Background Transplantation of adult bone marrow-derived mesenchymal stem cells （MSCs） has been proposed as a strategy for cardiac repair following myocardial damage. However cell transplantation strategies to replac...Background Transplantation of adult bone marrow-derived mesenchymal stem cells （MSCs） has been proposed as a strategy for cardiac repair following myocardial damage. However cell transplantation strategies to replace lost myocardium are limited by the inability to deliver large numbers of cells that resist peritransplantation graft cell death. Accordingly, we set out to isolate and expand adult swine bone marrow-derived MSCs, and to engineer these cells to overexpress AKT1 （protein kinase B）, to test the hypothesis that AKTl-engineered MSCs are more resistant to apoptosis and can enhance cardiac repair after transplantation into the ischemic swine heart. Methods The CDS （regulation domain of AKT1） AKTI-cDNA fragment was amplified, and MSCs were transfected following synthesis with a pCDH1-AKT1 shuttling plasmid. Western blotting analysis and real-time reverse transcription-polymerase chain reaction （RT-PCR） was performed. Myocardial infarction （MI） models were constructed in Meishan pigs, and cardiac function was evaluated by magnetic resonance imaging （MRI） measurements and echocardiography 4 weeks later. All pigs were assigned to four groups： control （A）, DMEM （B）, MSC （C）, and AKT-transfected （D）. MSCs were transfected with the AKT1 gene, and autologous BrdU-labeled stem cells （1 × 10^7/5 ml） were injected into left anterior descending coronary atery （LAD） of the infarct heart in groups C and D. In group B, DMEM was injected using the same approach. In group A, there was no injection following LAD occlusion. After 4 weeks, cardiac function and regional perfusion measurements were repeated by MRI and echocardiography, and histological characteristics of the hearts were assessed. Connecxin-43 （CX-43）, BrdU, and von Willebrand factor （VWF） immunoreactivity was tested using enzyme linked immunosorbent assay （ELISA）. Vascular endothelial growth factor （VEGF）, transforming growth factor-β1 （TGF-β1） were analyzed at the same time. Results AKTI-c展开更多
BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019(COVID-19),a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmu...BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019(COVID-19),a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases.Crohn's disease(CD)is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota.Patients who underwent hematopoietic stem cell transplantation(HSCT)are considered at risk for COVID-19.AIM To describe for the first time the impact of COVID-19 in CD patients who had undergone autologous,non-myeloablative HSCT.METHODS In this descriptive study a series of 19 patients were diagnosed with positive COVID-19.For two patients there were reports of the occurrence of two infectious episodes.Parameters related to HSCT,such as time elapsed since the procedure,vaccination status,CD status before and after infection,and clinical manifestations resulting from COVID-19,were evaluated.RESULTS Among the patients with COVID-19,three,who underwent Auto HSCT less than six months ago,relapsed and one,in addition to the CD symptoms,started to present thyroid impairment with positive anti-TPO.Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission.Nine patients reported late symptoms that may be related to COVID-19.There were no deaths,and a statistical evaluation of the series of COVID-19 patients compared to those who did not present any infectious episode did not identify significant differences regarding the analyzed parameters.CONCLUSION Despite the change in CD status in three patients and the presence of nine patients with late symptoms,we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD.展开更多
BACKGROUND Monomorphic epithelial intestinal T-cell lymphoma(MEITL)is a rare type of peripheral T-cell lymphoma.The clinical manifestations are diarrhea,abdominal pain,perforation and an abdominal mass.CASE SUMMARY We...BACKGROUND Monomorphic epithelial intestinal T-cell lymphoma(MEITL)is a rare type of peripheral T-cell lymphoma.The clinical manifestations are diarrhea,abdominal pain,perforation and an abdominal mass.CASE SUMMARY We present a 52-year-old female patient who was diagnosed with MEITL.Further disease progression was observed after multiline chemotherapy.Eventually,the patient died of a severe infection.CONCLUSION MEITL is a rare intestinal primary T-cell lymphoma with aggressive behavior,a high risk of severe life-threatening complications,and a poor prognosis.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
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
BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve comp...BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis(HLH) has a worse prognosis than B-cell lymphoma-triggered HLH.CASE SUMMARY We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL(Stage Ⅳ, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1;prednisone 100 mg on days 1-5;and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen(busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids.CONCLUSION It is possible that development of HLH is related to immune reconstitution after ASCT.展开更多
The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form.This review aims to provide an overview of the scientific evidence on the biology of adipose tissue,the ...The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form.This review aims to provide an overview of the scientific evidence on the biology of adipose tissue,the role of adipose-derived stem cells,and the indications of adipose tissue grafting in peripheral nerve surgery.Adipose tissue is easily accessible through the lower abdomen and inner thighs.Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress,resulting in variable survival of adipocytes within the first 24 hours.Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts.Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization,and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue.In clinical studies,the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results.Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new,more studies are needed to explore safety and long-term effects on peripheral nerve regeneration.The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated,enzyme-free,and used in the same surgical procedure,e.g.adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction.Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival.Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.展开更多
