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Recent advances in the construction of humanized animal models and applications in translational medicine 认领 引用
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作者 Yanan Lyu Yong-Guang Yang Zheng Hu 《Animal Models and Experimental Medicine》 CAS CSCD 2026年第5期914-931,共18页
Over the past several decades,humanized mouse models have undergone significant refinement and become essential tools in biomedical research.Advances in genetic engineering,particularly the targeted knock-in of human ... Over the past several decades,humanized mouse models have undergone significant refinement and become essential tools in biomedical research.Advances in genetic engineering,particularly the targeted knock-in of human cytokines,have enabled robust development and function of human immune cells in these models.Recent breakthroughs-including the directed differentiation of human pluripotent stem cells into thymic epithelial cells and the efficient expansion of hematopoietic stem cells-have alleviated the constraint of scarce human tissue sources.Furthermore,the reconstruction of lymph node structures and successful engraftment of solid organ tissues have significantly improved the efficiency and physiological relevance of human immune system reconstitution.These models now provide a unique plat-form for in vivo studies in cancer immunotherapy,infectious diseases,regenerative medicine,and autoimmune disorders under near-physiological conditions.Beyond rodents,substantial progress in humanized large animals,such as pigs,offers prom-ising avenues for large-scale immune system reconstruction and mass production of immunotherapeutic cells.This review presents a comprehensive overview of the development,optimization,and expanding applications of humanized animal models,highlighting their transformative role in advancing translational medicine. 展开更多
关键词 cancer immunotherapy disease models humanized animal models regenerative medicine translational medicine
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A humanized NOG-EXL mouse model for producing severe fever with thrombocytopenia syndrome virus-reactive human antibodies 认领 引用
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作者 Dong Hoon Lee Jiyeong Bae +9 位作者 Sumi Kim Chan Young Song Jung Hyu Shin Eun Hee Kim Chan Ho Jang Young-sun Yun Dong-sook Lee Hyuk Chu Jang-Hoon Choi Chan Woo Kim 《Animal Models and Experimental Medicine》 CAS CSCD 2026年第2期378-388,共11页
Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To over... Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34+hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering. 展开更多
关键词 human immunoglobulin G(IgG) humanized mouse severe fever with thrombocytopenia syndrome virus(SFTSV)
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Humanized Design Strategies for Pocket Gardens in Old Communities in Hainan 认领 引用
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作者 Tongbin Cui 《Journal of World Architecture》 2026年第1期51-55,共5页
Old communities in Hainan face challenges like insufficient public spaces and aging facilities.Pocket gardens,as a micro-regeneration practice,can enhance living environments.However,current designs often overlook tro... Old communities in Hainan face challenges like insufficient public spaces and aging facilities.Pocket gardens,as a micro-regeneration practice,can enhance living environments.However,current designs often overlook tropical climates and residents’needs,leading to low utilization.This paper proposes humanized design strategies for pocket gardens,integrating climate adaptability,functional suitability,and community participation.Strategies include creating comfortable microclimates with natural shade and permeable pavements,establishing all-ages-friendly zones,fostering community co-creation,and utilizing low-cost,local materials.These strategies aim to craft usable,sustainable green spaces that foster a sense of belonging,providing practical references for urban regeneration and community governance in Hainan. 展开更多
关键词 Humanized design Pocket gardens Tropical climate adaptation
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Application of humanized mice in the safety experiments of antibody drugs 认领 引用 被引量：1
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作者 Zhimin Sun Mengyun Gu +7 位作者 Zixuan Yang Lei Shi Liyuan Zhao Minhui Zheng Yan Wang Wei Zhang Kexin Han Naping Tang 《Animal Models and Experimental Medicine》 CAS CSCD 2025年第6期1023-1032,共10页
Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safet... Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safety using suitable animal models.In this context,we review the various categories and applications of humanized mice,which have been engrafted with human cells or tissues to mimic the human immune system.These models are extensively utilized in the nonclinical assessment and development of various antibody drugs,acting as a conduit to clinical research.However,several challenges remain,including the limited lifespan of humanized mice,inadequate en-graftment of human cells,and the rudimentary nature of the immune environment in these models.The development of humanized immune system models in mice pre-sents both opportunities and challenges,potentially leading to new insights into the evolution and application of antibody therapeutics. 展开更多
关键词 antibody drugs humanized mice immunogenicity preclinical evaluation
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Fast-track rehabilitation plus humanized nursing improves gastrointestinal function and quality of life in post-surgical gastric cancer patients 认领 引用
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作者 Hua Li Hai-Jie Gao +2 位作者 Mei-Dai Wan Wan-Zhen Wang Xia Wu 《World Journal of Gastrointestinal Surgery》 SCIE 2025年第10期135-142,共8页
BACKGROUND Postoperative complications(POCs)can arise in patients who underwent surgery for gastric cancer(GC).Effective nursing may help in minimizing these negative outcomes.AIM To elucidate the influence of fast-tr... BACKGROUND Postoperative complications(POCs)can arise in patients who underwent surgery for gastric cancer(GC).Effective nursing may help in minimizing these negative outcomes.AIM To elucidate the influence of fast-track rehabilitation(FTR)plus humanized nursing on gastrointestinal(GI)function and quality of life(QOL)of patients who underwent GC surgery.METHODS The study participants were 102 patients admitted between December 2018 and December 2020 for GC surgery,of which 52 and 50 patients who received FTR+humanized nursing(research group)and routine nursing(control group),respectively.GI function,QOL,POCs(abdominal distension,infection,GI bleeding,anastomotic leakage,and deep vein thrombosis)and nursing satisfaction were compared between the two groups.RESULTS Compared with the control group,the research group had better GI function,which was mainly manifested by earlier food intake,shorter bowel sound recovery time,short time to first postoperative anal exhaustion and defecation,and shorter length of stay.Besides,the research group exhibited better QOL,lower overall POC rate,and higher nursing satisfaction than the control group.CONCLUSION FTR+humanized nursing not only improve the GI function and QOL of patients undergoing GC surgery but also reduce the incidence of POCs and improve nursing satisfaction.Thus,this intervention deserves popularization in clinical practice. 展开更多
关键词 Fast-track rehabilitation Humanized nursing Gastric cancer Gastrointestinal function Quality of life
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Research on the Application of Humanized Nursing in Clinical Obstetrics and Gynecology Nursing 认领 引用
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作者 Xiaohua Ding 《Journal of Clinical and Nursing Research》 2025年第12期237-243,共7页
Clinical nursing in obstetrics and gynecology is far more than mere disease treatment and technical operations;it also carries profound humanistic care connotations.Through clinical practice analysis,this study system... Clinical nursing in obstetrics and gynecology is far more than mere disease treatment and technical operations;it also carries profound humanistic care connotations.Through clinical practice analysis,this study systematically elaborates on the risks existing in clinical obstetrics and gynecology nursing,analyzes the importance of humanized nursing,and proposes corresponding application countermeasures.It is found that the application of the humanized nursing model in clinical obstetrics and gynecology nursing can effectively meet the physical,psychological,and social needs of patients,establish a harmonious nurse-patient relationship,and have positive clinical value in promoting the physical and mental rehabilitation of patients.It is worthy of extensive promotion and application in clinical practice. 展开更多
关键词 Humanized nursing Clinical obstetrics and gynecology nursing Application
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Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement 认领 引用 被引量：1
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作者 Hanwei Yue Lin Bai 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第1期3-11,共9页
In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking ... In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development. 展开更多
关键词 antitumor antiviral CAR-T humanized immune system model humanized mice preclinical research
