograft LT, Lewis to BN rat);and (4) CSA group (R group treated with CSA). The intestinal microbiota was assayed by denaturing gradient gel electrophoresis profiles and by using real-time polymerase chain reaction. The liver histopathology and the alanine/aspartate aminotransferase ratio after LT were both ameliorated by CSA. In the CSA group, the numbers of rDNA gene copies of Clostridium cluster I, Clostridium cluster XIV, and Enterobacteriaceae decreased, whereas those of Faecalibacterium prausnitzii increased compared with the R group. Cluster analysis indicated that the samples from the N, I, and CSA groups were clustered, whereas the other clusters contained the samples from the R group. Hence, CSA ameliorates hepatic graft injury and partially restores gut microbiota following LT, and these may benefit hepatic graft rejection.

关键词： microbial community liver transplantation immunosuppressive agents cyclosporine A

MiR-516a-3p is a Novel Mediator of Hepatocellular Carcinoma Oncogenic Activity and Cellular Metabolism

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Engineering 2022年第9期16卷 162-175页

作者： Tao Rui Xueyou Zhang Shi Feng Haitao Huang Shaowei Zhan haiyang xie Lin Zhou Shusen Zheng Qi Ling Department of Surgery Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310003China Department of Surgery Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory of Organ Transplantation Research Center for Diagnosis and Treatment of Hepatobiliary DiseasesZhejiang ProvinceHangzhou 310003China

Hepatocellular carcinoma(HCC)remains one of the most lethal *** previously demonstrated that the chromosome 19 microRNA cluster(C19MC)was associated with tumor burden and prognosis in patients with *** the current study,we aim to explore the role of miR-516a-3p-an identical mature microRNA(miRNA)co-spliced by four oncogenic pre-miRNAs of C19MC(i.e.,mir-516a-1,mir-516a-2,mir-516b-1,and mir-516b-2)-in *** our cohort of HCC patients,miR-516a-3p was highly expressed in HCC tissues in comparison with adjacent non-tumor *** expression of tumor miR-516a-3p significantly correlated with advanced tumor stages,distinguished high HCC recurrence and mortality,and independently predicted poor *** further found that miR-516a-3p enhanced the proliferation,migration,and invasiveness of HCC cells in vitro and promoted tumor growth and metastasis in *** cancer cells,miR-516a-3p could be delivered via exosomes or extracellular vesicles and increased the oncogenic activity of recipient ***,we performed comprehensive transcriptomics,proteomics,and metabolomics analysis on the potential mechanism underlying miR-516a-3p-promoted *** DIABLO analysis showed a close correlation and strong cluster consistency between the proteomics and metabolomics *** further confirmed six proteins(i.e.,LMBR1,CHST9,RBM3,SLC7A6,PTGFRN,and NOL12)as the direct targets of miR-516a-3p and as central players in miR-516a-3p-mediated metabolism *** integrated multi-omics and co-enriched pathway analysis showed that miR-516a-3p regulates the metabolic pathways of HCC cells,particularly purine and pyrimidine *** conclusion,our findings suggest that miR-516a-3p promotes malignant behaviors in HCC cells by regulating cellular metabolism and affecting neighboring cells via the exosome delivery ***,we suggest miR-516a-3p as a novel molecular target for HCC therapy.

关键词： Hepatocellular carcinoma MicroRNA cluster Exosome Multi-omics

Integrated microfluidic single-cell immunoblotting chip enables high-throughput isolation,enrichment and direct protein analysis of circulating tumor cells

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Microsystems & Nanoengineering 2022年第1期8卷 211-222页

作者： Aynur Abdulla Ting Zhang Shanhe Li Wenke Guo Antony RWarden Yufang Xin Nokuzola Maboyi Jiatao Lou haiyang xie Xianting Ding Institute for Personalized Medicine School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200030China Shanghai General Hospital Shanghai Jiao Tong UniversityNo.85 Wujing RoadShanghai 200080China

Effective capture and analysis of a single circulating tumor cell(CTC)is instrumental for early diagnosis and personalized therapy of ***,due to their extremely low abundance and susceptibility to interference from other cells,high-throughput isolation,enrichment,and single-cell-level functional protein analysis of CTCs within one integrated system remains a major ***,we present an integrated multifunctional microfluidic system for highly efficient and label-free CTC isolation,CTC enrichment,and single-cell immunoblotting(ieSCI).The ieSCI-chip is a multilayer microfluidic system that combines an inertia force-based cell sorter with a membrane filter for label-free CTC separation and enrichment and a thin layer of a photoactive polyacrylamide gel with microwell arrays at the bottom of the chamber for single-cell *** ieSCI-chip successfully identified a subgroup of apoptosis-negative(Bax-negative)cells,which traditional bulk analysis did not detect,from cisplatin-treated ***,we demonstrated the clinical application of the ieSCI-chip with blood samples from breast cancer patients for personalized CTC epithelial-to-mesenchymal transition(EMT)*** expression level of a tumor cell marker(EpCAM)can be directly determined in isolated CTCs at the single-cell level,and the therapeutic response to anticancer drugs can be simultaneously ***,the ieSCI-chip provides a promising clinical translational tool for clinical drug response monitoring and personalized regimen development.

