Therapeutic Effect of Convalescent Plasma Transfusion on Fulminant Viral Infectious Diseases--Review / 中国实验血液学杂志

Novel coronavirus disease 2019 (COVID-19) has started to erupt in Wuhan since December 2019, and then the cases of COVID-19 increased rapidly, the epidemic situation spreaded to most area of China. Owing to the lack of specific drugs at present, convalescent plasma therapy becomes an alternative treatment. However, the choice of the donor, suitable patients, timing of treatment, administrate dose, the advantages and disadvantages of the treatment are not clear. This article reviews the clinical studies and case reports of convalescent plasma therapy in several previous viral infectious diseases in order to provide clues for the treatment of COVID-19.

Efficacy Analysis of Unrelated Cord Blood Transplantation in the Treatment of Juvenile Myelomonocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Juvenile myelomonocytic leukemia (JMML).@*METHODS@#The clinical data of 5 children with JMML who were treated with unrelated UCBT from October 2011 to July 2019 were retrospectively analyzed. The age of onset for the five children (male) ranged from 0.4 to 5.0 years old, with a median age of 1.5 years old. All the patients received myeloablative conditioning regimen without ATG to whom cyclosporine A (CsA) with short-term mycophenolate mofetil (MMF) was given for GVHD prophylaxis.@*RESULTS@#Four children acquired engraftment. One patient received secondary haploidentical hematopoietic stem cell transplantation because of the failure in the first unrelated UCBT. Grade Ⅲ to Ⅳ aGVHD occurred in 2 cases and was controlled, and none of the patients developed cGVHD. Three cases achieved long-time disease free survival，and no patient relapsed.@*CONCLUSION@#UCBT is an effective treatment for children with JMML.

Effect of KIR/HLA receptor-ligand mode on prognosis of single unrelated cord blood transplantation in patients with hematological malignancies / 中华血液学杂志

Objective: To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen (KIR/HLA) receptor-ligand model in single unrelated cord blood transplantation (sUCBT) . Methods: Between July 2012 and June 2018, 270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups. Group 1 (n=174) patients lacked a C-ligand for inhibitory KIR on UCB NK cells (patients homozygous C1/C1 or C2/C2) . Group 2 (n=96) patients expressed both C ligands for inhibitory KIR in the receptor (patients heterozygous C1/C2) . Results: A total of 270 patients (146 males, 124 females) with a median age of 13 years (1-62) were included in this retrospective study. All patients received a myeloablative conditioning regimen (without ATG) . The ratio of neutrophil engraftment for group 1 and 2 were both 98.9%, the median time of neutrophil engraftment for group 1 and 2 was 16 (10-41) days vs 17 (11-33) days (P=0.705) . The ratio of platelet engraftment was 88.5% for group 1 and 87.5% for group 2, the median time of platelet engraftment was 35 (11-113) days vs 38.5 (13-96) days (P=0.317) . The cumulative incidence of Ⅱ-Ⅳ acute GVHD in 100 days was 38.7% (95%CI 31.4%-45.9%) for group 1 and 50.0% (95%CI 39.6%-59.6%) for group 2 (P=0.075) , but multivariate analysis showed that HLA-C ligand absence was an independent protective factor for Ⅱ-Ⅳ acute GVHD after transplantation (P=0.036) . Patients in absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2) : 17.7% (95%CI 11.7%-24.9%) vs 22.7% (95%CI 4.4%-32.2%) after 3 years (P=0.288) . The median follow-up time was 742 (335-2 512) days. The 3-year OS was 72.1% for group 1 and 60.5% for group 2 (P=0.079) . There was no statistically significant difference between the two groups in 3-year disease-free survival [64.9% (95%CI 56.2%-72.3%) vs 55.4% (95%CI 44.4%-65.0%) (χ(2)=3.027, P=0.082) ]. Non-relapse mortality for group 1 was 12.1% (95%CI 7.7%-17.4%) and for group 2 was 16.7% (95%CI 10.0%-24.8%) (P=0.328) . Conclusion: Patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades Ⅱ-Ⅳ acute GVHD after sUCBT.

