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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1138-1147页

作者： hao-zhen ren Sen-Zhe Xia Xue-Qian Qin An-Yin Hu Jing-Lin Wang Department of Hepatobiliary Surgery Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJi-angsuChina Department of Hepatobiliary Surgery Nanjing Drum Tower Hospital Clinical College of Jiangsu UniversityNanjingJiangsuChina Department of Hepatobiliary Surgery Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingJiangsuChina

Background and Aims:Hepatic ischemic reperfusion in-jury(IRI)occurring during surgery seriously affects patient *** specific mechanism of IRI has not been fully *** study aim was to explore the changes of in-flammatory environment,and the relationship of the Th17/Treg cell ratio and FOXO1 expression in hepatic ***:Liver samples at different ischemic times were collected from patients and *** expression of inflammatory markers and FOXO1 in the liver was detected by western blotting and *** changes of liver lymphocytes were analyzed by flow *** AKT/Stat3/FOXO1 pathway was veri-fied by targeting AKT with *** role of FOXO1 in liver inflammation and changes in lymphocyte phenotype was confirmed by upregulating FOXO1 with ***-sults:Prolonged ischemic time aggravates liver injury in both humans and mouse models of hepatic ***-stress caused Th17/Treg imbalance and FOXO1 down-regulation by activat-ing the AKT/Stat3/FOXO1 signaling *** of FOXO1 reversed the Th17/Treg cytokine imbalance and altered the inflammation environment in the ***:Liver IRI induced Th17/Treg *** of FOXO1 re-versed the imbalance and alleviated liver inflammation.

关键词： Liver ischemia-reperfusion injury Inflammatory factors Th17 Treg AKT/Stat3/FOXO1 pathway

Targeted migration of mesenchymal stem cells modified with CXCR4 to acute failing liver improves liver regeneration

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World Journal of Gastroenterology 2014年第40期20卷 14884-14894页

作者： Hu-Cheng Ma Xiao-Lei Shi hao-zhen ren Xian-Wen Yuan Yi-Tao Ding Department of Hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical School Key Medical Center for Hepatobiliary Diseases of Jiangsu Province

AIM: To improve the colonization rate of transplanted mesenchymal stem cells (MSCs) in the liver and effect of MSC transplantation for acute liver failure (ALF).

关键词： Acute liver failure Cell transplantation Chemokine CXC receptor 4 Mesenchymal stem cells Cell mobilization

Intraportal mesenchymal stem cell transplantation prevents acute liver failure through promoting cell proliferation and inhibiting apoptosis

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Hepatobiliary & Pancreatic Diseases International 2016年第6期15卷 602-611页

作者： Jian-Feng Sang Xiao-Lei Shi Bin Han Tao Huang Xu Huang hao-zhen ren Yi-Tao Ding Department of General Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical School

BACKGROUND： Transplantation of mesenchymal stem cells （MSCs） has been regarded as a potential treatment for acute liver failure （ALF）, but the optimal route was unknown. The present study aimed to explore the most effective MSCs transplantation route in a swine ALF model. METHODS： The swine ALF model induced by intravenous injection of D-Gal was treated by the transplantation of swine MSCs through four routes including intraportal injection （InP group）, hepatic intra-arterial injection （AH group）, peripheral intravenous injection （PV group） and intrahepatic injection （IH group）. The living conditions and survival time were recorded. Blood samples before and after MSCs trans- plantation were collected for the analysis of hepatic function. The histology of liver injury was interpreted and scored in terminal samples. Hepatic apoptosis was detected by TUNEL assay. Apoptosis and proliferation related protein expressions including cleaved caspase-3, survivin, AKT, phospho-AKT （Ser473）, ERK and phospho-ERK （Tyr204） were analyzed by Western blotting. RESULTS： The average survival time of each group was 10.7± 1.6 days （InP）, 6.0±0.9 days （AH）, 4.7±1.4 days （PV）, 4.3± 0.8 days （IH）, respectively, when compared with the average survival time of 3.8±0.8 days in the D-Gal group. The survival rates between the InP group and D-Gal group revealed a statistically significant difference （P〈0.01）. Pathological and biochemical analysis showed that liver damage was the worst in the D-Gal group, while less injury in the InP group. Histopathological scores revealed a significant decrease in the InP group （3.17±1.04, P〈0.01） and AH group （8.17±0.76, P〈0.05） as compared with that in the D-Gal group （11.50±1.32）. The apoptosis rate in the InP group （25.0%±3.4%, P〈0.01） and AH group （40.5%±1.0% , P〈0.05） was lower than that in the D-Gal group （70.6%±8.5%）. The expression of active caspase-3 was inhibited, while the expression of survivin, AKT, phospho- AKT （Ser473）, ERK and phospho-ERK （Tyr20

