Hematologic malignancies are one of the most common malignant tumors caused by the clonal proliferation and differentiation of hematopoietic and lymphoid stem cells.The examination of bone marrow cells combined with i...Hematologic malignancies are one of the most common malignant tumors caused by the clonal proliferation and differentiation of hematopoietic and lymphoid stem cells.The examination of bone marrow cells combined with immunodeficiency typing is of great significance to the diagnostic type,treatment and prognosis of hematologic malignancies.Super-resolution fluorescence microscopy(SRM)is a special kind of optical microscopy technology,which breaks the resolution limit and was awarded the Nobel Prize in Chemistry in 2014.With the development of SRM,many related technologies have been applied to the diagnosis and treatment of clinical diseases.It was reported that a major type of SRM technique,single molecule localization microscopy(SMLM),is more sensitive than flow cytometry(FC)in detecting cell membrane antigens'expression,thus enabling better chances in detecting antigens on hematopoietic cells than traditional analytic tools.Furthermore,SRM may be applied to clinical pathology and may guide precision medicine and personalized medicine for clone hematopoietic cell diseases.In this paper,we mainly discuss the application of SRM in clone hematological malignancies.展开更多
Imaging flow cytometry(IFC)combines the imaging capabilities of microscopy with the high throughput of flow cytometry,offering a promising solution for high-precision and high-throughput cell analysis in fields such a...Imaging flow cytometry(IFC)combines the imaging capabilities of microscopy with the high throughput of flow cytometry,offering a promising solution for high-precision and high-throughput cell analysis in fields such as biomedicine,green energy,and environmental monitoring.However,due to limitations in imaging framerate and realtime data processing,the real-time throughput of existing IFC systems has been restricted to approximately 1000-10,000 events per second(eps),which is insufficient for large-scale cell analysis.In this work,we demonstrate IFC with real-time throughput exceeding 1,000,000 eps by integrating optical time-stretch(OTS)imaging,microfluidic-based cell manipulation,and online image processing.Cells flowing at speeds up to 15 m/s are clearly imaged with a spatial resolution of 780 nm,and images of each individual cell are captured,stored,and analyzed.The capabilities and performance of our system are validated through the identification of malignancies in clinical colorectal samples.This work sets a new record for throughput in imaging flow cytometry,and we believe it has the potential to revolutionize cell analysis by enabling highly efficient,accurate,and intelligent measurement.展开更多
This study provides a comprehensive bibliometric analysis of the development and current status of digital and intelligence education in medicine over the past decade,with a focus on the integration of digital technol...This study provides a comprehensive bibliometric analysis of the development and current status of digital and intelligence education in medicine over the past decade,with a focus on the integration of digital technologies in professional training.Using bibliometric methods,we analyzed publications between 2015 and 2024,identifying key research themes,emerging technologies,and the contributions of leading institutions and countries.The results show a steady increase in publications,particularly from 2022 to 2024,reflecting a growing global interest in digital and intelligence education in medicine,driven by technological advancements and the COVID-19 pandemic.Key themes identified include artificial intelligence-powered personalization,virtual reality in training,deep learning for medical imaging,and the use of language models for interactive teaching.However,challenges such as disparities in global research capacity,data privacy concerns,ethical issues,and resource inequality are also highlighted.Notably,the integration of intelligent digital platforms in education has been found to be transformative,particularly in clinical training,adaptive learning,and medical diagnostics simulation.The study concludes that while digital and intelligent technologies have the potential to revolutionize medical education,addressing ethical,technical,and resource-based challenges is crucial for equitable global implementation.Future research should focus on fostering international collaboration,developing standardized frameworks,and creating inclusive,low-cost digital tools to democratize medical education,thereby improving healthcare outcomes worldwide.展开更多
