Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have describe...Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have described the mechanisms underlying the pathogenesis of NTG.In addition to controlling intraocular pressure,neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG.In this review,we summarized the main regulatory mechanisms of RGC death in NTG,including autophagy,glutamate neurotoxicity,oxidative stress,neuroinflammation,immunity,and vasoconstriction.Autophagy can be induced by retinal hypoxia and axonal damage.In this process,ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway.Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate,which occurs in RGCs and induces progressive glaucomatous optic neuropathy.Oxidative stress also participates in NTG-related glaucomatous optic neuropathy.It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinase-JUN N-terminal kinase pathway.Moreover,it increases inflammation and the immune response of RGCs.Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow,promoting vasospasm and glaucomatous optic neuropathy,as a result of NTG.In conclusion,we discussed research progress on potential options for the protection of RGCs,including TANK binding kinase 1 inhibitors regulating autophagy,N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity,ASK1 inhibitors regulating mitochondrial function,and antioxidants inhibiting oxidative stress.In NTG,RGC death is regulated by a network of mechanisms,while various potential targets protect RGCs.Collectively,these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.展开更多
Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-c...Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.展开更多
Objective: This study aims to evaluate the natural history of patients with chronic lymphocytic leukemia (CLL) and a 17p deletion (17p-) and identify the predictive factors within this subgroup. Methods: The sam...Objective: This study aims to evaluate the natural history of patients with chronic lymphocytic leukemia (CLL) and a 17p deletion (17p-) and identify the predictive factors within this subgroup. Methods: The sample of patients with CLL were analyzed by fluorescence in situ hybridization for deletions in chromosome bands 1 lq22, 13q14 and 17p13; trisomy of bands 12q13; and translocation involving band 14q32. The data from 456 patients with or without a 17p- were retrospectively collected and analyzed. Results: The overall response rate (ORR) in patients with a 17p- was 56.9%, and patients with a high percentage of 17p- (defined as more than 25% of cells harbouring a 17p-) had a lower ORR. The median overall survival (OS) in patients with a 17p- was 78.0 months, which was significantly shorter than the OS in patients without this genetic abnormality (median 162.0 months, P〈0.001). Within the subgroup with a 17p-, the progression-free survival was significantly shorter in patients at Binet stage B-C and patients with elevated lactate dehydrogenase (LDH), B symptoms, unmutated IGHVand a high percentage of 17p-. Conclusions: These results indicated that patients with a 17p- CLL have a variable prognosis that might be predicted using simple clinical and laboratory characteristics.展开更多
Objective:Epithelial cancers often originate from progenitor cells,while the origin of hepatocellular carcinoma(HCC)is still controversial.HCC,one of the deadliest cancers,is closely linked with liver injuries and chr...Objective:Epithelial cancers often originate from progenitor cells,while the origin of hepatocellular carcinoma(HCC)is still controversial.HCC,one of the deadliest cancers,is closely linked with liver injuries and chronic inflammation,which trigger massive infiltration of bone marrow-derived cells(BMDCs)during liver repair.Methods:To address the possible roles of BMDCs in HCC origination,we established a diethylnitrosamine(DEN)-induced HCC model in bone marrow transplanted mice.Immunohistochemistry and frozen tissue immunofluorescence were used to verify DENinduced HCC in the pathology of the disease.The cellular origin of DEN-induced HCC was further studied by single cell sequencing,single-cell nested PCR,and immunofluorescence-fluorescence in situ hybridization.Results:Studies by using single cell sequencing and biochemical analysis revealed that HCC cells in these mice were coming from donor mice BMDCs,and not from recipient mice.Furthermore,the copy numbers of mouse orthologs of several HCC-related genes previously reported in human HCC were also altered in our mouse model.DEN-induced HCCs exhibited a similar histological phenotype and genomic profile as human HCCs.Conclusions:These results suggested that BMDCs are an important origin of HCC,which provide important clues to HCC prevention,detection,and treatments.展开更多
A comprehensive understanding of the cellular heterogeneity and molecular mechanisms underlying the development,homeostasis,and disease of human intervertebral disks(IVDs)remains challenging.Here,the transcriptomic la...A comprehensive understanding of the cellular heterogeneity and molecular mechanisms underlying the development,homeostasis,and disease of human intervertebral disks(IVDs)remains challenging.Here,the transcriptomic landscape of 108108 IVD cells was mapped using single-cell RNA sequencing of three main compartments from young and adult healthy IVDs,including the nucleus pulposus(NP),annulus fibrosus,and cartilage endplate(CEP).The chondrocyte subclusters were classified based on their potential regulatory,homeostatic,and effector functions in extracellular matrix(ECM)homeostasis.Notably,in the NP,a PROCR+resident progenitor population showed enriched colony-forming unit-fibroblast(CFU-F)activity and trilineage differentiation capacity.Finally,intercellular crosstalk based on signaling network analysis uncovered that the PDGF and TGF-βcascades are important cues in the NP microenvironment.In conclusion,a single-cell transcriptomic atlas that resolves spatially regulated cellular heterogeneity together with the critical signaling that underlies homeostasis will help to establish new therapeutic strategies for IVD degeneration in the clinic.展开更多