Effects of High Cytomegalovirus DNA Load on Immune Reconstitution and Clinical Outcomes after Single Unrelated Cord Blood Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of cytomegalovirus (CMV) DNA load on immune reconstitution and clinical outcomes of patients after unrelated cord blood transplantation (UCBT).@*METHODS@#Eight-color flow cytometry was used to dynamically monitor the changes of peripheral blood lymphocyte subsets of 41 patients at one year after UCBT, and 10 healthy volunteers were enroled as controls. Patients were divided into two groups according to the DNA load of CMV (DNA copies <1000/ml and DNA copies ≥1000/ml). Comparative analyse of the effect of CMV DNA load on lymphocyte subsets and transplantation outcomes were carried out after transplantation.@*RESULTS@#The high CMV DNA load group showed a faster and expanded T cell reconstitution, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.38×10 /L vs 0.25×10 /L, P=0.015 and 2.53×10 /L vs 1.36×10 /L, P=0.006, respectively). Further analysis of T cell subsets suggested that CD8 T cells presented a higher and faster recovery in the high DNA load group, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.20×10 /L vs 0.10×10 /L, P=0.038 and 1.62×10 /L vs 0.68×10 /L, P=0.003, respectively). In addition, there were no significant differences in levels of B cells, regulatory B cells and NK cells between the two groups. Outcomes after one- and a-half-year transplantation showed that there were no significant difference in relapse, non-relapse mortality and overall survival between the high and the low DNA load groups (7.7% vs 7.5%) (P=0.900) (15.4% vs 21.4%) (P=0.686) and (76.9% vs 78.6%) (P=0.889) respectively.@*CONCLUSION@#The high CMV DNA load induces a faster and long-lasting expansion of T cells, mainly as the expansion of CD8 T cells after UCBT. Besides, under the current pre-emptive treatment of CMV, the high CMV DNA load does not affect the early survival of patients with acute myeloid leukemia after UCBT.

Efficacy Analysis of Unrelated Cord Blood Transplantation for High-Risk Refractory AML1-ETO Positive Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT).@*METHODS@#Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD.@*RESULTS@#The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)＞0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival.@*CONCLUSION@#UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.

Comparison of umbilical cord blood transplantation and hematopoietic stem cell transplantation from HLA-matched sibling donors in the treatment of myelodysplastic syndrome-EB or acute myeloid leukemia with myelodysplasia-related changes / 中华血液学杂志

Objective: To compare the clinical efficacy of umbilical cord blood transplantation (UCBT) and hematopoietic stem cell transplantation from HLA-matched sibling donors (MSD-HSCT) in the treatment of myelodysplastic syndrome-EB (MDS-EB) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) . Methods: A cohort of 64 patients (including 38 cases of MDS-EB and 26 cases of AML-MRC) who received UCBT/MSD-HSCT from February 2011 to December 2017 were retrospectively analyzed. Results: ①Compared with MSD-HSCT group, UCBT group had a higher proportion of AML-MRC patients [52.8% (19/36) vs 25.0% (7/28) , P=0.025], and a lower median age [13 (1.5-52) years vs 32 (10-57) years, P=0.001]. ②The engraftment of neutrophils both in UCBT and MSD-HSCT groups on +42 d was 100%, and the median engraftment time was 17.5 (11-31) d and 11.5 (10-20) d, respectively. The engraftment of platelet at +100 d in UCBT group was 91.4%, the median engraftment time was 40 (15-96) d; The engraftment of platelet at +100 d in MSD-HSCT group was 100%, and the median engraftment time was 15 (11-43) d. ③There were no statistically significant differences in terms of the cumulative incidence of Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD of 100 d and transplant related mortality (TRM) of 180 d, relapse rate, overall survival (OS) , disease-free survival (DFS) between UCBT and MSD-HSCT groups (P>0.05) . ④The 3-year cumulative incidence of chronic GVHD (cGVHD) and severe chronic GVHD in UCBT group were lower than of MSD-HSCT group [28.3% (95%CI 13.4%-45.3%) vs 67.9% (95%CI 46.1%-82.4%) , P=0.002; 10.3% (95%CI 2.5%-24.8%) vs 50.0% (95%CI 30.0%-67.1%) , respectively, P<0.001]. The cumulative 3-year incidence of GVHD-free and relapse-free survival (GRFS) of UCBT group was significantly higher than of MSD-HSCT group [55.0% (95%CI 36.0%-70.6%) vs 28.6% (95%CI 13.5%-45.6%) , P=0.038]. Conclusion: UCBT could obtain better quality of life after transplantation than MSD-HSCT in treatment of MDS-EB/AML-MRC.

