The clinical efficacy of immunotherapy in acute myeloid leukemia(AML)remains significantly limited by early relapse and treatment-associated toxicities.This review examines recent advances in antibody-and cell-based i...The clinical efficacy of immunotherapy in acute myeloid leukemia(AML)remains significantly limited by early relapse and treatment-associated toxicities.This review examines recent advances in antibody-and cell-based immunotherapies for AML,focusing on established targets(CD33,CD123,and CLL1)as well as emerging targets(including CD7,CD70,CD38,and FLT3).Therapeutic modalities discussed include immunoconjugates,bispecific T-cell engagers and chimeric antigen receptor T(CAR-T)cells.Furthermore,we summarize the current challenges impeding the success of immunotherapy in AML and propose strategies to enhance its efficacy.These include combination therapies,structural optimization of CAR constructs,functional enhancement of CAR-T cells,identification of novel targets,and the development of next-generation cellular therapies.Collectively,these approaches aim to offer new insights for improving immunotherapeutic outcomes in AML.展开更多
CD5-positive(CD5+)diffuse large B-cell lymphoma(DLBCL)represents a special subgroup of DLBCL with a more aggressive disease course and is more likely to develop into relapsed/refractory(r/r)DLBCL in response to immuno...CD5-positive(CD5+)diffuse large B-cell lymphoma(DLBCL)represents a special subgroup of DLBCL with a more aggressive disease course and is more likely to develop into relapsed/refractory(r/r)DLBCL in response to immunochemotherapy.The incidence of CD5+DLBCL is 5%–10%among DLBCL patients1.展开更多
Objective Chinese allergic subjects have high levels of sensitization to house dust mite （HDM） and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households. Methods Dust samp...Objective Chinese allergic subjects have high levels of sensitization to house dust mite （HDM） and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households. Methods Dust samples were collected from nine cities. Major allergens Der p 1 and Der f I from Dermatophagoides pteronyssinus and D. farinae, and specific antigens of Blomia tropicalis, Tyrophagus putrescentiae, Acarus siro, and cockroach species Blattella germanica and Periplaneta americana were measured by ELISA.Results HDM allergens were found in dust samples from bedding in 95% of the Chinese households. The median levels varied from 〈0.006 to 9.2 μg/g of dust, depending on the city. The percentages of households having HDM allergen levels associated with the risk of developing allergy sensitization and asthma were 65% and 25%, respectively. Specific antigens of the storage mite and cockroach were only found in samples from the southern and tropical regions of China. Levels of mite allergens were generally higher in samples from bedding compared to samples from the living room, even for storage mites, whereas levels of cockroach antigens were higher in the living room samples.Conclusion HDM allergens are present in bedding dust samples from most Chinese households. Cities in southern and central China have relatively high levels of HDM major allergens compared to cities in northern and western China. Antigens of storage mites and cockroaches are not as common as HDM allergens.展开更多
OBJECTIVE CD4^＋CD25^＋ T regulatory （Treg） cells are a population of T cells which suppress an overactive immune system. CCR4 is a chemokine receptor involved in the recruitment of lymphocytes. Nasopharyngeal carci...OBJECTIVE CD4^＋CD25^＋ T regulatory （Treg） cells are a population of T cells which suppress an overactive immune system. CCR4 is a chemokine receptor involved in the recruitment of lymphocytes. Nasopharyngeal carcinoma （NPC） is resistant to immunosurveillance, owing to the increased number of tumor-infiltrating Treg cells which are recruited to the tumor bv CCR4.展开更多
AIM To characterize the understanding of hepatitis B virus(HBV)and determine if outreach improves HBV understanding among Greater Boston Area immigrants.METHODS Six outreach sessions were held in various community ven...AIM To characterize the understanding of hepatitis B virus(HBV)and determine if outreach improves HBV understanding among Greater Boston Area immigrants.METHODS Six outreach sessions were held in various community venues in the Greater Boston Area.Verbal consent was obtained from participants prior to starting each session.Each session included a pre-session questionnaire,followed by a teaching session,and then a post-session questionnaire.In person interpreters were present for translation during the teaching session and assistance for questionnaire completion when needed.The questions were developed based on the HBV clinical experience of physicians who serve largely immigrant populations.Questionnaires included Likerttype scale,open-ended,and true-false questions.All results were anonymous.RESULTS One hundred and one people participated in this study.Participants were 30%male with ages ranging from 19 to 87 years.The study population included immigrants from 21 countries,as well as seven United States-born participants.The greatest numbers of participants were from Somalia(44%),Morocco(10%),and Cameroon(8%).Pre session questionnaires revealed that 42%of participants were unaware that HBV can cause cancer,and 50%were unaware that therapies for HBV exist.Our brief teaching intervention led to improved scores on post session questionnaires.For example,at baseline,58%of participants responded correctly to the question"HBV infection can cause scarring of the liver and liver cancer",whereas 79%of participants responded correctly after the teaching session(P=0.01).Furthermore,the mean of total correct answers in the true or false portion of the questionnaire increased from 5.5 to 7.6(P<0.001).CONCLUSION A teaching session targeting Boston Immigrants atrisk for HBV helped improve scores on HBV knowledge questionnaires.Outreach may empower at-risk patients to pro-actively seek HBV care.展开更多