Neutrophils play an essential role in the defense against bacterial infections and orchestrate both the innate and adaptive immune responses.With their abundant numbers,diverse function and short life span,these cells...Neutrophils play an essential role in the defense against bacterial infections and orchestrate both the innate and adaptive immune responses.With their abundant numbers,diverse function and short life span,these cells are at the forefront of immune responses,and have gained attention in recent years because of their presence in tumor sites.Neutrophil involvement pertains to tumor cells'ability to construct a suitable tumor microenvironment(TME)that accelerates their own growth and malignancy,by facilitating their interaction with surrounding cells through the circulatory and lymphatic systems,thereby influencing tumor development and progression.Studies have indicated both pro-and anti-tumor properties of infiltrating neutrophils.The TME can exploit neutrophil function,recruitment,and even production,thus resulting in pro-tumor properties of neutrophils,including promotion of genetic instability,tumor cell proliferation,angiogenesis and suppression of anti-tumor or inflammatory response.In contrast,neutrophils can mediate anti-tumor resistance by direct cytotoxicity to the tumor cells or by facilitating anti-tumor functions via crosstalk with T cells.Here,we summarize current knowledge regarding the effects of neutrophil heterogeneity under homeostatic and tumor conditions,including neutrophil phenotype and function,in cancer biology.展开更多
Objective: More than half of human glioblastomas show EGFR gene amplification and mutation, but EGFR inhibitors have not been effective in treating EGFR-positive glioblastoma patients.The mechanism behind this type of...Objective: More than half of human glioblastomas show EGFR gene amplification and mutation, but EGFR inhibitors have not been effective in treating EGFR-positive glioblastoma patients.The mechanism behind this type of primary resistance is not well understood.The aim of this study was to investigate gefitinib resistance in glioblastoma, and explore ways to circumvent this significant clinical problem.Methods: MTT method was used to test the cell viability after EGFR-positive glioblastoma cells were treated with indicated drugs;real-time quantitative PCR method was included to detect the TNFα mRNA levels in glioma tissues and cell lines.ELISA was introduced to measure the TNFα protein levels in cell culture supernatant of glioblastoma cells treated with gefitinib.Western blot was used to detect the activity change of intracellular kinases in drug-treated glioblastoma cells.Two mouse xenograft tumor models were carried out to evaluate the in vivo effects of a combination of EGFR and TNFα inhibitors.Results: We found that glioblastoma resistance to gefitinib may be mediated by an adaptive pro-survival TNFα-JNK-Axl signaling axis, and that high TNFα levels in the glioblastoma microenvironment may further intensify primary resistance.A combination of the TNFα-specific small-molecule inhibitor C87 and gefitinib significantly enhanced the sensitivity of glioblastoma cells to gefitinib in vitro and in vivo.Conclusions: Our findings provide a possible explanation for the primary resistance of glioblastoma to EGFR inhibitors and suggest that dual blockade of TNFα and EGFR may be a viable therapeutic strategy for the treatment of patients with chemotherapy-refractory advanced glioblastoma.展开更多
Relapse and metastasis are frequent in colon cancer and may be linked to stem cell characteristics.This study isolated side population(SP) cells from a colon cancer cell line(Colo-320) and examined their self-rene...Relapse and metastasis are frequent in colon cancer and may be linked to stem cell characteristics.This study isolated side population(SP) cells from a colon cancer cell line(Colo-320) and examined their self-renewal and differentiation abilities.Compared to non-SP(NSP) cells,SP colon cancer cells were more tumorigenic in vivo and exhibited more invasive characteristics and a greater ability to form colonies.Additionally,more cells were in G0/G1 phase and more highly expressed the multidrug resistance protein BCRP/ABCG2.We achieved enhanced chemotherapy sensitivity by transfecting SP cells with a hairpin-like,small interfering RNA(si RNA) eukaryotic expression plasmid targeting BCRP/ABCG2.展开更多
Objective: To explore the effects of nuclear M-CSF on the process of tumorigenesis. Methods: Functional part of M-CSF cDNA was inserted into an eukaryotic expression plasmid pCMV/myc/nuc, which can add three NLS to t...Objective: To explore the effects of nuclear M-CSF on the process of tumorigenesis. Methods: Functional part of M-CSF cDNA was inserted into an eukaryotic expression plasmid pCMV/myc/nuc, which can add three NLS to the C-terminal of the expressed protein and direct the protein into the cell nuclei. The constructed plasmid was transferred into NIH3T3 cells and the cell clones were selected by G-418 selection. Cell clones stable expressing target protein were identified by RT-PCR, ABC immunohistochemistry assayand Western blot. Cell growth kinetics analyses throughgrowth curves, cell doubling time, MTT test and anti-sense oligodeoxynucleotide (ASODN) inhibiting cell growth testwere performed to identify cells proliferation potential.Results: The transfected cells showed elevated proliferation potential over the control cells. Conclusion: Abnormalappearance of M-CSF in nucleus could enhance cellproliferation, which suggests that cytokine isoforms within cell nucleus might play transcription factor-like role.展开更多
Legumain is a C13 family cysteine protease.It plays diverse roles under both physiological and pathological conditions.The high-level expression of legumain is detected in solid tumors.Legumain promotes the proliferat...Legumain is a C13 family cysteine protease.It plays diverse roles under both physiological and pathological conditions.The high-level expression of legumain is detected in solid tumors.Legumain promotes the proliferation and migration of tumor cells.However,the effect of legumain in blood diseases has not been established.In this report,we studied the effect of legumain on leukemia cells by overexpressing it in THP1 cells.The results demonstrated that legumain promoted cell proliferation,whereas it had little effect on cell apoptosis.Furthermore,legumain promoted the migration of THP1 cells.It was worth noting that legumain decreased the stemness of THP1 cells.Further evidence showed that legumain decreased the expression of Oct4,Sox2,Myc in THP1 cells.Our study reveals the multifaced effects of legumain in leukemia cells and broadens the knowledge of legumain in malignancies.展开更多