Efficacy analysis of unrelated cord blood transplantation in the treatment of refractory and relapsed adult acute leukemia / 中华血液学杂志

Objective: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of refractory and relapsed acute leukemia (AL) patients. Methods: The clinical data of 22 refractory and relapsed AL patients who were treated with UCBT as salvage therapy from November 2009 to May 2017 were retrospectively analyzed. All patients received a myeloablative conditioning regimen for prevention of graft-versus-host disease (GVHD) with cyclosporine A (CSA)/short course of mycophenolate mofetil (MMF). Results: ①Of 22 patients, 9 cases were male and 13 female. The median age was 23 (15-44) years and median weight of 52.5 (43-82) kg. All patients were transplanted with a median umbilical cord blood nucleated cells of 3.07 (1.71-5.30)×107/kg (by weight), the median CD34+ cells was 1.60 (0.63-3.04)×105/kg (by weight). ②The myeloid cumulative implantation rate was 95.5% (95%CI 45.2-99.7%) after transplantation of 42 d, with the median implantation time of 19 (13-27) d. The platelet cumulative implantation rate after transplantation of 120 d was 81.8% (95%CI 54.2-93.6%), the median implantation time of 42 (20-164) d. ③The incidence of Ⅱ-Ⅳ, Ⅲ-Ⅳ aGVHD and the 2 year cumulative incidence of cGVHD were 36.4%, 13.6% and 40.3% respectively. ④ The transplant related mortality (TRM) after transplantation of 180d was 22.7%, 2 year cumulative rate of relapse was 18.7% (95%CI 3.6-42.5%), 2 year disease-free survival rate (DFS) and overall survival rate (OS) were 53.7% and 58.1%, respectively. Conclusion: The preliminary results show that the use of UCBT is safe and effective for refractory and relapsed AL patients who fail to respond to conventional chemotherapy.

Comparative analysis of early reconstitution of T-lymphocyte subsets and T-cell receptor excision cycles in patients after myeloablative unrelated cord blood and sibling donor transplantation / 中国实验血液学杂志

This study was purposed to comparatively analyze the early T-lymphocyte subsets and T-cell receptor excision cycles (TREC) reconstruction in recipients with hematologic malignancies after myeloablative unrelated cord blood transplantation (UCBT) and sibling donor bone marrow and/or peripheral blood stem cell transplantation (BMT/PBSCT). The peripheral blood T lymphocyte subsets were detected using flow cytometry and TREC were detected using real-time quantitative PCR for 40 patients with hematologic malignancies in the first six months after myeloablative allogenic hematopoietic stem cell transplantation. The results showed that in the first month after transplantation, the absolute counts of CD3(+), CD3(+) CD4(+), CD3(+) CD8(+) cells were lower significantly in the UCBT group than those in the BMT/PBSCT group. And later the absolute counts of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) cells were not different between two groups. The ratio of CD3(+)T subset in the peripheral blood lymphocytes of the UCBT recipients was lower, but the difference was not statistically significant within 2 months after transplantation. The ratio of CD3(+)CD4(+) cells in the patients received the UCBT and BMT/PBSCT decreased obviously since engraftment happened. The CD3(+)CD4(+) cells on the 2 months after transplantation fell to the lowest level, then gradually increased, but did not reach to the normal level until 6 months after transplantation. CD3(+)CD8(+)cells were well reconstituted, rising to normal at the engraftment after transplantation, with a low CD4(+): [KG-*2] CD8(+) ratio over the first 6 months after transplantation. Compared with the BMT/ PBSCT group, the naive T cells (CD3(+)CD4(+)CD45RA(+)CD62L(+)) were more in the first month after transplantation and the terminally differentiated effector memory T cells (CD3(+)CD4(+)CD45RA(+)CD62L(-)) were more at the 3 month after transplantation in the UCBT group, and those were significantly more than the normal control group. TREC were lower and did not recovered until 6 months after transplantation in the recipients of the two groups. It is concluded that compared with sibling donor's BMT/PBSCT, early T cell reconstitution significantly delayed after UCBT, but the terminally differentiated effector memory T cells are higher after transplantation, and thus play a anti-infective or anti-leukemia role.