This consensus on multiple myeloma-related bone diseases(MBDs)underscores the importance of a multidisciplinary approach that encompasses hematology,radiology,orthopedics,and additional specialties to tackle its intri...This consensus on multiple myeloma-related bone diseases(MBDs)underscores the importance of a multidisciplinary approach that encompasses hematology,radiology,orthopedics,and additional specialties to tackle its intricate challenges.MBD,a prevalent and debilitating complication of multiple myeloma,leads to bone pain,fractures,and skeletal-related events(SREs),which profoundly impact patients’quality of life.The guidelines offer a thorough framework for diagnosis,treatment,and continual assessment,emphasizing early detection and consistent monitoring using imaging techniques such as positron emission tomography-computed tomography(PET-CT)and magnetic resonance imaging(MRI).Treatment strategies prioritize the careful application of antimyeloma agents,bisphosphonates,and denosumab to minimize bone loss and decrease SRE risk,complemented by surgical and radiotherapy interventions for structural or pain-related issues.Supportive care measures,including pain management,rehabilitation,nutritional support,and dental evaluations,play a crucial role in enhancing patient outcomes and preserving quality of life.This consensus advocates a standardized,evidencebased approach to managing MBD,ensuring comprehensive and coordinated care for patients.展开更多
Hematopoietic homeostasis is maintained by hematopoietic stem cells(HSCs),and it is tightly controlled at multiple levels to sustain the self-renewal capacity and differentiation potential of HSCs.Dysregulation of sel...Hematopoietic homeostasis is maintained by hematopoietic stem cells(HSCs),and it is tightly controlled at multiple levels to sustain the self-renewal capacity and differentiation potential of HSCs.Dysregulation of self-renewal and differentiation of HSCs leads to the development of hematologic diseases,including acute myeloid leukemia(AML).Thus,understanding the underlying mechanisms of HSC maintenance and the development of hematologic malignancies is one of the fundamental scientific endeavors in stem cell biology.N^(6)-methyladenosine(m^(6)A)is a common modification in mammalian messenger RNAs(mRNAs)and plays important roles in various biological processes.In this study,we performed a comparative analysis of the dynamics of the RNA m^(6)A methylome of hematopoietic stem and progenitor cells(HSPCs)and leukemia-initiating cells(LICs)in AML.We found that RNA m^(6)A modification regulates the transition of long-term HSCs into short-term HSCs and determines the lineage commitment of HSCs.Interestingly,m^(6)A modification leads to reprogramming that promotes cellular transformation during AML development,and LIC-specific m^(6)A targets are recognized by different m^(6)A readers.Moreover,the very long chain fatty acid transporter ATP-binding cassette subfamily D member 2(ABCD2)is a key factor that promotes AML development,and deletion of ABCD2 damages clonogenic ability,inhibits proliferation,and promotes apoptosis of human leukemia cells.This study provides a comprehensive understanding of the role of m^(6)A in regulating cell state transition in normal hematopoiesis and leukemogenesis,and identifies ABCD2 as a key factor in AML development.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical pro...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis.In an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity.By virtual screening of a U.S.FDA approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in vitro.In a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(P<0.05),increased lymphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control patients.In particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.展开更多
Clustered regularly interspaced short palindromic repeat(CRISPR)has been gaining much attention in the modern medical field and has been widely used for the diagnosis and treatment of diseases in recent years.In this ...Clustered regularly interspaced short palindromic repeat(CRISPR)has been gaining much attention in the modern medical field and has been widely used for the diagnosis and treatment of diseases in recent years.In this review,we will introduce the application of CRISPR in disease diagnosis and treatment,including its use in detecting pathogens,gene mutations,and genetic diseases,as well as its application in gene therapy for single-gene diseases,cancer,viral infectious diseases,and cardiovascular diseases.Additionally,we will discuss the potential future directions and challenges of CRISPR in the diagnosis and treatment of diseases,and provide a thorough overview of the ways in which CRISPR is used for diagnosing and treating diseases.展开更多
