From November 26 to December 3,2023,Professor Wu Dong of the International Wushu Development Research Center of the China Wushu School,Beijing Sport University went to Tanzania and Mauritius to give lectures.During th...From November 26 to December 3,2023,Professor Wu Dong of the International Wushu Development Research Center of the China Wushu School,Beijing Sport University went to Tanzania and Mauritius to give lectures.During the 8-day China Story Taijiquan lecture series,the people of Tanzania and Mauritius have got close to Taijiquan,understood the mystery of Taijiquan and experienced its effects on health.展开更多
一、参照对比,其意自明1.英语中多义词很多,如何确定某个关键词在句子中的确切含义,有时字典是帮不了很多忙。一个在实践中行之有效的方法是在句子中找到同它关系密切的词,与之参照对比,往往能够得出十分贴切的含义。例如:Automation ha...一、参照对比,其意自明1.英语中多义词很多,如何确定某个关键词在句子中的确切含义,有时字典是帮不了很多忙。一个在实践中行之有效的方法是在句子中找到同它关系密切的词,与之参照对比,往往能够得出十分贴切的含义。例如:Automation has been,and still is,agreatly misused word,but its propermeaning,and therefore its implications,展开更多
A wide variety of human tumors express interleukin10 (IL-10) for reasons poorly understood. We haveanalysed the effect of spontaneous IL-10 expression by amouse tumor (J558L) on its immunparalysing effect.Because cros...A wide variety of human tumors express interleukin10 (IL-10) for reasons poorly understood. We haveanalysed the effect of spontaneous IL-10 expression by amouse tumor (J558L) on its immunparalysing effect.Because cross-priming" of T cells by host antigenpresenting cells for MHC class I restricted tumor antigensis a major pathway for induction of tumor immunity andthat is enhanced by granulocyte-macrophage colony-stimulating factor (GM-CSF), we expressed this cytokinein J558L cells. GM-CSF secreting cells were not展开更多
Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplanta...Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction,angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action,and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke.We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.展开更多
Electroacupuncture at the head acupoints Baihui(GV20) and Shuigou(GV26) improves recovery of neurological function following ischemic cerebrovascular events,but its mechanism remains incompletely understood.We hyp...Electroacupuncture at the head acupoints Baihui(GV20) and Shuigou(GV26) improves recovery of neurological function following ischemic cerebrovascular events,but its mechanism remains incompletely understood.We hypothesized that the action of electroacupuncture at these acupoints is associated with elevated serum levels of transforming growth factor beta 1(TGF-β1).To test this,we established a rat model of cerebral ischemia by middle cerebral artery occlusion.Electroacupuncture was performed at Baihui and Shuigou with a “dispersedense” wave at an alternating frequency of 2 and 150 Hz,and at a constant intensity of 3 m A.Each electroacupuncture session lasted 30 minutes and was performed every 12 hours for 3 days.Neurological severity scores were lower in injured rats after acupuncture than in those not subjected to treatment.Furthermore,serum level of TGF-β1 was greater after electroacupuncture than after no treatment.Our results indicate that electroacupuncture at Baihui and Shuigou increases the serum level of TGF-β1 in rats with acute cerebral ischemia/reperfusion injury,and exerts neuroprotective effects.展开更多
Intracranial aneurysms remain important clinical concern. There is relatively low risk of rupture of symptomless aneurysms incidentally found in MRA or CTA performed due to other indications. Not all of the intracrani...Intracranial aneurysms remain important clinical concern. There is relatively low risk of rupture of symptomless aneurysms incidentally found in MRA or CTA performed due to other indications. Not all of the intracranial aneurysms should or can be treated with neurosurgery intervention or endovascular embolization. Clinical strategy for small, symptomless, unruptured aneurysms is still questionable. Mechanisms underlying aneurysms formation,progression and rupture are poorly understood. Inflammation is one of the factors suspected to participate in these processes. Therefore the aim of this manuscript is to present current state of knowledge about the role of inflammation in the formation and progression of intracranial aneurysms and in their rupture process. Current knowledge about possible pharmacological treatment of intracranial aneurysms will also be presented. Macrophages infiltration seems to participate in the formation of intracranial aneurysms. Inhibition of signals sent by macrophages may prevent the aneurysms formation. Inflammation present in the wall of the aneurysm seems to be also related to the aneurysm's rupture risk. However it does not seem to be the only cause of the degeneration,but it can be a possible target of drug therapy. Some preliminary studies in humans indicate the potential role of aspirin as a factor that decrease the level of inflammation and lower the risk of rupture of intracranial aneurysms. However further research including a greater number of subjects and a prospective randomized design are necessary to assess the role of aspirin in preventing strategy for small,symptomless,unruptured intracranial aneurysms.展开更多