Detection of Th17/treg cell-associated cytokines in peripheral blood of patients with graft-versus-host disease and its clinical significance / 中国实验血液学杂志

To investigate the peripheral levels and clinical significance of Th17/Treg cell-associated cytokines in patients with acute graft versus host disease (aGVHD) or chronic GVHD (cGVHD), blood samples were collected from 39 hematopoietic stem-cell transplantation patients and 20 healthy donors. The patients included 10 patients with aGVHD, 13 patients with cGVHD and 16 patients without evidence of GVHD. Th17/Treg cell-associated cytokines such as IFNγ, IL-4, IL-6, IL-10, TGF-β(1), IL-17 and IL-23 were detected by ELISA. The results showed that the plasma levels of IFN-γ, IL-4, IL-6, IL-17 and IL-23 significantly increased in patients with aGVHD or cGVHD, compared with the patients without clinical signs of GVHD and the healthy donors (p < 0.05), while IL-10 and TGF-β(1) were obviously lower than that of them (p < 0.05). After aGVHD and cGVHD patients were treated effectively, the plasma levels of IL-6, IL-17 and IL-23 were significantly decreased, and IL-10, TGF-β(1) were significantly increased, while the levels of IFN-γ and IL-4 did not markedly change. The TGF-β(1) level were negatively correlated with IL-6 (r = -0.36, p < 0.05), IL-17 (r = -0.51, p < 0.05) and IL-23 (r = -0.44, p < 0.05) respectively, while there were positive correlations between IL-6 and IL-17 (r = 0.62, p < 0.05), IL-6 and IL-23 (r = 0.71, p < 0.05), IL-17 and IL-23 (r = 0.93, p < 0.05). It is concluded that Th17/Treg cell-associated cytokines may play an important role in the development of a/cGVHD, which helps to find novel targets for developing new strategies of GVHD treatment.

Influence of TLR2 and TLR4 agonists on migration of cord blood CD34(+) cells / 中国实验血液学杂志

This study was aimed to investigate the influence of TLR2 and TLR4 agonists on the migration and adhesion activity of umbilical cord blood (UCB) CD34(+) cells and to explore the underlying mechanism. The expression of TLR2 and TLR4 on UCB CD34(+) cells was detected with flow cytometry. The effect of TLR2 agonist (PAM3CSK4) and TLR2 agonist (LPS) on the migration and adhesion ability of UCB CD34(+) cells was evaluated with chemotaxis and adhesion assays. The results indicated that expression levels of TLR2 and TLR4 were (14.2 ± 3.8)%, (19.6 ± 4.1)% respectively. Compared with the control group, the migration activity of UCB CD34(+) cells toward SDF-1 decreased significantly in LPS group (p < 0.01). The adhesion activity was not altered significantly in LPS group. However, both the migration activity towards SDF-1 and the adhesion activity of UCB CD34(+) cells were not changed significantly in PAM3CSK4 group. Further study found that LPS did not affect the expression level of CXCR4 on CD34(+) cells, but could inhibit the spontaneous migration ability of CD34(+) cells. It is concluded that TLR4 activation can decrease the chemotaxis function of CD34(+) cells towards SDF-1, which may associate with the decreased spontaneous migration ability of CD34(+) cells.