Aminoglycosides(AGs)are a class of antibiotics with a broad spectrum of activity.However,their use is limited by safety concerns associated with nephrotoxicity and ototoxicity,as well as drug resistance.To address the...Aminoglycosides(AGs)are a class of antibiotics with a broad spectrum of activity.However,their use is limited by safety concerns associated with nephrotoxicity and ototoxicity,as well as drug resistance.To address these issues,semi-synthetic approaches for modifying natural AGs have generated new generations of AGs,however,with limited types of modification due to significant challenges in synthesis.This study explores a novel approach that harness the bacterial biosynthetic machinery of gentamicins and kanamycins to create hybrid AGs.This was achieved by glycodiversification of gentamicins via swapping the glycosyltransferase(GT)in their producer with the GT from kanamycins biosynthetic pathway and resulted in the creation of a series of novel AGs,therefore referred to as genkamicins(GKs).The manipulation of the hybrid biosynthetic pathway enabled the targeted accumulation of different GK species and the isolation and characterization of six GK components.These compounds display retained antimicrobial activity against a panel of World Health Organization(WHO)critical priority pathogens,and GK-C2a,in particular,demonstrates low ototoxicity compared to clinical drugs in zebrafish embryos.This study provides a new strategy for diversifying the structure of AGs and a potential avenue for developing less toxic AG drugs to combat infectious diseases.展开更多
Hematopoietic stem cells(HSCs)maintain homeostasis in the hematopoietic ecosystem,which is tightly regulated at multiple layers.Acute myeloid leukemia(AML)is a severe hematologic malignancy driven by genetic and epige...Hematopoietic stem cells(HSCs)maintain homeostasis in the hematopoietic ecosystem,which is tightly regulated at multiple layers.Acute myeloid leukemia(AML)is a severe hematologic malignancy driven by genetic and epigenetic changes that lead to the transformation of leukemia stem cells(LSCs).Since somatic mutations in DNA methylation-related genes frequently occur in AML,DNA methylation is widely altered and functions as a starting engine for initiating AML.Additionally,RNA modifications,especially N^(6)-methyladenosine(m^(6)A),also play an important role in the generation and maintenance of the hematopoietic ecosystem,and AML development requires reprogramming of m^(6)A modifications to facilitate cells with hallmarks of cancer.Given the complex pathogenesis and poor prognosis of AML,it is important to fully understand its pathogenesis.Here,we mainly focus on DNA methylation and RNA m^(6)A modification in hematopoiesis and AML and summarize recent advances in this field.展开更多
As a crucial biophysical property,red blood cell(RBC)deformability is pathologically altered in numerous disease states,and biochemical and structural changes occur over time in stored samples of otherwise normal RBCs...As a crucial biophysical property,red blood cell(RBC)deformability is pathologically altered in numerous disease states,and biochemical and structural changes occur over time in stored samples of otherwise normal RBCs.However,there is still a gap in applying it further to point-of-care blood devices due to the large external equipment(high-resolution microscope and microfluidic pump),associated operational difficulties,and professional analysis.Herein,we revolutionarily propose a smart optofluidic system to provide a differential diagnosis for blood testing via precise cell biophysics property recognition both mechanically and morphologically.Deformation of the RBC population is caused by pressing the hydrogel via an integrated mechanical transfer device.The biophysical properties of the cell population are obtained by the designed smartphone algorithm.Artificial intelligence-based modeling of cell biophysics properties related to blood diseases and quality was developed for online testing.We currently achieve 100%diagnostic accuracy for five typical clinical blood diseases(90 megaloblastic anemia,78 myelofibrosis,84 iron deficiency anemia,48 thrombotic thrombocytopenic purpura,and 48 thalassemias)via real-world prospective implementation;furthermore,personalized blood quality(for transfusion in cardiac surgery)monitoring is achieved with an accuracy of 96.9%.This work suggests a potential basis for next-generation blood smart health care devices.展开更多
Optical time-stretch(OTS)imaging flow cytometry offers a promising solution for high-throughput and highprecision cell analysis due to its capabilities of high-speed,high-quality,and continuous imaging.Compressed sens...Optical time-stretch(OTS)imaging flow cytometry offers a promising solution for high-throughput and highprecision cell analysis due to its capabilities of high-speed,high-quality,and continuous imaging.Compressed sensing(CS)makes it practically applicable by significantly reducing the data volume while maintaining its highspeed and high-quality imaging properties.To enrich the information of the images acquired with CS-equipped OTS imaging flow cytometry,in this work we propose and experimentally demonstrate Fourier-domaincompressed OTS quantitative phase imaging flow cytometry.It is capable of acquiring intensity and quantitative phase images of cells