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Development of a humanized HLA-A30 transgenic mouse model 认领 引用 被引量：8
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作者 Meng-min Zhu Bo-wen Niu +10 位作者 Ling-ling Liu Hua Yang Bo-yin Qin Xiu-hua Peng Li-xiang Chen Yang Liu Chao Wang Xiao-nan Ren Chun-hua Xu Xiao-hui Zhou Feng Li 《Animal Models and Experimental Medicine》 CAS CSCD 2022年第4期350-361,共12页
Background:There are remarkable genetic differences between animal major histocompatibility complex(MHC)systems and the human leukocyte antigen(HLA)system.HLA transgenic humanized mouse model systems offer a much bett... Background:There are remarkable genetic differences between animal major histocompatibility complex(MHC)systems and the human leukocyte antigen(HLA)system.HLA transgenic humanized mouse model systems offer a much better method to study the HLA-A-related principal mechanisms for vaccine development and HLA-Arestricted responses against infection in human.Methods:A recombinant gene encoding the chimeric HLA-A30 monochain was constructed.This HHD molecule contains the following:α1-α2 domains of HLA-A30,α3 and cytoplasmic domains of H-2D~b,linked at its N-terminus to the C-terminus of humanβ2m by a 15-amino-acid peptide linker.The recombinant gene encoding the chimeric HLA-A30 monochain cassette was introduced into bacterial artificial chromosome(BAC)CH502-67J3 containing the HLA-A01 gene locus by Red-mediated homologous recombination.Modified BAC CH502-67J3 was microinjected into the pronuclei of wild-type mouse oocytes.This humanized mouse model was further used to assess the immune responses against influenza A virus(H1N1)pdm09 clinically isolated from human patients.Immune cell population,cytokine production,and histopathology in the lung were analyzed.Results:We describe a novel humanβ2m-HLA-A30(α1α2)-H-2D~b(α3 transmembrane cytoplasmic)(HHD)monochain transgenic mouse strain,which contains the intact HLA-A01 gene locus including 49 kb 5’-UTR and 74 kb 3’-UTR of HLA-A01*01.Five transgenic lines integrated into the large genomic region of HLA-A gene locus were obtained,and the robust expression of exogenous transgene was detected in various tissues from A30-18#and A30-19#lines encompassing the intact flanking sequences.Flow cytometry revealed that the introduction of a large genomic region in HLA-A gene locus can influence the immune cell constitution in humanized mice.Pdm09 infection caused a similar immune response among HLA-A30 Tg humanized mice and wild-type mice,and induced the rapid increase of cytokines,including IFN-γ,TNF-α,and IL-6,in both HLA-A30 humanized Tg mice and wild-type mice.The expression of HLA-A30 transgene was dramatically promoted in tissues from A30-9#line at 3 days post-infection(dpi).Conclusions:We established a promising preclinical research animal model of HLA-A30 Tg humanized mouse,which could accelerate the identification of novel HLA-A30-restricted epitopes and vaccine development,and support the study of HLA-A-restricted responses against infection in humans. 展开更多
关键词 HLA-A30 humanized mouse immunology major histocompatibility complex(MHC)
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Generation and expression analysis of BAC humanized mice carrying HLA-DP401 haplotype 认领 引用 被引量：5
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作者 Feng Li Meng-min Zhu +7 位作者 Bo-wen Niu Ling-ling Liu Xiu-hua Peng Hua Yang Bo-yin Qin Meixiang Wang Xiaonan Ren Xiaohui Zhou 《Animal Models and Experimental Medicine》 CAS CSCD 2021年第2期116-128,共13页
Background:Human leukocyte antigen(HLA)-DP is much less studied than other HLA class Ⅱ antigens,that is,HLA-DR and HLA-DQ,etc.However,the accumulating data have suggested the important roles of DP-restricted response... Background:Human leukocyte antigen(HLA)-DP is much less studied than other HLA class Ⅱ antigens,that is,HLA-DR and HLA-DQ,etc.However,the accumulating data have suggested the important roles of DP-restricted responses in the context of cancer,allergy,and infectious disease.Lack of animal models expressing these genes as authentic cis-haplotypes blocks our understanding for the role of HLA-DP haplotypes in immunity.Methods:To explore the potential cis-acting control elements involved in the tran-scriptional regulation of the HLA-DPA1/DPB1 gene,we performed the expression analysis using bacterial artificial chromosome(BAC)-based transgenic humanized mice in the C57BL/6 background,which carried the entire HLA-DP401 gene locus.We further developed a mouse model of Staphylococcus aureus pneumonia in HLA-DP401 humanized transgenic mice,and performed the analysis on the expres-sion pattern of HLA-DP401 and immunological responses in the model.Results:In this study,we screened and