Association between metabolic syndrome and incidence of atrial fibrillation in essential hypertensive patients without left ventricular hypertrophy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between metabolic syndrome (MS) and the incidence of atrial fibrillation (AF) in essential hypertensive (EH) patients without left ventricular hypertrophy.</p><p><b>METHODS</b>A total of 972 EH without left ventricular hypertrophy were divided into EH + non MS group (n = 606) and EH + MS group (n = 366). Incidence of AF were compared between two groups.</p><p><b>RESULTS</b>(1) Incidence of AF in EH + MS group was significantly higher than that in EH + non MS group (12.84% vs. 6.93%, P < 0.01). (2) Left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDd), interventricular septum thickness (IVS), left ventricular posterior wall thickness (LVPW) and left ventricular mass (LVM) were all significantly higher in EH + MS group than those in EH + non MS group (all P < 0.01) while left ventricular mass index (LVMI) and ejection fraction (EF) were similar between two groups. (3) Logistic regression analysis showed age, hypertension duration, LAD, LVEDd and MS were significantly correlated with incidence of AF in EH patients (OR: 1.683, 1.308, 2.262, 3.848 and 1.853, P < 0.05) and obesity was the independent predictor for incidence of AF (OR: 1.706, P = 0.029).</p><p><b>CONCLUSION</b>MS was associated with increased incidence of AF in EH patients without left ventricular hypertrophy in this cohort.</p>

Unrelated cord blood transplantation in adult patients with hematologic malignancies / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the engraftment, transplant-related complications and survival after unrelated cord blood transplantation (UCBT) in patients with hematologic malignancies.</p><p><b>METHODS</b>Twenty eight consecutive adult patients with hematological malignancies were treated with UCBT and 20 of them were advanced-stage diseases. Double or multiple UCB grafts were used for 18 patients, while single UCB graft for 10 patients. Myeloablative conditioning regimens were given to 26 cases and nonmyeloablative regimens to 2 cases. All patients were given a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis.</p><p><b>RESULTS</b>Median time to neutrophil engraftment (≥ 0.5 × 10(9)/L) in 26 patients was 18 (14 - 37) days and platelet engraftment (≥ 20 × 10(9)/L) in 22 patients was 30 (25 - 49) days. Chimerism was weekly assessed by PCR analysis of short tandem repeat (STR) sequences in whole blood or bone marrow and 22 cases were confirmed of fully donor chimeric from 7 to 21 days after transplantation. Eighteen cases developed acute GVHD, greater than grade II in 1, and 6 of 22 patients who survived more than 100 days developed limited chronic GVHD. Eighteen cases were alive in hematologic remission at a median follow-up of 9.5 (2.5 - 72.0) months. The probability of event-free survival at 3 years was 56.7%. Two cases relapsed and 8 of 10 cases died of transplant related complications.</p><p><b>CONCLUSIONS</b>UCBT could be safely and effectively used for adult patients with hematologic malignancies. Use of double UCB units is a strategy extending the feasibility of UCBT.</p>

Expression and abscission of activated receptors and their ligands on/from NK cells in peripheral blood of patients with acute leukemia / 中国实验血液学杂志

This study was aimed to explore the immune escaping mechanisms based on expression and abscission of human natural killer (NK) cell activating receptors NKG2D and their ligands MICA/B, ULBP-1, 2, 3 in patients with acute leukemia (AL). 30 de novo AL patients and 10 healthy persons (control) were enrolled in study. Flow cytometry was used to detect the expression levels of MICA/B, ULBP-1, 2, 3 on leukemic cells. ELISA was used to detect the levels of soluble MICA (sMICA), solube MICB (sMICB) and soluble ULBP-1, -2, -3 in the serum. The results showed that sMICA, sMICB and ULBP-1, -2, -3 were not expressed or expressed at very low levels on leukemia cells of the patients; the levels of free sMICA and sMICB in serum of AL patients were higher than that in serum of healthy persons, there was significant difference (p<0.01). But the levels of ULBP 1-3 in serum of AL patients did not show obvious statistical difference as compared with healthy persons (p>0.05). It is concluded that the negative or low expression of NKG2D ligands (MICA, MICB and ULBPs) on surface of acute leukemia cells may lead to the immune escape of leukemia cells, the abscission of MICA and MICB, and the deficiency of ULBP expression on leukemia cells may be one of immune escape mechanisms of leukemia cells.