simultaneously from the compressed data.To evaluate the performance of our method,static microparticles and a corn root cross section are experimentally measured under various compression ratios.Furthermore,to show how our method can be applied in practice,we utilize it in the drug response analysis of breast cancer cells.Experimental results show that our method can acquire high-quality intensity and quantitative phase images of flowing cells at a flowing speed of 1 m/s and a compression ratio of 30%.Combined with machine-learning-based image analysis,it can distinguish drug-treated and drug-untreated cells with an accuracy of over 95%.We believe our method can facilitate cell analysis in both scientific research and clinical settings where both high-throughput and high-content cell analysis is required.展开更多
Objective:To identify the effectiveness of a personnel protection strategy in protection of healthcare workers from SARS-CoV-2 infection.Design:During the COVID-19 pandemic,943 healthcare staff sent from Guangzhou to ...Objective:To identify the effectiveness of a personnel protection strategy in protection of healthcare workers from SARS-CoV-2 infection.Design:During the COVID-19 pandemic,943 healthcare staff sent from Guangzhou to Wuhan to care for patients with suspected/confirmed COVID-19 received infection precaution training before their mission and were equipped with Level 2/3 personal protective equipment(PPE),in accordance with guidelines from the National Health Commission of China.We conducted a serological survey on the cumulative attack rate of SARS-CoV-2 among the healthcare workers sent to Wuhan and compared the seropositive rate to that in local healthcare workers from Wuhan and Jingzhou.Results:Serial tests for SARS-CoV-2 RNA and tests for SARS-CoV-2 immunoglobulin M and G after the 6-8 week mission revealed a zero cumulative attack rate.Among the local healthcare workers inWuhan and Jingzhou of Hubei Province,2.5%(113 out of 4495)and 0.32%(10 out of 3091)had RT-PCR confirmed COVID-19,respectively.The seropositivity for SARS-CoV-2 antibodies(IgG,IgM,or both IgG/IgM positive)was 3.4%(53 out of 1571)in local healthcare workers from Wuhan with Level 2/3 PPE working in isolation areas and 5.4%(126 out of 2336)in healthcare staff with Level 1 PPE working in non-isolation medical areas,respectively.Conclusions and relevance:Our study confirmed that adequate training/PPE can protect medical personnel against SARS-CoV-2.展开更多
N^(6)-Methyladenosine(m^(6)A)is the most abundant modification in eukaryotic mRNA,and plays important biological functions via regulating RNA fate determination.Recent studies have shown that m^(6)A modification plays...N^(6)-Methyladenosine(m^(6)A)is the most abundant modification in eukaryotic mRNA,and plays important biological functions via regulating RNA fate determination.Recent studies have shown that m^(6)A modification plays a key role in hematologic malignancies,including acute myeloid leukemia.The current growth of epitranscriptomic research mainly benefits from technological progress in detecting RNA m^(6)A modification in a transcriptome-wide manner.In this review,we first briefly summarize the latest advances in RNA m^(6)A biology by focusing on writers,readers,and erasers of m^(6)A modification,and describe the development of high-throughput methods for RNA m^(6)A mapping.We further discuss the important roles of m^(6)A modifiers in acute myeloid leukemia,and highlight the identification of potential inhibitors for AML treatment by targeting of m^(6)A modifiers.Overall,this review provides a comprehensive summary of RNA m^(6)A biology in acute myeloid leukemia.展开更多
基金This work was supported by the Innovation Fund of WNLO(2018WNLOKF023)the Start-up Fund of Hainan University(KYQD(ZR)-20077).
文摘Hematologic malignancies are one of the most common malignant tumors caused by the clonal proliferation and differentiation of hematopoietic and lymphoid stem cells.The examination of bone marrow cells combined with immunodeficiency typing is of great significance to the diagnostic type,treatment and prognosis of hematologic malignancies.Super-resolution fluorescence microscopy(SRM)is a special kind of optical microscopy technology,which breaks the resolution limit and was awarded the Nobel Prize in Chemistry in 2014.With the development of SRM,many related technologies have been applied to the diagnosis and treatment of clinical diseases.It was reported that a major type of SRM technique,single molecule localization microscopy(SMLM),is more sensitive than flow cytometry(FC)in detecting cell membrane antigens'expression,thus enabling better chances in detecting antigens on hematopoietic cells than traditional analytic tools.Furthermore,SRM may be applied to clinical pathology and may guide precision medicine and personalized medicine for clone hematopoietic cell diseases.In this paper,we mainly discuss the application of SRM in clone hematological malignancies.