Acute lymphoblastic leukemia(ALL)is a common pediatric cancer.The second malignant neoplasms(SMNs)in long-term survivors of pediatric ALL are relatively rare.Herein we report a 10-year-old girl who was diagnosed as pr...Acute lymphoblastic leukemia(ALL)is a common pediatric cancer.The second malignant neoplasms(SMNs)in long-term survivors of pediatric ALL are relatively rare.Herein we report a 10-year-old girl who was diagnosed as primitive neuroectodermal tumor(PNET)5 years after the initial diagnosis of ALL with radiotherapy・free treatment.PNET is an exceedingly rare neoplasm in SMNs of survivors of childhood ALL.It is predisposed to be misdiagnosed and the pathogenesis is unclear.The outcome is poor.Long-term follow-up is necessary for the survival children of ALL.展开更多
BACKGROUND Myeloid neoplasm(MN)with eosinophilia and rearrangement of platelet-derived growth factor receptor beta(PDGFRB)shows a good therapeutic response to imatinib in adults.MN is rarely found in children,and the ...BACKGROUND Myeloid neoplasm(MN)with eosinophilia and rearrangement of platelet-derived growth factor receptor beta(PDGFRB)shows a good therapeutic response to imatinib in adults.MN is rarely found in children,and the efficacy of imatinib on pediatric patients remain unclear.CASE SUMMARY We report 2 pediatric cases diagnosed with MN with eosinophilia and PDGFRB rearrangement who were treated with imatinib.Case 1 was a 1-year-old girl admitted to the hospital because of“abdominal distension with hyperleukocytosis for 3 mo”.She had leukocytosis,anemia,and eosinophilia(the absolute eosinophil count(AEC)was 8960/μL),and her fluorescence in situ hybridization(FISH)test revealed that PDGFRB rearrangement was detected in 70%of 500 interphase cells.Case 2 was a 2-year-old girl admitted to the hospital because of“recurrent fever and rashes for 1 mo”.Her blood cell count showed an AEC of 3540/μL.The FISH test revealed that PDGFRB rearrangement was detected in 71%of 500 interphase cells.Both patients were diagnosed as MN with eosinophilia and PDGFRB rearrangement.Imatinib was added into their treatment regimen.As expected,complete hematologic remission was achieved after 1 mo of treatment,and symptoms disappeared.CONCLUSION Although MN with eosinophilia and PDGFRB rearrangement usually occurs in adults,it can be found in children.The therapeutic benefits of imatinib in these 2 pediatric patients were consistent with its reported effects in adult patients.展开更多
Great progresses have been made in fundamental and clinical stem cell research in China in recent years. The official policy on stem cells, which was announced in 2015, seems as the spring of stem cell therapy in Chin...Great progresses have been made in fundamental and clinical stem cell research in China in recent years. The official policy on stem cells, which was announced in 2015, seems as the spring of stem cell therapy in China. However, the regulation, governance, and management of clinical expectations are still challenging. This review summarized the current stem cell research and development in the field, as well as its rapidly evolving commercial, regulatory and ethical environment in China. As expected, the prospects of stem cells in China look prospective.展开更多
Objective:To express the soluble recombinant hemangiopoietin protein in E.coli BL21(DE3).Methods:Using human fetal live cDNA as a template,a partial cDNA fragment of HAPO coding N-terminal region was subcloned into pl...Objective:To express the soluble recombinant hemangiopoietin protein in E.coli BL21(DE3).Methods:Using human fetal live cDNA as a template,a partial cDNA fragment of HAPO coding N-terminal region was subcloned into plasmids pTrc99,pQE60 and pET32c to construct different recombinant prokaryotic expression systems.After selecting,the soluble rhHAPO fusion protein was expressed stably in E.coli BL21(DE3) by vector pET32c-HAPO and further isolated by nickelnitrilotriacetic acid(NTA) affinity chromatography.After cleavage with enterokinase,the rhHAPO protein was applied to Fast Flow SP sepharose column.Results:The rhHAPO protein had a purity of more than 95% and a good bioactivity based on the cell adhesion assay in ECV304 cells.Conclusion:We have established a protein engineering system to produce rhHAPO which may provide the possibility for clinical application.展开更多
Objective:Cytogenetic abnormalities have been proven to be the most valuable parameter for risk stratification of childhood acute lymphoblastic leukemia(ALL).However,studies on the prevalence of cytogenetic abnormalit...Objective:Cytogenetic abnormalities have been proven to be the most valuable parameter for risk stratification of childhood acute lymphoblastic leukemia(ALL).However,studies on the prevalence of cytogenetic abnormalities and their correlation to clinical features in Chinese pediatric patients are limited,especially large-scale studies.Methods:We collected the cytogenetics and clinical data of 1541 children newly diagnosed with ALL between 2001 and 2014 in four Chinese hospitals,and retrospectively analyzed their clinical features,prognosis and risk factors associated with pediatric ALL.展开更多
Objective:Trained immunity of natural killer(NK)cells has shown great potential in the treatment of cancers by eliciting enhanced effector responses to restimulation by cytokines or cancer cells for long time periods ...Objective:Trained immunity of natural killer(NK)cells has shown great potential in the treatment of cancers by eliciting enhanced effector responses to restimulation by cytokines or cancer cells for long time periods after preactivation.However,the human NK cells responsible for the generation and maintenance of trained immunity are largely unknown.We hypothesized that heterogeneous human NK cells would respond differentially to stimulation with a combination of IL-12,IL-15,and IL-18,and that an NK cell subset might exist that is mainly responsible for the induction of trained immunity.On the basis of our hypothesis,we aimed to identify the subset from which cytokine-trained human NK cells originate and to explore possible regulatory targets for drug intervention.Methods:Flow cytometry assays were performed to analyze the functions of cytokine-trained NK cells and examine cell division and protein expression in NK cell subsets.Single-cell RNA sequencing(scRNA-seq)plus TotalSeq™technology was used to track the heterogeneity of NK cells during the induction of trained immunity.Results:Traditional developmental markers for peripheral NK cells were unable to identify the precursors of human NK cells with trained immunity.Therefore,we used scRNA-seq plus TotalSeq™technology to track the heterogeneity of NK cells during the induction of trained immunity and identified a unique cluster of CD57−NKG2A+EZH2+IFNG+MKI67+IL12R+IL15R+IL18R+NK cells.Enrichment and pseudotime trajectory analyses suggested that this cluster of NK cells contained the precursor of trained NK cells.We then used flow cytometry to further investigate the role of EZH2 in trained NK precursors and found that CD57−NKG2A+EZH2+NK cells had faster cell cycles and an enhanced trained phenotype,and EZH2 inhibition significantly impaired the induction of trained immunity in NK cells.These results suggested that EZH2 is a unique epigenetic marker of precursors of human NK cells with trained immunity.Conclusions:Our work revealed human NK heterogeneity in the induction of trained immunity,identified the precursor subset for trained NK cells,and demonstrated the critical role of EZH2 in the induction of trained immunity in human NK cells.展开更多
