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Transforming layered 2D mats into multiphasic 3D nanofiber scaffolds with tailored gradient features for tissue regeneration

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BMEMat(BioMedical Engineering Materials) 2024年第1期2卷 160-179页

作者： S.M.Shatil Shahriar Navatha Shree Polavoram Syed Muntazir Andrabi Yajuan Su Donghee Lee Huy Quang Tran Samantha J.Schindler Jingwei Xie Department of Surgery-transplant and Mary&Dick Holland Regenerative Medicine Program College of MedicineUniversity of Nebraska Medical CenterOmahaNebraskaUSA Eppley Institute for Research in Cancer and Allied Diseases College of MedicineUniversity of Nebraska Medical CenterOmahaNebraskaUSA Department of Mechanical and Materials Engineering University of Nebraska LincolnLincolnNebraskaUSA

Multiphasic scaffolds with tailored gradient features hold significant promise for tissue regeneration applications. Herein, this work reports the transformation of two-dimensional (2D) layered fiber mats into three-dimensional (3D) multiphasic scaffolds using a ‘solids-of-revolution’ inspired gas-foaming expansion technology. These scaffolds feature precise control over fiber alignment, pore size, and regional structure. Manipulating nanofiber mat layers and Pluronic F127 concentrations allows further customization of pore size and fiber alignment within different scaffold regions. The cellular response to multiphasic scaffolds demonstrates that the number of cells migrated and proliferated onto the scaffolds is mainly dependent on the pore size rather than fiber alignment. In vivo subcutaneous implantation of multiphasic scaffolds to rats reveals substantial cell infiltration, neo tissue formation, collagen deposition, and new vessel formation within scaffolds, greatly surpassing the capabilities of traditional nanofiber mats. Histological examination indicates the importance of optimizing pore size and fiber alignment for the promotion of cell infiltration and tissue regeneration. Overall, these scaffolds have potential applications in tissue modeling, studying tissue-tissue interactions, interface tissue engineering, and highthroughput screening for optimized tissue regeneration.

关键词： expansion gradients multiphasic scaffolds nanofiber mats tissue regeneration

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Impact of hepatitis B immunoglobulin mode of administration on treatment experiences of patients after liver transplantation: Results from an online survey

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World Journal of transplantation 2024年第3期14卷 144-155页

作者： Giorgia Rizza Kyriaki Glynou Masha Eletskaya General Surgery and Liver transplant center S.Giovanni Battista HospitalTurin I-10126Italy Medical Affairs Biotest AGDreieich 63303Germany Lumanity Insight(Cello Health Insight) London SE11PPUnited Kingdom

BACKGROUND Hepatitis B immunoglobulin(HBIG)in combination with a potent nucleos(t)ide analog is considered the standard of care for prophylaxis against hepatitis B virus(HBV)reinfection after liver transplantation for HBV-associated *** To evaluate patients’satisfaction,preferences,and requirements for subcutaneous(SC),intramuscular(IM),and intravenous(IV)HBIG *** A self-completion,cross-sectional,online,22-question survey was conducted to examine perceptions and satisfaction with current HBIG treatment in adults receiving HBIG treatment following liver transplantation for HBV-associated disease in France,Italy,and *** HBIG products with different administration modes were evaluated using target product profile assessment and a conjoint(trade-off)*** Ninety patients were enrolled;32%,17%,and 51%were SC,IM,and IV HBIG users,*** duration of treatment was 36.2 *** HBIG had the least negative impact on emotional well-being and social life and was perceived as the most convenient,easiest to administer,least painful,and had the highest self-rating of treatment *** IM HBIG users than SC or IV HBIG users reported that administration frequency was excessive(67%,28%,and 28%,respectively).In the target product profile assessment,76%of patients were likely to use hypothetical SC *** the conjoint exercise,administration route,frequency,and duration were key drivers of treatment *** Ease,frequency,duration,and side effects of HBIG treatment administration were key drivers of treatment preferences,and SC HBIG appeared advantageous over IM and IV HBIG for administration ease,convenience,and pain.A hypothetical SC HBIG product elicited a favorable *** demographics,personal preferences,and satisfaction with HBIG treatment modalities may influence long-term treatment compliance.