基金supported by the National Key R&D Program of China(2023YFF0723300)National Natural Science Foundation of China(62475198,62075200,12374295)+8 种基金Fundamental Research Funds for the Central Universities(2042024kf0003,2042024kf1010,2042023kf0105)Hubei Provincial Natural Science Foundation of China(2023AFB133)Jiangsu Science and Technology Program(BK20221257)Shenzhen Science and Technology Program(JCYJ20220530140601003,JCYJ20230807090207014)Translational Medicine and Multidisciplinary Research Project of Zhongnan Hospital of Wuhan University(ZNJC202217,ZNJC202232)The Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University(JCRCYR-2022-006)Hubei Province Young Science and Technology Talent Morning Hight Lift Project(202319)The Fund of National Key Laboratory of Plasma Physics(6142A04230201)We gratefully acknowledge Serendipity Lab for facilitating collaboration opportunities.
文摘Imaging flow cytometry(IFC)combines the imaging capabilities of microscopy with the high throughput of flow cytometry,offering a promising solution for high-precision and high-throughput cell analysis in fields such as biomedicine,green energy,and environmental monitoring.However,due to limitations in imaging framerate and realtime data processing,the real-time throughput of existing IFC systems has been restricted to approximately 1000-10,000 events per second(eps),which is insufficient for large-scale cell analysis.In this work,we demonstrate IFC with real-time throughput exceeding 1,000,000 eps by integrating optical time-stretch(OTS)imaging,microfluidic-based cell manipulation,and online image processing.Cells flowing at speeds up to 15 m/s are clearly imaged with a spatial resolution of 780 nm,and images of each individual cell are captured,stored,and analyzed.The capabilities and performance of our system are validated through the identification of malignancies in clinical colorectal samples.This work sets a new record for throughput in imaging flow cytometry,and we believe it has the potential to revolutionize cell analysis by enabling highly efficient,accurate,and intelligent measurement.
基金funded by the Teaching Reform Research Project of the Medical School of Wuhan University(Grant No.2024ZD29)the Comprehensive Reform Project for Undergraduate Education Quality Construction at Wuhan University(Digital and Intelligence Education in Health and Medicine).
文摘This study provides a comprehensive bibliometric analysis of the development and current status of digital and intelligence education in medicine over the past decade,with a focus on the integration of digital technologies in professional training.Using bibliometric methods,we analyzed publications between 2015 and 2024,identifying key research themes,emerging technologies,and the contributions of leading institutions and countries.The results show a steady increase in publications,particularly from 2022 to 2024,reflecting a growing global interest in digital and intelligence education in medicine,driven by technological advancements and the COVID-19 pandemic.Key themes identified include artificial intelligence-powered personalization,virtual reality in training,deep learning for medical imaging,and the use of language models for interactive teaching.However,challenges such as disparities in global research capacity,data privacy concerns,ethical issues,and resource inequality are also highlighted.Notably,the integration of intelligent digital platforms in education has been found to be transformative,particularly in clinical training,adaptive learning,and medical diagnostics simulation.The study concludes that while digital and intelligent technologies have the potential to revolutionize medical education,addressing ethical,technical,and resource-based challenges is crucial for equitable global implementation.Future research should focus on fostering international collaboration,developing standardized frameworks,and creating inclusive,low-cost digital tools to democratize medical education,thereby improving healthcare outcomes worldwide.
文摘This consensus on multiple myeloma-related bone diseases(MBDs)underscores the importance of a multidisciplinary approach that encompasses hematology,radiology,orthopedics,and additional specialties to tackle its intricate challenges.MBD,a prevalent and debilitating complication of multiple myeloma,leads to bone pain,fractures,and skeletal-related events(SREs),which profoundly impact patients’quality of life.The guidelines offer a thorough framework for diagnosis,treatment,and continual assessment,emphasizing early detection and consistent monitoring using imaging techniques such as positron emission tomography-computed tomography(PET-CT)and magnetic resonance imaging(MRI).Treatment strategies prioritize the careful application of antimyeloma agents,bisphosphonates,and denosumab to minimize bone loss and decrease SRE risk,complemented by surgical and radiotherapy interventions for structural or pain-related issues.Supportive care measures,including pain management,rehabilitation,nutritional support,and dental evaluations,play a crucial role in enhancing patient outcomes and preserving quality of life.This consensus advocates a standardized,evidencebased approach to managing MBD,ensuring comprehensive and coordinated care for patients.
