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Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0％(95％CI:64.1％～75.9％)and 20.0％(95％CI:11.9％～32.5％),respectively,while those of the fungal infection patients were 54.5％(95％CI:49.5％～69.5％)and 36.4％(95％ CI:15.5％～70.3％),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.
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Objective@#To investigate herpesvirus infection in early stage of hematopoietic stem cell transplantation (HSCT) by multiplex polymerase chain reaction (PCR), and to explore the association between multiple herpesviruses infection and clinical characteristics in HSCT patients and its impact on post-transplant complications and prognosis.@*Methods@#A total of 734 peripheral blood samples were collected from 90 patients undergoing HSCT in the Department of Hematology, the First Affiliated Hospital of Soochow University between February 2017 and August 2017. The peripheral blood specimens were obtained before and within 90 days after transplantation at different time points. Lab-Aid824 Nucleic Acid Extraction Mini Reagent was used to extract DNA and multiplex PCR assay was used to simultaneously detect 8 kinds of human herpesviruses from genomic DNA. The incidence of various herpesvirus infections, its correlation with clinical features and effects on post-transplant complications and prognosis were analyzed.@*Results@#The median follow-up time was 192 (range: 35-308) days. Among the 90 patients before transplantation, the incidence of herpes virus infection was 35.6% (32/90), including 12.2% (11/90) with one herpes virus infection and 23.3% (21/90) with multiple viruses infection. The incidence of herpes virus infection after transplantation was 77.8% (70/90), including 20.0% (18/90) with one herpes virus infection and 57.8% (52/90) with multiple herpes virus infection. Among the 52 patients with multiple herpes viruses infection, 30 (57.7%) patients were infected by 2 kinds of viruses, 18 (34.6%) patients by 3 kinds of viruses and 4 (7.7%) patients by 4 kinds of viruses. There was a correlation between HHV-6 and HHV-7 herpesvirus infection (OR=13.880, Q=0.026). EBV infection was related to HHV-7 infection (OR=0.093, Q=0.044). The age of patients was correlated with the incidence of HHV-1 infection before transplantation. There were 24 patients in our study experienced clinical symptoms associated with viral infection. The main manifestations were hemorrhagic cystitis (HC), interstitial pneumonia, enteritis, viral encephalitis and fever of unknown origin. EBV infection was related to HLA incompatibility and the inconsistent of the ABO blood group and grade Ⅱ-Ⅳ aGVHD after transplantation. HLA incompatibility and the unrelated donor and grade Ⅱ-Ⅳ aGVHD were related to multiple viruses infection.@*Conclusion@#Multiple herpesviruses were common in patients undergoing HSCT, which were closely related to HLA mismatch, unrelated donor and grade Ⅱ-Ⅳ aGVHD.
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Objective: To investigate herpesvirus infection in early stage of hematopoietic stem cell transplantation (HSCT) by multiplex polymerase chain reaction (PCR), and to explore the association between multiple herpesviruses infection and clinical characteristics in HSCT patients and its impact on post-transplant complications and prognosis. Methods: A total of 734 peripheral blood samples were collected from 90 patients undergoing HSCT in the Department of Hematology, the First Affiliated Hospital of Soochow University between February 2017 and August 2017. The peripheral blood specimens were obtained before and within 90 days after transplantation at different time points. Lab-Aid824 Nucleic Acid Extraction Mini Reagent was used to extract DNA and multiplex PCR assay was used to simultaneously detect 8 kinds of human herpesviruses from genomic DNA. The incidence of various herpesvirus infections, its correlation with clinical features and effects on post-transplant complications and prognosis were analyzed. Results: The median follow-up time was 192 (range: 35-308) days. Among the 90 patients before transplantation, the incidence of herpes virus infection was 35.6% (32/90), including 12.2% (11/90) with one herpes virus infection and 23.3% (21/90) with multiple viruses infection. The incidence of herpes virus infection after transplantation was 77.8% (70/90), including 20.0% (18/90) with one herpes virus infection and 57.8% (52/90) with multiple herpes virus infection. Among the 52 patients with multiple herpes viruses infection, 30 (57.7%) patients were infected by 2 kinds of viruses, 18 (34.6%) patients by 3 kinds of viruses and 4 (7.7%) patients by 4 kinds of viruses. There was a correlation between HHV-6 and HHV-7 herpesvirus infection (OR=13.880, Q=0.026). EBV infection was related to HHV-7 infection (OR=0.093, Q=0.044). The age of patients was correlated with the incidence of HHV-1 infection before transplantation. There were 24 patients in our study experienced clinical symptoms associated with viral infection. The main manifestations were hemorrhagic cystitis (HC), interstitial pneumonia, enteritis, viral encephalitis and fever of unknown origin. EBV infection was related to HLA incompatibility and the inconsistent of the ABO blood group and grade Ⅱ-Ⅳ aGVHD after transplantation. HLA incompatibility and the unrelated donor and grade Ⅱ-Ⅳ aGVHD were related to multiple viruses infection. Conclusion: Multiple herpesviruses were common in patients undergoing HSCT, which were closely related to HLA mismatch, unrelated donor and grade Ⅱ-Ⅳ aGVHD.