Neural stem cells(NSCs) proliferation can be influenced by repetitive transcranial magnetic stimulation(r TMS) in vivo via micro RNA-106b-25 cluster,but the underlying mechanisms are poorly understood. This study ...Neural stem cells(NSCs) proliferation can be influenced by repetitive transcranial magnetic stimulation(r TMS) in vivo via micro RNA-106b-25 cluster,but the underlying mechanisms are poorly understood. This study investigated the involvement of micro RNA-106b-25 cluster in the proliferation of NSCs after repetitive magnetic stimulation(r MS) in vitro. NSCs were stimulated by r MS(200/400/600/800/1000 pulses per day,with 10 Hz frequency and 50% maximum machine output) over a 3-day period. NSCs proliferation was detected by using ki-67 and Ed U staining. Ki-67,p21,p57,cyclin D1,cyclin E,cyclin A,cdk2,cdk4 proteins and mi R-106 b,mi R-93,mi R-25 m RNAs were detected by Western blotting and q RT-PCR,respectively. The results showed that r MS could promote NSCs proliferation in a dose-dependent manner. The proportions of ki-67+ and Edu+ cells in 1000 pulses group were 20.65% and 4.00%,respectively,significantly higher than those in control group(9.25%,2.05%). The expression levels of mi R-106 b and mi R-93 were significantly upregulated in 600–1000 pulses groups compared with control group(P〈0.05 or 0.01 for all). The expression levels of p21 protein were decreased significantly in 800/1000 pulses groups,and those of cyclin D1,cyclin A,cyclin E,cdk2 and cdk4 were obviously increased after r MS as compared with control group(P〈0.05 or 0.01 for all). In conclusion,our findings suggested that r MS enhances the NSCs proliferation in vitro in a dose-dependent manner and mi R-106b/p21/cdks/cyclins pathway was involved in the process.展开更多
Angiotensin Ⅱ type 2 receptor(AT2R) activation has been shown to protect against stroke,but its precise mechanism remains poorly understood.We investigated whether the protective effect of AT2 R against ischemia/re...Angiotensin Ⅱ type 2 receptor(AT2R) activation has been shown to protect against stroke,but its precise mechanism remains poorly understood.We investigated whether the protective effect of AT2 R against ischemia/reperfusion injury is mediated by the suppression of immune and inflammatory responses.Rat models of middle cerebral artery occlusion were intraperitoneally injected with physiological saline,the AT2 R agonist CGP42112(1 mg/kg per day) or antagonist PD123319(1 mg/kg per day).In the CGP42112 group,AT2 R expression increased,the infarct area decreased,interleukin-1β and tumor necrosis factor-α expression decreased,and interleukin-10 expression increased compared with the saline group.Antagonisin AT2 R using PD123319 produced the opposite effects.These results indicate that AT2 R activation suppresses immune and inflammatory responses,and protects against cerebral ischemia/reperfusion injury.展开更多
MicroRNAs(miRNAs) are small,non-coding RNAs that negatively adjust gene expression in multifarious biological processes.However,the regulatory effects of miRNAs on Schwann cells remain poorly understood.Previous mic...MicroRNAs(miRNAs) are small,non-coding RNAs that negatively adjust gene expression in multifarious biological processes.However,the regulatory effects of miRNAs on Schwann cells remain poorly understood.Previous microarray analysis results have shown that miRNA expression is altered following sciatic nerve transaction,thereby affecting proliferation and migration of Schwann cells.This study investigated whether miR-148b-3p could regulate migration of Schwann cells by directly targeting cullin-associated and neddylation-dissociated 1(Cand1).Up-regulated expression of miR-148b-3p promoted Schwann cell migration,whereas silencing of miR-148b-3p inhibited Schwann cell migration in vitro.Further experiments confirmed that Candl was a direct target of miR-148b-3p,and Candl knockdown reversed suppression of the miR-148b-3p inhibitor on Schwann cell migration.These results suggested that miR-148b-3p promoted migration of Schwann cells by directly targeting Candl in vitro.展开更多