基金supported by the grants to Haojian Zhang from the National Natural Science Foundation of China(Grant Nos.82230007 and 82325003)the National Key R&D Program of China(Grant No.2022YFA1103200)supported by the Fundamental Research Funds for the Central Universities,China(Grant Nos.2042021kf0225 and 2042022dx0003).
文摘Hematopoietic homeostasis is maintained by hematopoietic stem cells(HSCs),and it is tightly controlled at multiple levels to sustain the self-renewal capacity and differentiation potential of HSCs.Dysregulation of self-renewal and differentiation of HSCs leads to the development of hematologic diseases,including acute myeloid leukemia(AML).Thus,understanding the underlying mechanisms of HSC maintenance and the development of hematologic malignancies is one of the fundamental scientific endeavors in stem cell biology.N^(6)-methyladenosine(m^(6)A)is a common modification in mammalian messenger RNAs(mRNAs)and plays important roles in various biological processes.In this study,we performed a comparative analysis of the dynamics of the RNA m^(6)A methylome of hematopoietic stem and progenitor cells(HSPCs)and leukemia-initiating cells(LICs)in AML.We found that RNA m^(6)A modification regulates the transition of long-term HSCs into short-term HSCs and determines the lineage commitment of HSCs.Interestingly,m^(6)A modification leads to reprogramming that promotes cellular transformation during AML development,and LIC-specific m^(6)A targets are recognized by different m^(6)A readers.Moreover,the very long chain fatty acid transporter ATP-binding cassette subfamily D member 2(ABCD2)is a key factor that promotes AML development,and deletion of ABCD2 damages clonogenic ability,inhibits proliferation,and promotes apoptosis of human leukemia cells.This study provides a comprehensive understanding of the role of m^(6)A in regulating cell state transition in normal hematopoiesis and leukemogenesis,and identifies ABCD2 as a key factor in AML development.
基金National Key R&D Program of China(2017YFB0202600 and 2020YFC0841400)National Natural Science Foundation of China(91742109,8152204,31770978,81773674,and 21877134)+8 种基金National Health&Medical Research of Australia(1080321,1143976 and 1150425)Science Foundation of Guangzhou City(201904020023,China)Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme(2016 and 2019,China)Guangdong Provincial Key Laboratory of Construction Foundation(2017B030314030,China)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y093,China)Zhejiang University special scientific research fund for COVID-19 prevention and control(China)National Health&Medical Research of Australia(1080321,1143976,and 1150425)Taikang Insurance Group Co.,Ltd.Beijing Taikang Yicai Foundation(Beijing,China)
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis.In an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity.By virtual screening of a U.S.FDA approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in vitro.In a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(P<0.05),increased lymphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control patients.In particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.
基金supported by the National Natural Science Foundation of China(21907077,92153303,21721005,91940000)Fundamental Research Funds for the Central Universities(2042023kf0118)。
文摘Clustered regularly interspaced short palindromic repeat(CRISPR)has been gaining much attention in the modern medical field and has been widely used for the diagnosis and treatment of diseases in recent years.In this review,we will introduce the application of CRISPR in disease diagnosis and treatment,including its use in detecting pathogens,gene mutations,and genetic diseases,as well as its application in gene therapy for single-gene diseases,cancer,viral infectious diseases,and cardiovascular diseases.Additionally,we will discuss the potential future directions and challenges of CRISPR in the diagnosis and treatment of diseases,and provide a thorough overview of the ways in which CRISPR is used for diagnosing and treating diseases.
基金the National Key R&D Program of China(2018YFA0903200)the Funds for International Cooperation and Exchange of the National Natural Science Foundation of China(31920103001).