Functional defect of partial homing receptor on human cord blood hematopoietic stem/progenitor cells / 中国实验血液学杂志

This study was aimed to investigate the function defect of partial homing receptor on cord blood hematopoietic stem cells (CBHSC) and explore efficacy and feasibility of intervention in vitro. The expression and activity of active groups in P, E-selectin ligands on CD34+ cells from cord blood, bone marrow and peripheral blood were detected by flow cytometry; meanwhile the expression of active groups in selectin ligands on CD34+ cells treated by fucosyl transferase in vitro was determined by flow cytometry. The results indicated that the expression levels of CD26 on the surface of stem/progenitor cells (CD34+) from cord blood, bone marrow and peripheral blood were (7.62+/-0.63)%, (6.35+/-0.89)% and (6.18+/-0.91)% (p>0.05) respectively. And the activities of CD26 of the three sources of stem cells were 67.15 U/1000 cells (1 U=1 pmol/min), 26.85 U/1000 cells and 20.95 U/1000 cells respectively, in which the activity of CD26 on surface of CD34+ from cord blood was significantly higher than that from other both sources (p<0.01). The expression levels of P-selectin ligand on the stem/progenitor cells three kinds were (83.46+/-6.33)%, (15.65+/-0.89)% and (80.17+/-6.85)%, and the expression levels of E-selectin ligand on stem/progenitor cells of three kinds were (25.31+/-1.03)%, (26.34+/-0.89)% and (29.79+/-1.78)% respectively. The expression of E-selectin ligand on the surface of cord blood stem/progenitor cell CD34+ increased from (25.31+/-1.03)% to (63.23+/-1.08)% after glycosylation engineering. It is concluded that there is no significant difference of the expression of CD26 between the three sources of stem/progenitor cells, but the activity of CD26 in cord blood was obviously higher than that in bone marrow and peripheral blood. The expression of P-selectin ligand on bone marrow stem/progenitor cell was lower than that on stem cells of cord blood and peripheral blood. Glycosylation engineering can promote and elevate the expression of E-selectin ligand on the surface of CD34+ cells from cord blood.

Effects of HMGB1 on human cord blood CD34(+) hematopoietic stem cells proliferation and differentiation in vitro / 中华血液学杂志

<p><b>OBJECTIVE</b>To study both the release of HMGB1 from irradiation-treated mesenchymal stem cells (MSCs) and the effects of HMGB1 on human cord blood CD34(+) hematopoietic progenitor cell proliferation and differentiation.</p><p><b>METHODS</b>MSCs were obtained from human bone marrow. HMGB1 released by the MSCs after treatment with 12 Gy gamma-ray irradiation was determined by enzyme linked immunosorbent assay (ELISA). CD34(+) cells were positively selected with a MACS CD34 isolation kit. The freshly isolated CD34(+) cells were cultured in the presence of HMGB1 for 6 days. Phenotype of cultured cells surface molecules (CD13, CD14, CD11c, CD41 and CD71) were analyzed by flow cytometry. The proliferation and differentiation capacities of cord blood HSCs were assayed by colony forming cell assay. The receptors of HMGB1 (RAGE, TLR2 and TLR4) on cord blood CD34(+) cells were detected by flow cytometry.</p><p><b>RESULTS</b>HMGB1 level in the supernatant \[(4.3 +/- 0.9) ng/ml\] of the irradiated MSC was significantly higher than that in control \[(0.4 +/- 0.2) ng/ml\] (P < 0.01). Human cord blood CD34(+) cells expressed the HMGB1 receptors RAGE, TLR2 and TLR4. The HMGB1-treated CD34(+) cells contained higher proportions of CD13(+) \[(32.6 +/- 5.9)% vs (18.4 +/- 3.8)%\], CD14(+)\[(25.4 +/- 4.4)% vs (12.6 +/- 2.7)%\], CD11c(+) \[(20.3 +/- 3.9)% vs (9.8 +/- 2.1)%\], CD71(+) \[(47.1 +/- 7.4)% vs (26.6 +/- 4.6)%\] cells compared with control group did. But HMGB1 did not induce the generation of CD41(+) cells \[(1.3 +/- 0.5)% vs (1.1 +/- 0.4)%\]. Furthermore, HMGB1 profoundly induced the growth of BFU-E, CFU-GM and total CFU in a dose-dependent manner, and this effect was partially inhibited by TLR2 and TLR4 antibodies.</p><p><b>CONCLUSION</b>Human MSC treated with gamma-ray irradiation can release HMGB1, which can induce the proliferation and differentiation of human cord CD34(+) cells.</p>