identified a BAC clone spanning the entire HLA-DP gene locus.DNA from this clone was analyzed for integrity by pulsed-field gel electrophoresis and then microinjected into fertilized mouse oocytes to produce transgenic founder animals.Nine sets of PCR primers for regional markers with an average distance of 15 kb between each primer were used to confirm the integrity of the transgene in the five transgenic lines carrying the HLA-DPA1/DPB1 gene.Transgene copy numbers were determined by real-time PCR analysis.HLA-DP401 gene expression was analyzed at the mRNA and protein level.Although infection with S aureus Newman did not alter the percentage of immune cells in the spleen and thymus from the HLA-DP401-H2-Aβ1 humanized mice.Increased expression of HLA-DP401 was observed in the thymus of the humanized mice infected by S aureus.Conclusions:We generated several BAC transgenic mice,and analyzed the expres-sion of HLA-DPA1/DPB1 in those mice.A model of S aureus-induced pneumonia in the HLA-DP401-H2-Aβ1-/-humanized mice was further developed,and S aureus in-fection upregulated the HLA-DP401 expression in thymus of those humanized mice.These findings demonstrate the potential of those HLA-DPA1/DPB1 transgenic humanized mice for developing animal models of infectious diseases and MHC-associated immunological diseases. 展开更多
关键词 bacterial artificial chromosome(BAC) gene expression HLA-DP4 humanized mice Staphylococcus aureus pneumonia
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Effects of humanized nursing care on negative emotions and complications in patients undergoing hysteromyoma surgery 认领 引用 被引量：9
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作者 Li Liu Ya-Hong Xiao Xue-Hua Zhou 《World Journal of Clinical Cases》 SCIE 2023年第28期6763-6773,共11页
BACKGROUND Uterine fibroids,are prevalent benign tumors affecting women of reproductive age.However,surgical treatment is often necessary for symptomatic hysteromyoma cases.This study examines the impact of humanized ... BACKGROUND Uterine fibroids,are prevalent benign tumors affecting women of reproductive age.However,surgical treatment is often necessary for symptomatic hysteromyoma cases.This study examines the impact of humanized nursing care on reducing negative emotions and postoperative complications in patients receiving hysteromyoma surgery.AIM To investigate the impact of humanized nursing care on patients undergoing hysteromyoma surgery.METHODS Among patients who underwent hysteromyoma surgery at the Fudan University Affiliated Obstetrics and Gynecology Hospital,200 were randomly assigned to either the control group(n=100)or the humanized nursing care group(n=100).The control group received traditional nursing care,while the humanized nursing care group received a comprehensive care plan encompassing psychological support,pain management,and tailored rehabilitation programs.In addition,anxiety and depression levels were assessed using the hospital anxiety and depression scale preoperatively and postoperatively.Postoperative complications were evaluated during follow-up assessments and compared between both groups.RESULTS The humanized nursing care group demonstrated a significant decrease in anxiety and depression levels compared to the control group(P<0.05).The rate of postoperative complications,including infection,bleeding,and deep venous thrombosis,was also markedly lower in the humanized nursing care group(P<0.05).CONCLUSION Humanized nursing care can effectively alleviate negative emotions and reduce the incidence of postoperative complications in patients undergoing hysteromyoma surgery.This approach should be considered a crucial component of perioperative care for these patients.Further research may be needed to explore additional benefits and long-term outcomes of implementing humanized nursing care in this population. 展开更多
关键词 Hysteromyoma Humanized nursing care Anxiety Depression Postoperative complications
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Skin care efficacy study of recombinant humanized collagen based on in vitro level 认领 引用 被引量：3
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作者 Jian Wang Yuhui Fan +3 位作者 Danfeng Li Ningwen Cheng Ling Li Yufeng Yu 《日用化学工业（中英文）》 CAS 北大核心 2024年第9期1030-1038,共9页