文摘Aminoglycosides(AGs)are a class of antibiotics with a broad spectrum of activity.However,their use is limited by safety concerns associated with nephrotoxicity and ototoxicity,as well as drug resistance.To address these issues,semi-synthetic approaches for modifying natural AGs have generated new generations of AGs,however,with limited types of modification due to significant challenges in synthesis.This study explores a novel approach that harness the bacterial biosynthetic machinery of gentamicins and kanamycins to create hybrid AGs.This was achieved by glycodiversification of gentamicins via swapping the glycosyltransferase(GT)in their producer with the GT from kanamycins biosynthetic pathway and resulted in the creation of a series of novel AGs,therefore referred to as genkamicins(GKs).The manipulation of the hybrid biosynthetic pathway enabled the targeted accumulation of different GK species and the isolation and characterization of six GK components.These compounds display retained antimicrobial activity against a panel of World Health Organization(WHO)critical priority pathogens,and GK-C2a,in particular,demonstrates low ototoxicity compared to clinical drugs in zebrafish embryos.This study provides a new strategy for diversifying the structure of AGs and a potential avenue for developing less toxic AG drugs to combat infectious diseases.
基金supported by the grants to H.Z.from the National Key R&D Program of China(2022YFA0103200)the National Natural Science Foundation of China(82325003,82230007)+4 种基金supported by the grants to R.G.from the Fundamental Research Funds for the Central Universities(2042023kf0057)the National Natural Science Foundation(NSFC)(82301997)supported by the grants to R.Y.from the National Natural Science Foundation of China(82200188)the Special Fund of China Postdoctoral Science Foundation(2022TQ0238)supported by the grants to H.Z.from the Fundamental Research Funds for the Central Universities(2042022dx0003 and 2042024kf1022).
文摘Hematopoietic stem cells(HSCs)maintain homeostasis in the hematopoietic ecosystem,which is tightly regulated at multiple layers.Acute myeloid leukemia(AML)is a severe hematologic malignancy driven by genetic and epigenetic changes that lead to the transformation of leukemia stem cells(LSCs).Since somatic mutations in DNA methylation-related genes frequently occur in AML,DNA methylation is widely altered and functions as a starting engine for initiating AML.Additionally,RNA modifications,especially N^(6)-methyladenosine(m^(6)A),also play an important role in the generation and maintenance of the hematopoietic ecosystem,and AML development requires reprogramming of m^(6)A modifications to facilitate cells with hallmarks of cancer.Given the complex pathogenesis and poor prognosis of AML,it is important to fully understand its pathogenesis.Here,we mainly focus on DNA methylation and RNA m^(6)A modification in hematopoiesis and AML and summarize recent advances in this field.
基金This work was supported by the National Key R&D Program of China(2018YFC1003200)the National Natural Science Foundation of China(Nos.62175190,11774274,81860276,and 81770179)+1 种基金Foundation Research Fund of Shenzhen Science and Technology Program(No.JCYJ20190808154409678)Support Projects of Medical Science and Technology Innovation Platform of Wuhan University Zhongnan Hospital in 2020(lcyf202010).
文摘As a crucial biophysical property,red blood cell(RBC)deformability is pathologically altered in numerous disease states,and biochemical and structural changes occur over time in stored samples of otherwise normal RBCs.However,there is still a gap in applying it further to point-of-care blood devices due to the large external equipment(high-resolution microscope and microfluidic pump),associated operational difficulties,and professional analysis.Herein,we revolutionarily propose a smart optofluidic system to provide a differential diagnosis for blood testing via precise cell biophysics property recognition both mechanically and morphologically.Deformation of the RBC population is caused by pressing the hydrogel via an integrated mechanical transfer device.The biophysical properties of the cell population are obtained by the designed smartphone algorithm.Artificial intelligence-based modeling of cell biophysics properties related to blood diseases and quality was developed for online testing.We currently achieve 100%diagnostic accuracy for five typical clinical blood diseases(90 megaloblastic anemia,78 myelofibrosis,84 iron deficiency anemia,48 thrombotic thrombocytopenic purpura,and 48 thalassemias)via real-world prospective implementation;furthermore,personalized blood quality(for transfusion in cardiac surgery)monitoring is achieved with an accuracy of 96.9%.This work suggests a potential basis for next-generation blood smart health care devices.