OBJECTIVE To investigate the influence of O-(4-ethoxyl-butyl)- berbamine(EBB)on the expression of cyclin B1 and cdc2-p34 in the human drug-resistant breast cancer MCF-7/ADR cell line. METHODS The MTT assay was used to...OBJECTIVE To investigate the influence of O-(4-ethoxyl-butyl)- berbamine(EBB)on the expression of cyclin B1 and cdc2-p34 in the human drug-resistant breast cancer MCF-7/ADR cell line. METHODS The MTT assay was used to assess the cytotoxicity of EBB.Different levels of EBB were added to different cell lines at series of time points solely or combined with doxorubicin(DOX) to detect the effect on the expression of cyclinB1 and cdc2-p34 by Western blots.cdc2-p34 tyrosine phosphorylation was detected by immunoprecipitation.In addition,apoptosis and cytoplastic Ca 2+ concentrations were systematically examined by laser scanning confocal microscopy(LSCM). RESULTS EBB showed little inhibitory activity on human umbilical vein endothelial cells(ECV304),whereas EBB inhibited cell growth(IC50 range,4.55~15.74μmol/L)in a variety of sensitive and drug-resistance cell lines.EBB also down-regulated the expression of cyclin B1 and cdc2-p34 in a concentration and time dependent manner,which was an important reason for the G2/M phase arrest.EBB was shown to induce apoptosis of MCF-7/ADR cells while increasing the level of cytoplastic Ca 2+ . CONCLUSION The low cytotoxicity of EBB suggests it may be useful as a rational reversal agent.The effect of EBB on cell cycle arrest and related proteins,apoptosis,and cytoplastic Ca 2+ concentration may be involved in reversing multidrug resistance.展开更多
Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It is closely related to multiple biological processes, including iron metabolism, polyunsaturated fatt...Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It is closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid metabolism, and the biosynthesis of compounds with antioxidant activities, including glutathione. In the past 10 years, increasing evidence has indicated a potentially strong relationship between ferroptosis and the onset and progression of age-related orthopedic diseases, such as osteoporosis and osteoarthritis. Therefore, in-depth knowledge of the regulatory mechanisms of ferroptosis in age-related orthopedic diseases may help improve disease treatment and prevention. This review provides an overview of recent research on ferroptosis and its influences on bone and cartilage homeostasis. It begins with a brief overview of systemic iron metabolism and ferroptosis,particularly the potential mechanisms of ferroptosis. It presents a discussion on the role of ferroptosis in age-related orthopedic diseases, including promotion of bone loss and cartilage degradation and the inhibition of osteogenesis. Finally, it focuses on the future of targeting ferroptosis to treat age-related orthopedic diseases with the intention of inspiring further clinical research and the development of therapeutic strategies.展开更多
Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objectiv...Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).展开更多
Introduction Multiple myeloma(MM),characterized by the proliferation of monoclonal plasma cells in the bone marrow,has the second highest incidence among hematologic malignancies1.Because of its incurable nature,treat...Introduction Multiple myeloma(MM),characterized by the proliferation of monoclonal plasma cells in the bone marrow,has the second highest incidence among hematologic malignancies1.Because of its incurable nature,treatments for MM are aimed primarily at obtaining minimal residual disease(MRD)negativity and achieving persistent control,both of which are believed to be important strategies to prolong survival and improve prognosis in patients with MM.展开更多
基金supported in part by the Technology Foundation of Tianjin Eye Hospital of China, No. YKQN1911 (to WCS)Tianjin Health Science and Technology Project, No. TJWJ2021QN071 (to WCS)Translational Medicine Research Project of State Key Laboratory of Experimental Hematology of China, No. Z21-11 (to BQH)
文摘Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have described the mechanisms underlying the pathogenesis of NTG.In addition to controlling intraocular pressure,neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG.In this review,we summarized the main regulatory mechanisms of RGC death in NTG,including autophagy,glutamate neurotoxicity,oxidative stress,neuroinflammation,immunity,and vasoconstriction.Autophagy can be induced by retinal hypoxia and axonal damage.In this process,ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway.Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate,which occurs in RGCs and induces progressive glaucomatous optic neuropathy.Oxidative stress also participates in NTG-related glaucomatous optic neuropathy.It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinase-JUN N-terminal kinase pathway.Moreover,it increases inflammation and the immune response of RGCs.Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow,promoting vasospasm and glaucomatous optic neuropathy,as a result of NTG.In conclusion,we discussed research progress on potential options for the protection of RGCs,including TANK binding kinase 1 inhibitors regulating autophagy,N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity,ASK1 inhibitors regulating mitochondrial function,and antioxidants inhibiting oxidative stress.In NTG,RGC death is regulated by a network of mechanisms,while various potential targets protect RGCs.Collectively,these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.