Neuroinflammation plays an important role in the pathogenesis of various central nervous system(CNS)diseases.The NLRP3 inflammasome is an important intracellular multiprotein complex composed of the innate immune rece...Neuroinflammation plays an important role in the pathogenesis of various central nervous system(CNS)diseases.The NLRP3 inflammasome is an important intracellular multiprotein complex composed of the innate immune receptor NLRP3,the adaptor protein ASC,and the protease caspase-1.The activation of the NLRP3 inflammasome can induce pyroptosis and the release of the proinflammatory cytokines IL-1βand IL-18,thus playing a central role in immune and inflammatory responses.Recent studies have revealed that the NLRP3 inflammasome is activated in the brain to induce neuroinflammation,leading to further neuronal damage and functional impairment,and contributes to the pathological process of various neurological diseases,such as multiple sclerosis,Parkinson’s disease,Alzheimer’s disease,and stroke.In this review,we summarize the important role of the NLRP3 inflammasome in the pathogenesis of neuroinflammation and the pathological course of CNS diseases and discuss potential approaches to target the NLRP3 inflammasome for the treatment of CNS diseases.展开更多
Cytokine storm(CS)is a severe systemic inflammatory syndrome characterized by the excessive activation of immune cells and a significant increase in circulating levels of cytokines.This pathological process is implica...Cytokine storm(CS)is a severe systemic inflammatory syndrome characterized by the excessive activation of immune cells and a significant increase in circulating levels of cytokines.This pathological process is implicated in the development of life-threatening conditions such as fulminant myocarditis(FM),acute respiratory distress syndrome(ARDS),primary or secondary hemophagocytic lymphohistiocytosis(HLH),cytokine release syndrome(CRS)associated with chimeric antigen receptor-modified T(CAR-T)therapy,and grade Ⅲ to Ⅳ acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.The significant involvement of the JAK-STAT pathway,Toll-like receptors,neutrophil extracellular traps,NLRP3 inflammasome,and other signaling pathways has been recognized in the pathogenesis of CS.Therapies targeting these pathways have been developed or are currently being investigated.While novel drugs have demonstrated promising therapeutic efficacy in mitigating CS,the overall mortality rate of CS resulting from underlying diseases remains high.In the clinical setting,the management of CS typically necessitates a multidisciplinary team strategy encompassing the removal of abnormal inflammatory or immune system activation,the preservation of vital organ function,the treatment of the underlying disease,and the provision of life supportive therapy.This review provides a comprehensive overview of the key signaling pathways and associated cytokines implicated in CS,elucidates the impact of dysregulated immune cell activation,and delineates the resultant organ injury associated with CS.In addition,we offer insights and current literature on the management of CS in cases of FM,ARDS,systemic inflammatory response syndrome,treatment-induced CRS,HLH,and other related conditions.展开更多
Coronaviruses(CoVs)pose a continual threat to global public health due to their broad host range and potential for cross-species transmission.Notable examples include the severe acute respiratory syndrome coronavirus(...Coronaviruses(CoVs)pose a continual threat to global public health due to their broad host range and potential for cross-species transmission.Notable examples include the severe acute respiratory syndrome coronavirus(SARS-CoV)in 2002 andMiddle East respiratory syndrome coronavirus(MERS-CoV)in 2012,each causing worldwide health emergencies.Despite vaccine and antiviral development targeting theseCoVs,newCoVs regularly emerge in animals,often without attracting significant attention.展开更多
Microglia dysfunction-associated neuroinflammation is an important driver of Alzheimer’s disease(AD),but the mechanism is poorly understood.Here,we show that demyelination promotes neuroinflammation and cognitive imp...Microglia dysfunction-associated neuroinflammation is an important driver of Alzheimer’s disease(AD),but the mechanism is poorly understood.Here,we show that demyelination promotes neuroinflammation and cognitive impairment via the lysophosphatidylserine(LysoPS)-GPR34 axis in AD.Demyelination is observed at the early stage and is accompanied by an increase in LysoPS in myelin debris in a 5xFAD mouse model of AD.Reducing the content of LysoPS in myelin or inhibiting its receptor GPR34 via genetic or pharmacological approaches can reduce microglial dysfunction and neuroinflammation and improve microglial Aβphagocytosis,subsequently resulting in less Aβdeposition and memory restoration in 5xFAD mice.Furthermore,increased LysoPS production and microglial GPR34 expression were also observed in the brains of AD patients.These results reveal the pathogenic role of demyelination-derived LysoPS in microglial dysfunction and AD pathology and suggest that blocking GPR34 as a therapeutic strategy beyond targeting Aβ.展开更多
Pluripotent stem cells(PSCs)possess the ability to proliferate indefinitely,self-renew,and differentiate into three germ layers.These pluripotent characteristics allow PSCs to be used to treat many incurable diseases,...Pluripotent stem cells(PSCs)possess the ability to proliferate indefinitely,self-renew,and differentiate into three germ layers.These pluripotent characteristics allow PSCs to be used to treat many incurable diseases,such as spinal cord injury with the embryonic stem cells(ESCs)-derived oligodendrocyte progenitor cells,and dry age-related macular degeneration(AMD)with the ESCs-derived retinal pigment epithelium,and have great application value in clinical regenerative medicine.展开更多
Basal signal transducer and activator of transcription 3(STAT3)activation is well-documented in the tumor microenvironment(TME)due to its association with cancer prognosis[1].However,its presence and clinical relevanc...Basal signal transducer and activator of transcription 3(STAT3)activation is well-documented in the tumor microenvironment(TME)due to its association with cancer prognosis[1].However,its presence and clinical relevance in the bloodstream remain unexplored.Given that STAT3-inducing cytokines,such as interleukin-6(IL-6),are often elevated in the bloodstream of various cancer patients[2,3],we aimed to investigate basal STAT3 activation in blood by developing a methodology to assess ex vivo phosphorylation of STAT3(pSTAT3ex vivo)in circulating immune cells.展开更多