Studying the skin care efficacy of recombinant humanized collagen based on in vitro level.The stability of the recombinant humanized collagen was first analyzed by treating at different temperatures,then its skincare ... Studying the skin care efficacy of recombinant humanized collagen based on in vitro level.The stability of the recombinant humanized collagen was first analyzed by treating at different temperatures,then its skincare efficacy based on in vitro level was evaluated by detecting the inhibition rate of elastase,the inhibition rate of collagenase,the protein content of type I collagen in human fibroblasts,the inhibition of reactive oxygen species(ROS)with human keratinocytes,and the effects of the recombinant humanized collagen on the expression of hyaluronic acid(HA),filaggrin(FLG)and transglutaminase 1(TGM1)in keratinocytes.The results showed that recombinant humanized collagen was able to maintain stability at temperatures below 70℃.With regard to its skincare efficacy,recombinant humanized collagen could inhibit elastase and collagenase activities and promote the increase of type I collagen content in human fibroblasts.It also showed good inhibition of ROS in keratinocytes in vitro and could increase the expression of HA,FLG,and TGM1 in keratinocytes.In short,the recombinant humanized collagen exhibited a favourable skin care effect in vitro level.This study proved that it has potential firming,anti-wrinkle,moisturizing,and repairing efficacy,and is a valuable cosmetic raw material. 展开更多
关键词 recombinant humanized collagen stability human fibroblast cell in vitro keratinocytes skin care efficacy
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Characterization of genetic humanized mice with transgenic HLA DP401 or DRA but deficient in endogenous murine MHC classⅡgenes upon Staphylococcus aureus pneumonia 认领 引用 被引量：1
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作者 Feng Li Bowen Niu +7 位作者 Lingling Liu Mengmin Zhu Hua Yang Boyin Qin Xiuhua Peng Lixiang Chen Chunhua Xu Xiaohui Zhou 《Animal Models and Experimental Medicine》 CAS CSCD 2023年第6期585-597,共13页
Background:Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in“carrier”or“pathogenic”states.HLA DQ and HLA DR humanized mice have been used as a small animal model to stu... Background:Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in“carrier”or“pathogenic”states.HLA DQ and HLA DR humanized mice have been used as a small animal model to study the role of two molecules during S.aureus infection.However,the contribution of HLA DP to S.aureus infection is unknown yet.Methods:In this study,we have produced HLA DP401 and HLA DRA0101 humanized mice by microinjection of C57BL/6J zygotes.Neo-floxed IAβ+/-mice were crossbred with Ella-Cre and further crossbred with HLA DP401 or HLA-DRA0101 humanized mice.After several rounds of traditional crossbreeding,we finally obtained HLA DP401-IAβ-/-and HLA DRA-IAβ-/-humanized mice,in which human DP401 or DRA0101 molecule was introduced into IAβ-/-mice deficient in endogenous murine MHC classⅡmolecules.A transnasal infection murine model of S.aureus pneumonia was induced in the humanized mice by administering 2×108CFU of S.aureus Newman dropwise into the nasal cavity.The immune responses and histopathology changes were further assessed in lungs in these infected mice.Results:We evaluated the local and systemic effects of S.aureus delivered intranasally in HLA DP401-IAβ-/-and HLA DRA-IAβ-/-transgenic mice.S.aureus Newman infection significantly increased the m RNA level of IL 12p40 in lungs in humanized mice.An increase in IFN-γand IL-6 protein was observed in HLA DRA-IAβ-/-mice.We observed a declining trend in the percentage of F4/80+macrophages in lungs in HLA DP401-IAβ-/-mice and a decreasing ratio of CD4+to CD8+T cells in lungs in IAβ-/-mice and HLA DP401-IAβ-/-mice.A decreasing ratio of Vβ3+to Vβ8+T cells was also found in the lymph node of IAβ-/-mice and HLA DP401-IAβ-/-mice.S.aureus Newman infection resulted in a weaker pathological injury in lungs in IAβ-/-genetic background mice.Conclusion:These humanized mice will be an invaluable mouse model to resolve the pathological mechanism of S.aureus pneumonia and study what role DP molecule plays in S.aureus infection. 展开更多
关键词 HLA DP401 HLA-DRA humanized mice MHC II Staphylococcus aureus pneumonia transgene
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Bioengineered humanized livers as better three-dimensional drug testing model system 认领 引用 被引量：1
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作者 Sandeep Kumar Vishwakarma Avinash Bardia +3 位作者 Chandrakala Lakkireddy Raju Nagarapu Md Aejaz Habeeb Aleem Ahmed Khan 《World Journal of Hepatology》 2018年第1期22-33,共12页