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Humanos , ADN Viral , Trasplante de Células Madre Hematopoyéticas , Herpesviridae , Infecciones por Herpesviridae , Reacción en Cadena de la Polimerasa Multiplex , Activación ViralRESUMEN
Myasthenia gravis is autoimmune diseases which mediated with acetylcholine receptor antibody.Based on the studies in rencent years,treatment of MG has made great progress.Thisreview will discuss several aspects,such as immune tolerance induced by dendritic cells,blocking monoclonal antibodies,hematopoietic stem cell transplantion,and provide new ideas and methods for the treatment of myasthenia gravis.
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Objective To evaluate the influence of granulocyte colony-stimulating factor (G-CSF) on the quantity and ratio of type 1 dendritic cells (DC1) and type 2 dendritic cells (DC2) in normal allogeneic hematopoietic stem cell graft donor peripheral blood (PB) and bone marrow (BM). Methods G-CSF treatment with 10 μg/kg per day for 5 days, the quantity, ratio of DC1 and DC2 in G-CSF primed allogeneic peripheral blood stem cell graft (G-PBSC) were detected in 11 donors, 20 donors in G-CSF primed allogeneic bone marrow stem cell graft (G-BMSC), 8 donors in unprimed PB, and 10 normal individuals in unprimed BM,respectively. by flow cytometry method. Results After treated by G-CSF, the mean BMDC2 was increased from 14.37×106/L to 29.68×106/L ( t = 2.433, P = 0.022) in control group, whereas BMDC1 count did not change (13.77×106/L vs 18.88×106L, t = 1.169, P = 0.251). The ratio of DC2 to DC1 was significantly higher in G-CSF treated donor BM (1.83±0.81 vs 1.12±0.32, t = 2.658, P =0.013). After G-CSF treatment of normal donor, the number of PBDC2 (14.92×106/L vs 26.76×106/L, t = 2.390, P = 0.029), and the ratio of DC2 to DC1 was increased (1.00±0.37 vs 2.02±1.43, t = 2.158, P = 0.044), but the number of PBDC1 was similar (14.21×106/L vs 18.02×106/L, t = 0.625, P=0.541). Conclusion G-CSF treatment of normal allogeneic HSC donor selectively increase the number of PBDC2 and BMDC2, but do not change PBDC1 and BMDC1.
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Objective To study the reconstitution of nature kill cell early after non-myeloablative allogeneic stem cell transplantation (NAST). Methods Cell phenotypes and in vitro immune functions were analyzed by direct immune fluorescence with FCM, T-cell activation test and MTT assay, respectively. Results The percentages of CD+3, CD+4 cells were low, (2.03±15.60) % and (22.69±12.29)%, respectively, while CD+8 lymphocytes were normal or high [(29.26±8.99)%] 1 month after NAST. Proliferative response to a T lymphocyte activator (PHA) was blunted, 94.60±44.87. The percentage of NK cells was within normal limits or high (n=7) in allotransplanted patients. It is (18.77±9.11) %. The percentage of CD+56 NK cells expressing IL-2R (CD25) was high and values obtained from transplanted patients were significantly different from control values . They are (3.71±2.23) % (t = 2.116, P = 0.044). NK cell activity in part of patients was higher than that observed in control cells (25.30±12.39) % vs (16.60±3.53) % (t = 2.135, P= 0.047). Conclusion NK cell has recovered early after transplantation and may be particularly relevant as a first line of defence in immunosurveillance against neoplastic cells or microbial infections, until a full reconstitution of T cellmediated immune response can be achieved.
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Objective To investigate the protective effect of human umbilical cord mesenchymal stem cells (huc-MSC) on the ischemia-reperfusion injury (IRI) of moderately fatty liver in rats. Methods The rat fatty liver model was established by fat-rich diet feeding. 60 female SD rats were randomly divided into MSC-treated and control groups (n = 30). MSC-treated group was infused with MSC (2 x 106 cells resuspended in 1.5 ml of sterile phosphate-buffered saline solution, PBS) by intra-venous injection through the tail vein. The first dose was administered on day 1 before IRI, followed by another dose on day 3 postIRI. The control group was injected with sterile PBS alone at the same intervals. Blood and liver samples were collected at day 1,4 and 7 (10 rats at each time point) post-IRI respectively to test enzyme activities,biochemical and histological changes. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor α (TNF-α) in liver tissue were measured. The pathological changes of liver tissue and apoptosis of hepatocytes were also assessed. Results Compared to the control group, the levels of ALT, AST, TNF-α, and MDA declined in the MSC-treated group on day 1 and day 4 post-IRI ( P ＜ 0. 05 ), while no difference was observed on day 7 post-IRI ( P ＞ 0. 05). There was no difference of the level of SOD between the two groups on day 1,4 and 7 post-IRI (P ＞0. 05). Pathological examination revealed inflammatory injury in the MSC-treated group was alleviated compared with that in the control group. Conclusion huc-MSC effects protection on the IRI of fatty liver in rats.