Electrocardiography analysis of residents in Keshan disease area in Shaanxi Province / 中国地方病学杂志

Objective To explore the Electrocardiography (ECG) changes of residents in Keshan disease area and the status of growth and decline of Keshan disease in Shaanxi Province. Methods Using stratified randomized sampling method,2 mild,2 moderate and 2 serious disease counties were selected respectively in 2005 and 2006. A total of 6 counties were sampled,2 villages,one with severe disease and one with mild,were selected from each sampled county. A total of 12 villages were selected. The clinical examination and ECG were conducted in 3-year old children of agricultural population of the selected villages. Results ECG of 5692 cases were performed in the selected 12 village in the 6 counties,in which 4917 cases showed normal electrocardiogram,up to 86.38% (4917/5692). Two hundred and fifty-two cases showed roughly normal electrocardiograms,up to 4.43%(252/5692). Five hundred and twenty-three cases had abnormal electrocardiogram,accounting for 9.19% (523/5692). Among them,the abnormal electrocardiogram rates in mild,moderate and serious disease areas were 7.07% (144/2036), 11.41%(167/1646) and 10.54%(212/2010),respectively. Atrioventricular block was the major abnormal electrocardiogram change,followed by arrhythmia,ST-T changes,and low voltage. One hundred and thirty-nine cases were confirmed as latent and chronic Keshan diseases. One hundred and thirty-one cases were latent Keshan, and detection rate was 2.30%(131/5692). Eight cases were chronic Keshan,and the detective rate was 0.14% (8/5692). Complete right bundle branch block [37.06% (63/170) ],ST-T changes [22.35% (38/170) ],multiple premature ventricular beats [12.94% (22/170)] were the major abnormal electrocardiogram change of Keshan patients. Conclusions Atrioventricular block and arrhythmia are the major abnormal electrocardiogram changes. Keshan disease incidences are controlled under a stable condition.

Influence of high mobility group box 1 on migration of human cord blood CD34(+) cells / 中国实验血液学杂志

The objective of study was to explore the influence of high mobility group box 1 (HMGB1) on migration of cord blood CD34(+) cells and their mechanism of migration. The expressions of receptor for advanced glycation end products (RAGE), toll-like receptor-2 (TLR2) and TLR4 were detected by flow cytometry. The CD34(+) cells in umbilical cord blood (CB) were enriched by MiniMACS and were exposed to various concentration of HMGB1 (10, 50, 100, 1, 000 ng/ml), then the migration effect of HMGB1 on umbilical cord blood (UCB) CD34(+) cell count was determined by microscopy, the chemotactic index was calculated. The CD34(+) cells untreated with HMGB1 were used as control. The results indicated that the purity of the isolated CD34(+) cells was more than 98%. The HMGB1 could promote the migration of CD34(+) cells, and the migration effect of HMGB1 on CD34(+) cells in certain concentrations gradually increased along with raise of concentration, the strongest effect was observed in concentration of 100 ng/ml, there was significant difference as compared with control (p < 0.01). Anti-RAGE antibody partially inhibited the migration effect of HMGB1 on CD34(+) cells. It is concluded that the HMGB1 in certain concentration can enhance migration of CD34(+) cells, which may be mediated through RAGE.