Tcells are an important component of adaptive immunity and protect the host from infectious diseases and cancers.However,uncontrolled T cell immunity may cause autoimmune disorders.In both situations,antigen-specific ...Tcells are an important component of adaptive immunity and protect the host from infectious diseases and cancers.However,uncontrolled T cell immunity may cause autoimmune disorders.In both situations,antigen-specific T cells undergo clonal expansion upon the engagement and activation of antigens.Cellular metabolism is reprogrammed to meet the increase in bioenergetic and biosynthetic demands associated with effector T cell expansion.Metabolites not only serve as building blocks or energy sources to fuel cell growth and expansion but also regulate a broad spectrum of cellular signals that instruct the differentiation of multiple T cell subsets.The realm of immunometabolism research is undergoing swift advancements.Encapsulating all the recent progress within this concise review in not possible.Instead,our objective is to provide a succinct introduction to this swiftly progressing research,concentrating on the metabolic intricacies of three pivotal nutrient classes—lipids,glucose,and amino acids—in T cells.We shed light on recent investigations elucidating the roles of these three groups of metabolites in mediating the metabolic and immune functions of T cells.Moreover,we delve into the prospect of“editing”metabolic pathways within T cells using pharmacological or genetic approaches,with the aim of synergizing this approach with existing immunotherapies and enhancing the efficacy of antitumor and antiinfection immune responses.展开更多
Background Haikou locates in tropical island with unique mite allergens levels in Haikou, and to investigate the prevalence of between house dust mites. propagation. The aim of this stuy is to determine mite mite spec...Background Haikou locates in tropical island with unique mite allergens levels in Haikou, and to investigate the prevalence of between house dust mites. propagation. The aim of this stuy is to determine mite mite specific IgE-sensitization and IgE cross-reactivity Methods Allergen and antigen concentrations against six mite species were tested by enzyme-linked immunosorbent assay （ELISA）. Specific IgE concentrations and cross-inhibitions were measured with ADVIA Centaur . Results Allergen or antigen Dermatophagoides pteronyssinus （Der p 1 ）, Blomia tropicalis （BIot ） and Tyrophagus putrescentia （Tyr p） were detected in dust samples. Dermatophagoides farinae （Der f 1 ）, Lepidoglyphus destructor （Lep d 2）, and Acarus siro （Aca s ） were found in very few samples. Specific IgE tests showed high prevalence of sensitizations against all tested mites with high IgE levels to Der p, Der f, and BIot. Storage mites, BIo t, Tyr p, Lep d, and Aca s, could inhibit Der p from 0 to 50%. Storage mites could inhibit Der f between 30% and 100%. Der p IgE could be inhibited by Der f with up to 90%, and vice versa. Der p could inhibit BIot from 40% to 80%. BIot was able to fully inhibit IgE binding to Lep d, Tyr p, and Aca s compared to partial inhibition by Der p. Conclusions Der p is the dominating mite and has the highest specific IgE prevalence among asthmatic children. BIot represents an important source of storage mite sensitization and some patients may be independently sensitized to both Der p and BIot. High prevalence of sensitization to Der f may be due to IgE-mediated cross-reactivity with Der p and BIo t.展开更多
TP53 gene alteration confers inferior prognosis in refractory/relapse aggressive B-cell non-Hodgkin lymphoma(r/r B-NHL).From September 2016 to September 2020,257 r/r B-NHL patients were assessed for eligibility for tw...TP53 gene alteration confers inferior prognosis in refractory/relapse aggressive B-cell non-Hodgkin lymphoma(r/r B-NHL).From September 2016 to September 2020,257 r/r B-NHL patients were assessed for eligibility for two trials in our center,assessing anti-CD19 and anti-CD22 chimeric antigen receptor(CAR19/22)T-cell cocktail treatment alone or in combination with autologous stem cell transplantation(ASCT).TP53 alterations were screened in 123 enrolled patients and confirmed in 60.CAR19/22 T-cell administration resulted in best objective(ORR)and complete(CRR)response rate of 87.1%and 45.2%in patients with TP53 alterations.展开更多
Gene engineering and combinatorial approaches with other cancer immunotherapy agents may confer capabilities enabling full tumor rejection by adoptive T cell therapy(ACT).The provision of proper costimulatory receptor...Gene engineering and combinatorial approaches with other cancer immunotherapy agents may confer capabilities enabling full tumor rejection by adoptive T cell therapy(ACT).The provision of proper costimulatory receptor activity and cytokine stimuli,along with the repression of inhibitory mechanisms,will conceivably make the most of these treatment strategies.In this sense,T cells can be genetically manipulated to become refractory to suppressive mechanisms and exhaustion,last longer and differentiate into memory T cells while endowed with the ability to traffic to malignant tissues.Their antitumor effects can be dramatically augmented with permanent or transient gene transfer maneuvers to express or delete/repress genes.A combination of such interventions seeks the creation of the ultimate bionic T cell,perfected to seek and destroy cancer cells upon systemic or local intratumor delivery.展开更多
Background:Increased Galectin 3-binding protein(LGALS3BP)serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma(HCC).Considering the crucial role of transforming gro...Background:Increased Galectin 3-binding protein(LGALS3BP)serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma(HCC).Considering the crucial role of transforming growth factor-β1(TGF-β1)in the emergence of these diseases,the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling pathway.Methods:The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis(MASH)and HCC.Multiple omics techniques,such as RNA-sequencing,transposaseaccessible chromatin-sequencing assay,and liquid chromatography-tandem mass spectrometry proteomics,were used to identify the regulatory mechanisms for the LGALS3BP-TGF-β1 axis.The effects of altered TGF-β1 signaling by LGALS3BP were investigated in conditional LGALS3BP-knockin and LGALS3BP-knockout mice.Results:In patients with MASH and HCC,the levels of LGALS3BP and TGFB1 exhibited positive correlations.Stimulation of LGALS3BP by the inflammatory cytokine interferonαin HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of TGFB1.Aggravated fibrosis was observed in the livers of hepatocyte-specific LGALS3BP-knockin mice,with increased TGFB1 levels.LGALS3BP directly bound to and assembled integrinαV,an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin cytoskeleton.The released TGF-β1 activated JunB transcription factor,which in turn promoted the TGF-β1 positive feedback loop.LGALS3BP deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced fibrosis.Moreover,LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β1.Conclusion:LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway,making it a promising therapeutic target in TGF-β1-related diseases.展开更多
