Purpose: The aim of this study is to determine the impact of solute carrier family 3 member 2 (SLC3A2) on the malignant phenotype of gliomas and its role in regulating ferroptosis sensitivity. Materials and Methods: The malignant phenotype of glioma was assessed by cell proliferation assay, colony formation assay, EdU assay, wound healing, and Transwell experiments. We further validated the impact of reduced SLC3A2 expression on the sensitivity to ferroptosis in glioma cells through Cell Counting Kit-8 assays, flow cytometry, western blotting, and transmission electron microscopy. Western blot was used to explore how SLC3A2 affects glioma sensitivity to ferroptosis through the AKT/NF-E2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) axis. By establishing a subcutaneous xenograft tumor model in BALB/c-nude mice, we investigated the growth of tumors following the knockout of SLC3A2 in glioma cells. Results: Downregulation of SLC3A2 suppressed the malignant phenotype of glioma by blocking the cell cycle and epithelial-mesenchymal transition processes. On the other hand, loss of SLC3A2 not only downregulated SLC7A11 but also prevented the activation of the AKT/NRF2/GPX4 axis. These lead to increased accumulation of reactive oxygen species and lipid peroxides, ultimately enhancing the susceptibility of glioma to ferroptosis. Conclusion Our findings suggest that SLC3A2 is an oncogene in gliomas, promoting their occurrence and development. It plays a critical role in ferroptosis resistance through the AKT/NRF2/GPX4 axis.

Objective:To explore the feasibility and efficacy of umbilical cord blood transplantation (UCBT) in the treatment of paroxysmal nocturnal hemoglobinuria (PNH).Methods:From May 2014 to December 2019, clinical data were retrospectively reviewed for 7 PNH patients undergoing UCBT. The grades were severe ( n=6) and extremely severe ( n=1). The causes were primary PNH ( n=4) and PNH-aplastic anemia (AA) syndrome ( n=3). There were 5 males and 2 females with a median age of 29 (20-47) years, a median weight of 60(50-71) kg and a median time from diagnosis to transplantation of 62.5(7.7-171) months. All of them were accompanied by transfusion dependence. Myeloablative ( n=6) and reduced-intensity ( n=1) pretreatment was offered. The regimen of preventing GVHD was cyclosporine A plus short-term mycophenolate mofetil without ATG. The median number of input nucleated cells was 2.4(1.71-4.28)×10 7/kg and the median number of CD34+ cells 1.58(0.88-3.02)×10 5/kg. Results:Neutrophil and erythroid engraftment was obtained with a median neutrophil engraftment time of 17(15-21) days and a median erythroid engraftment time of 27. Engraftment time of 37(25-101) days for platelets >20×10 9/L and 62(27-157) days for platelets >50×10 9/L. The incidence of 100-day acute GVHD was 28.6%(95%CI 0-55.3%). The severity of GVHD was grade Ⅱ° acute ( n=2) and mild ( n=1). The median follow-up period was 13.5(3-71.4) months. Six patients survived while another with PNH-AA syndrome with iron overload died of gastrointestinal hemorrhage. The 2-year overall survival rate was 83.3%(95%CI 27.3-97.5%). Conclusions:With excellent engraftment and survival in the treatment of PNH, UCBT is indicated for patients without HLA full-match donor. PNH-AA syndrome with iron overload may be one of the important prognostic factors.

Objective:To retrospectively analyze the clinical outcomes of single unrelated cord blood transplantation (UCBT) in children with high risk and refractory acute myeloid leukemia (AML) .Methods:Between June 2008 and December 2018, a total of 160 consecutive pediatric patients with AML received single UCBT (excluding acute promyelocytic leukemia) . Myeloablative conditioning (MAC) regimen were applied. All patients received a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft -versus- host disease (GVHD) .Results:The cumulative incidence of neutrophil cells engraftment at day +42 and platelet recovery at day +120 was 95.0% (95% CI 90.0%-97.5%) at a median of 16 days after transplantation (range, 11-38 days) and 85.5% (95% CI 83.3%-93.4%) with a median time to recovery of 35 days (range, 13-158) , respectively. Incidence of grades Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD and chronic GVHD were 37.3% (95%CI 29.3%-45.2%) , 27.3% (95% CI 20.0%-35.0%) and 22.4% (95% CI 15.5%-28.7%) , respectively. The transplant-related mortality (TRM) at 360 day was 13.1% (95% CI 8.4%-18.9%) . The 5-year cumulative incidence of relapse was 13.8% (95% CI 8.5%-20.3%) . The 5-year disease-free survival (DFS) and overall survival (OS) were 71.7% (95% CI 62.7%-77.8%) and 72.2% (95% CI 64.1%-78.7%) , respectively. The 5-year GVHD and relapse free survival (GRFS) was 56.1% (95% CI 46.1%-64.9%) . The 5-year cumulative recurrence rates of CR1, CR2, and NR groups were 5.3%, 19.9%, and 30.9% ( P=0.001) , and the 5-year OS rates were 79.9% (95% CI 70.3%-86.7%) , 71.1% (95% CI 50.4%-84.4%) and 52.9% (95% CI 33.0%-69.3%) ( χ2=7.552, P=0.020) , respectively. Conclusions:For pediatric patients with high risk and refractory AML, UCBT is a safe and effective treatment option, and it is favorable to improve the survival rate in CR1 stage.