关键词： mesenchymal stem cells stem cell transplantation acute liver failure apoptosis regeneration

Combined mesenchymal stem cell transplantation and interleukin-1 receptor antagonism after partial hepatectomy

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World Journal of Gastroenterology 2016年第16期22卷 4120-4135页

作者： Jian-Feng Sang Xiao-Lei Shi Bing Han Xu Huang Tao Huang hao-zhen ren Yi-Tao Ding Department of General Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical School

AIM: To study the therapeutic effects of mesenchymal stem cells (MSCs) and an interleukin-1 receptor antagonist (IL-1Ra) in acute liver ***: Chinese experimental miniature swine (15 ± 3 kg, 5-8 mo) were obtained from the Laboratory Animal Centre of the Affiliated Drum Tower Hospital of Nanjing University Medical School. Acute liver failure was induced via 85% hepatectomy, and animals were treated by MSC transplantation combined with IL-1Ra injection. Blood samples were collected for hepatic function analysis, and the living conditions and survival time were recorded. Liver injury was histologically analyzed. Hepatic cell regeneration and apoptosis were studied by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. The levels of protein kinase B and nuclear factor-κB expression were analyzed by Western ***: MSCs were infected with a lentivirus for expression of green fluorescent protein (GFP) for subsequent identification; 97.3% of the MSCs were positive for GFP as assessed by flow cytometry. Additional flow cytometric analysis of cell surface marker expression demonstrated that > 90% of GFP-expressing MSCs were also positive for CD29, CD44, and CD90, indicating that most of these cells expressed typical markers of MSCs, and the population of MSCs was almost pure. Transplantation of MSCs in combination with 2 mg/kg IL-1Ra therapy significantly improved survival time compared to the acute liver failure model group (35.3 ± 6.7 d vs 17.3 ± 5.5 d, P < 0.05). Combined therapy also promoted improvement in serum inflammatory cytokines and biochemical conditions. The observed hepatic histopathologic score was significantly lower in the group with combined therapy than in the model group (3.50 ± 0.87 vs 8.17 ± 1.26, P < 0.01). In addition, liver cell apoptosis in the combined therapy group was significantly inhibited (18.1 �

关键词： Mesenchymal stem cells Interleukin-1 receptor antagonist Stem cell transplantation Acute liver failure Hepatoectomy

No transmission of porcine endogenous retrovirus in an acute liver failure model treated by a novel hybrid bioartificial liver containing porcine hepatocytes

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Hepatobiliary & Pancreatic Diseases International 2015年第5期14卷 492-501页

作者： Bing Han Xiao-Lei Shi Yue Zhang Zhong-Ze Gu Xian-Wen Yuan hao-zhen ren Yong Qiu Yi-Tao Ding Department of Hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical School Department of General Surgery the Third Affiliated Hospital of Suzhou University State Key Laboratory of Bioelectronics Southeast University Department of Osteology the Affiliated Drum Tower Hospital of Nanjing University Medical School

BACKGROUND： A novel hybrid bioartificial liver（HBAL） was constructed using an anionic resin adsorption column and a multi-layer flat-plate bioreactor containing porcine hepatocytes co-cultured with bone marrow mesenchymal stem cells（MSCs）. This study aimed to evaluate the microbiological safety of the HBAL by detecting the transmission of porcine endogenous retroviruses（PERVs） into canines with acute liver failure（ALF） undergoing ***： Eight dogs with ALF received a 6-hour HBAL treatment on the first day after the modeling by D-galactosamine administration. The plasma in the HBAL and the whole blood in the dogs were collected for PERV detection at regular intervals until one year later when the dogs were sacrificed to retrieve the tissues of several organs for immunohistochemistry and Western blotting for the investigation of PERV capsid protein gag p30 in the tissue. Furthermore, HEK293 cells were incubated to determine the in vitro ***： PERV RNA and reverse transcriptase activity were observed in the plasma of circuit 3, suggesting that PERV particles released in circuit 3. No positive PERV RNA and reverse transcriptase activity were detected in other plasma. No HEK293 cells were infected by the plasma in vitro. In addition, all PERV-related analyses in peripheral blood mononuclear cells and tissues were ***： No transmission of PERVs into ALF canines suggested a reliable microbiological safety of HBAL based on porcine hepatocytes.