Dear Editor,Chimeric antigen receptor-engineered(CAR)-T cell therapy has achieved unprecedented efficacy on refractory/relapsed B-cell malignancies[1].Yet,CAR-T recipients are highly susceptible to infection due to th...Dear Editor,Chimeric antigen receptor-engineered(CAR)-T cell therapy has achieved unprecedented efficacy on refractory/relapsed B-cell malignancies[1].Yet,CAR-T recipients are highly susceptible to infection due to the immunodeficiency caused by B-cell aplasia and the pretreatment with chemotherapy.However,due to the systematic use of empirical broad-spectrum antibiotics and immunosuppressors to control cytokine release syndrome(CRS)reaction,microbiological diagnosis of infection has remained challenging in CAR-T recipients.展开更多
Internal tandem duplication(ITD)mutations of FMS-like tyrosine kinase-3(FLT3)are the most frequent genetic alterations in acute myeloid leukemia(AML)and predict a poor prognosis.FLT3 tyrosine kinase inhibitors(TKIs)pr...Internal tandem duplication(ITD)mutations of FMS-like tyrosine kinase-3(FLT3)are the most frequent genetic alterations in acute myeloid leukemia(AML)and predict a poor prognosis.FLT3 tyrosine kinase inhibitors(TKIs)provide short-term clinical responses,but the long-term prognosis of FLT3/ITD^(+)AML patients remains poor.Notch signaling is important in numerous types of tumors.However,the role of Notch signaling in FLT3/ITD^(+)AML remains to be elucidated.In the current study,we found that Notch signaling was activated upon FLT3-TKI treatment in FLT3/ITD^(+)cell lines and primary cells.As Notch signaling can be blocked byγ-secretase inhibitors(GSIs),we examined the combinatorial antitumor efficacy of FLT3-TKIs and GSIs against FLT3/ITD^(+)AML and explored the underlying molecular mechanisms.As a result,we observed synergistic cytotoxic effects,and the treatment preferentially reduced cell proliferation and induced apoptosis in FLT3/ITD^(+)AML cell lines and in primary AML cells.Furthermore,the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in an FLT3/ITD^(+)patient-derived xenograft AML model.Mechanistically,differential expression analysis suggested that CXCR3 may be partially responsible for the observed synergy,possibly through ERK signaling.Our findings suggest that combined therapies of FLT3-TKIs with GSI may be exploited as a potential therapeutic strategy to treat FLT3/ITD^(+)AML.展开更多
Sterile neuroinflammation is a major driver of multiple neurological diseases.Myelin debris can act as an inflammatory stimulus to promote inflammation and pathologies,but the mechanism is poorly understood.Here,we sh...Sterile neuroinflammation is a major driver of multiple neurological diseases.Myelin debris can act as an inflammatory stimulus to promote inflammation and pathologies,but the mechanism is poorly understood.Here,we showed that lysophosphatidylserine(LysoPS)-GPR34 axis played a critical role in microglia-mediated myelin debris sensing and the subsequent neuroinflammation.Myelin debris-induced microglia activation and proinflammatory cytokine expression relied on its lipid component LysoPS.Both myelin debris and LysoPS promoted microglia activation and the production of proinflammatory cytokines via GPR34 and its downstream PI3K-AKT and ERK signaling.In vivo,reducing the content of LysoPS in myelin or inhibition of GPR34 with genetic or pharmacological approaches reduced neuroinflammation and pathologies in the mouse models of multiple sclerosis and stroke.Thus,our results identify GPR34 as a key receptor to sense demyelination and CNS damage and promote neuroinflammation,and suggest it as a potential therapeutic target for demyelination-associated diseases.展开更多
Epstein–Barr virus(EBV)-associated lymphoproliferative diseases(EBV-LPDs)are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation(HSCT).However,their...Epstein–Barr virus(EBV)-associated lymphoproliferative diseases(EBV-LPDs)are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation(HSCT).However,their occurrence and treatment post-chimeric antigen receptor-modified T(CAR-T)cell therapy has not been reported.Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment.After receiving CAR-T cell therapy in tandem with autologous HSCT,the patients achieved complete remission.However,with a median time of 38.5 months after CAR-T cell therapy,B-cell-derived EBV-LPDs were diagnosed,and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting agents.Collectively,our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy,especially in patients who previously had EBV-positive disorders,and they can be resolved by immune normalization strategy or B-cell depleting therapy.展开更多
基金supported by grants from the National High Technology Research and Development Program of China(No.2021YFA1101500)the National Natural Science Foundation of China(No.81873427 and No.82070217)the Research and Innovation Team Project for Scientific Breakthroughs at Shanxi Bethune Hospital(No.2024ZHANCHI12)。
文摘The clinical efficacy of immunotherapy in acute myeloid leukemia(AML)remains significantly limited by early relapse and treatment-associated toxicities.This review examines recent advances in antibody-and cell-based immunotherapies for AML,focusing on established targets(CD33,CD123,and CLL1)as well as emerging targets(including CD7,CD70,CD38,and FLT3).Therapeutic modalities discussed include immunoconjugates,bispecific T-cell engagers and chimeric antigen receptor T(CAR-T)cells.Furthermore,we summarize the current challenges impeding the success of immunotherapy in AML and propose strategies to enhance its efficacy.These include combination therapies,structural optimization of CAR constructs,functional enhancement of CAR-T cells,identification of novel targets,and the development of next-generation cellular therapies.Collectively,these approaches aim to offer new insights for improving immunotherapeutic outcomes in AML.
