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Adjuvant therapies after curative treatments for hepatocellular carcinoma: Current status and prospects

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Genes & Diseases 2020年第3期7卷 359-369页

作者： xiao-dong zhu Kang-Shuai Li Hui-Chuan Sun Department of Liver Surgery and Transplantation Liver Cancer Institute and Zhongshan HospitalFudan UniversityShanghai200032China

Tumor recurrence rate after surgery or ablation of hepatocellular carcinoma(HCC)is as high as 70%.However,there are no widely accepted adjuvant therapies;therefore,no treatment has been recommended by guidelines from the American Association for the Study of Liver Disease or the European Association for the Study of the *** the registered trials failed to find any treatment to prolong recurrence-free survival,which is the primary outcome in most studies,including *** investigator-initiated studies revealed that antihepatitis B virus agents,interferon-a,transcatheter chemoembolization,chemokine-induced killer cells,and other treatments prolonged patient recurrence-free survival or overall survival after curative *** this review,we summarize the current status of adjuvant treatments for HCC and explain the challenges associated with designing a clinical trial for adjuvant *** new treatments being used as adjuvant therapy,especially anti-PD-1 antibodies,are also discussed.

关键词： Adjuvant therapy Anti-PD-1 antibody Clinical trial Hepatocellular carcinoma Molecular targeted therapy Recurrence-free survival

Targeting angiogenesis for liver cancer: Past, present, and future

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Genes & Diseases 2020年第3期7卷 328-335页

作者： xiao-dong zhu Zhao-You Tang Hui-Chuan Sun Department of Liver Surgery and Transplantation Liver Cancer Institute and Zhongshan HospitalFudan UniversityShanghai200032China

Liver cancer,mostly hepatocellular carcinoma(HCC),is the second leading cause of cancer mortality *** patients were diagnosed at an advanced stage,and systemic therapy is the standard of *** the approved systemic therapies for HCC are molecular targeted therapies with anti-angiogenic effects targeting the vascular endothelial growth factor signaling *** and lenvatinib are the first-line treatment,and regorafenib,ramucirumab,and cabozantinib are second-line treatment *** anti-PD-1 antibodies,including nivolumab and pembrolizumab,demonstrated promising anti-tumor effects as monotherapy for advanced HCC in phase II clinical trials,both failed in phase III ***-angiogenic treatment remains the backbone of systemic therapy for *** this review,we summarized the approved anti-angiogenic medicines and discussed the potential strategies to improve the efficacy of anti-angiogenic therapy,including combination therapy with other treatments,and discussed the approaches to overcome the drawbacks of anti-angiogenic therapies.

关键词： Anti-angiogenic therapy Combinational therapy Hepatocellular carcinoma Molecular targeted therapy Systemic therapy

LRP5 polymorphism—A potential predictor of the clinical outcome in advanced gastric cancer patients treated with EOF regimen

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Chinese Journal of Cancer Research 2014年第4期26卷 478-485页

作者： Xin Liu Ming-zhu Huang Zhi-Yu Chen xiao-Yin Zhao Chen-Chen Wang Wei Peng Ji-Liang Yin Jin Li xiao-dong zhu Department of Medical Oncology Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical CollegeFudan University

Purpose： Wnt pathways control key biological processes that potentially impact on tumor progression and patient survival. The present study analyzed the polymorphism of lipoprotein-related receptor 5 （LRPS）（gene with key functions in Wnt signaling） and its impact on the response to chemotherapy and survival of patients with advanced gastric cancer （AGC）. Methods： A total of 107 consecutive patients with AGC treated with first-line chemotherapy of EOF regimen were enrolled in the present retrospective study. The association between single nucleotide polymorphism （SNP） of rs3736228 in LRP5 and the clinical outcomes of the patients was studied. Results： The CC genotype of rs3736228 was significantly correlated with a higher disease control rate when compared to the CT and TT genotypes （89.3% and 61.8%, respectively, P〈0.001）. A univariate survival analysis also showed that the progression free survival （PFS） and overall survival （OS） for the patients with the TC and TF genotypes of rs3736228 were worse than for the patients with the CC genotype （PFS： 3.3 and 6.7 months, respectively, HR =0.454, P〈0.001; OS： 8.1 months and 18.8 months, respectively, HR =3.056, P〈0.001）. A multivariate Cox model incorporates rs3736228 and clinical features, also identified rs3736228 was significantly associated with the PFS and OS. Conclusions： Our results firstly highlight the importance of LRPY gene of Wnt pathway in the treatment of AGC and identify polymorphism of rs3736228 as independent predictor of disease control rate, PFS and OS in AGC patients treated with first-line chemotherapy of EOF regimen in the Chinese Han population.