基金National Key Research and Development Program of China(2023YFF0723300)Fundamental Research Funds for the Central Universities(2042023kf0105,2042024kf0003,2042024kf1010)+6 种基金Science Fund for Distinguished Young Scholars of Hubei Province(2021CFA042)Natural Science Foundation of Hubei Province(2023AFB133)National Natural Science Foundation of China(12374295,62075200)Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University(JCRCYR-2022-006)Jiangsu Science and Technology Program(BK20221257)Shenzhen Science and Technology Program(JCYJ20220530140601003,JCYJ20230807090207014)Translational Medicine and Multidisciplinary Research Project of Zhongnan Hospital of Wuhan University(ZNJC202217)。
文摘Optical time-stretch(OTS)imaging flow cytometry offers a promising solution for high-throughput and highprecision cell analysis due to its capabilities of high-speed,high-quality,and continuous imaging.Compressed sensing(CS)makes it practically applicable by significantly reducing the data volume while maintaining its highspeed and high-quality imaging properties.To enrich the information of the images acquired with CS-equipped OTS imaging flow cytometry,in this work we propose and experimentally demonstrate Fourier-domaincompressed OTS quantitative phase imaging flow cytometry.It is capable of acquiring intensity and quantitative phase images of cells simultaneously from the compressed data.To evaluate the performance of our method,static microparticles and a corn root cross section are experimentally measured under various compression ratios.Furthermore,to show how our method can be applied in practice,we utilize it in the drug response analysis of breast cancer cells.Experimental results show that our method can acquire high-quality intensity and quantitative phase images of flowing cells at a flowing speed of 1 m/s and a compression ratio of 30%.Combined with machine-learning-based image analysis,it can distinguish drug-treated and drug-untreated cells with an accuracy of over 95%.We believe our method can facilitate cell analysis in both scientific research and clinical settings where both high-throughput and high-content cell analysis is required.
基金This work is supported by the Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(Grants No.2018GZR0201003 and 2020GZR110306001)the National Innovation Team Program(Grant No.81521003)Recruitment Program of Leading Talent in Guangdong Province(Grant No.2016LJ06Y375),and a Macao FDCT(Grant No.0035/2020/A).
文摘Objective:To identify the effectiveness of a personnel protection strategy in protection of healthcare workers from SARS-CoV-2 infection.Design:During the COVID-19 pandemic,943 healthcare staff sent from Guangzhou to Wuhan to care for patients with suspected/confirmed COVID-19 received infection precaution training before their mission and were equipped with Level 2/3 personal protective equipment(PPE),in accordance with guidelines from the National Health Commission of China.We conducted a serological survey on the cumulative attack rate of SARS-CoV-2 among the healthcare workers sent to Wuhan and compared the seropositive rate to that in local healthcare workers from Wuhan and Jingzhou.Results:Serial tests for SARS-CoV-2 RNA and tests for SARS-CoV-2 immunoglobulin M and G after the 6-8 week mission revealed a zero cumulative attack rate.Among the local healthcare workers inWuhan and Jingzhou of Hubei Province,2.5%(113 out of 4495)and 0.32%(10 out of 3091)had RT-PCR confirmed COVID-19,respectively.The seropositivity for SARS-CoV-2 antibodies(IgG,IgM,or both IgG/IgM positive)was 3.4%(53 out of 1571)in local healthcare workers from Wuhan with Level 2/3 PPE working in isolation areas and 5.4%(126 out of 2336)in healthcare staff with Level 1 PPE working in non-isolation medical areas,respectively.Conclusions and relevance:Our study confirmed that adequate training/PPE can protect medical personnel against SARS-CoV-2.
基金This work is supported by grants to H.Z.from Medical Science Advancement Program(Basic Medical Sciences)of Wuhan University(TFJC2018005)from the Fundamental Research Funds for the Central Universities(2042021kf0225).
文摘N^(6)-Methyladenosine(m^(6)A)is the most abundant modification in eukaryotic mRNA,and plays important biological functions via regulating RNA fate determination.Recent studies have shown that m^(6)A modification plays a key role in hematologic malignancies,including acute myeloid leukemia.The current growth of epitranscriptomic research mainly benefits from technological progress in detecting RNA m^(6)A modification in a transcriptome-wide manner.In this review,we first briefly summarize the latest advances in RNA m^(6)A biology by focusing on writers,readers,and erasers of m^(6)A modification,and describe the development of high-throughput methods for RNA m^(6)A mapping.We further discuss the important roles of m^(6)A modifiers in acute myeloid leukemia,and highlight the identification of potential inhibitors for AML treatment by targeting of m^(6)A modifiers.Overall,this review provides a comprehensive summary of RNA m^(6)A biology in acute myeloid leukemia.