BACKGROUND: Umbilical cord blood hematopoietic stem cell transplantation is more and more widely used as a radical treatment for acute leukemia, but its therapeutic effect in different leukemias has not been compared. By comparing the efficacy of diseases, it can guide different patients to choose the transplantation method.OBJECTIVE: To compare and analyze the therapeutic effect of umbilical cord blood hematopoietic stem cell transplantation on acute myeloid leukemia and acute lymphocytic leukemia. METHODS: Clinical data of 306 cases of acute leukemia treated by unrelated umbilical cord blood hematopoietic stem cell transplantation were retrospectively analyzed, including 112 patients with acute myeloid leukemia and 194 with acute lymphoblastic leukemia. All patients received myeloablative conditioning without antithymocyte, and the prevention of graft-versus-host disease was cyclosporine combined with mycophenolate mofetil. RESULTS AND CONCLUSION: (1) Except that the relapse rate after acute lymphoblastic leukemia transplantation was slightly higher than acute myeloid leukemia, the efficacy of the two groups of patients after receiving unrelated umbilical cord blood hematopoietic stem cell transplantation was basically the same. (2) In the group of adolescents and young adults (aged 15-39 years), the rate of neutrophil and platelet implantation in acute myeloid leukemia was faster than in acute lymphoblastic leukemia. Among them, CD34+ cell number and pretreatment program were independent influencing factors for neutrophil implantation, while CD34+ cell number was also an independent influencing factor for platelet implantation. In this age group, the recurrence rate of acute lymphoblastic leukemia patients after transplantation was still higher than that of acute myeloid leukemia, in which chronic graft-versus-host disease was an independent influencing factor. (3) Immune reconstruction testing after transplantation suggests that cord blood CD8+ T cell reconstruction in patients with acute myeloid leukemia was better than in acute lymphoblastic leukemia patients 4 months after transplantation. (4) The above data show that pre-treatment of unrelated cord blood transplantation without antithymocyte globulin has a good effect on acute lymphocytic leukemia and acute myeloid leukemia. Department of Hematology of The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China is qualified for stem cell transplantation.

Objective To evaluate the effect of pretransplant iron overload on the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with severe aplastic anemia (SAA). Methods Clinical data of 80 SAA recipients who underwent allo-HSCT for the first time were retrospectively analyzed. According to the incidence of iron overload, all recipients were divided into the iron overload group (n=20) and non-iron overload group (n=60). The engraftment rate, incidence of postoperative complications and clinical prognosis of the recipients afterallo-HSCT were statistically compared between two groups. The influencing factors of 2-year overall survival (OS) and 180 d transplantation related mortality (TRM) were analyzed by Cox proportional hazards regression model. Results The engraftment rate of neutrophils in the non-iron overload group was 98% (59/60), significantly higher than 75% (15/20) in the iron overload group (P < 0.05). The engraftment rate of platelet in the non-iron overload group was 90% (54/60), significantly higher than 65% (13/20) in the iron overload group (P < 0.05). The incidence rate of bloodstream infection in the non-iron overload group was 23% (14/60), remarkably lower than 40% (8/20) in the iron overload group (P < 0.05). The 180 d TRM of the recipients in the non-iron overload group was 17%, significantly lower than 45% in the iron overload group (P < 0.05). The 1- and 2-year OS of the recipients in the non-iron overload group were 82% and 80%, significantly higher than 50% and 44% in the iron overload group (both P < 0.05). Iron overload or not was an independent risk factor of the OS and TRM of the recipients (both P < 0.05). Conclusions Iron overload can affect the OS and TRM of SAA patients after allo-HSCT.

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.