关键词： porcine endogenous retrovirus hybrid bioartificial liver porcine hepatocyte acute liver failure

Evaluation of a novel hybrid bioartificial liver based on a multi-layer flat-plate bioreactor

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World Journal of Gastroenterology 2012年第28期18卷 3752-3760页

作者： Xiao-Lei Shi Yue Zhang Xue-Hui Chu Bing Han Jin-Yang Gu Jiang-Qiang Xiao Jia-Jun Tan Zhong-Ze Gu hao-zhen ren Xian-Wen Yuan Yi-Tao Ding Department of Hepatobiliary Surgery Jiangsu Province's Key Medical Center for Hepatobiliary Disease The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 Jiangsu Province China State Key Laboratory of Bioelectronics Southeast University Nanjing 210008 Jiangsu Province China

AIM: To evaluate the efficacy and safety of a hybrid bioartificial liver (HBAL) system in the treatment of acute liver failure. METHODS: Canine models with acute liver failure were introduced with intravenous administration of D-galactosamine. The animals were divided into: the HBAL treatment group (n = 8), in which the canines received a 3-h treatment of HBAL; the bioartificial liver (BAL) treatment group (n = 8), in which the canines received a 3-h treatment of BAL; the non-bioartificial liver (NBAL) treatment group (n = 8), in which the canines received a 3-h treatment of NBAL; the control group (n = 8), in which the canines received no additional treatment. Biochemical parameters and survival time were determined. Levels of xenoantibodies, RNA of porcine endogenous retrovirus (PERV) and reverse transcriptase (RT) activity in the plasma were detected. RESULTS: Biochemical parameters were significantly decreased in all treatment groups. The TBIL level in the HBAL group was lower than that in other groups (2.19 ± 0.55 mmol/L vs 24.2 ± 6.45 mmol/L, 12.47 ± 3.62 mmol/L, 3.77 ± 1.83 mmol/L, P rence in ammonia levels between other the groups (P < 0.05). The levels of antibodies were similar before and after treatment. The PERV RNA and the RT activity in the canine plasma were all negative. CONCLUSION: The HBAL showed great efficiency and safety in the treatment of acute liver f

关键词： Hybrid bioartificial liver Acute liver failure Flat plate bioreactor Co-culture Nanofiber scaffold

Constructing 2D bismuth-based heterostructure for highly efficient photocatalytic CO2 reduction

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Tungsten 2025年第1期7卷 71-79页

作者： Ruo-Hang Xu hao-Yu Jiang Dan-Dan Cui Kun-Rong Du Hong-Run Zhang Sheng-Jie Xu Ya-Qi Li Zhi-zhen ren Liang Wang Wei-Chang hao Yi Du School of Physics and BUAA-UOW Joint Research Centre Beihang University Shenzhen Institute of Beihang University Centre for Catalysis and Clean Energy School of Environment and Science Griffith University

Reforming carbon dioxide（CO2） into fuels and valuable chemicals using solar energy holds significant potential for emission reduction and addressing energy supply *** recombination of photocarriers remains a major obstacle,however,to enhancing solar energy conversion efficiency in the photocatalytic reaction *** two-dimensional materials,constructing heterogeneous structures has emerged as an effective strategy to enhance the separation of photoexcited carriers by leveraging the internal electric field at the heterogeneous ***,we present a facile strategy for preparing Bi4NbO8Br/Bi2WO6plate-on-plate Z-scheme junctions with a strong internal electric field by in situ *** unique heterostructure facilitates efficient separation and transport of photoexcited charges by harnessing the internal electric field induced by chemical bonding at the lateral ***,the Bi4NbO8Br/Bi2WO6heterostructure exhibits enhanced CO2photoreduction properties,along with a CO yield rate of approximately 35 μmol·g-1·h-1under full light *** work offers novel insights into the synthesis of unique hetero structures intended to enhance the efficiency of photocatalytic CO2reduction.