关键词： diagnosis analysis enable

A promising ex vivo liver protection strategy: machine perfusion and repair

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Hepatobiliary Surgery and Nutrition 2019年第2期8卷 142-143页

作者： Junjun Jia Jianhui Li Shiyu Zhang haiyang xie Lin Zhou Shusen Zheng Division of Hepatobiliary Pancreatic Surgery Ministry of Public HealthFirst Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory of Combined Multi-organ Transplantation Ministry of Public HealthFirst Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Liver transplantation is a lifesaving procedure for patients with end-stage liver *** the development of surgical technique,imaging,and immunosuppressant agents,postoperative survival rate has increased ***,organ shortage is still a major *** solve the organ shortage crisis,extended criteria donors are used which include aged donors,fatty donors,and cardiac death donors;these donors need more protection.

关键词： shortage protection. repair

Application of biocompatible custom ceria nanoparticles in improving the quality of liver grafts for transplantation

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Nano Research 2023年第4期16卷 5176-5188页

作者： Yinbiao Qiao Jianhui Li Suchen Bian Chenyue Zhan Jia Luo Li Jiang Haoyu Li Hao Wu Cheng Zhang Shusen Zheng haiyang xie Penghong Song Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China National Health Commission(NHC)Key Laboratory of Combined Multi-organ Transplantation Hangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Department of Liver TransplantationShulan(Hangzhou)HospitalZhejiang Shuren University School of MedicineHangzhou 310015China The Organ Repair and Regeneration Medicine Institute of Hangzhou Hangzhou 310003China

Liver transplantation(LT),an ultimate and vital method for treating end-stage liver disease,is often accompanied by ischemiareperfusion injury(IRI)resulting from warm or cold ischemia of the donor *** protection techniques are used to improve the quality of liver grafts(from retrieval to implantation).Reactive oxygen species(ROS)cause oxidative stress,which is considered a crucial factor in IRI after *** antioxidants capable of scavenging ROS alleviate IRI in multiple types of organs and *** this study,we synthesized ceria nanoparticles(NPs)with antioxidant properties using a pyrolysis method and covered them with phospholipid-polyethylene glycol to improve their biocompatibility in *** investigated the potential organprotective effect of ceria NPs and the underlying *** NPs promoted liver function recovery after LT by attenuating IRI in liver grafts in *** protective effect of ceria NPs on liver grafts was investigated by applying hypothermic oxygenated machine perfusion ex *** NPs attenuated hypoxia reoxygenation-or H_(2)O_(2)-induced hepatocyte injury by enhancing mitochondrial activity and ROS scavenging in *** effects may be associated with the activation of the nuclear factor erythroid-derived 2-related factor 2(Nrf2)/Kelch-like ECH-associated protein 1(Keap1)/heme oxygenase 1(HO-1)signaling *** conclusion,ceria NPs may serve as a promising antioxidant agent for the treatment of hepatic IRI after LT.

关键词： ceria nanoparticles liver transplantation hypothermic oxygenated machine perfusion(HOPE) ischemia-reperfusion injury(IRI) antioxidant

The circFASN/miR-33a pathway participates in tacrolimusinduced dysregulation of hepatic triglyceride homeostasis

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2132-2141页

作者： Chenzhi Zhang Kangchen Chen Rongli Wei Guanghan Fan Xuechun Cai Li Xu Beini Cen Jianguo Wang haiyang xie Shusen Zheng Xiao Xu Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryFirst Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China Key Lab of Combined Multi-Organ Transplantation Ministry of Public HealthHangzhou 310000China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou 310000China

Dyslipidemia exhibits a high incidence after liver transplantation,in which tacrolimus,a widely used immunosuppressant,plays a fundamental *** and related circRNAs represent a class of noncoding RNAs that have been recognized as important regulators of genes associated with lipid ***,their transcriptional activities and functional mechanisms in tacrolimus-related dyslipidemia remain *** this study,we observed that tacrolimus could induce triglyceride accumulation in hepatocytes by stimulating sterol response element-binding proteins(SREBPs)and *** in silico and experimental analyses identified miR-33a as a direct target of *** could downregulate circFASN and result in elevated miR-33a in vivo and in *** of circFASN or silencing of miR-33a decreased the promoting effects of tacrolimus on triglyceride ***,the incidence of dyslipidemia in liver transplant recipients with elevated serum miR-33a after liver transplantation was higher than that in patients without elevated serum miR-33a(46.3%vs.18.8%p=0.012,n=73).Our results showed that the circFASN/miR-33a regulatory system plays a distinct role in tacrolimus-induced disruption of lipid ***-33a is likely a risk factor for tacrolimus-related dyslipidemia,providing a potential therapeutic target to combat tacrolimus-induced dyslipidemia after liver transplantation.

关键词： tacrolimus homeostasis elevated