Background Bone is a dynamic tissue that constantly undergoes remodeling in which a coupled process of bone formation and resorption continues throughout life.This remodeling is necessary to maintain the structural in...Background Bone is a dynamic tissue that constantly undergoes remodeling in which a coupled process of bone formation and resorption continues throughout life.This remodeling is necessary to maintain the structural integrity of the skeleton under conditions of changing mechanical forces.It is important to develop bone remodeling theory in order to explain bone development and to instruct bone disease therapy and rehabilitation.However,the process and mechanism are not fully understood.Our study was carried out to investigate biomechanical mechanism of bone remodeling with the respect to bone tissue/cell mechanobiology,computational biomechanics and animal model.展开更多
The significant increase in the number of older adults in China,coupled with continuing industrialization and urbanization,has profound social and economic ramifications,including the evolution of major challenges to ...The significant increase in the number of older adults in China,coupled with continuing industrialization and urbanization,has profound social and economic ramifications,including the evolution of major challenges to public health,elder care services,policy-making,and the nation’s healthcare system.While the unprecedented changes in political and economic structures have obviously increased China’s productivity and revenues,what is less well understood is how they展开更多
Endothelial progenitor cells(EPCs)are a circulating,bone marrow-derived cell population that participate in both vasculogenesis and vascular homeostasis.Recent studies have shown that EPCs are reduced by^50% in diabet...Endothelial progenitor cells(EPCs)are a circulating,bone marrow-derived cell population that participate in both vasculogenesis and vascular homeostasis.Recent studies have shown that EPCs are reduced by^50% in diabetes that correlates inversely with its mortality rate.In addition,EPC angiogenic functions are severely impaired in diabetes.However,the molecular and cellular mechanisms underlying EPC dysfunction are poorly understood.Our current studies have focused on in vitro and in展开更多
Grifolin,a secondary metabolite isolated from the fresh fruiting bodies of mushroom Albatrellus confluens,inhibits the growth of some cancer cell lines in vitro by induction of apoptosis in the previous studies of our...Grifolin,a secondary metabolite isolated from the fresh fruiting bodies of mushroom Albatrellus confluens,inhibits the growth of some cancer cell lines in vitro by induction of apoptosis in the previous studies of our group.However,the mechanisms are not completely understood.An expression profiling analysis of apoptosis-related gene provided a clue that death-associated protein kinase 1(dapk1)gene was upregulated at least twofold in response to grifolin treatment in展开更多
Acute graft-versus-host disease(a GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation(allo-HSCT). However,the mechanisms of a GVHD are not well understood. We aim to investigat...Acute graft-versus-host disease(a GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation(allo-HSCT). However,the mechanisms of a GVHD are not well understood. We aim to investigate the roles of the three angiogenic factors: angiopoietin-1(Ang-1),Ang-2 and vascular endothelial growth factor(VEGF) in the development of a GVHD. Twenty-one patients who underwent allo-HSCT were included in our study. The dynamic changes of Ang-1,Ang-2 and VEGF were monitored in patients before and after allo-HSCT. In vitro,endothelial cells(ECs) were treated with TNF-α in the presence or absence of Ang-1,and then the Ang-2 level in the cell culture medium and the tubule formation by ECs were evaluated. After allo-HSCT,Ang-1,Ang-2 and VEGF all exhibited significant variation,suggesting these factors might be involved in the endothelial damage in transplantation. Patients with a GVHD had lower Ang-1 level at day 7 but higher Ang-2 level at day 21 than those without a GVHD,implying that Ang-1 may play a protective role in early phase yet Ang-2 is a promotion factor to a GVHD. In vitro,TNF-α promoted the release of Ang-2 by ECs and impaired tubule formation of ECs,which were both weakened by Ang-1,suggesting that Ang-1 may play a protective role in a GVHD by influencing the secretion of Ang-2,consistent with our in vivo tests. It is concluded that monitoring changes of these factors following allo-HSCT might help to identify patients at a high risk for a GVHD.展开更多
文摘From November 26 to December 3,2023,Professor Wu Dong of the International Wushu Development Research Center of the China Wushu School,Beijing Sport University went to Tanzania and Mauritius to give lectures.During the 8-day China Story Taijiquan lecture series,the people of Tanzania and Mauritius have got close to Taijiquan,understood the mystery of Taijiquan and experienced its effects on health.