基金supported by funds from the National Natural Science Foundation of China(Grant Nos.81830002,81830004,82070168,and 32070951)the Translational Research grant of NCRCH(Grant No.2020ZKZC04)National Key R&D Program of China(Grant No.2021YFA1100800)。
文摘Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.
基金supported by grants from the National Nature Science Foundation of China (No. 81200395, 81370632)the National Science and Technology supporting Program (No. 2014BAI09B12)+1 种基金the Fundamental Application and Advanced Technology Research Program of Tianjin (No. 15JCYBJC27900)the National Public Health Grand Research Foundation (No. 201202017)
文摘Objective: This study aims to evaluate the natural history of patients with chronic lymphocytic leukemia (CLL) and a 17p deletion (17p-) and identify the predictive factors within this subgroup. Methods: The sample of patients with CLL were analyzed by fluorescence in situ hybridization for deletions in chromosome bands 1 lq22, 13q14 and 17p13; trisomy of bands 12q13; and translocation involving band 14q32. The data from 456 patients with or without a 17p- were retrospectively collected and analyzed. Results: The overall response rate (ORR) in patients with a 17p- was 56.9%, and patients with a high percentage of 17p- (defined as more than 25% of cells harbouring a 17p-) had a lower ORR. The median overall survival (OS) in patients with a 17p- was 78.0 months, which was significantly shorter than the OS in patients without this genetic abnormality (median 162.0 months, P〈0.001). Within the subgroup with a 17p-, the progression-free survival was significantly shorter in patients at Binet stage B-C and patients with elevated lactate dehydrogenase (LDH), B symptoms, unmutated IGHVand a high percentage of 17p-. Conclusions: These results indicated that patients with a 17p- CLL have a variable prognosis that might be predicted using simple clinical and laboratory characteristics.
基金supported by the grants from the National Natural Science Foundation of China(Grant No.81902401,81972656,31671421,81970107,81600083)the National 135 Major Project of China(Grant No.2018ZX10723204,2018ZX10302205)+3 种基金the Natural Science Foundation of Tianjin(Grant No.19JCQNJC09000)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018PT32034)CAMS Innovation Fund for Medical Sciences(Grant No.2016-12M-1-003)supported by the China Scholarship Council(Grant No.201906940003)。
文摘Objective:Epithelial cancers often originate from progenitor cells,while the origin of hepatocellular carcinoma(HCC)is still controversial.HCC,one of the deadliest cancers,is closely linked with liver injuries and chronic inflammation,which trigger massive infiltration of bone marrow-derived cells(BMDCs)during liver repair.Methods:To address the possible roles of BMDCs in HCC origination,we established a diethylnitrosamine(DEN)-induced HCC model in bone marrow transplanted mice.Immunohistochemistry and frozen tissue immunofluorescence were used to verify DENinduced HCC in the pathology of the disease.The cellular origin of DEN-induced HCC was further studied by single cell sequencing,single-cell nested PCR,and immunofluorescence-fluorescence in situ hybridization.Results:Studies by using single cell sequencing and biochemical analysis revealed that HCC cells in these mice were coming from donor mice BMDCs,and not from recipient mice.Furthermore,the copy numbers of mouse orthologs of several HCC-related genes previously reported in human HCC were also altered in our mouse model.DEN-induced HCCs exhibited a similar histological phenotype and genomic profile as human HCCs.Conclusions:These results suggested that BMDCs are an important origin of HCC,which provide important clues to HCC prevention,detection,and treatments.
基金supported by grants from the National Natural Science Foundation of China(81802165 and 31930054)National Key Research and Development Program of China(2017YFA0103401 and 2019YFA0110201)+2 种基金raining Plan of Talents’Innovation of Army Medical Center of PLA(2019CXJSB013)Postdoctoral Innovative Talent Support Program in Chongqing(2019-298)Fund for Excellent Young Scholars of the State Key Laboratory of Trauma,Burns and Combined Injury(SKLYQ201902).
文摘A comprehensive understanding of the cellular heterogeneity and molecular mechanisms underlying the development,homeostasis,and disease of human intervertebral disks(IVDs)remains challenging.Here,the transcriptomic landscape of 108108 IVD cells was mapped using single-cell RNA sequencing of three main compartments from young and adult healthy IVDs,including the nucleus pulposus(NP),annulus fibrosus,and cartilage endplate(CEP).The chondrocyte subclusters were classified based on their potential regulatory,homeostatic,and effector functions in extracellular matrix(ECM)homeostasis.Notably,in the NP,a PROCR+resident progenitor population showed enriched colony-forming unit-fibroblast(CFU-F)activity and trilineage differentiation capacity.Finally,intercellular crosstalk based on signaling network analysis uncovered that the PDGF and TGF-βcascades are important cues in the NP microenvironment.In conclusion,a single-cell transcriptomic atlas that resolves spatially regulated cellular heterogeneity together with the critical signaling that underlies homeostasis will help to establish new therapeutic strategies for IVD degeneration in the clinic.