关键词： Hepatitis B immunoglobulin Liver transplantation Subcutaneous Intramuscular Intravenous Patient satisfaction

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L-GrAFT_(7) has High Accuracy in Predicting Early Allograft Failure after Liver transplantation: A Multicenter Cohort Study in China

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Journal of Clinical and Translational Hepatology 2024年第1期12卷 62-69页

作者： Songming Li Qijie Luo Shirui Chen Zehua Jia Tielong Wang Xinyu Yu Wenjing Wang YuyiZhang Jiaxing Zhu Feiwen Deng Qiang Sun Zhiyong Guo Xiaoshun He Organ transplant center The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongChina Guangdong Provincial Key Laboratory of Organ Donation and transplant Immunology GuangzhouGuangdongChina Guangdong Provincial International Cooperation Base of Science and Technology GuangzhouGuangdongChina NHC Key Laboratory of Assisted Circulation(Sun Yat-sen University) GuangzhouGuangdongChina General Surgery Dept.1 Zhongshan People’s HospitalZhongshan Hospital of Sun Yat-Sen UniversityZhongshanGuangdongChina Department of Hepatobiliary Surgery The First People’s Hospital of FoshanFoshanGuangdongChina

Background and Aims:Increasing utilization of extended criteria donor leads to an increasing rate of early allograft failure after liver ***,consensus of definition of early allograft failure is ***:A retrospective,multicenter study was performed to validate the Liver Graft Assessment Following transplantation(L-GrAFT)risk model in a Chinese cohort of 942 adult patients undergoing primary liver transplantation at three Chinese centers.L-GrAFT(L-GrAFT7 and L-GrAFT10)was compared with existing models:the Early Allograft Failure Simplified Estimation(EASE)score,the model of early allograft function(MEAF),and the Early Allograft Dysfunction(EAD)*** and multivariate logistic regression were used to find risk factors of L-GrAFT high-risk ***:L-GrAFT7 had an area under the curve of 0.85 in predicting 90-day graft survival,significantly superior to MEAF[area under the curve(AUC=0.78,p=0.044)]and EAD(AUC=0.78,p=0.006),while there was no statistical significance between the predicting abilities of L-GrAFT7 and EASE(AUC=0.84,p>0.05).Furthermore,L-GrAFT7 maintains good predicting ability in the subgroup of high-donor risk index(DRI)cases(AUC=0.83 ***,p=0.007 ***,p=0.014)and recipients of donors after cardiac death(AUC=0.92 ***,ptransplant bilirubin level,units of packed red blood cells,and the DRI score were selected as independent risk factors of a L-GrAFT7 high-risk ***:The accuracy of L-GrAFT7 in predicting early allograft failure was validated in a Chinese multicenter cohort,indicating that it has the potential to become an accurate endpoint of clinical practice and transitional study of machine perfusion.

关键词： Early allograft failure Graft survival Liver transplantation Risk prediction model Multicenter study

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Bridging the gap: Addressing disparities in hepatitis C screening, access to care, and treatment outcomes

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World Journal of Hepatology 2024年第8期16卷 1091-1098页

作者： Maram Alenzi Mohammad Almeqdadi Department of Medicine St.Elizabeth’s Medical CenterBoston UniversityMA 02135United States Department of transplant and Hepatobiliary Disease Tufts Medical CenterBostonMA 02111United States

Hepatitis C virus(HCV)is a significant public health challenge globally,with substantial morbidity and mortality due to chronic liver *** the availability of highly effective and well-tolerated direct-acting antiviral therapies,widespread disparities remain in hepatitis C screening,access to treatment,linkage to care,and therapeutic *** review article synthesizes evi-dence from various studies to highlight the multifactorial nature of these dispari-ties,which affects ethnic minorities,people with lower socioeconomic status,in-dividuals with substance use disorders,and those within correctional *** review also discusses policy implications and targeted strategies needed to overcome barriers and ensure equitable care for all individuals with ***-mendations for future research to address gaps in knowledge and evaluation of the effectiveness of interventions designed to reduce disparities are provided.

关键词： Hepatitis C virus disparities Access to care Health equity Healthcare policy Patient education

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Corneal collagen cross-linking in patients with keratoconus from the Dresden protocol to customized solutions:theoretical basis

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 951-962页

作者： Ciro Caruso Luca D’Andrea Mario Troisi Michele Rinaldi Raffaele Piscopo Salvatore Troisi Ciro Costagliola Corneal transplant center Pellegrini HospitalVia Portamedina alla Pignasecca 41Napoli 80127Italy Eye Clinic Department of NeurosciencesReproductive and Odontostomatological SciencesUniversity of Naples Federico IINaples 80131Italy Public Health Department University of Naples Federico IINaples 80131Italy Salerno Hospital University Ophthalmologic UnitBaronissiCampania 84131Italy

