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Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia:a prospective,single arm,phase I trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2250-2259页

作者： Yunfei Chen Yanmei Xu Ying Chi Ting Sun Yuchen Gao Xueqing Dou Zhibo Han Feng Xue Huiyuan Li Wei Liu Xiaofan Liu Huan Dong Rongfeng Fu Mankai Ju Xinyue Dai Wentian Wang Yueshen Ma Zhen Song Jundong Gu Wei Gong Renchi Yang Lei Zhang State Key Laboratory of Experimental Hematology National Clinical Research Centre for Blood DiseasesHaihe Laboratory of Cell EcosystemTianjin Key Laboratory of Gene Therapy for Blood DiseasesCAMS Key Laboratory of Gene Therapy for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China national Clinical Research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhou 215006China national Engineering Research centre of Cell Products Tianjin Key Laboratory of Engineering Technologies for Cell PharmaceuticalAmCellGene Engineering Co.LtdTianjin 300457China School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical College100730 BeijingChina

Patients with refractory immune thrombocytopenia(ITP)frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing *** cord-derived mesenchymal stem cells(UC-MSCs)present a promising alternative,capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune *** prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory *** research design included administering UC-MSCs at escalating doses of 0.5×10^(6)cells/kg,1.0×10^(6)cells/kg,and 2.0×10^(6)cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase,followed by a dose of 2.0×10^(6)cells/kg weekly for the dose-expansion *** events,platelet counts,and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up ***,12(with an addition of three patients in the 2.0×10^(6)cells/kg group due to dose-limiting toxicity)and six patients were enrolled in the dose-escalation and dose-expansion phase,*** patients(13/18,72.2%)experienced one or more treatment emergent adverse *** adverse events occurred in four patients(4/18,22.2%),including gastrointestinal hemorrhage(2/4),profuse menstruation(1/4),and acute myocardial infarction(1/4).The response rates were 41.7%in the dose-escalation phase(5/12,two received 1.0×10^(6)cells/kg per week,and three received 2.0×10^(6)cells/kg per week)and 50.0%(3/6)in the dose-expansion *** overall response rate was 44.4%(8/18)among all enrolled *** sum up,UC-MSCs are effective and well tolerated in treating refractory ITP(*** ID:NCT04014166).

关键词： doses immunity treatment

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Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

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World Journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K Jacobs Steven D Morley Kay Samuel Katie Morgan Lyndsey Boswell Timothy J Kendall David A Dorward Jonathan A Fallowfield Peter C Hayes John N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish national blood transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVID-19 COVID-19-associated cholangiopathy

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REDH:A database of RNA editome in hematopoietic differentiation and malignancy

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Chinese Medical Journal 2024年第3期137卷 283-293页

作者： Jiayue Xu Jiahuan He Jiabin Yang Fengjiao Wang Yue Huo Yuehong Guo Yanmin Si Yufeng Gao Fang Wang Hui Cheng Tao Cheng Jia Yu Xiaoshuang Wang Yanni Ma State Key Laboratory of Common Mechanism Research for Major Diseases Haihe Laboratory of Cell EcosystemInstitute of Basic Medical SciencesChinese Academy of Medical SciencesBeijing 100005China Key Laboratory of RNA and Hematopoietic Regulation Chinese Academy of Medical SciencesBeijing 100005China Department of Biochemistry and Molecular Biology Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China Institute of blood transfusion Chinese Academy of Medical SciencesChengduSichuan 610052China

Background:The conversion of adenosine(A)to inosine(I)through deamination is the prevailing form of RNA editing,impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic *** of high-confidence RNA editing sites have been identified and integrated into various RNA databases,providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic ***,the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still ***:We downloaded RNA sequencing(RNA-seq)data of 29 leukemia patients and 19 healthy donors from national Center for Biotechnology Information(NCBI)Gene Expression Omnibus(GEO)database,and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also *** performed sequence alignment,identified RNA editing sites,and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic ***:We established a new database,"REDH",represents RNA editome in hematopoietic differentiation and *** is a curated database of associations between RNA editome and *** integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts(human).Through the Differentiation,Disease,Enrichment,and knowledge modules,each A-to-I editing site is systematically integrated,including its distribution throughout the genome,its clinical information(human sample),and functional editing sites under physiological and pathological ***,REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy ***:REDH is accessible at http://***/.This user-friendly database