基金A.Y.H. was supported by NRSA Institutional Postdoctoral Training grant T32 (Grant No. 5T32HL066987-20)C.S. was supported by grants from the National Natural Science Foundation of China (Grant No. 82001661)+1 种基金F.X.M. and C.S. were supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund (Grant No. HH22KYZX0019)F.X.M. was supported by the National Natural Science Foundation of China (Grant No. 82171756)
文摘Neutrophils play an essential role in the defense against bacterial infections and orchestrate both the innate and adaptive immune responses.With their abundant numbers,diverse function and short life span,these cells are at the forefront of immune responses,and have gained attention in recent years because of their presence in tumor sites.Neutrophil involvement pertains to tumor cells'ability to construct a suitable tumor microenvironment(TME)that accelerates their own growth and malignancy,by facilitating their interaction with surrounding cells through the circulatory and lymphatic systems,thereby influencing tumor development and progression.Studies have indicated both pro-and anti-tumor properties of infiltrating neutrophils.The TME can exploit neutrophil function,recruitment,and even production,thus resulting in pro-tumor properties of neutrophils,including promotion of genetic instability,tumor cell proliferation,angiogenesis and suppression of anti-tumor or inflammatory response.In contrast,neutrophils can mediate anti-tumor resistance by direct cytotoxicity to the tumor cells or by facilitating anti-tumor functions via crosstalk with T cells.Here,we summarize current knowledge regarding the effects of neutrophil heterogeneity under homeostatic and tumor conditions,including neutrophil phenotype and function,in cancer biology.
基金supported by National Basic Research Program of China (Grant No.2015CB964903)Natural Science Foundation of Tianjin (Grant No.15JCQNJC44800 and 18JCQNJC81300)+3 种基金National Natural Science Foundation of China (Grant No.81702481, 81701224, 81802873 and 81600083)CAMS Innovation Fund for Medical Sciences (Grant No.201612M-1-003 2017-12M-1-015)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Grant No.2017PT31033, 2018RC31002, 2018PT32034)
文摘Objective: More than half of human glioblastomas show EGFR gene amplification and mutation, but EGFR inhibitors have not been effective in treating EGFR-positive glioblastoma patients.The mechanism behind this type of primary resistance is not well understood.The aim of this study was to investigate gefitinib resistance in glioblastoma, and explore ways to circumvent this significant clinical problem.Methods: MTT method was used to test the cell viability after EGFR-positive glioblastoma cells were treated with indicated drugs;real-time quantitative PCR method was included to detect the TNFα mRNA levels in glioma tissues and cell lines.ELISA was introduced to measure the TNFα protein levels in cell culture supernatant of glioblastoma cells treated with gefitinib.Western blot was used to detect the activity change of intracellular kinases in drug-treated glioblastoma cells.Two mouse xenograft tumor models were carried out to evaluate the in vivo effects of a combination of EGFR and TNFα inhibitors.Results: We found that glioblastoma resistance to gefitinib may be mediated by an adaptive pro-survival TNFα-JNK-Axl signaling axis, and that high TNFα levels in the glioblastoma microenvironment may further intensify primary resistance.A combination of the TNFα-specific small-molecule inhibitor C87 and gefitinib significantly enhanced the sensitivity of glioblastoma cells to gefitinib in vitro and in vivo.Conclusions: Our findings provide a possible explanation for the primary resistance of glioblastoma to EGFR inhibitors and suggest that dual blockade of TNFα and EGFR may be a viable therapeutic strategy for the treatment of patients with chemotherapy-refractory advanced glioblastoma.
基金supported by grants from the National Nature Science Foundation of China(No.81101870)the National Key Clinical Specialist Construction Programs of China(No.2013-544)the Key Programs of National Health and Family Planning Commission of Tianjin(No.16KG127)
文摘Relapse and metastasis are frequent in colon cancer and may be linked to stem cell characteristics.This study isolated side population(SP) cells from a colon cancer cell line(Colo-320) and examined their self-renewal and differentiation abilities.Compared to non-SP(NSP) cells,SP colon cancer cells were more tumorigenic in vivo and exhibited more invasive characteristics and a greater ability to form colonies.Additionally,more cells were in G0/G1 phase and more highly expressed the multidrug resistance protein BCRP/ABCG2.We achieved enhanced chemotherapy sensitivity by transfecting SP cells with a hairpin-like,small interfering RNA(si RNA) eukaryotic expression plasmid targeting BCRP/ABCG2.
基金This work was supported by a grant from Tianjin Science and Technology Development Project (No. 003119311).
文摘Objective: To explore the effects of nuclear M-CSF on the process of tumorigenesis. Methods: Functional part of M-CSF cDNA was inserted into an eukaryotic expression plasmid pCMV/myc/nuc, which can add three NLS to the C-terminal of the expressed protein and direct the protein into the cell nuclei. The constructed plasmid was transferred into NIH3T3 cells and the cell clones were selected by G-418 selection. Cell clones stable expressing target protein were identified by RT-PCR, ABC immunohistochemistry assayand Western blot. Cell growth kinetics analyses throughgrowth curves, cell doubling time, MTT test and anti-sense oligodeoxynucleotide (ASODN) inhibiting cell growth testwere performed to identify cells proliferation potential.Results: The transfected cells showed elevated proliferation potential over the control cells. Conclusion: Abnormalappearance of M-CSF in nucleus could enhance cellproliferation, which suggests that cytokine isoforms within cell nucleus might play transcription factor-like role.
基金supported by the following grants and programs:G.Z.received the grants(Nos.81770183 and 81970155)from the National Natural Science Foundation of China(NSFC,http://www.nsfc.gov.cn/english/site_1/index.html)the CAMS Innovation Fund for Medical Sciences(CIFMS)program(No.2016-I2M-2-006)from Chinese Academy of Medical Sciences&Peking Union Medical College(CAMS,http://english.cams.cn/index.html)+1 种基金L.W.received the program(No.2017-I2M-1-015)from the CIFMSG.Z.was a recipient of the New Century Excellent Talents in University(No.NCET-08-0329)from the Ministry of Education of the People’s Republic of China(http://en.moe.gov.cn/).