基金supported by funding from the National Natural Science Foundation of China(Grant No.82170167 to Xiaoxi Zhou and Grant No.82300226 to Hui Luo)。
文摘CD5-positive(CD5+)diffuse large B-cell lymphoma(DLBCL)represents a special subgroup of DLBCL with a more aggressive disease course and is more likely to develop into relapsed/refractory(r/r)DLBCL in response to immunochemotherapy.The incidence of CD5+DLBCL is 5%–10%among DLBCL patients1.
文摘Objective Chinese allergic subjects have high levels of sensitization to house dust mite （HDM） and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households. Methods Dust samples were collected from nine cities. Major allergens Der p 1 and Der f I from Dermatophagoides pteronyssinus and D. farinae, and specific antigens of Blomia tropicalis, Tyrophagus putrescentiae, Acarus siro, and cockroach species Blattella germanica and Periplaneta americana were measured by ELISA.Results HDM allergens were found in dust samples from bedding in 95% of the Chinese households. The median levels varied from 〈0.006 to 9.2 μg/g of dust, depending on the city. The percentages of households having HDM allergen levels associated with the risk of developing allergy sensitization and asthma were 65% and 25%, respectively. Specific antigens of the storage mite and cockroach were only found in samples from the southern and tropical regions of China. Levels of mite allergens were generally higher in samples from bedding compared to samples from the living room, even for storage mites, whereas levels of cockroach antigens were higher in the living room samples.Conclusion HDM allergens are present in bedding dust samples from most Chinese households. Cities in southern and central China have relatively high levels of HDM major allergens compared to cities in northern and western China. Antigens of storage mites and cockroaches are not as common as HDM allergens.
基金the National Natural Science Foundation of China
文摘OBJECTIVE CD4^＋CD25^＋ T regulatory （Treg） cells are a population of T cells which suppress an overactive immune system. CCR4 is a chemokine receptor involved in the recruitment of lymphocytes. Nasopharyngeal carcinoma （NPC） is resistant to immunosurveillance, owing to the increased number of tumor-infiltrating Treg cells which are recruited to the tumor bv CCR4.
文摘AIM To characterize the understanding of hepatitis B virus(HBV)and determine if outreach improves HBV understanding among Greater Boston Area immigrants.METHODS Six outreach sessions were held in various community venues in the Greater Boston Area.Verbal consent was obtained from participants prior to starting each session.Each session included a pre-session questionnaire,followed by a teaching session,and then a post-session questionnaire.In person interpreters were present for translation during the teaching session and assistance for questionnaire completion when needed.The questions were developed based on the HBV clinical experience of physicians who serve largely immigrant populations.Questionnaires included Likerttype scale,open-ended,and true-false questions.All results were anonymous.RESULTS One hundred and one people participated in this study.Participants were 30%male with ages ranging from 19 to 87 years.The study population included immigrants from 21 countries,as well as seven United States-born participants.The greatest numbers of participants were from Somalia(44%),Morocco(10%),and Cameroon(8%).Pre session questionnaires revealed that 42%of participants were unaware that HBV can cause cancer,and 50%were unaware that therapies for HBV exist.Our brief teaching intervention led to improved scores on post session questionnaires.For example,at baseline,58%of participants responded correctly to the question"HBV infection can cause scarring of the liver and liver cancer",whereas 79%of participants responded correctly after the teaching session(P=0.01).Furthermore,the mean of total correct answers in the true or false portion of the questionnaire increased from 5.5 to 7.6(P<0.001).CONCLUSION A teaching session targeting Boston Immigrants atrisk for HBV helped improve scores on HBV knowledge questionnaires.Outreach may empower at-risk patients to pro-actively seek HBV care.
基金supported by the National Key Research and Development Program of China(grant number(2020YFA0509101))the National Natural Science Foundation of China(grant numbers 82130107,82330052,and 82202038)+4 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0940000),the CAS Project for Young Scientists in Basic Research(YSBR-074)the Fundamental Research Funds for the Central Universities,the outstanding Youth Project of Anhui Provincial Natural Science Foundation(2408085Y049)the Research Start-up Funding of the Institute of Health and Medicine,Hefei Comprehensive National Science Center(2024KYQD004)the Natural Science Foundation of Jiangsu Province(BK20221085)the key project of Anhui Provincial Department of Education Fund(2024AH052060).
文摘Neuroinflammation plays an important role in the pathogenesis of various central nervous system(CNS)diseases.The NLRP3 inflammasome is an important intracellular multiprotein complex composed of the innate immune receptor NLRP3,the adaptor protein ASC,and the protease caspase-1.The activation of the NLRP3 inflammasome can induce pyroptosis and the release of the proinflammatory cytokines IL-1βand IL-18,thus playing a central role in immune and inflammatory responses.Recent studies have revealed that the NLRP3 inflammasome is activated in the brain to induce neuroinflammation,leading to further neuronal damage and functional impairment,and contributes to the pathological process of various neurological diseases,such as multiple sclerosis,Parkinson’s disease,Alzheimer’s disease,and stroke.In this review,we summarize the important role of the NLRP3 inflammasome in the pathogenesis of neuroinflammation and the pathological course of CNS diseases and discuss potential approaches to target the NLRP3 inflammasome for the treatment of CNS diseases.