关键词： Gastric cancer chemotherapy biomarker lipoprotein-related receptor 5 (LRP5) rs3736228

Fibrous MXene Aerogels with Tunable Pore of Contaminated Seawater

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Nano-Micro Letters 2023年第5期15卷 298-312页

作者： Fan Wu Siyu Qiang xiao-dong zhu Wenling Jiao Lifang Liu Jianyong Yu Yi-Tao Liu Bin Ding Innovation Center for Textile Science and Technology College of TextilesDonghua UniversityShanghai 201620People’s Republic of China State Key Laboratory Base of Eco-Chemical Engineering College of Chemical EngineeringQingdao University of Science&TechnologyQingdao 266042People’s Republic of China

The seawater desalination based on solardriven interfacial evaporation has emerged as a promising technique to alleviate the global crisis on freshwater ***,achieving high desalination performance on actual,oil-contaminated seawater remains a critical challenge,because the transport channels and evaporation interfaces of the current solar evaporators are easily blocked by the oil slicks,resulting in undermined evaporation rate and conversion ***,we propose a facile strategy for fabricating a modularized solar evaporator based on flexible MXene aerogels with arbitrarily tunable,highly ordered cellular/lamellar pore structures for high-efficiency oil interception and *** core design is the creation of 1D fibrous MXenes with sufficiently large aspect ratios,whose superior flexibility and plentiful link forms lay the basis for controllable 3D assembly into more complicated pore *** cellular pore structure is responsible for effective contaminants rejection due to the multi-sieving effect achieved by the omnipresent,isotropic wall apertures together with underwater superhydrophobicity,while the lamellar pore structure is favorable for rapid evaporation due to the presence of continuous,large-area evaporation *** modularized solar evaporator delivers the best evaporation rate(1.48 kg m-2h-1)and conversion efficiency(92.08%)among all MXene-based desalination materials on oil-contaminated seawater.

关键词： Fibrous MXene aerogels Tunable pore structures Modularized solar evaporator Photothermal desalination

SMRI: A New Method for siRNA Design for COVID-19 Therapy

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Journal of Computer Science & Technology 2022年第4期37卷 991-1002页

作者： Meng-Xin Chen xiao-dong zhu Hao Zhang Zhen Liu Yuan-Ning Liu College of Software Jilin UniversityChangchun 130012China Key Laboratory of Symbolic Computation and Knowledge Engineering of the Ministry of Education Jilin UniversityChangchun 130012China College of Computer Science and Technology Jilin UniversityChangchun 130012China Graduate School of Engineering Nagasaki Institute of Applied ScienceNagasaki 851-0193Japan

First discovered in Wuhan, China, SARS-CoV-2 is a highly pathogenic novel coronavirus, which rapidly spreads globally and becomes a pandemic with no vaccine and limited distinctive clinical drugs available till March 13th, 2020. Ribonucleic Acid interference (RNAi) technology, a gene-silencing technology that targets mRNA, can cause damage to RNA viruses effectively. Here, we report a new efficient small interfering RNA (siRNA) design method named Simple Multiple Rules Intelligent Method (SMRI) to propose a new solution of the treatment of COVID-19. To be specific, this study proposes a new model named Base Preference and Thermodynamic Characteristic model (BPTC model) indicating the siRNA silencing efficiency and a new index named siRNA Extended Rules index (SER index) based on the BPTC model to screen high-efficiency siRNAs and filter out the siRNAs that are difficult to take effect or synthesize as a part of the SMRI method, which is more robust and efficient than the traditional statistical indicators under the same circumstances. Besides, to silence the spike protein of SARS-CoV-2 to invade cells, this study further puts forward the SMRI method to search candidate high-efficiency siRNAs on SARS-CoV-2's S gene. This study is one of the early studies applying RNAi therapy to the COVID-19 treatment. According to the analysis, the average value of predicted interference efficiency of the candidate siRNAs designed by the SMRI method is comparable to that of the mainstream siRNA design algorithms. Moreover, the SMRI method ensures that the designed siRNAs have more than three base mismatches with human genes, thus avoiding silencing normal human genes. This is not considered by other mainstream methods, thereby the five candidate high-efficiency siRNAs which are easy to take effect or synthesize and much safer for human body are obtained by our SMRI method, which provide a new safer, small dosage and long efficacy solution for the treatment of COVID-19.