Keratoconus is an ectatic condition characterized by gradual corneal thinning,corneal protrusion,progressive irregular astigmatism,corneal fibrosis,and visual *** therapeutic options regarding improvement of visual function include glasses or soft contact lenses correction for initial stages,gas-permeable rigid contact lenses,scleral lenses,implantation of intrastromal corneal ring or corneal transplants for most advanced *** keratoconus cases showing disease progression corneal collagen crosslinking(CXL)has been proven to be an effective,minimally invasive and safe *** consists of a photochemical reaction of corneal collagen by riboflavin stimulation with ultraviolet A radiation,resulting in stromal crosslinks *** aim of this review is to carry out an examination of CXL methods based on theoretical basis and mathematical models,from the original Dresden protocol to the most recent developments in the technique,reporting the changes proposed in the last 15y and examining the advantages and disadvantages of the various treatment ***,the limits of non-standardized methods and the perspectives offered by a customization of the treatment are highlighted.

关键词： corneal collagen cross linking keratoconus custom fast protocol Dresden protocol lambert-beer law Bunsen-roscoe law

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Association of Mosaic Chromosomal Alterations and Genetic Factors with the Risk of Cirrhosis

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Journal of Clinical and Translational Hepatology 2024年第6期12卷 562-570页

作者： Xinyuan Ge Lu Zhang Maojie Liu Xiao Wang Xin Xu Yuqian Yan Chan Tian Juan Yang Yang Ding Chengxiao Yu Jing Lu Longfeng Jiang Qiang Wang Qun Zhang Ci Song Department of Epidemiology China International Cooperation Center on Environment and Human HealthCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsuChina The Dumont-UCLA transplant center Division of Liver and Pancreas TransplantationDepartment of SurgeryDavid Geffen School of Medicine at UCLALos AngelesCAUSA Department of Health Promotion center Jiangsu Province Hospital and Nanjing Medical University First Affiliated HospitalNanjingJiangsuChina Department of Infectious Disease The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuChina Department of Clinical Science Intervention and Technology(CLINTEC)Karolinska InstitutetStockholmSweden Changzhou Medical center Nanjing Medical UniversityNanjingJiangsuChina Research Units of Cohort Study on Cardiovascular Diseases and Cancers Chinese Academy of Medical SciencesBeijingChina Collaborative Innovation center for Cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsuChina

Background and Aims:Age-related mosaic chromosomal alterations(mCAs)detected from genotyping of blood-de-rived DNA are structural somatic variants that indicate clonal *** study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score(PRS)on cirrhosis risk ***:mCA call sets of individuals with European ancestry were obtained from the UK *** PRS was constructed based on 12 susceptible single-nucleotide poly-morphisms for *** proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis ***:Among 448,645 individuals with a median follow-up of 12.5 years,we identified 2,681 cas-es of cirrhosis,1,775 cases of compensated cirrhosis,and 1,706 cases of decompensated *** to non-carriers,individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis(hazard ratio(HR)1.42,95%confidence interval(CI)1.12-1.81).This risk was higher in patients with expanded cell fractions of mCAs(cell fractions≥10%*** fractions<10%),especially for the risk of decompensated cirrhosis(HR 2.03[95%CI 1.09-3.78]vs.1.14[0.80-1.64]).In comparison to non-carriers of mCAs with low genetic risk,individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk(HR5.39[95%CI 2.41-12.07]).Conclusions:The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.

关键词： UK Biobank Cirrhosis Mosaic chromosomal alterations Polygenic risk score Genetic susceptibility Interaction effect

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Continuous Expression of Interferon Regulatory Factor 4 Sustains CD8^(+)T Cell Immunity against Tumor

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Research 2024年第3期2023卷 433-444页

作者： Anze Yu Jinfei Fu Zheng Yin Hui Yan Xiang Xiao Dawei Zou Xiaolong Zhang Xiongbing Zu Xian C.Li Wenhao Chen Immunobiology and transplant Science center Department of SurgeryHouston Methodist Research Institute and Institute for Academic MedicineHouston Methodist HospitalHoustonTXUSA Department of Urology First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongChina Systems Medicine and Bioengineering Department Houston Methodist Neal Cancer CenterHoustonTXUSA Department of Radiology Houston Methodist HospitalWeill Cornell MedicineHoustonTXUSA Department of Urology Xiangya HospitalCentral South UniversityChangshaHunanChina Department of Surgery Weill Cornell MedicineCornell UniversityNew YorkNYUSA.

