目的：观察芍药汤对湿热型溃疡性结肠炎（ulcerative colitis,UC）大鼠模型结肠组织中高迁移率族蛋白B1（high mobility group protein B1,HMGB1）的调控,分析其对衔接蛋白髓样分化因子88（My D88）和核转录因子-κB（NF-κB）的影响,...目的：观察芍药汤对湿热型溃疡性结肠炎（ulcerative colitis,UC）大鼠模型结肠组织中高迁移率族蛋白B1（high mobility group protein B1,HMGB1）的调控,分析其对衔接蛋白髓样分化因子88（My D88）和核转录因子-κB（NF-κB）的影响,探讨芍药汤对湿热型UC的作用机制。方法：Wistar大鼠雌雄各60只,分为空白组、模型组、芍药汤高、中、低剂量组、柳氮磺砒啶组,以2,4,6-三硝基苯磺酸（TNBS）结合乙醇复合法复制湿热型UC大鼠模型,芍药汤高、中、低剂量灌胃,柳氮磺砒啶组予柳氮磺砒啶研磨成粉配置成与中药等体积液体灌胃,空白组及模型组予等体积生理盐水灌胃,连续21 d。取结肠组织,运用实时荧光定量聚合酶链式反应（Real-time,PCR）法、蛋白免疫印迹法（Western blot）检测mRNA及蛋白表达,苏伊红-木精（HE）染色观察病理切片。结果：与空白组比较,模型组HMGB1,My D88,NF-κB蛋白及mRNA表达明显升高（P〈0.05）;与模型组比较,芍药汤各组、柳氮磺砒啶组HMGB1,My D88,NF-κB蛋白及mRNA表达均有不同程度地下降,芍药汤高剂量组及柳氮磺砒啶组最为显著（P〈0.05）。结论：芍药汤可调控HMGB1抑制TLRs信号通路中My D88,NF-κB基因表达,减弱湿热型UC的炎症反应。展开更多
Background Chimerism analysis is an important tool for the surveillance of post-transplant engraftment. It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-...Background Chimerism analysis is an important tool for the surveillance of post-transplant engraftment. It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease. Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation （HSCT）. Methods A panel of 29 selected sequence polymorphism （SP） markers was screened by real-time polymerase chain reaction （RT-PCR） to obtain the informative marker for every leukemia patient. Quantitative chimerism analysis of bone marrow （BM） samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally. The chimerisms of BM and peripheral blood （PB） samples of 14 patients at relapse were compared. Results Twenty-one patients experienced leukemia relapse at a median of 135 days （range, 30-720 days） after transplantation. High recipient chimerism in BM was found in all patients at relapse, and increased recipient chimerism in BM samples was observed in 90% （19/21） of patients before relapse. With 0.5% recipient DNA as the cut-off, median time between the detection of increased recipient chimerism and relapse was 45 days （range, 0-120 days）, with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse. Median percentage of recipient DNA in 20 stable remission patients was 0.28%, 0.04%, 0.05%, 0.05%, 0.08%, and 0.05% at 1, 2, 3, 6, 9, and 12 months, respectively, after transplantation. This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination. The recipient chimerisms in BM were significantly higher than those in PB at relapse （P=-0.001）. Conclusions This SP-based RT-PCR assay is a reliable method for chimerism analysis. Chimerism kinetics in BM can be used as a marker of impending leukemia relapse, especially when no other specific marker is available. Based on our findings, we recommend examining not only PB samples but also BM samples in HSCT patients.展开更多
Background Umbilical cord blood （UCB） has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the ...Background Umbilical cord blood （UCB） has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the leukemia-free survival （LFS） and some primary results, such as hematologic recovery, risk of graft-versus-host disease （GVHD）, relapse, and long-term survival, after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source. Methods The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood （UCBT） as a primary unrelated stem cell source （n=38）, bone marrow （UBMT n=28, transplanted before January 2003）, or peripheral blood stem cells （UPBSCT n=46, transplanted after January 2003） between July 2000 and July 2008 were analyzed. Results Except that the patients were much younger in the UCBT group （median age, 10.5 years in UCBT, 30 years in UPBSCT, and 20 years in UBMT）, other pre-transplant parameters, such as gender, diagnosis, and the phase of disease, were comparable. All patients received myeloablative regimens, primarily including BUCY; however, there was less anti- thymocyte globulin （ATG） used for the UBMT patients （2/38 in UCBT, 0/46 in UPBSCT, and 8/28 in UBMT did not use ATG, P=0.000）. Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets. The cumulative allo-engraftment rates were also significantly lower （87.8% vs. 97.8% vs. 100% for WBC, P=0.000; 73.0% vs. 97.5% vs. 89.5% for PLT, P=0.000） for UCBT. The incidence of Grade 2-4 and 3-4 acute graft versus host disease （aGVHD） was much higher in the UBMT group but did not differ among the other groups （51% and 13.2%, 40.2% and 10.5%, and 77.4% and 41.2%, respectively, for UCBT, UPBSCT, and UBMT, P=0.000）. The occurrence of extensive chronic GVHD （cGVHD） was significantly decreased for recipients of UCBT （4%） compared with that of UPBSCT （39.1%） and UBMT （49.1%, P=0.000）, although the rates of whole cGVHD were not significantly different （30.3%, 63.1%, and 60.1% for UCBT, UPBSCT, and UBMT, respectively）. The patients had a similar rate of CMV infection （21/38, 28/46, and 22/28 for UCBT, UPBSCT, and UBMT, respectively）, while the HC occurrence was lower after UCBT （7/38, 16/46, and 14/28 for UCBT, UPBSCT, and UBMT, respectively）. As of August 2012, there was no apparent difference in 5-year overall survival （OS）, LFS, or the relapse rate for each graft source （52.5%, 52.6%, and 20.8% in UCBT; 48.7%, 46.4%, and 27.9% in UPBSCT; and 46.4%, 42.9%, and 16.0% in UBMT）. Conclusion These data support the use of UCB donors as an alternative allogeneic donor.展开更多
Both human hereditary spherocytosis （HS） and chronic myelogenous leukemia （CML） are life threatening. Herein we have reported the case of a woman with a combined disorder of HS and CML who underwent the matched si...Both human hereditary spherocytosis （HS） and chronic myelogenous leukemia （CML） are life threatening. Herein we have reported the case of a woman with a combined disorder of HS and CML who underwent the matched sibling allogeneic stem cell transplantation. The complete donor erythroid cells were obtained. The red blood cell counts significantly improved throughout life comparing with pre-hematopoietic stem cell transplantation （HSCT）. Reticulocyte counts normalized, and BCR-ABL was cleared away. The total bilirubin level was also corrected in this recipient. Our case is a rare example with a combined disorder of HS and CML following allogeneic stem cell transplantation. HS was not a contraindication for patient in the matched sibling transplant setting.展开更多
文摘Background Chimerism analysis is an important tool for the surveillance of post-transplant engraftment. It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease. Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation （HSCT）. Methods A panel of 29 selected sequence polymorphism （SP） markers was screened by real-time polymerase chain reaction （RT-PCR） to obtain the informative marker for every leukemia patient. Quantitative chimerism analysis of bone marrow （BM） samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally. The chimerisms of BM and peripheral blood （PB） samples of 14 patients at relapse were compared. Results Twenty-one patients experienced leukemia relapse at a median of 135 days （range, 30-720 days） after transplantation. High recipient chimerism in BM was found in all patients at relapse, and increased recipient chimerism in BM samples was observed in 90% （19/21） of patients before relapse. With 0.5% recipient DNA as the cut-off, median time between the detection of increased recipient chimerism and relapse was 45 days （range, 0-120 days）, with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse. Median percentage of recipient DNA in 20 stable remission patients was 0.28%, 0.04%, 0.05%, 0.05%, 0.08%, and 0.05% at 1, 2, 3, 6, 9, and 12 months, respectively, after transplantation. This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination. The recipient chimerisms in BM were significantly higher than those in PB at relapse （P=-0.001）. Conclusions This SP-based RT-PCR assay is a reliable method for chimerism analysis. Chimerism kinetics in BM can be used as a marker of impending leukemia relapse, especially when no other specific marker is available. Based on our findings, we recommend examining not only PB samples but also BM samples in HSCT patients.