基金supported by grants from the National High Technology Research and Development Program of China(Grant 2021YFA1101500)the National Natural Science Foundation of China(Nos.82070217,82100401,81873427,82330010,81630010,82473220,81790624,81772477,81201848)+8 种基金the Hubei Provincial Natural Science Foundation(No.2024AFB050)the Fundamental Research Program of Shanxi Province(No.202303021221192)2023 COVID-19 Emergency Project of Shanxi Health Commission(Nos.2023XG001,2023XG005)the Project of Shanxi Bethune Hospital(No.2023xg02)Fundamental Research Program of Shanxi Province(No.202303021211224)the Key Scientific Research Project of COVID-19 Infection Emergency Treatment of Shanxi Bethune Hospital(No.2023xg01)the Four“Batches”Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province(2023XM003)the Cancer special Fund research project of Shanxi Bethune Hospital(No.2020-ZL04)External Expert Workshop Fund Program of Shanxi Provincial Health Commission(Proteomics Shanxi studio for Huanghe professor).
文摘Cytokine storm(CS)is a severe systemic inflammatory syndrome characterized by the excessive activation of immune cells and a significant increase in circulating levels of cytokines.This pathological process is implicated in the development of life-threatening conditions such as fulminant myocarditis(FM),acute respiratory distress syndrome(ARDS),primary or secondary hemophagocytic lymphohistiocytosis(HLH),cytokine release syndrome(CRS)associated with chimeric antigen receptor-modified T(CAR-T)therapy,and grade Ⅲ to Ⅳ acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.The significant involvement of the JAK-STAT pathway,Toll-like receptors,neutrophil extracellular traps,NLRP3 inflammasome,and other signaling pathways has been recognized in the pathogenesis of CS.Therapies targeting these pathways have been developed or are currently being investigated.While novel drugs have demonstrated promising therapeutic efficacy in mitigating CS,the overall mortality rate of CS resulting from underlying diseases remains high.In the clinical setting,the management of CS typically necessitates a multidisciplinary team strategy encompassing the removal of abnormal inflammatory or immune system activation,the preservation of vital organ function,the treatment of the underlying disease,and the provision of life supportive therapy.This review provides a comprehensive overview of the key signaling pathways and associated cytokines implicated in CS,elucidates the impact of dysregulated immune cell activation,and delineates the resultant organ injury associated with CS.In addition,we offer insights and current literature on the management of CS in cases of FM,ARDS,systemic inflammatory response syndrome,treatment-induced CRS,HLH,and other related conditions.
基金supported by the National Natural Science Foun-dation of China(grant number 32222006 to P.H.)。
文摘Coronaviruses(CoVs)pose a continual threat to global public health due to their broad host range and potential for cross-species transmission.Notable examples include the severe acute respiratory syndrome coronavirus(SARS-CoV)in 2002 andMiddle East respiratory syndrome coronavirus(MERS-CoV)in 2012,each causing worldwide health emergencies.Despite vaccine and antiviral development targeting theseCoVs,newCoVs regularly emerge in animals,often without attracting significant attention.
基金supported by the National Key Research and Development Program of China(grant number 2020YFA0509101)the National Natural Science Foundation of China(grant numbers 81821001,82130107,U20A20359)the CAS Project for Young Scientists in Basic Research(YSBR-074)。
文摘Microglia dysfunction-associated neuroinflammation is an important driver of Alzheimer’s disease(AD),but the mechanism is poorly understood.Here,we show that demyelination promotes neuroinflammation and cognitive impairment via the lysophosphatidylserine(LysoPS)-GPR34 axis in AD.Demyelination is observed at the early stage and is accompanied by an increase in LysoPS in myelin debris in a 5xFAD mouse model of AD.Reducing the content of LysoPS in myelin or inhibiting its receptor GPR34 via genetic or pharmacological approaches can reduce microglial dysfunction and neuroinflammation and improve microglial Aβphagocytosis,subsequently resulting in less Aβdeposition and memory restoration in 5xFAD mice.Furthermore,increased LysoPS production and microglial GPR34 expression were also observed in the brains of AD patients.These results reveal the pathogenic role of demyelination-derived LysoPS in microglial dysfunction and AD pathology and suggest that blocking GPR34 as a therapeutic strategy beyond targeting Aβ.
基金supported by the National Key Research and Development Program of China(2024YFA0916400)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0480000)+5 种基金the National Natural Science Foundation of China(32025010,32488301,92254301,92357302,92157202,32241002,32261160376,32322022,and 32471358)Major Project of Guangzhou National Laboratory(GZNL2024A03006 and GZNL2024B01003)the Key Research Program,CAS(ZDBS-ZRKJZ-TLC003,YSBR-075 and 188GJHZ2024048GC)Guangdong Province Science and Technology Program(2023B0303000023,2023B1111050005,2023B1212060050,2023B1212120009,2024B1515040020,and 2024A1515010782)Guangzhou Science and Technology Program(202206060002 and 2025A04J7110)Health@InnoHK funding support from the Innovation Technology Commission of the Hong Kong SAR,and Major Research Project(GIBHMRP25-01)Basic Research Project of Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences.
文摘Pluripotent stem cells(PSCs)possess the ability to proliferate indefinitely,self-renew,and differentiate into three germ layers.These pluripotent characteristics allow PSCs to be used to treat many incurable diseases,such as spinal cord injury with the embryonic stem cells(ESCs)-derived oligodendrocyte progenitor cells,and dry age-related macular degeneration(AMD)with the ESCs-derived retinal pigment epithelium,and have great application value in clinical regenerative medicine.
基金funded by National Research Foundation of Korea(2020R1A5A2031185,2020M3A9G3080281,2022R1A2C2009385,2020M3A9G3080330,and 2022R1A6A3A01086438).
文摘Basal signal transducer and activator of transcription 3(STAT3)activation is well-documented in the tumor microenvironment(TME)due to its association with cancer prognosis[1].However,its presence and clinical relevance in the bloodstream remain unexplored.Given that STAT3-inducing cytokines,such as interleukin-6(IL-6),are often elevated in the bloodstream of various cancer patients[2,3],we aimed to investigate basal STAT3 activation in blood by developing a methodology to assess ex vivo phosphorylation of STAT3(pSTAT3ex vivo)in circulating immune cells.