关键词： RNA editing Hematopoietic differentiation Hematopoietic malignancy Database management systems

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Extracorporeal membrane oxygenation versus cardiopulmonary bypass during transcatheter aortic valve implantation: a meta-analysis of survival benefits

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World Journal of Emergency Medicine 2024年第4期15卷 306-310页

作者： Huiruo Liu Liangshan Wang Xing Hao Zhongtao Du Chenglong Li Hong Wang Xiaotong Hou centre for Cardiac Intensive Care Beijing Institute of HeartLung and Blood Vessel DiseasesBeijing Anzhen HospitalCapital Medical UniversityBeijing 100029China

Since its approval by the Food and Drug Administration in 2011,transcatheter aortic valve implantation(TAVI)has rapidly evolved to become the preferred ultimate intervention for high-and intermediate-risk patients with severe symptomatic aortic stenosis.[1]This is due to its non-open-heart,minimally invasive and off-pump advantages.[1]Nevertheless,as a result of the frequent frailty and comorbidity profiles of patients undergoing TAVI,such as advanced cardiac dysfunction and extensive coronary artery disease,or technically difficult anatomy for the procedure itself,[2-4]it is common for these patients to experience critical circulatory collapse *** factors are linked to elevated mortality rates,necessitating suitable mechanical circulatory support(MCS)to reverse the disastrous situations.[5]

关键词： anatomy bypass elevated

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GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

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World Journal of Stem Cells 2024年第5期16卷 538-550页

作者： Yang-Zhou Jiang Lan-Yue Hu Mao-Shan Chen Xiao-Jie Wang Cheng-Ning Tan Pei-Pei Xue Teng Yu Xiao-Yan He Li-Xin Xiang Yan-Ni Xiao Xiao-Liang Li Qian Ran Zhong-Jun Li Li Chen Laboratory of Radiation Biology Department of Blood TransfusionLaboratory Medicine CenterThe Second Affiliated HospitalThird Military Medical UniversityChongqing 400037China Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center Ministry of Education of the People’s Republic of ChinaChongqing 400037China

BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ***,the positive regulators of ANKRD26 are still *** To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 *** Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family *** to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activi

关键词： Ankyrin repeat domain containing 26 GATA binding protein 2 Thrombocytopenia 2 Transcriptional regulation Myeloid-derived cell lines

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Neural stem cell-derived exosomes promote mitochondrial biogenesis and restore abnormal protein distribution in a mouse model of Alzheimer's disease

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Neural Regeneration Research 2024年第7期19卷 1593-1601页

作者： Bo Li Yujie Chen Yan Zhou Xuanran Feng Guojun Gu Shuang Han Nianhao Cheng Yawen Sun Yiming Zhang Jiahui Cheng Qi Zhang Wei Zhang Jianhui Liu Department of Radiology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Morphology and Spatial Multi-Omics Technology Platform Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghaiChina Department of Anesthesiology Tongji HospitalSchool of MedicineTongji UniversityShanghaiChina Department of blood transfusion Huashan HospitalFudan UniversityShanghaiChina

Mitochondrial dysfunction is a hallmark of Alzheimer’s *** previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 *** Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a ***,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial ***,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse *** findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-β***,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial *** addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.