文摘Background Umbilical cord blood （UCB） has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the leukemia-free survival （LFS） and some primary results, such as hematologic recovery, risk of graft-versus-host disease （GVHD）, relapse, and long-term survival, after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source. Methods The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood （UCBT） as a primary unrelated stem cell source （n=38）, bone marrow （UBMT n=28, transplanted before January 2003）, or peripheral blood stem cells （UPBSCT n=46, transplanted after January 2003） between July 2000 and July 2008 were analyzed. Results Except that the patients were much younger in the UCBT group （median age, 10.5 years in UCBT, 30 years in UPBSCT, and 20 years in UBMT）, other pre-transplant parameters, such as gender, diagnosis, and the phase of disease, were comparable. All patients received myeloablative regimens, primarily including BUCY; however, there was less anti- thymocyte globulin （ATG） used for the UBMT patients （2/38 in UCBT, 0/46 in UPBSCT, and 8/28 in UBMT did not use ATG, P=0.000）. Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets. The cumulative allo-engraftment rates were also significantly lower （87.8% vs. 97.8% vs. 100% for WBC, P=0.000; 73.0% vs. 97.5% vs. 89.5% for PLT, P=0.000） for UCBT. The incidence of Grade 2-4 and 3-4 acute graft versus host disease （aGVHD） was much higher in the UBMT group but did not differ among the other groups （51% and 13.2%, 40.2% and 10.5%, and 77.4% and 41.2%, respectively, for UCBT, UPBSCT, and UBMT, P=0.000）. The occurrence of extensive chronic GVHD （cGVHD） was significantly decreased for recipients of UCBT （4%） compared with that of UPBSCT （39.1%） and UBMT （49.1%, P=0.000）, although the rates of whole cGVHD were not significantly different （30.3%, 63.1%, and 60.1% for UCBT, UPBSCT, and UBMT, respectively）. The patients had a similar rate of CMV infection （21/38, 28/46, and 22/28 for UCBT, UPBSCT, and UBMT, respectively）, while the HC occurrence was lower after UCBT （7/38, 16/46, and 14/28 for UCBT, UPBSCT, and UBMT, respectively）. As of August 2012, there was no apparent difference in 5-year overall survival （OS）, LFS, or the relapse rate for each graft source （52.5%, 52.6%, and 20.8% in UCBT; 48.7%, 46.4%, and 27.9% in UPBSCT; and 46.4%, 42.9%, and 16.0% in UBMT）. Conclusion These data support the use of UCB donors as an alternative allogeneic donor.
基金This work was supported by the grants from the National Natural Science Foundation of China （No. 30770911 and No. 81070449） the Science Foundation of Beijing City in China （No. 7112139）.
文摘Both human hereditary spherocytosis （HS） and chronic myelogenous leukemia （CML） are life threatening. Herein we have reported the case of a woman with a combined disorder of HS and CML who underwent the matched sibling allogeneic stem cell transplantation. The complete donor erythroid cells were obtained. The red blood cell counts significantly improved throughout life comparing with pre-hematopoietic stem cell transplantation （HSCT）. Reticulocyte counts normalized, and BCR-ABL was cleared away. The total bilirubin level was also corrected in this recipient. Our case is a rare example with a combined disorder of HS and CML following allogeneic stem cell transplantation. HS was not a contraindication for patient in the matched sibling transplant setting.