文摘一、参照对比,其意自明1.英语中多义词很多,如何确定某个关键词在句子中的确切含义,有时字典是帮不了很多忙。一个在实践中行之有效的方法是在句子中找到同它关系密切的词,与之参照对比,往往能够得出十分贴切的含义。例如:Automation has been,and still is,agreatly misused word,but its propermeaning,and therefore its implications,
文摘A wide variety of human tumors express interleukin10 (IL-10) for reasons poorly understood. We haveanalysed the effect of spontaneous IL-10 expression by amouse tumor (J558L) on its immunparalysing effect.Because cross-priming" of T cells by host antigenpresenting cells for MHC class I restricted tumor antigensis a major pathway for induction of tumor immunity andthat is enhanced by granulocyte-macrophage colony-stimulating factor (GM-CSF), we expressed this cytokinein J558L cells. GM-CSF secreting cells were not
基金supported by the Natural Science Foundation of Heilongjiang Province of China,No.H2015083a grant from Higher Education Reform Project of Mudanjaing Medical University of China,No.2013016
文摘Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction,angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action,and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke.We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.
基金supported by the Key Project Fund of Henan Medical Science and Technology of Henan Province Health Bureau in China,No.200902009
文摘Electroacupuncture at the head acupoints Baihui(GV20) and Shuigou(GV26) improves recovery of neurological function following ischemic cerebrovascular events,but its mechanism remains incompletely understood.We hypothesized that the action of electroacupuncture at these acupoints is associated with elevated serum levels of transforming growth factor beta 1(TGF-β1).To test this,we established a rat model of cerebral ischemia by middle cerebral artery occlusion.Electroacupuncture was performed at Baihui and Shuigou with a “dispersedense” wave at an alternating frequency of 2 and 150 Hz,and at a constant intensity of 3 m A.Each electroacupuncture session lasted 30 minutes and was performed every 12 hours for 3 days.Neurological severity scores were lower in injured rats after acupuncture than in those not subjected to treatment.Furthermore,serum level of TGF-β1 was greater after electroacupuncture than after no treatment.Our results indicate that electroacupuncture at Baihui and Shuigou increases the serum level of TGF-β1 in rats with acute cerebral ischemia/reperfusion injury,and exerts neuroprotective effects.