T-cell-based immunotherapy is gaining momentum in cancer treatment;however,our comprehension of the transcriptional regulation governing T cell antitumor activity remains *** objective of this study was to explore the function of interferon regulatory factor 4(IRF4)in antitumor CD8^(+)T cells using the TRAMP-C1 prostate cancer and B16F10 melanoma *** achieve this,we generated an Irf4^(GFP-DTR) mouse strain and discovered that CD8^(+)tumor-infiltrating lymphocytes(TILs)expressing high levels of *** exhibited a more differentiated PD-1high cell *** administering diphtheria toxin to tumor-bearing Irf4^(GFP-DTR) mice,we partially depleted ***^(+)TILs and observed an accelerated tumor *** specifically explore the function of IRF4 in antitumor CD8^(+)T cells,we conducted 3 adoptive cell therapy(ACT)***,depleting ***^(+)CD8^(+)TILs derived from ACT significantly accelerated tumor growth,emphasizing their crucial role in controlling tumor ***,deleting the Irf4 gene in antitumor CD8^(+)T cells used for ACT led to a reduction in the frequency and effector differentiation of CD8^(+)TILs,completely abolishing the antitumor effects of ***,we performed a temporal deletion of the Irf4 gene in antitumor CD8^(+)T cells during ACT,starting from 20 days after tumor implantation,which significantly compromised tumor ***,sustained expression of IRF4 is essential for maintaining CD8^(+)T cell immunity in the melanoma model,and these findings carry noteworthy implications for the advancement of more potent immunotherapies for solid tumors.

关键词： sustained immunity implantation

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Diagnosis and therapy of tacrolimus toxicity in a liver transplant recipient during COVID-19 treatment

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 326-330页

作者： Feng Zhu Yi-Ming Wang Ming Ni Yuan Liang Jie-Hui Huang Xue-Hao Wang Feng Cheng Ling Lu Hepatobiliary center The First Affiliated Hospital of Nanjing Medical UniversityKey Laboratory of Liver TransplantationChinese Academy of Medical SciencesNHC Key Laboratory of Liver TransplantationResearch Unit of Liver Transplantation and Transplant ImmunologyChinese Academy of Medical SciencesNanjing 210000China Department of Respiratory and Critical Care Medicine Wuxi Fifth People’s HospitalWuxi 214000China Jiangsu Key Laboratory of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 210000China

To the Editor:SARS-CoV-2,the pathogen responsible for the pandemic of coronavirus disease 2019(COVID-19),has had profound impacts on human health,and its antagonist Paxlovid is a commonly used treatment option[1].However,treatment selection for immunosuppressed patients,such as liver recipients,remains uncertain due to potential drug interactions and the risk of immunosuppressant dosage adjustment,which can cause liver injury[2].

关键词： dosage treatment antagonist

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Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

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World Journal of Gastroenterology 2024年第7期30卷 759-769页

作者： Maja Cigrovski Berkovic Alessandro Coppola Vibor Sesa Anna Mrzljak Quirino Lai Department for Sport and Exercise Medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Surgery Sapienza University of RomeRome 00185Italy Department of Gastroenterology and Hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia Department of Medicine School of MedicineZagreb 10000Croatia General Surgery and Organ transplantation Unit Department of SurgerySapienza University of RomeRome 00018Italy

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor ***,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is *** this perspective,metformin is emerging as a molecule of *** studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR *** systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with *** To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of *** A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free *** A total of 13 studies(5674 patients)were included in this *** of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of *** T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS

关键词： Pancreatic neuroendocrine tumors Type 2 diabetes mellitus Prognosis Treatment Metformin

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Sarcopenic obesity in patients awaiting liver transplant: Unique challenges for nutritional recommendations

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World Journal of transplantation 2024年第2期14卷 40-47页

作者： Darya M Herscovici Katherine M Cooper Alessandro Colletta Michelle Rightmyer Alexandra Shingina Lauren D Feld Department of Medicine UMass Chan Medical SchoolWorcesterMA 01655United States Division of transplant Nutrition UMass Chan Medical SchoolWorcesterMA 01655United States Department of Medicine Vanderbilt University Medical CenterNashvilleTN 37215United States Division of Gastroenterology UMass Chan Medical SchoolWorcesterMA 01655United States

Sarcopenic obesity increases the risk of mortality in patients with liver disease awaiting liver transplantation and in the post-transplant *** recommendations for individuals with sarcopenia differ from recommendations for patients with obesity or sarcopenic *** these nutrition guidelines have been established in non-cirrhotic patients,established guidelines for liver transplant candidates with sarcopenic obesity are *** this paper,we review existing literature on sarcopenic obesity in patients with chronic liver disease and address opportunities to improve nutritional counseling in patients awaiting liver transplantation.

关键词： Nutrition Sarcopenia Sarcopenic obesity Liver transplant Cirrhosis Chronic liver disease Body composition Myostatin

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