关键词： Alzheimer’s disease mitochondrial biogenesis neural stem cell-derived exosome SIRT1-PGC1α regional brain distribution whole brain clearing and imaging

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A novel mutation of glycogen synthase kinase-3β leads to a reduced level of GSK3βprotein in a patient with dilated cardiomyopathy

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Genes & Diseases 2024年第1期11卷 84-86页

作者： Ke Gong Zhiping Tan Haidan Liu Xiaobo Liao Xinmin Zhou Bangliang Yin Shi Zeng Yao Yao Yifeng Yang Li Xie Department of Cardiovascular Surgery The Second Xiangya Hospital of Central South UniversityCentral South UniversityChangshaHunan410011China Department of Ultrasound The Second Xiangya Hospital of Central South UniversityCentral South UniversityChangshaHunan 410011China Department of blood transfusion The Second Xiangya Hospital of Central South UniversityCentral South UniversityChangshaHunan 410011China

Dilated cardiomyopathy(DCM)is a frequently inherited heart condition.A familial transmission rate of 20%-35%has been documented,and most of these cases are autosomal *** condition has a high rate of morbidity and mort... 详细信息

关键词： GSK3β cardiomyopathy mortality

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Seroprevalence of Human Immunodeficiency Virus and Hepatitis B in blood Donors at the N’Zérékoré Regional blood transfusion centre in Guinea

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Open Journal of Immunology 2024年第2期14卷 33-45页

作者： Alimou Camara Ernest Thea Ives Nyankoye Haba Yamoussa Youla Ibrahima Sory Diallo Mariama Sadio Diallo Djiba Kaba Jacob Camara Moussa Condé Barré Soropogui Kaba Kourouma Thierno Mamadou Tounkara Babacar Mbengue Abdoulaye Touré Sanaba Boumbaly Virology Research centre Guinea Viral Haemorrhagic Fevers Laboratory Conakry Guinea Faculty of Health Sciences and Techniques Gamal Abdel Nasser University Conakry Guinea national blood transfusion centre Ministry of Health and Public Hygiene Conakry Guinea Institute of Health and Childhood Donka National Hospital Conakry Guinea African centre of Excellence for the Prevention and Control of Communicable Diseases Conakry Guinea Department of Dermatology and Venereology Donka University Hospital Conakry Guine Immunology Laboratory Cheikh Anta Diop University Dakar Senegal centre for Research and Training in Infectious Diseases of Guinea Conakry Guinea

blood transfusion saves lives and reduces morbidity and mortality for a large number of diseases and clinical conditions, but it is not without danger. The aim of this study was to determine the seroprevalence of HIV and hepatitis B in blood donors received at the regional blood transfusion centre of N’Zérékoré (Guinea). This was a 5-year retrospective analytical study. We included records of blood donors aged 18 to 60 years admitted to the N’Zérékoré Regional blood transfusion centre for blood donation from January 2016 to December 2020. We performed a descriptive analysis followed by Chi-2 or Fish-er-exact tests and the Student or Wilcoxon test, followed by multivariate logistic regression. In this study, donor age ranged from 18 - 60 years, with a pre-dominance of donors aged 25 - 34 (44.2%). Male donors were the most represented in our study (79.0% versus 21.0% female). More than half of the donors were blood group O (55.6%). We observed a seroprevalence of 3.6% for HIV, 13.4% for HBsAg and 0.2% for co-infection. In our series, age 25 - 34 (OR = 1.89 and P = 0.001) and 35 - 44 for HIV (OR = 2.01 and P = 0.001), HBsAgserostatus (OR = 3.04 and P = 0.001) and blood donation history (OR of 3.04 and P = 0.001) were factors associated with HIV positivity (P blood donation history (OR = 0.01 and P = 0.001) were factors associated with HBsAgseropositivity. We reported a high prevalence of HIV and HBsAg. Sex, serological status and blood donation history were associated factors.

关键词： Seroprevalence HIV Hepatitis B blood Donors N’Zérékoré Guinea

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Antibiotic Resistance Profile of Salmonella Strains Isolated at the national Clinical Biology and Public Health Laboratory in Bangui, Central African Republic

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Health 2024年第2期16卷 160-171页

作者： Marceline Djeintote Ernest Lango-Yaya Zéphirin-Dalengat Vogbia Clotaire Donatien Rafaï Augustin Balekouzou Henri Saint-Claver Djemer Wilfried Sylvain Nambei Boniface Koffi Gérard Gresenguet national blood transfusion Center Bangui Central African Republic Faculty of Health Sciences University of Bangui Bangui Central African Republic national Laboratory of Clinical Biology and Public Health Bangui Central African Republic national Reference Center for Sexually Transmitted Infections and Anti-Retroviral Therapy Bangui Central African Republic national Center for the Fight against AIDS Bangui Central African Republic