Objective To analyze the epidemiologic and clinical features of post-engraftment blood stream infection (pePSI) after unrelated cord blood transplant (UCBT) in our hospital,and provide the basis for empiric antibacterial treatment.Methods 484 patients with hematological malignancies who received single-unit high intensity myeloablative UCBT in our hospital between April 2011 and November 2017 were enrolled.The incidence,etiology of BSI and associated mortality,drug resistance rate in the post-engraftment phase were investigated.Results Totally 25 episodes of BSI among 22 patients in the post-engraftment phase were documented,and the incidence of peBSI was 5 ％.Gram-negative organisms predominated over Gram positive,with Escherichia coli being the most frequent Gram-negative organism isolated (31.5％).Among Gram positive organisms,methicillin resistant Staphylococcus (MRS) was the most frequent species isolated (66％).Nearly 33％ of Escherichia coli isolates and 60％ Klebsiella pneumonia isolates were carbapenem-resistant.All Grampositive bacteria were sensitive to vaneomyein and linezolid.Among the 22 patients,14 patients were cured and survived (63％) eventually.Conclusion The most frequent causative agents of the peBSI after UCBT were Escherichia coli,Klebsiella pneumonia and MRS,etc.Combined antibacterial treatment including a carbapenem or beta lactamase inhibitor can be used for patients suffering fever in the post-engraftment phase as empiric antibacterial therapy.Vaneomyein and linezolid can be used as the first-line therapy for Gram-positive bacteria.

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.

BACKGROUND:The elderly hip fracture patients with chronic obstructive pulmonary disease (COPD) have a higher postoperative mortality than those only with hip fractures. In recent years, it has become an issue of concerns. Because the mechanism is unknown, however, there are no effective clinical interventions for these patients. OBJECTIVE:To observe the effect of bone marrow stromal stem cel s (BMSCs) on the level of pulmonary inflammation in aged rats with chronic obstructive pulmonary disease (COPD) after hip fractures. METHODS:Thirty male Sprague-Dawley rats, 12 months old, were exposed to smoking for 4 months and randomized into three groups, smoking, smoking+hip fracture+normal saline, smoking+hip fracture+BMSCs groups. Animal models of hip fracture were made in the latter two groups. Twenty-four hours after hip fracture, the lower lobe and peripheral blood samples were taken from al rats in the three groups, to evaluate the pathological changes of lung tissue and detect levels of inflammatory factors in the lung tissue and peripheral blood. RESULTS AND CONCLUSION:After closed hip fracture, aged COPD rats exhibited inflammatory cel infiltration, mucus secretion, airway stenosis or occlusion;the levels of interleukin-6, tumor necrosis factor-αand interleukin-10 in the lung tissue and peripheral blood were increased. After intravenous injection of BMSCs, the pathological changes of the lung tissue were reduced, and the levels of pro-inflammatory factors, tumor necrosis factor-αand interleukin-6, decreased, but the level of anti-inflammatory factor interleukin-10 further increased, which were significantly different from those in the normal saline group (P<0.05). These findings indicate that BMSCs can relieve acute lung injury in aged COPD rats with hip fractures.

BACKGROUND:Caffeic acid phenethyl ester (CAPE) can inhibit lipid peroxidation after rat brain injury. However, the trend of 5-lipoxygenaseis (5-LOX) and cysteinyl leukotrienes (CysLTs) in model of Parkinson’s disease, and whether CAPE protects against rotenone-induced cel ular injuries by inhibiting the levels of 5-LOX and CysLTs stil need further research.
OBJECTIVE:To investigate the protective effect of CAPE on the rotenone-induced Parkinson-like injury, and to determine whether 5-LOX involved.
METHODS:(1) PC12 cel s in good-growth were col ected and divided into five groups cultured with different concentrations of rotenone (0, 0.01, 0.1, 1, 10μmol/L). 24 and 48 hours later, changes of cel ular morphology and activity were observed to single out the optimum concentration of rotenone;at 24 hours, the levels of 5-LOX and CysLTs were detected by western blotting and ELISA, respectively. (2) PC12 cel s were pretreated with different concentrations of CAPE (0, 0.01, 0.1, 1, 10 μmol/L) for 30 minutes, and 1 μmol/L rotenone was then added. The other cel s received no intervention as blank control group. Subsequently, the cel activity was detected, and the CysLTs production was detected by ELISA at 24 hours.
RESULTS AND CONCLUSION:(1) Rotenone (0.1-10μmol/L) could induce PC12 cel injury with overt morphological and cel activity changes at 24 hours, especial y the 1 μmol/L rotenone. (2) Rotenone also significantly increased the 5-LOX expression and CysLTs production in a concentration-dependant manner. (3) CAPE (1-10μmo/L) significantly attenuated rotenone-induced CysLTs production and cel viability reduction in a concentration-dependant manner. (4) These results suggest that CAPE protects against PC12 cel injuries in the model rat with Parkinson’s disease induced by rotenone involving 5-Lox.