关键词： COVID-19 SARS-CoV-2 RibonucleicAcid interference

NaBH4-induced phase transition of CoSe_(2) with abundant Se deficiency for acidic oxygen reduction to hydrogen peroxide

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Rare Metals 2024年第2期43卷 500-510页

作者： Cai-Di Han Yong-Chao Zhang Qian Zhang Jin-Ting Wu Jian Gao Ji-Jun Zou xiao-dong zhu State Key Laboratory Base of Eco-Chemical Engineering College of Chemical Engineering Qingdao University of Science and TechnologyQingdao266042China Key Laboratory for Green Chemical Technology of Ministry of Education School of Chemical Engineering and TechnologyTianjin UniversityTianjin300072China

Electrocatalytic oxygen reduction(ORR)via the 2e−pathway to form H_(2)O_(2) in acidic medium has attracted extensive ***,the low activity,insufficient selectivity and high cost of catalysts have been the ***,CoSe_(2) with abundant Se deficiency was synthesized by a simple hydrothermal method,and the addition of NaBH4-induced CoSe_(2) phase transition from orthorhombic to cubic phase with more Se *** cubic phase CoSe_(2) with abundant Se deficiency can effectively regulate the surface electronic structure with suitable binding energies of*OOH and*O,which shows high activity,selectivity and long-term stability for acidic ORR to H_(2)O_(2).The onset potential is as low as 0.73 V *** hydrogen electrode(RHE),the H_(2)O_(2) selectivity is 84%(0 V ***),and the average electron transfer number is about ***,the H_(2)O_(2) yield measured using a flow cell is as high as 115.92 mmol·gcat.^(−1)·h^(−1) and the Faradaic efficiency is 70%at 0 V ***,which presents high potential in electrocatalytic acidic ORR to H_(2)O_(2) and organic pollutant degradation using the electron-Fenton process.

关键词： Se defected CoSe_(2) Crystal phase transition Electrocatalysis Acidic oxygen reduction Hydrogen peroxide

Reversal of hyperglycemia in diabetic rats by portal vein transplantation of islet-like cells generated from bone marrow mesenchymal stem cells

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World Journal of Gastroenterology 2007年第24期13卷 3342-3349页

作者： xiao-Hong Wu Cui-Ping Liu Kuan-Feng Xu xiao-dong Mao Jian zhu Jing-Jing Jiang Dai Cui Mei Zhang Yu Xu Chao Liu Department of Endocrinology First Affiliated Hospital of Nanjing Medical University Nanjing 210029 Jiangsu Province China

AIM: To study the capacity of bone marrow mesenchymal stem cells (BM-MSCs) trans-differentiating into islet-like cells and to observe the effect of portal vein transplantation of islet-like cells in the treatment of streptozotocin-induced diabetic rat. METHODS: BM-MSCs were isolated from SD rats and induced to differentiate into islet-like cells under defined conditions. Differentiation was evaluated with electron microscopy, RT-PCR, immunofluorescence and flow cytometry. insulin release after glucose challenge was tested with ELiSA. Then allogeneic islet-like cells were transplanted into diabetic rats via portal vein. Blood glucose levels were monitored and islet hormones were detected in the liver and pancreas of the recipient by immunohistochemistry. RESULTS: BM-MSCs were spheroid adherent monolayers with high CD90, CD29 and very low CD45 expression. Typical islet-like cells clusters were formed after induction. Electron microscopy revealed that secretory granules were densely packed within the cytoplasm of the differentiated cells. The spheroid cells expressed islet related genes and hormones. The insulin-positive cells accounted for 19.8% and mean fluorescence intensity increased by 2.6 fold after induction. The cells secreted a small amount of insulin that was increased 1.5 fold after glucose challenge. After transplantation, islet-like cells could locate in the liver expressing islet hormones and lower the glucose levels of diabetic rats during d 6 to d ***: Rat BM-MSCs could be transdifferentiated into islet-like cells in vitro . Portal vein transplantation of islet-like cells could alleviate the hyperglycemia of diabetic rats.