文摘Legumain is a C13 family cysteine protease.It plays diverse roles under both physiological and pathological conditions.The high-level expression of legumain is detected in solid tumors.Legumain promotes the proliferation and migration of tumor cells.However,the effect of legumain in blood diseases has not been established.In this report,we studied the effect of legumain on leukemia cells by overexpressing it in THP1 cells.The results demonstrated that legumain promoted cell proliferation,whereas it had little effect on cell apoptosis.Furthermore,legumain promoted the migration of THP1 cells.It was worth noting that legumain decreased the stemness of THP1 cells.Further evidence showed that legumain decreased the expression of Oct4,Sox2,Myc in THP1 cells.Our study reveals the multifaced effects of legumain in leukemia cells and broadens the knowledge of legumain in malignancies.
文摘Acute lymphoblastic leukemia(ALL)is a common pediatric cancer.The second malignant neoplasms(SMNs)in long-term survivors of pediatric ALL are relatively rare.Herein we report a 10-year-old girl who was diagnosed as primitive neuroectodermal tumor(PNET)5 years after the initial diagnosis of ALL with radiotherapy・free treatment.PNET is an exceedingly rare neoplasm in SMNs of survivors of childhood ALL.It is predisposed to be misdiagnosed and the pathogenesis is unclear.The outcome is poor.Long-term follow-up is necessary for the survival children of ALL.
文摘BACKGROUND Myeloid neoplasm(MN)with eosinophilia and rearrangement of platelet-derived growth factor receptor beta(PDGFRB)shows a good therapeutic response to imatinib in adults.MN is rarely found in children,and the efficacy of imatinib on pediatric patients remain unclear.CASE SUMMARY We report 2 pediatric cases diagnosed with MN with eosinophilia and PDGFRB rearrangement who were treated with imatinib.Case 1 was a 1-year-old girl admitted to the hospital because of“abdominal distension with hyperleukocytosis for 3 mo”.She had leukocytosis,anemia,and eosinophilia(the absolute eosinophil count(AEC)was 8960/μL),and her fluorescence in situ hybridization(FISH)test revealed that PDGFRB rearrangement was detected in 70%of 500 interphase cells.Case 2 was a 2-year-old girl admitted to the hospital because of“recurrent fever and rashes for 1 mo”.Her blood cell count showed an AEC of 3540/μL.The FISH test revealed that PDGFRB rearrangement was detected in 71%of 500 interphase cells.Both patients were diagnosed as MN with eosinophilia and PDGFRB rearrangement.Imatinib was added into their treatment regimen.As expected,complete hematologic remission was achieved after 1 mo of treatment,and symptoms disappeared.CONCLUSION Although MN with eosinophilia and PDGFRB rearrangement usually occurs in adults,it can be found in children.The therapeutic benefits of imatinib in these 2 pediatric patients were consistent with its reported effects in adult patients.
基金Supported by the National Soft Science Research Program of China(2013GXS4B083)
文摘Great progresses have been made in fundamental and clinical stem cell research in China in recent years. The official policy on stem cells, which was announced in 2015, seems as the spring of stem cell therapy in China. However, the regulation, governance, and management of clinical expectations are still challenging. This review summarized the current stem cell research and development in the field, as well as its rapidly evolving commercial, regulatory and ethical environment in China. As expected, the prospects of stem cells in China look prospective.
基金the Natural Science Foundation of China (30300186)the Grant of 863 projects from the Ministry of Science & Technology of China (2002AA223354)
文摘Objective:To express the soluble recombinant hemangiopoietin protein in E.coli BL21(DE3).Methods:Using human fetal live cDNA as a template,a partial cDNA fragment of HAPO coding N-terminal region was subcloned into plasmids pTrc99,pQE60 and pET32c to construct different recombinant prokaryotic expression systems.After selecting,the soluble rhHAPO fusion protein was expressed stably in E.coli BL21(DE3) by vector pET32c-HAPO and further isolated by nickelnitrilotriacetic acid(NTA) affinity chromatography.After cleavage with enterokinase,the rhHAPO protein was applied to Fast Flow SP sepharose column.Results:The rhHAPO protein had a purity of more than 95% and a good bioactivity based on the cell adhesion assay in ECV304 cells.Conclusion:We have established a protein engineering system to produce rhHAPO which may provide the possibility for clinical application.
基金This study was supported by grants from the National Natural Science Foundation of China(No.81670136),VIVA-China Children's Cancer Foundation.
文摘Objective:Cytogenetic abnormalities have been proven to be the most valuable parameter for risk stratification of childhood acute lymphoblastic leukemia(ALL).However,studies on the prevalence of cytogenetic abnormalities and their correlation to clinical features in Chinese pediatric patients are limited,especially large-scale studies.Methods:We collected the cytogenetics and clinical data of 1541 children newly diagnosed with ALL between 2001 and 2014 in four Chinese hospitals,and retrospectively analyzed their clinical features,prognosis and risk factors associated with pediatric ALL.