文摘Intracranial aneurysms remain important clinical concern. There is relatively low risk of rupture of symptomless aneurysms incidentally found in MRA or CTA performed due to other indications. Not all of the intracranial aneurysms should or can be treated with neurosurgery intervention or endovascular embolization. Clinical strategy for small, symptomless, unruptured aneurysms is still questionable. Mechanisms underlying aneurysms formation,progression and rupture are poorly understood. Inflammation is one of the factors suspected to participate in these processes. Therefore the aim of this manuscript is to present current state of knowledge about the role of inflammation in the formation and progression of intracranial aneurysms and in their rupture process. Current knowledge about possible pharmacological treatment of intracranial aneurysms will also be presented. Macrophages infiltration seems to participate in the formation of intracranial aneurysms. Inhibition of signals sent by macrophages may prevent the aneurysms formation. Inflammation present in the wall of the aneurysm seems to be also related to the aneurysm's rupture risk. However it does not seem to be the only cause of the degeneration,but it can be a possible target of drug therapy. Some preliminary studies in humans indicate the potential role of aspirin as a factor that decrease the level of inflammation and lower the risk of rupture of intracranial aneurysms. However further research including a greater number of subjects and a prospective randomized design are necessary to assess the role of aspirin in preventing strategy for small,symptomless,unruptured intracranial aneurysms.
基金supported by grants from the National Natural Science Foundation of China(No.81071601,and No.81171858)
文摘Neural stem cells(NSCs) proliferation can be influenced by repetitive transcranial magnetic stimulation(r TMS) in vivo via micro RNA-106b-25 cluster,but the underlying mechanisms are poorly understood. This study investigated the involvement of micro RNA-106b-25 cluster in the proliferation of NSCs after repetitive magnetic stimulation(r MS) in vitro. NSCs were stimulated by r MS(200/400/600/800/1000 pulses per day,with 10 Hz frequency and 50% maximum machine output) over a 3-day period. NSCs proliferation was detected by using ki-67 and Ed U staining. Ki-67,p21,p57,cyclin D1,cyclin E,cyclin A,cdk2,cdk4 proteins and mi R-106 b,mi R-93,mi R-25 m RNAs were detected by Western blotting and q RT-PCR,respectively. The results showed that r MS could promote NSCs proliferation in a dose-dependent manner. The proportions of ki-67+ and Edu+ cells in 1000 pulses group were 20.65% and 4.00%,respectively,significantly higher than those in control group(9.25%,2.05%). The expression levels of mi R-106 b and mi R-93 were significantly upregulated in 600–1000 pulses groups compared with control group(P〈0.05 or 0.01 for all). The expression levels of p21 protein were decreased significantly in 800/1000 pulses groups,and those of cyclin D1,cyclin A,cyclin E,cdk2 and cdk4 were obviously increased after r MS as compared with control group(P〈0.05 or 0.01 for all). In conclusion,our findings suggested that r MS enhances the NSCs proliferation in vitro in a dose-dependent manner and mi R-106b/p21/cdks/cyclins pathway was involved in the process.
文摘Angiotensin Ⅱ type 2 receptor(AT2R) activation has been shown to protect against stroke,but its precise mechanism remains poorly understood.We investigated whether the protective effect of AT2 R against ischemia/reperfusion injury is mediated by the suppression of immune and inflammatory responses.Rat models of middle cerebral artery occlusion were intraperitoneally injected with physiological saline,the AT2 R agonist CGP42112(1 mg/kg per day) or antagonist PD123319(1 mg/kg per day).In the CGP42112 group,AT2 R expression increased,the infarct area decreased,interleukin-1β and tumor necrosis factor-α expression decreased,and interleukin-10 expression increased compared with the saline group.Antagonisin AT2 R using PD123319 produced the opposite effects.These results indicate that AT2 R activation suppresses immune and inflammatory responses,and protects against cerebral ischemia/reperfusion injury.
基金supported by the National Key Basic Research Program of China,No.2014CB542202the National High-Tech R&D Program of China(863 Program),No.2012AA020502+2 种基金the National Natural Science Foundation of China,No.81130080,81371389 and 81571198the Natural Science Foundation of Nantong University of China,No.13040397the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘MicroRNAs(miRNAs) are small,non-coding RNAs that negatively adjust gene expression in multifarious biological processes.However,the regulatory effects of miRNAs on Schwann cells remain poorly understood.Previous microarray analysis results have shown that miRNA expression is altered following sciatic nerve transaction,thereby affecting proliferation and migration of Schwann cells.This study investigated whether miR-148b-3p could regulate migration of Schwann cells by directly targeting cullin-associated and neddylation-dissociated 1(Cand1).Up-regulated expression of miR-148b-3p promoted Schwann cell migration,whereas silencing of miR-148b-3p inhibited Schwann cell migration in vitro.Further experiments confirmed that Candl was a direct target of miR-148b-3p,and Candl knockdown reversed suppression of the miR-148b-3p inhibitor on Schwann cell migration.These results suggested that miR-148b-3p promoted migration of Schwann cells by directly targeting Candl in vitro.