关键词： Bi4NbO8Br/Bi2WO6 CO2 reduction Heterostructures Photocatalysts

Gradient‑Layered MXene/Hollow Lignin Nanospheres Architecture Design for Flexible and Stretchable Supercapacitors

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Nano-Micro Letters 2025年第2期17卷 447-462页

作者： haonan Zhang Cheng hao Tongtong Fu Dian Yu Jane Howe Kaiwen Chen Ning Yan hao ren Huamin Zhai Jiangsu Provincial Key Lab of Sustainable Pulp and Paper Technology and Biomass Materials NanJing Forestry UniversityNanjing 210037People’s Republic of China Department of Chemical Engineering and Applied Chemistry University of Toronto200 College StreetTorontoON M5S 3E5Canada Department of Materials Science and Engineering University of Toronto184 College StreetTorontoON M5S 3E4Canada College of Materials Science and Engineering Nanjing Forestry UniversityNanjing 210037People’s Republic of China

With the rapid development of flexible wearable electronics,the demand for stretchable energy storage devices has *** this work,a novel gradient-layered architecture was design based on single-pore hollow lignin nanospheres(HLNPs)-intercalated two-dimensional transition metal carbide(Ti_(3)C_(2)T_(x) MXene)for fabricating highly stretchable and durable *** depositing and inserting HLNPs in the MXene layers with a bottom-up decreasing gradient,a multilayered porous MXene structure with smooth ion channels was constructed by reducing the overstacking of MXene ***,the micro-chamber architecture of thin-walled lignin nanospheres effectively extended the contact area between lignin and MXene to improve ion and electron accessibility,thus better utilizing the pseudocapacitive property of *** these strategies effectively enhanced the capacitive performance of the *** addition,HLNPs,which acted as a protective phase for MXene layer,enhanced mechanical properties of the wrinkled stretchable electrodes by releasing stress through slip and deformation during the stretch-release cycling and greatly improved the structural integrity and capacitive stability of the *** electrodes and symmetric flexible all-solid-state supercapacitors capable of enduring 600%uniaxial tensile strain were developed with high specific capacitances of 1273 mF cm^(−2)(241 F g^(−1))and 514 mF cm^(−2)(95 F g^(−1)),***,their capacitances were well preserved after 1000 times of 600%stretch-release *** study showcased new possibilities of incorporating biobased lignin nanospheres in energy storage devices to fabricate stretchable devices leveraging synergies among various two-dimensional nanomaterials.

关键词： Hollow lignin nanospheres MXene Gradient-layered architecture Wrinkled electrodes Stretchable supercapacitors

Phase Ⅰ clinical study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma

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World Journal of Gastroenterology 2017年第29期23卷 5395-5404页

作者： Jie Shen Li-Feng Wang zheng-Yun Zou Wei-Wei Kong Jing Yan Fan-Yan Meng Fang-Jun Chen Juan Du Jie Shao Qiu-Ping Xu hao-zhen ren Ru-Tian Li Jia Wei Xiao-Ping Qian Bao-Rui Liu Comprehensive Cancer Centre of Drum Tower Hospital Medical School of Nanjing University Clinical Cancer Institute of Nanjing University Department of Hepatobiliary Surgery Drum Tower Hospital Medical School of Nanjing Universit-y

AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma(HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases(the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with *** Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response(PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade Ⅱ bone marrow suppression and the remaining patients had no significant hematological side *** Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.

关键词： Personalized peptide vaccination TOMO radiotherapy Cytotoxic lymphocytes Hepatocellular carcinoma

Exosomes:the next-generation therapeutic platform for ischemic stroke

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Neural Regeneration Research 2025年第5期20卷 1221-1235页

作者： Wenjing Yin Hongyin Ma Yang Qu Jiaxin ren Yingying Sun zhen-Ni Guo Yi Yang Stroke Center Department of NeurologyFirst Hospital of Jilin UniversityChangchunJilin ProvinceChina Neuroscience Research Center Department of NeurologyFirst Hospital of Jilin UniversityChangchunJilin ProvinceChina

Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional ***,there is an urgent need to develop new methods for the treatment of this *** are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological *** have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain *** physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic *** rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages *** in technology have also driven clinical translational research on *** this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction ***,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified *** optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic ***,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.

关键词： blood–brain barrier electroacupuncture engineering exercise exosomes ischemic stroke mesenchymal stem cells microglia neuroprotection stents