基金This work was supported by grants from The National Key R&D Program(Grant Nos.2018YFC1313400,2018YFC1313000,and 2018YFC1313002)The National Natural Science Foundation of China(Grant Nos.81872166,U20A20375,31600705,81974416,and 81702405)The Tianjin Natural Science Foundation(Grant No.17JCQNJC09000)。
文摘Objective:Trained immunity of natural killer(NK)cells has shown great potential in the treatment of cancers by eliciting enhanced effector responses to restimulation by cytokines or cancer cells for long time periods after preactivation.However,the human NK cells responsible for the generation and maintenance of trained immunity are largely unknown.We hypothesized that heterogeneous human NK cells would respond differentially to stimulation with a combination of IL-12,IL-15,and IL-18,and that an NK cell subset might exist that is mainly responsible for the induction of trained immunity.On the basis of our hypothesis,we aimed to identify the subset from which cytokine-trained human NK cells originate and to explore possible regulatory targets for drug intervention.Methods:Flow cytometry assays were performed to analyze the functions of cytokine-trained NK cells and examine cell division and protein expression in NK cell subsets.Single-cell RNA sequencing(scRNA-seq)plus TotalSeq™technology was used to track the heterogeneity of NK cells during the induction of trained immunity.Results:Traditional developmental markers for peripheral NK cells were unable to identify the precursors of human NK cells with trained immunity.Therefore,we used scRNA-seq plus TotalSeq™technology to track the heterogeneity of NK cells during the induction of trained immunity and identified a unique cluster of CD57−NKG2A+EZH2+IFNG+MKI67+IL12R+IL15R+IL18R+NK cells.Enrichment and pseudotime trajectory analyses suggested that this cluster of NK cells contained the precursor of trained NK cells.We then used flow cytometry to further investigate the role of EZH2 in trained NK precursors and found that CD57−NKG2A+EZH2+NK cells had faster cell cycles and an enhanced trained phenotype,and EZH2 inhibition significantly impaired the induction of trained immunity in NK cells.These results suggested that EZH2 is a unique epigenetic marker of precursors of human NK cells with trained immunity.Conclusions:Our work revealed human NK heterogeneity in the induction of trained immunity,identified the precursor subset for trained NK cells,and demonstrated the critical role of EZH2 in the induction of trained immunity in human NK cells.
基金This work was supported by grants from the National Nature Science Foundation of China(No.30572203,30570772)the Key Fund of Science of TianJin Municipal Government(No.07JCZDJC04900)
文摘OBJECTIVE To investigate the influence of O-(4-ethoxyl-butyl)- berbamine(EBB)on the expression of cyclin B1 and cdc2-p34 in the human drug-resistant breast cancer MCF-7/ADR cell line. METHODS The MTT assay was used to assess the cytotoxicity of EBB.Different levels of EBB were added to different cell lines at series of time points solely or combined with doxorubicin(DOX) to detect the effect on the expression of cyclinB1 and cdc2-p34 by Western blots.cdc2-p34 tyrosine phosphorylation was detected by immunoprecipitation.In addition,apoptosis and cytoplastic Ca 2+ concentrations were systematically examined by laser scanning confocal microscopy(LSCM). RESULTS EBB showed little inhibitory activity on human umbilical vein endothelial cells(ECV304),whereas EBB inhibited cell growth(IC50 range,4.55~15.74μmol/L)in a variety of sensitive and drug-resistance cell lines.EBB also down-regulated the expression of cyclin B1 and cdc2-p34 in a concentration and time dependent manner,which was an important reason for the G2/M phase arrest.EBB was shown to induce apoptosis of MCF-7/ADR cells while increasing the level of cytoplastic Ca 2+ . CONCLUSION The low cytotoxicity of EBB suggests it may be useful as a rational reversal agent.The effect of EBB on cell cycle arrest and related proteins,apoptosis,and cytoplastic Ca 2+ concentration may be involved in reversing multidrug resistance.
基金National Natural Science Foundation of China (82071970,81874030, 82072506, 92268115, and 31930057)National Key R&D Program of China(2019YFA0111900 and 2018YFA0507802)+5 种基金Innovation-Driven Project of Central South University (2020CX045)Key Program of Health Commission of Hunan Province(20201902)Young Talents Project of Hubei Provincial Health Commission(WJ2021Q053)Science and Technology Innovation Program of Hunan Province (No.2021RC3025)Innovation Project for Postgraduate Students of Central South University (2021zzts1024)Science and Technology Innovation Project of Jianghan University (2021kjzx008)。
文摘Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It is closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid metabolism, and the biosynthesis of compounds with antioxidant activities, including glutathione. In the past 10 years, increasing evidence has indicated a potentially strong relationship between ferroptosis and the onset and progression of age-related orthopedic diseases, such as osteoporosis and osteoarthritis. Therefore, in-depth knowledge of the regulatory mechanisms of ferroptosis in age-related orthopedic diseases may help improve disease treatment and prevention. This review provides an overview of recent research on ferroptosis and its influences on bone and cartilage homeostasis. It begins with a brief overview of systemic iron metabolism and ferroptosis,particularly the potential mechanisms of ferroptosis. It presents a discussion on the role of ferroptosis in age-related orthopedic diseases, including promotion of bone loss and cartilage degradation and the inhibition of osteogenesis. Finally, it focuses on the future of targeting ferroptosis to treat age-related orthopedic diseases with the intention of inspiring further clinical research and the development of therapeutic strategies.
基金supported by grants from CAMS Innovation Fund for Medical Sciences(CIFMSGrant No.2022-I2M-1-022)。
文摘Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).
基金supported by the International Cooperation Projects of National Natural Science Foundation of China(Grant No.81920108006,to L.Qiu)CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2022-I2M-1-022,to L.Qiu)+1 种基金the National Natural Science Foundation of China(Grant No.81630007,to L.QiuGrant Nos.82270218,81670202,to G.An)。
文摘Introduction Multiple myeloma(MM),characterized by the proliferation of monoclonal plasma cells in the bone marrow,has the second highest incidence among hematologic malignancies1.Because of its incurable nature,treatments for MM are aimed primarily at obtaining minimal residual disease(MRD)negativity and achieving persistent control,both of which are believed to be important strategies to prolong survival and improve prognosis in patients with MM.