Reconstitution of NK cells and their receptors in patients with acute leukemia following unrelated cord blood stem cell transplantation / 中国实验血液学杂志

This study was to investigate the reconstitution of NK cells and their receptors after unrelated cord blood stem cell transplantation (UCBT) and its clinical importance. 11 cases of acute leukemia underwent UCBT were enrolled in this study. The reconstitution of NK cells and their surface receptors as well as the the recovery of T and B cells within 90 days after clinical engraftment following UCBT were measured and analysed by flow cytometry. The results indicated that the recovery of NK cells appears to be relatively early. CD3(-)56(+) NK cell count was (35.12 +/- 18.66)% of peripheral blood (PB) lymphocytes on the day of clinical engraftment and higher than that in normal. The peak of the NK cells reached to (37.8 +/- 17.52)% of lymphocyte at 30 days after clinical engraftment. NK count was (30.4 +/- 19.14)% at 60 days after clinical engraftment when the absolute NK cell count reached to the peak (up to 544 cells/microl) in PB. The activated receptor NKG2D was reconstituted fast and high expressed [(79.58 +/- 8.71)%] at the time of clinical engraftment with a tendency of gradual elevation, which reached to peak value (82.55 +/- 9.10)% at day 60. Another activated receptor NKp46 also reconstituted fast, and maintained at a high level even at 90 days after clinical engraftment. The expression of NKG2A was lower than that of the activated receptor of NK cells, which tendency lasted for at least 90 days after clinical engraftment. The reconstitution of T cells in PB after UCBT was relatively slow with lower expression rate. It is concluded that the reconstitution of NK cells in patients with acute leukemia is earlier following UCBT. The earlier recovery of activated receptor of NK cells, especially NKG2D, suggests that the activation of NK cells may play a role in graft versus leukemia (GVL) effect in the early period after UCBT.

Analysis of Keshan disease prevalence in Ganquan County of Shaanxi Province in 2007 / 中国地方病学杂志

Objective To master the Keshan disease situation, guide and evaluate Keshan disease control work scientifically, and consolidate the control achievements in Ganquan County of Shannxi Province. Methods According to the scheme of National Keshan Disease Surveillance, the residents were surveyed including the case history, blood-pressure, electrocardiogram and X-ray examinations for chronic and suspected cases. Levels of selenium in hair and grain were determined by the diaminonaphthalene method. Results Twenty latent and one chronic Keshan disease patients were detected, accounting for 2.67% (20/749) and 0.13% (1/749), respectively, of surveyed residents in Leoshan Village. Electrocardiography showed abnormalities in 82 of the 749 surveyed individuals(10.95%). The heart-chest ratio was increased in seven of 16 chronic or suspected Keshan disease patients. The content of selenium in hair, wheat and millet was (0.335±0.102), (0.045±0.019), (0.029±0.017)mg/kg, respectively. Conclusions Keshan disease prevalence showed a stable and decreasing tendency due to the general control measures, especially supplementation of selenium in food in Ganquan County. No acute or subacute Keshan disease occurred. Currently, latent and chronic Keshan diseases are the main types of Keshan disease.

Therapeutic effect of allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimens on hematological malignancies / 中国实验血液学杂志

This study was aimed to investigate the therapeutic efficiency and complications after allo-hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning regimens in hematologic malignancies. 10 patients (6 CML patients, 2 AML patients, 1 ALL patient and 1 NHL patient) underwent related allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimens. The conditioning regimens consisted of "FLU + CY + TBI" basically and was appropriately improved in accordance with status of patients. Cyclosporin A (CsA) and mycophenolate mofetil (MMF) were used to prevent the graft-versus-host disease (GVHD). Detection of bone marrow cells, chromosomes, fused gene, ABO blood group and STR-PCR were used to observe engraftment, relapse, GVHD, transplantation- related complications (TRC) after transplantation and to evaluate patients quality of life. The results showed that the 10 patients successfully accepted the transplantation and their primary diseases were cured. In one patient, severe pulmonary infection happened, and in another one CMV infection occurred. Grade IV of acute GVHD occurred in one case and grade I of acute GVHD in 2 cases, the no chronic GVHD appeared. 5 patients relapsed after transplantation at various time points, the donor lymphocytes infusion (DLI) or drugs rescued these 5 patients. During median follow-up of 5 - 35 months, 2 out of which died, 8 survived, the overall survival rate was 80%, and the survivors live in a high-quality life. In conclusion, the hematopoietic stem cell transplantation with reduced intensity conditioning regimens was feasible with relatively low toxicity for recipients. GVHD and TRC were low, and life quality of patients after transplantation was high. DLI could cure the primary diseases even relapsed after transplantation.