Kinetics and Mechanism of Catalytic Reduction of U(Ⅵ)with Hydrazine on Platinum Catalysts in Nitric Acid Media

The kinetics of U(IV)produced by hydrazine reduction of U(VI)with platinum as a catalyst in nitric acid media was studied to reveal the reaction mechanism and optimize the reaction process.Electron spin resonance(ESR)was used to determine the influence of nitric acid oxidation.The effects of nitric acid,hydrazine,U(VI)concentration,catalyst dosage and temperature on the reaction rate were also studied.In addition,the simulation of the reaction process was performed using density functional theory.The results show that the influence of oxidation on the main reaction is limited when the concentration of nitric acid is below 0.5 mol/L.The reaction kinetics equation below the concentration of 0.5 mol/L is found as:−dc(UO_(2)^(2+))/dt=kc^(0.5323)(UO_(2)^(2+))c^(0.2074)(N_(2)H_(5)^(+))c^(−0.2009)(H^(+)).When the temperature is 50℃,and the solid/liquid ratio r is 0.0667 g/mL,the reaction kinetics constant is k=0.00199(mol/L)^(0.4712)/min.Between 20℃ and 80℃,the reaction rate gradually increases with the increase of temperature,and changes from chemically controlled to diffusion-controlled.The simulations of density functional theory give further insight into the influence of various factors on the reaction process,with which the reaction mechanisms are determined according to the reaction kinetics and the simulation results.

Predictive Value of Dynamic Peri-Transplantation MRD Assessed By MFC Either Alone or in Combination with Other Variables for Outcomes of Patients with T-Cell Acute Lymphoblastic Leukemia

We performed a retrospective analysis to investigate dynamic peri-hematopoieticstem cell transplantation(HSCT)minimal/measurable residual disease(MRD)on outcomes inpatients with T-cell acute lymphoblastic leukemia(T-ALL).A total of 271 patients were enrolledand classified into three groups:unchanged ncgative MRD pre-and post-HSCT group(group A),post-MRD non-increase group(group B),and post-MRD increase group(group C).The patientsin group B and group C experienced a higher cumulative incidence of relapse(CIR)(42%vs.71%vs.16%,P<0.001)and lower leukemia-free survival(LFS)(46%vs.21%vs.70%,P<0.001)andoverall survival(OS)(50%vs.28%vs.72%,P<0.001)than in group A,but there was no significantdifference in non-relapse mortality(NRM)among three groups(14%vs.12%vs.8%,P=0.752).Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR(HR=2.392,95%CI,1.816-3.151,P<0.001),LFS(HR=1.964,95%CI,1.546-2.496,P<0.001)and os(HR=1.731,95%CI,1.348-2.222,P<0.001).We also established a risk scoring system based ondynamic peri-HSCT MRD combined with remission status pre-HSCT and onsct of chronic graft-versus-host disease(GVHD).This risk scoring system could better distinguish ClR(c=0.730)thanthat for pre-HSCT MRD(c=0.562),post-HSCT MRD(c=0.616)and pre-and post-MRD dynamics(c=0.648).Our results confirm the outcome predictive value of dynamic peri-HSCT MRD eitheralone or in combination with other variables for patients with T-ALL.