In Africa, each year, there are estimated to be more than 91 million cases of salmonellosis and 137,000 cases of death. The problem of antibiotic resistance in Salmonella strains is a threat to public health. The objective of this study is to evaluate the antibiotic resistance profile of Salmonella strains isolated in biological products analyzed at the national Laboratory of Clinical Biology and Public Health (NLCBPH) in Bangui. This is, therefore, a cross-sectional study with a descriptive aim, running from January to December 2022. It focused on the strains of Salmonella isolated and identified in stools, urines, and blood samples. For each strain of Salmonella isolated, an antibiogram was carried out following the recommendations of the French Society of Microbiology (CASFM, 2022). A total of 93 strains of Salmonella have been recorded. The age group 0 - 9 years was 29% and that of >50 years was 11%. The median age of patients was 30 years with a minimum of 1 and a maximum of 78 years. The female gender was more represented at 52.69% than the male gender at 47.31%, i.e. a sex ratio of 0.89 (M/F). Salmonella strains were much more isolated in stools at 62% followed by urines at 29% and blood at 6%. Salmonella arizonae strains were more represented with 52%. Salmonella strains have a resistance rate to Tetracycline of 62.37% followed by Penicillins of 50%. The rate of multi-antibiotic resistance of the Salmonella strains isolated represented 48.38%. Salmonella spp. strains were multi-resistant at 58.69% followed by Salmonella arizonae strains at 47.91%. There is a significant association between the different families of antibiotics and Salmonella strains (p < 0.05). According to the results obtained, Penicillins, Phenicoles, and Cyclins had a high rate of resistance on Salmonella strains. No strain-producing Broad Spectrum Beta-lactamase has been isolated. Salmonella strains represent a zoonotic health danger, constitute a public health problem and remain a curre

关键词： Salmonella Resistance Antibiotics Central African Republic

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Core–Shell Microfiber Encapsulation Enables Glycerol‑Free Cryopreservation of RBCs with High Hematocrit

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Nano-Micro Letters 2024年第1期16卷 35-54页

作者： Xianhui Qin Zhongrong Chen Lingxiao Shen Huilan Liu Xilin Ouyang Gang Zhao Department of Electronic Engineering and Information Science University of Science and Technology of ChinaHefei 230027People’s Republic of China School of Biomedical Engineering Anhui Medical UniversityHefei 230022People’s Republic of China Department of blood transfusion The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001People’s Republic of China The Fourth Medical Center Chinese PLA General HospitalBeijing 100089People’s Republic of China

Cryopreservation of red blood cells(RBCs)provides great potential benefits for providing transfusion timely in *** concentrations of glycerol(20%or 40%)are used for RBC cryopreservation in current clinical practice,which results in cytotoxicity and osmotic injuries that must be carefully ***,existing studies on the low-glycerol cryopreservation of RBCs still suffer from the bottleneck of low hematocrit levels,which require relatively large storage space and an extra concentration process before transfusion,making it inconvenient(time-consuming,and also may cause injury and sample lose)for clinical *** this end,we develop a novel method for the glycerol-free cryopreservation of human RBCs with a high final hematocrit by using trehalose as the sole cryoprotectant to dehydrate RBCs and using core–shell alginate hydrogel microfibers to enhance heat transfer during *** from previous studies,we achieve the cryopreservation of human RBCs at high hematocrit(>40%)with high recovery(up to 95%).Additionally,the washed RBCs post-cryopreserved are proved to maintain their morphology,mechanics,and functional *** may provide a nontoxic,high-efficiency,and glycerol-free approach for RBC cryopreservation,along with potential clinical transfusion benefits.

关键词： Cryopreservation Human red blood cells Core-shell microfibers Trehalose Hematocrit

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