关键词： Bone marrow mesenchymal stem cells Trans-differentiation Islet Insulin Transplantation

Effect of ultrasound-guided lumbar square muscle block on stress response in patients undergoing radical gastric cancer surgery

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World Journal of Gastrointestinal Oncology 2023年第12期15卷 2093-2100页

作者： Xin-Ran Wang Dan-Dan Xu Meng-Jiao Guo Yi-Xin Wang Meng Zhang dong-xiao zhu Department of Ultrasound Affiliated Hospital of Jiangnan UniversityWuxi 214122Jiangsu ProvinceChina

BACKGROUND Radical surgery is a common treatment for patients with gastric cancer;however,it can lead to postoperative complications and intestinal barrier ***-guided quadratus lumborum block is often used for postoperative analgesia,but its effects on stress response and intestinal barrier function are not well *** To investigate the effects of an ultrasound-guided quadratus lumborum block on stress response and intestinal barrier function in patients undergoing radical surgery for gastric *** A total of 100 patients undergoing radical surgery for gastric cancer were randomly categorized into observation and control *** adrenaline and cortisol levels,intestinal mucosal barrier indexes,and complication rates were compared between the two groups before,during,and 1 day after *** The observation group had significantly lower plasma adrenaline and cortisol levels during surgery and at 1 day postoperatively than that of the control group(P<0.05).Additionally,intestinal barrier indexes(endotoxin and D-dimer)at 1 day postoperatively were significantly lower in the observation group than in the control group(P<0.05).CONCLUSION Ultrasound-guided quadratus lumborum block could reduce stress response,protect intestinal barrier function,and decrease the incidence of complications in patients undergoing radical surgery for gastric *** technique has the potential for clinical applications.

关键词： Ultrasound-guided quadratus lumborum block Radical gastric cancer surgery Stress response Intestinal barrier function Postoperative analgesia Rehabilitation

Development and Validation of a Nomogram Based on Perioperative Factors to Predict Post-hepatectomy Liver Failure

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Journal of Clinical and Translational Hepatology 2021年第3期9卷 291-300页

作者： Bin Xu xiao-Long Li Feng Ye xiao-dong zhu Ying-Hao Shen Cheng Huang Jian Zhou Jia Fan Yong-Jun Chen Hui-Chuan Sun Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghaiChina Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education ShanghaiChina Department of Hepatobiliary Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

(PHLF)is a severe complication and main cause of death in patients undergoing *** aim of this study was to build a predictive model of PHLF in patients undergoing ***:We retrospectively analyzed patients undergoing hepatectomy at Zhongshan Hospital,Fudan University from July 2015 to June 2018,and randomly divided them into development and internal validation *** validation was performed in an independent *** absolute shrinkage and selection operator(commonly referred to as LASSO)logistic regression was applied to identify predictors of PHLF,and multivariate binary logistic regression analysis was performed to establish the predictive model,which was visualized with a ***:A total of 492 eligible patients were *** and multivariate analysis identified three preoperative variables,total bilirubin(p=0.001),international normalized ratio(p<0.001)and platelet count(p=0.004),and two intraoperative variables,extent of resection(p=0.002)and blood loss(p=0.004),as independent predictors of *** area under receiver operating characteristic curve(referred to as AUROC)of the predictive model was 0.838 and outperformed the model for end-stage liver disease score,albumin-bilirubin score and platelet-albumin-bilirubin score(AUROCs:0.723,0.695 and 0.663,respectively;p<0.001 for all).The optimal cut-off value of the predictive model was *** validation showed the model could predict PHLF accurately and distinguish high-risk ***:PHLF can be accurately predicted by this model in patients undergoing hepatectomy,which may significantly contribute to the postoperative care of these patients.

关键词： Hepatectomy Post-hepatectomy liver failure LASSO Nomogram