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Objective To investigate the curative effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the method of the pretreatment choice on myelodysplastic syndrome (MDS).Methods 13 cases who were undergoing allo-HSCT including 10 HLA-matched, 2 HLA partially matched,and one umbilical cord blood transplanted patients were enrolled in this study. The infusion number of MNC and CD+34 cells is 6.92 (2.65-21.33)×108/kg and 4.47 (1.49-10.22) ×106/kg, respectively. Of the 13 cases,5 adopted TBI, fludarabine(Flud), and cyclophosphamide(Cy) pretreatment, 3 chose BU/Cy pretreatment, and 3 chose TBI and Cy pretreatment, 2 chose Ara-C+BU+Cy+VM26 pretreatment. In order to prevent GVHD, 2cases of HLA partially matched were treated with ATG, cyclosporin A (CsA), MTX and MMF aftertransplantation, while the others were treated with CsA and MTX only. Results 9 out of 13 cases achieved hematopoietic reconstruction completely. 4 died of complications. Conclusion The allogeneic hematopoietic stem cell transplantation is an efficient regimen to cure MDS. The pretreatment should adopt the individuation.
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Bone marrow mesenchymal stem cells(BMSCs) are a population of multipotent cells. Many researchers have studied whether BMSCs could differentiate into neurons in vivo and ex vivo. Although some studies didn't agree with about some chemical induction medium inducing neurons, the application of cell transplantion and gene therapy of BMSCs has achieved certain progress showing good future for BMSCs in therapy of nervous system diseases.
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Objective To investigate the correlation of monocyte counts prior to the collection of recombinant human granulocyte colony-stimulating factor(rhG-CSF)primed bone marrow grafts(G-BM)with the quantities of CD34+ cells in the grafts.Methods From June 2004 to July 2007,fifty-three healthy donors were treated with rhG-CSF[5 ?g/(kg?d)]injected subcutaneously for five consecutive days.Bone marrow grafts and peripheral blood grafts were harvested on the 4th and 5th day,respectively.The quantities of CD34+ cells and blood routine prior to the collection of the G-BM were determined by flow cytometry and blood analyzer XL2100,respectively.Results The monocyte counts in peripheral blood(PB)of the 53 healthy donors were 896?424 per microliter.The counts of CD34+ cells per microliter and quantities of total CD34+ cells in the bone marrow grafts were 84?45 and(8.22?4.84)?107,respectively.Pearson correlation analysis indicated that the counts of monocyte in the PB correlated positively with the counts of CD34+ cells per microliter(r=0.573,P
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Objective To explore the effect of lipo-prostaglandin E1 plus dextran 40 in the prophylaxis of hepatic veno-occlusive disease(HVOD) after hematopoietic stem cell(HSC) transplantation.Methods Two hundred and thirty-four patients,162 males and 72 females,mean age 30.6(ranged from 3 to 64),were admitted during May 1999 to April 2007 and undergone HSC transplantation.Lipo-prostaglandin E1 associated with dextran 40 were administered to all patients for the prophylaxis of hepatic veno-occlusive disease.Lipo-prostaglandin E1,10?g dissolved in 100ml saline,20?g per day iv,were administered from day 7 before transplantation(-7 day) to day 30 after transplantation(+30 day).Dextran 40,500ml per day iv,were administered from-1 day to +5 day.In order to identify the risk factors inducing HVOD,patients were allocated to 2 groups according to following factors:age(
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There have been great developments in pancreas and pancreatic islet cell transplantion in the last few years. The isolation of the islet cells in capsules with semi-permeable membranes may become ideal means of treating diabetes, and the use of immunossuppression could be avoided. The ideal material for the confection of the capsules has remained a dream. A new material derived from natural latex was implanted in the subcutaneous tissue of normal and diabetic rats to study the biocompatibility and the vascular neoformation. After 21 days, an analysis of the implant showed intense vascular neoformation on the membrane-tissue interface and little fibrotic tissue. The inicial results show great promise for utilization of this material in capsules for the isolation of cells.
O transplante de pâncreas e de ilhotas pancreáticas vem apresentando grande desenvolvimento nos últimos anos. O isolamento das ilhotas em cápsulas com membrana semi-permeáveis pode ser tratamento de escolha para o diabetes, pois dispensa o uso de imunossupressores. O material ideal para a confecção de uma cápsula para o isolamento celular ainda permanece um sonho. Um novo material a base de látex natural foi implantado no subcutâneo de ratos normais e diabéticos para estudar a biocompatibilidade e a neoformação vascular. A análise após 21 dias de implante mostrou intensa formação capilar na interface membrana-tecido e pouco tecido fibrótico. Estes achados iniciais mostram que o material pode ter algum potencial para a confecção de dispositivos de isolamento celular.
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98%.Thick myofibers were observed by transmission electron microscopy after induction with 5-aza.Four weeks after transplantation,the left ventricle ejection fraction,the movement extent of left ventricle,left ventricle systolic wall thickening and dp/dt of rabbits were all higher than those of the control group and cardiac infarction model group(P