文摘Background Transplantation of adult bone marrow-derived mesenchymal stem cells （MSCs） has been proposed as a strategy for cardiac repair following myocardial damage. However cell transplantation strategies to replace lost myocardium are limited by the inability to deliver large numbers of cells that resist peritransplantation graft cell death. Accordingly, we set out to isolate and expand adult swine bone marrow-derived MSCs, and to engineer these cells to overexpress AKT1 （protein kinase B）, to test the hypothesis that AKTl-engineered MSCs are more resistant to apoptosis and can enhance cardiac repair after transplantation into the ischemic swine heart. Methods The CDS （regulation domain of AKT1） AKTI-cDNA fragment was amplified, and MSCs were transfected following synthesis with a pCDH1-AKT1 shuttling plasmid. Western blotting analysis and real-time reverse transcription-polymerase chain reaction （RT-PCR） was performed. Myocardial infarction （MI） models were constructed in Meishan pigs, and cardiac function was evaluated by magnetic resonance imaging （MRI） measurements and echocardiography 4 weeks later. All pigs were assigned to four groups： control （A）, DMEM （B）, MSC （C）, and AKT-transfected （D）. MSCs were transfected with the AKT1 gene, and autologous BrdU-labeled stem cells （1 × 10^7/5 ml） were injected into left anterior descending coronary atery （LAD） of the infarct heart in groups C and D. In group B, DMEM was injected using the same approach. In group A, there was no injection following LAD occlusion. After 4 weeks, cardiac function and regional perfusion measurements were repeated by MRI and echocardiography, and histological characteristics of the hearts were assessed. Connecxin-43 （CX-43）, BrdU, and von Willebrand factor （VWF） immunoreactivity was tested using enzyme linked immunosorbent assay （ELISA）. Vascular endothelial growth factor （VEGF）, transforming growth factor-β1 （TGF-β1） were analyzed at the same time. Results AKTI-c
文摘BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019(COVID-19),a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases.Crohn's disease(CD)is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota.Patients who underwent hematopoietic stem cell transplantation(HSCT)are considered at risk for COVID-19.AIM To describe for the first time the impact of COVID-19 in CD patients who had undergone autologous,non-myeloablative HSCT.METHODS In this descriptive study a series of 19 patients were diagnosed with positive COVID-19.For two patients there were reports of the occurrence of two infectious episodes.Parameters related to HSCT,such as time elapsed since the procedure,vaccination status,CD status before and after infection,and clinical manifestations resulting from COVID-19,were evaluated.RESULTS Among the patients with COVID-19,three,who underwent Auto HSCT less than six months ago,relapsed and one,in addition to the CD symptoms,started to present thyroid impairment with positive anti-TPO.Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission.Nine patients reported late symptoms that may be related to COVID-19.There were no deaths,and a statistical evaluation of the series of COVID-19 patients compared to those who did not present any infectious episode did not identify significant differences regarding the analyzed parameters.CONCLUSION Despite the change in CD status in three patients and the presence of nine patients with late symptoms,we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD.
基金Supported by Zhejiang Province Traditional Chinese Medicine Science and Technology Project,No.2024ZL1296.
文摘BACKGROUND Monomorphic epithelial intestinal T-cell lymphoma(MEITL)is a rare type of peripheral T-cell lymphoma.The clinical manifestations are diarrhea,abdominal pain,perforation and an abdominal mass.CASE SUMMARY We present a 52-year-old female patient who was diagnosed with MEITL.Further disease progression was observed after multiline chemotherapy.Eventually,the patient died of a severe infection.CONCLUSION MEITL is a rare intestinal primary T-cell lymphoma with aggressive behavior,a high risk of severe life-threatening complications,and a poor prognosis.
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.
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 Jinan Clinical Medical Science and Technology Innovation Plan,No.202019141Norman Bethune Foundation-Feifan Iron Supplement Project,No.ffbt-C-2022-010.
文摘BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis(HLH) has a worse prognosis than B-cell lymphoma-triggered HLH.CASE SUMMARY We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL(Stage Ⅳ, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1;prednisone 100 mg on days 1-5;and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen(busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids.CONCLUSION It is possible that development of HLH is related to immune reconstitution after ASCT.
文摘The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form.This review aims to provide an overview of the scientific evidence on the biology of adipose tissue,the role of adipose-derived stem cells,and the indications of adipose tissue grafting in peripheral nerve surgery.Adipose tissue is easily accessible through the lower abdomen and inner thighs.Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress,resulting in variable survival of adipocytes within the first 24 hours.Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts.Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization,and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue.In clinical studies,the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results.Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new,more studies are needed to explore safety and long-term effects on peripheral nerve regeneration.The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated,enzyme-free,and used in the same surgical procedure,e.g.adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction.Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival.Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.