AIM To develop appropriate humanized three-dimensional ex-vivo model system for drug testing. METHODS Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the ... AIM To develop appropriate humanized three-dimensional ex-vivo model system for drug testing. METHODS Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the acellularized liver scaffolds which mimics with the natural organ anatomy and physiology. Six cytochrome P-450 probes were used to enable efficient identification of drug metabolism in bioengineered humanized livers. The drug metabolism study in bioengineered livers was evaluated to identify the absorption, distribution, metabolism, excretion and toxicity responses.RESULTS The bioengineered humanized livers showed cellular and molecular characteristics of human livers. The bioengineered liver showed three-dimensional natural architecture with intact vasculature and extra-cellular matrix. Human hepatic cells were engrafted similar to the human liver. Drug metabolism studies provided a suitable platform alternative to available ex-vivo and in vivo models for identifying cellular and molecular dynamics of pharmacological drugs.CONCLUSION The present study paves a way towards the development of suitable humanized preclinical model systems for pharmacological testing. This approach may reduce the cost and time duration of preclinical drug testing and further overcomes on the anatomical and physiological variations in xenogeneic systems. 展开更多
关键词 Acellularization Repopulation Drug testing Humanized liver Bioengineering
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A humanized mouse model to study human immune response in xenotransplantation 认领 引用
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作者 Ming Ji Xi Jin +1 位作者 Peta Phillips Shounan Yi 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2012年第5期494-498,共5页
BACKGROUND:A major barrier to the clinical application of xenotransplantation as a treatment option for patients is T cell-mediated rejection.Studies based on experimental rodent models of xenograft tolerance or rejec... BACKGROUND:A major barrier to the clinical application of xenotransplantation as a treatment option for patients is T cell-mediated rejection.Studies based on experimental rodent models of xenograft tolerance or rejection in vivo have provided useful information about the role of T cell immune response in xenotransplantation.However not all observations seen in rodents faithfully recapitulate the human situation This study aimed to establish a humanized mouse model of xenotransplantation,which mimics xenograft rejection in the context of the human immune system.METHODS:NOD-SCID IL2rγ-/-mice were transplanted with neonatal porcine islet cell clusters(NICC)followed by reconstitution of human peripheral blood mononuclear cells(PBMC).Human leukocyte engraftment and islet xenograft rejection were confirmed by flow cytometric and histological analyses.RESULTS:In the absence of human PBMC,porcine NICC transplanted into NOD-SCID IL2rγ-/-mice revealed excellent graft integrity and endocrine function.Human PBMC demonstrated a high level of engraftment in NOD-SCID IL2rγ-/-mice.Reconstitution of NICC recipient NOD-SCID IL2rγ-/-mice with human PBMC led to the rapid destruction of NICC xenografts in a PBMC number-dependent manner.CONCLUSIONS:Human PBMC-reconstituted NOD-SCID IL2rγ-/-mice provide an ideal model to study human immune responses in xenotransplantation.Studies based on this humanized mouse model will provide insight for improving the outcomes of clinical xenotransplantation. 展开更多
关键词 humanized mice xenotransplantation neonatal porcine islet cell cluster xenorejection tolerance
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Establishment of a humanized ST6GAL1 mouse model for influenza research 认领 引用
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作者 Lyu Chao Han Feng +10 位作者 Gao Qian Lv Limin Lu Ziwei Lu Shuangshuang Li Xiaoyan Hu Yuechao Yang Mengjie Zhao Yingze Liu Jun Lu Xuancheng Duo Shuguang 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第3期337-346,共10页
Background:This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.Methods:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encodi... Background:This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.Methods:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of mice.The manipulated embryos were transferred into the oviducts of pseudopregnant female mice.The offspring were identified using PCR.Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for screening.Expression of the humanized gene was tested by performing immunohistochemical(IHC)analysis.Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed.Results:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1.Seven mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection characteristics.The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice.Moreover,the hematologic and biochemical parameters of the positive mice were within the normal range.Conclusion:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized. 展开更多
关键词 hST6GAL1 humanized mice influenza animal model
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High efficient mammalian expression and secretion of a functional humanized single-chain Fv/human interleukin-2 molecules 认领 引用 被引量：1