文摘Tcells are an important component of adaptive immunity and protect the host from infectious diseases and cancers.However,uncontrolled T cell immunity may cause autoimmune disorders.In both situations,antigen-specific T cells undergo clonal expansion upon the engagement and activation of antigens.Cellular metabolism is reprogrammed to meet the increase in bioenergetic and biosynthetic demands associated with effector T cell expansion.Metabolites not only serve as building blocks or energy sources to fuel cell growth and expansion but also regulate a broad spectrum of cellular signals that instruct the differentiation of multiple T cell subsets.The realm of immunometabolism research is undergoing swift advancements.Encapsulating all the recent progress within this concise review in not possible.Instead,our objective is to provide a succinct introduction to this swiftly progressing research,concentrating on the metabolic intricacies of three pivotal nutrient classes—lipids,glucose,and amino acids—in T cells.We shed light on recent investigations elucidating the roles of these three groups of metabolites in mediating the metabolic and immune functions of T cells.Moreover,we delve into the prospect of“editing”metabolic pathways within T cells using pharmacological or genetic approaches,with the aim of synergizing this approach with existing immunotherapies and enhancing the efficacy of antitumor and antiinfection immune responses.
基金The project was partly supported by a grant from Natural Science Foundation of Hainan Province, China （No. 808206）.
文摘Background Haikou locates in tropical island with unique mite allergens levels in Haikou, and to investigate the prevalence of between house dust mites. propagation. The aim of this stuy is to determine mite mite specific IgE-sensitization and IgE cross-reactivity Methods Allergen and antigen concentrations against six mite species were tested by enzyme-linked immunosorbent assay （ELISA）. Specific IgE concentrations and cross-inhibitions were measured with ADVIA Centaur . Results Allergen or antigen Dermatophagoides pteronyssinus （Der p 1 ）, Blomia tropicalis （BIot ） and Tyrophagus putrescentia （Tyr p） were detected in dust samples. Dermatophagoides farinae （Der f 1 ）, Lepidoglyphus destructor （Lep d 2）, and Acarus siro （Aca s ） were found in very few samples. Specific IgE tests showed high prevalence of sensitizations against all tested mites with high IgE levels to Der p, Der f, and BIot. Storage mites, BIo t, Tyr p, Lep d, and Aca s, could inhibit Der p from 0 to 50%. Storage mites could inhibit Der f between 30% and 100%. Der p IgE could be inhibited by Der f with up to 90%, and vice versa. Der p could inhibit BIot from 40% to 80%. BIot was able to fully inhibit IgE binding to Lep d, Tyr p, and Aca s compared to partial inhibition by Der p. Conclusions Der p is the dominating mite and has the highest specific IgE prevalence among asthmatic children. BIot represents an important source of storage mite sensitization and some patients may be independently sensitized to both Der p and BIot. High prevalence of sensitization to Der f may be due to IgE-mediated cross-reactivity with Der p and BIo t.
基金We are grateful to the faculty and staff of the Clinical and Laboratory Unit of the Department of Hematology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,for clinical and technical support.Wuhan BioRaid Biotechnology CO.,LTD.is acknowledged for cell manufacturing and qualitycontrol.Dr.Pengcheng Wang of Hubei Clinical Research Center for Emergency and Resuscitation,Zhongnan Hospital of Wuhan University,is appreciated for kind assistance in statistical analysis.The current project was funded by the Key Program of the National Natural Science Foundation of China(81830008 and 81630006,to Dr.J.Z.)the National Natural Science Foundation of China(82070211 and 81670152,to Dr.L.H.,82070217 and 81873427,to Dr.J.W.,81770211 to Dr.M.X.)the Young Topnotch Talent Cultivation Program of Hubei Province(to Dr.L.H.)and CHEN XIAO-PING Foundation for the Development of Science and Technology of Hubei Province(CXPJJH12000009-113,to Dr.J.W.).
文摘TP53 gene alteration confers inferior prognosis in refractory/relapse aggressive B-cell non-Hodgkin lymphoma(r/r B-NHL).From September 2016 to September 2020,257 r/r B-NHL patients were assessed for eligibility for two trials in our center,assessing anti-CD19 and anti-CD22 chimeric antigen receptor(CAR19/22)T-cell cocktail treatment alone or in combination with autologous stem cell transplantation(ASCT).TP53 alterations were screened in 123 enrolled patients and confirmed in 60.CAR19/22 T-cell administration resulted in best objective(ORR)and complete(CRR)response rate of 87.1%and 45.2%in patients with TP53 alterations.
文摘Gene engineering and combinatorial approaches with other cancer immunotherapy agents may confer capabilities enabling full tumor rejection by adoptive T cell therapy(ACT).The provision of proper costimulatory receptor activity and cytokine stimuli,along with the repression of inhibitory mechanisms,will conceivably make the most of these treatment strategies.In this sense,T cells can be genetically manipulated to become refractory to suppressive mechanisms and exhaustion,last longer and differentiate into memory T cells while endowed with the ability to traffic to malignant tissues.Their antitumor effects can be dramatically augmented with permanent or transient gene transfer maneuvers to express or delete/repress genes.A combination of such interventions seeks the creation of the ultimate bionic T cell,perfected to seek and destroy cancer cells upon systemic or local intratumor delivery.