基金supported by the National Natural Science Foundation of China(No.10832012)
文摘Background Bone is a dynamic tissue that constantly undergoes remodeling in which a coupled process of bone formation and resorption continues throughout life.This remodeling is necessary to maintain the structural integrity of the skeleton under conditions of changing mechanical forces.It is important to develop bone remodeling theory in order to explain bone development and to instruct bone disease therapy and rehabilitation.However,the process and mechanism are not fully understood.Our study was carried out to investigate biomechanical mechanism of bone remodeling with the respect to bone tissue/cell mechanobiology,computational biomechanics and animal model.
文摘The significant increase in the number of older adults in China,coupled with continuing industrialization and urbanization,has profound social and economic ramifications,including the evolution of major challenges to public health,elder care services,policy-making,and the nation’s healthcare system.While the unprecedented changes in political and economic structures have obviously increased China’s productivity and revenues,what is less well understood is how they
基金Supported by Grants from NIH R01GM077352,VA Merit Award I01RX000244,AHA GIA0855601G,ADA Research Award7-08-RA-23NSFC Overseas Collaborative Grant#30728021
文摘Endothelial progenitor cells(EPCs)are a circulating,bone marrow-derived cell population that participate in both vasculogenesis and vascular homeostasis.Recent studies have shown that EPCs are reduced by^50% in diabetes that correlates inversely with its mortality rate.In addition,EPC angiogenic functions are severely impaired in diabetes.However,the molecular and cellular mechanisms underlying EPC dysfunction are poorly understood.Our current studies have focused on in vitro and in
文摘Grifolin,a secondary metabolite isolated from the fresh fruiting bodies of mushroom Albatrellus confluens,inhibits the growth of some cancer cell lines in vitro by induction of apoptosis in the previous studies of our group.However,the mechanisms are not completely understood.An expression profiling analysis of apoptosis-related gene provided a clue that death-associated protein kinase 1(dapk1)gene was upregulated at least twofold in response to grifolin treatment in
基金supported by grants from the National Natural Science Foundation of China(No.81172826)Collaborative Innovation Center of Hematology,China
文摘Acute graft-versus-host disease(a GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation(allo-HSCT). However,the mechanisms of a GVHD are not well understood. We aim to investigate the roles of the three angiogenic factors: angiopoietin-1(Ang-1),Ang-2 and vascular endothelial growth factor(VEGF) in the development of a GVHD. Twenty-one patients who underwent allo-HSCT were included in our study. The dynamic changes of Ang-1,Ang-2 and VEGF were monitored in patients before and after allo-HSCT. In vitro,endothelial cells(ECs) were treated with TNF-α in the presence or absence of Ang-1,and then the Ang-2 level in the cell culture medium and the tubule formation by ECs were evaluated. After allo-HSCT,Ang-1,Ang-2 and VEGF all exhibited significant variation,suggesting these factors might be involved in the endothelial damage in transplantation. Patients with a GVHD had lower Ang-1 level at day 7 but higher Ang-2 level at day 21 than those without a GVHD,implying that Ang-1 may play a protective role in early phase yet Ang-2 is a promotion factor to a GVHD. In vitro,TNF-α promoted the release of Ang-2 by ECs and impaired tubule formation of ECs,which were both weakened by Ang-1,suggesting that Ang-1 may play a protective role in a GVHD by influencing the secretion of Ang-2,consistent with our in vivo tests. It is concluded that monitoring changes of these factors following allo-HSCT might help to identify patients at a high risk for a GVHD.