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作者 Yue-Chun Shen Xue-HaoWang +4 位作者 Xiao-Ming Wang Zao-Lai Chen Xi-Ping Shen Chao-Chen Zhao Jun Li 《World Journal of Gastroenterology》 SCIE CAS 2006年第24期3859-3865,共7页
AIM： To construct and produce a recombinant bispecific humanized single-chain Fv （sFv） /Interleukin-2 （IL-2） fusion protein by using mammalian cells. METHODS： The sFv/IL-2 protein was genetically engineered, and... AIM： To construct and produce a recombinant bispecific humanized single-chain Fv （sFv） /Interleukin-2 （IL-2） fusion protein by using mammalian cells. METHODS： The sFv/IL-2 protein was genetically engineered, and transfected to mammalian cells to determine whether the mammalian protein folding machinery can produce and secrete active sFv/IL-2 with high efficiency. RESULTS： The fusion protein was constructed and high efficiently expressed with yields up to 102 ±4.2 mg/L in culture supernatant of the stably transfected 293 cell line. This recombinant fusion protein consisted of humanized variable heavy （VH） and light （VL） domains of monoclonal antibody （mAb） 520C9 directed against the human HER-2eu （c-erbB2） proto-oncogene product p185, and human IL-2 connected by polypeptide linker. The fusion protein was shown to retain the immunostimulatory activities of IL-2 as measured by IL- 2-dependent cell proliferation and cytotoxicity assays. In addition to its IL-2 activities, this fusion protein also possessed antigen-binding specificity against p185, as determined by indirect ELISA using p185 positive SKOV 3ip1 cells. CONCLUSION： The large-scale preparation of the recombinant humanized sFv antibody/IL-2 fusion protein is performed with 293 cells. The recombinant humanized sFv antibody/IL-2 fusion protein may provide an effective means.of targeting therapeutic doses of IL-2 to p185 positive tumors without increasing systemic toxicity or immunogenicity. 展开更多
关键词 Interleukin-2 Humanization Antibody Fusion protein HER-2eu
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Operation room nursing based on humanized nursing mode combined with nitric oxide on rehabilitation effect after lung surgery 认领 引用 被引量：1
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作者 Qiao-Li Wang Zhi-Bo Wang Jin-Fu Zhu 《World Journal of Clinical Cases》 SCIE 2024年第18期3368-3377,共10页
BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as com... BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as complications and adverse outcomes persist.Incorporating humanized nursing modes and novel treatments like nitric oxide inhalation may enhance recovery and reduce postoperative complications.AIM To evaluate the effects of a humanized nursing mode combined with nitric oxide inhalation on the rehabilitation outcomes of patients undergoing lung surgery,focusing on pulmonary function,recovery speed,and overall treatment costs.METHODS A total of 79 patients who underwent lung surgery at a tertiary hospital from March 2021 to December 2021 were divided into a control group(n=39)receiving a routine nursing program and an experimental group(n=40)receiving additional humanized nursing interventions and atomized inhalation of nitric oxide.Key indicators were compared between the two groups alongside an analysis of treatment costs.RESULTS The experimental group demonstrated significant improvements in pulmonary function,reduced average recovery time,and lower total treatment costs compared to the control group.Moreover,the quality of life in the experimental group was significantly better in the 3 months post-surgery,indicating a more effective rehabilitation process.CONCLUSION The combination of humanized nursing mode and nitric oxide inhalation in postoperative care for lung surgery patients significantly enhances pulmonary rehabilitation outcomes,accelerates recovery,and reduces economic burden.This approach offers a promising reference for improving patient care and rehabilitation efficiency following lung surgery. 展开更多
关键词 Humanized nursing Nitric oxide Lung segment surgery Rehabilitation Pulmonary function
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Antitumor Response of Anti-B7-H3 CAR-T Cells with Humanized scFv in Solid Tumors 认领 引用
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作者 SI Ke XU Huantian +9 位作者 YE Zheng JAFFAR ALI Doulathunnisa HE Cong DING Bo YUAN Shubin DAI Zhu LI Zhanping SUN Bo SHEN Yang XIAO Zhongdang 《Wuhan University Journal of Natural Sciences》 CAS CSCD 2022年第2期177-184,共8页