基金Bio&Medical Technology Development Program of the National Research Foundation,Grant/Award Numbers:NRF-2020M3A9G3080281,NRF-2020R1A5A2031185Korean Government。
文摘Background:Increased Galectin 3-binding protein(LGALS3BP)serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma(HCC).Considering the crucial role of transforming growth factor-β1(TGF-β1)in the emergence of these diseases,the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling pathway.Methods:The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis(MASH)and HCC.Multiple omics techniques,such as RNA-sequencing,transposaseaccessible chromatin-sequencing assay,and liquid chromatography-tandem mass spectrometry proteomics,were used to identify the regulatory mechanisms for the LGALS3BP-TGF-β1 axis.The effects of altered TGF-β1 signaling by LGALS3BP were investigated in conditional LGALS3BP-knockin and LGALS3BP-knockout mice.Results:In patients with MASH and HCC,the levels of LGALS3BP and TGFB1 exhibited positive correlations.Stimulation of LGALS3BP by the inflammatory cytokine interferonαin HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of TGFB1.Aggravated fibrosis was observed in the livers of hepatocyte-specific LGALS3BP-knockin mice,with increased TGFB1 levels.LGALS3BP directly bound to and assembled integrinαV,an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin cytoskeleton.The released TGF-β1 activated JunB transcription factor,which in turn promoted the TGF-β1 positive feedback loop.LGALS3BP deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced fibrosis.Moreover,LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β1.Conclusion:LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway,making it a promising therapeutic target in TGF-β1-related diseases.
基金This work was supported by fundings from the National Natural Science Foundation of China(82070217 and 81873427,toDr.JiaWei,81770211,toDr.Min Xiao,81670152,to Dr.Liang Huang,and 81700145 to Dr.Li Yang)fundings from the Key Program of the National Natural Science Foundation of China(81830008 and 81630006,to Dr.Jianfeng Zhou)funding from CHEN XIAO-PING Foundation for the Development of Science and Technology of Hubei Province(CXPJJH12000009-113,to Dr.JiaWei).
文摘Dear Editor,Chimeric antigen receptor-engineered(CAR)-T cell therapy has achieved unprecedented efficacy on refractory/relapsed B-cell malignancies[1].Yet,CAR-T recipients are highly susceptible to infection due to the immunodeficiency caused by B-cell aplasia and the pretreatment with chemotherapy.However,due to the systematic use of empirical broad-spectrum antibiotics and immunosuppressors to control cytokine release syndrome(CRS)reaction,microbiological diagnosis of infection has remained challenging in CAR-T recipients.
基金supported by the National Natural Science Foundation of China(8170010813 to Z.S.,81830008 to J.Z.,81600125 to J.W.,81800160 to T.L.,and 81400122 to K.Z.)the Natural Science Foundation of Hubei Province(2016CFA011 and 2018ACA140).
文摘Internal tandem duplication(ITD)mutations of FMS-like tyrosine kinase-3(FLT3)are the most frequent genetic alterations in acute myeloid leukemia(AML)and predict a poor prognosis.FLT3 tyrosine kinase inhibitors(TKIs)provide short-term clinical responses,but the long-term prognosis of FLT3/ITD^(+)AML patients remains poor.Notch signaling is important in numerous types of tumors.However,the role of Notch signaling in FLT3/ITD^(+)AML remains to be elucidated.In the current study,we found that Notch signaling was activated upon FLT3-TKI treatment in FLT3/ITD^(+)cell lines and primary cells.As Notch signaling can be blocked byγ-secretase inhibitors(GSIs),we examined the combinatorial antitumor efficacy of FLT3-TKIs and GSIs against FLT3/ITD^(+)AML and explored the underlying molecular mechanisms.As a result,we observed synergistic cytotoxic effects,and the treatment preferentially reduced cell proliferation and induced apoptosis in FLT3/ITD^(+)AML cell lines and in primary AML cells.Furthermore,the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in an FLT3/ITD^(+)patient-derived xenograft AML model.Mechanistically,differential expression analysis suggested that CXCR3 may be partially responsible for the observed synergy,possibly through ERK signaling.Our findings suggest that combined therapies of FLT3-TKIs with GSI may be exploited as a potential therapeutic strategy to treat FLT3/ITD^(+)AML.
基金supported by the National Key Research and Development Program of China(grant number 2020YFA0509101)the National Natural Science Foundation of China(grant numbers 81821001,82130107,U20A20359)the CAS Project for Young Scientists in Basic Research(YSBR-074).
文摘Sterile neuroinflammation is a major driver of multiple neurological diseases.Myelin debris can act as an inflammatory stimulus to promote inflammation and pathologies,but the mechanism is poorly understood.Here,we showed that lysophosphatidylserine(LysoPS)-GPR34 axis played a critical role in microglia-mediated myelin debris sensing and the subsequent neuroinflammation.Myelin debris-induced microglia activation and proinflammatory cytokine expression relied on its lipid component LysoPS.Both myelin debris and LysoPS promoted microglia activation and the production of proinflammatory cytokines via GPR34 and its downstream PI3K-AKT and ERK signaling.In vivo,reducing the content of LysoPS in myelin or inhibition of GPR34 with genetic or pharmacological approaches reduced neuroinflammation and pathologies in the mouse models of multiple sclerosis and stroke.Thus,our results identify GPR34 as a key receptor to sense demyelination and CNS damage and promote neuroinflammation,and suggest it as a potential therapeutic target for demyelination-associated diseases.
基金supported by the funding from the National Natural Science Foundation of China(No.82070211 to Dr.Liang Huang)the National Key R&D Program of China(No.2022YFC2502604 to Dr.Liang Huang).
文摘Epstein–Barr virus(EBV)-associated lymphoproliferative diseases(EBV-LPDs)are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation(HSCT).However,their occurrence and treatment post-chimeric antigen receptor-modified T(CAR-T)cell therapy has not been reported.Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment.After receiving CAR-T cell therapy in tandem with autologous HSCT,the patients achieved complete remission.However,with a median time of 38.5 months after CAR-T cell therapy,B-cell-derived EBV-LPDs were diagnosed,and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting agents.Collectively,our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy,especially in patients who previously had EBV-positive disorders,and they can be resolved by immune normalization strategy or B-cell depleting therapy.