We prepared a humanized alternative B7-H3 CAR(B7-H3-haCAR-T)targeting B7-H3 which contained the humanized singl-chain varinlde fragment(scFv)from humanized 8H9 Monoclonal Antibody(hu8H9m Ab).The antitumor effects of B... We prepared a humanized alternative B7-H3 CAR(B7-H3-haCAR-T)targeting B7-H3 which contained the humanized singl-chain varinlde fragment(scFv)from humanized 8H9 Monoclonal Antibody(hu8H9m Ab).The antitumor effects of B7-H3-haCAR-T cells were evaluated in B7-H3 overexpressed tumor cells(in vitro)and B7-H3 xenograft models(in vivo).The specific tumour killing ability of B7-H3-haCAR-T in overexpressing B7-H3 tumour cells was verified by cytotoxicity and ELISA tests.In addition,B7-H3 haCAR-T cells were also noted to suppress the tumour growth remarkably well in the xenograft murine models,and the survival time in the haCAR-T cell treatment group was appreciably longer than that in the control group.The specific recognition and highly efficient tumoricidal behavior of B7-H3 haCAR-T provide a basis for future clinical studies with humanized scFv-transduced CAR-T cells targeting solid tumors. 展开更多
关键词 expressing Human verified
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Single-cell RNA-sequencing reveals a profound immune cell response in human cytomegalovirus-infected humanized mice 认领 引用
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作者 An Wang Xiao-Xu Zhu +6 位作者 Yuanyuan Bie Bowen Zhang Wenting Ji Jing Lou Muhan Huang Xi Zhou Yujie Ren 《Virologica Sinica》 SCIE CAS CSCD 2024年第5期782-792,共11页
Human cytomegalovirus(HCMV)is a common herpesvirus that persistently infects a large portion of the world's population.Despite the robust host immune response,HCMV is able to replicate,evade host defenses,and esta... Human cytomegalovirus(HCMV)is a common herpesvirus that persistently infects a large portion of the world's population.Despite the robust host immune response,HCMV is able to replicate,evade host defenses,and establish latency throughout the lifespan by developing multiple immunomodulatory strategies,making the studies on the interaction between HCMV infection and host response particularly important.HCMV has a strict host specificity that specifically infects humans.Therefore,most of the in vivo researches of HCMV rely on clinical samples.Fortunately,the establishment of humanized mouse models allows for convenient in-lab animal experiments involving HCMV infection.Single-cell RNA sequencing enables the study of the relationship between viral and host gene expressions at the single-cell level within host cells.In this study,we assessed the gene expression alterations of PBMCs at the single-cell level within HCMV-infected humanized mice,which sheds light onto the virus-host interactions in the context of HCMV infection of humanized mice and provides a valuable dataset for the related researches. 展开更多
关键词 Human cytomegalovirus(HCMV) Single-cell RNA-Sequencing PBMC Viral infection
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The Effects of Humanized Psychological Nursing Model in General Surgery Nursing 认领 引用 被引量：2
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作者 Guifeng Xue Huafang Yi +1 位作者 Ping Xue Wenmin Sun 《Proceedings of Anticancer Research》 2021年第4期98-102,共5页
Objective:To analyze and comprehensively study the clinical effects of humanized psychological nursing model in general surgery nursing.Methods:The study period was from January 2018 to December 2020.A sample of 200 p... Objective:To analyze and comprehensively study the clinical effects of humanized psychological nursing model in general surgery nursing.Methods:The study period was from January 2018 to December 2020.A sample of 200 patients who were admitted to The Second People's Hospital of Taizhou City for general surgery were selected.Random lottery grouping was used to divide the subjects into a study group and a control group.The sample within each group was n=100.The patients in the control group were provided with conventional general surgery nursing plan whereas the patients in the study group received the same nursing plan but with addition of the humanized psychological nursing model.The indicators of the two groups were compared and analyzed.Results:Comparing the scores from Hamilton Anxiety Rating Scale(HAMA)and Hamilton Depression Rating Scale(HAMD)after nursing intervention,postoperative visual analog scale(VAS),hospital stay,and patient satisfaction with the nursing services between the two groups,the study group was better(P<0.05).Conclusion:The implementation of humanized psychological nursing model in general surgery nursing had a significant effect in which there were improvements in regard to the patientsJ mental state and their satisfaction with the nursing services.Hence,it is worthy of promotion. 展开更多
关键词 General surgery Humanized psychological nursing Effect
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