Spinocerebellar ataxia type 3 with dopamine-responsive dystonia:A case report

BACKGROUND Spinocerebellar ataxia type 3(SCA3)is a rare neurodegenerative disease with high genetic heterogeneity.SCA3 mainly manifests as progressive cerebellar ataxia accompanied by paralysis of extraocular muscles,dysphagia,lingual fibrillation,pyramidal tract sign,and extrapyramidal system sign.However,it rarely has clinical manifestations similar to Parkinson-like symptoms,and is even rarer in patients sensitive to dopamine.We report a patient initially diagnosed with dopamine-responsive dystonia who was ultimately diagnosed with SCA3 by genetic testing,which was completely different from the initial diagnosis.CASE SUMMARY A 40-year-old Chinese woman was admitted to hospital due to severe inflexibility.At the beginning of the disease,she presented with anxiety and sleep disorder.At the later stage,she presented with gait disorder,which was similar to Parkinson's disease.Her medical history was unremarkable,but her mother,grandmother,and uncle all had similar illnesses and died due to inability to take care of themselves and related complications.Laboratory and imaging examinations showed no abnormalities,but electromyography and electroencephalography revealed delayed somatosensory evoked potentials and slow background rhythm,respectively.Her symptoms fluctuated during the daytime,and we initially diagnosed her with dopamine-responsive dystonia.After treatment with lowdose levodopa,the patient’s symptoms were significantly improved,but the final genetic diagnosis was SCA3.CONCLUSION SCA3 has various clinical phenotypes and needs to be differentiated from Parkinson's syndrome and dopamine-responsive dystonia.

A Simplified Continuous Two-stitch Suture for Bronchial Anastomosis of Left Single Lung Transplant in Dogs

Large animal models are essential to pre-clinical trials of pulmonary transplantation and bronchial anastomosis poses a great technical challenge to the procedure.Presented here is a simplified continuous two-stitch suture technique into bronchial anastomosis during the course of left single lung transplantation in canine.Animals were divided into three groups with each group having 6 animals.Left single lung transplantation in canine was performed to assess the feasibility of using this technique for bronchial anastomosis.In the control groups,all anastomoses were done by using traditional technique.Allograft functions and hemodynamic parameters were monitored during a 3-h reperfusion period.Quality of bronchial healing and airway complications were assessed by bronchoscopic surveillance after transplantation.We successfully completed left lung transplantation in 18 dogs,and all the dogs survived the procedures.The new technique substantially simplified the procedures for bronchial anastomosis and greatly reduced the time for bronchial anastomosis(P<<0.01)and the ischemic time of the grafts(P<0.05)compared to the control group.The continuous two-stitch suture attenuated the tissue injury to allografts and led to better blood gas exchange function as compared to the control group(P<0.05).Good bronchial healing(Grade I)was observed in all the groups.A canine left single lung transplantation model is feasible by using the novel suture technique,and the new technique is as safe as the traditional method.The technique is easy to learn,particularly for less experienced operators.Simpler and time-saving,the technique has great potential to be widely employed in clinical lung transplantation.

Dynamic immune profiling identifies the stronger graft-versus-leukemia (GVL) effects with haploidentical allografts compared to HLA-matched stem cell transplantation

Haploidentical stem cell transplantation(haplo-SCT)achieves superior or at least comparable clinical outcomes to HLA-matched sibling donor transplantation(MSDT)in treating hematological malignancies.To define the underlying regulatory dynamics,we analyzed time courses of leukemia burden and immune abundance of haplo-SCT or MSDT from multiple dimension.First,we employed two nonirradiated leukemia mouse models which carried human AML-ETO or MLL-AF9 fusion gene to establish haplo-identical and major histocompatibility(MHC)-matched transplantation models and investigated the immune cell dynamic response during leukemia development in vivo.We found that haplo-matching the MHCs of leukemia cells with recipient mouse T cells prolonged leukemic mice survival and reduced leukemia burden.The stronger graft-versus-leukemia activity in haplo-SCT group mainly induced by decreased apoptosis and increased cytotoxic cytokine secretion including tumor necrosis factor–α,interferon-γ,pore-forming proteins and CD107a secreted by T cells or natural killer cells.Furthermore,we conducted a prospective clinical trial which enrolled 135 patients with t(8;21)acute myeloid leukemia that displayed minimal residual disease before transplantation and underwent either haplo-SCT or MSDT.The results showed that the haplo-SCT slowed the kinetics of the leukemia burden in vivo and reduced the cumulative incidence of relapse compared with MSDT.Ex vivo experiments showed that,1 year after transplantation,cytotoxic T lymphocytes from the haplo-SCT group had higher cytotoxicity than those from the MSDT group during the same period.Our results unraveled the role of immune cells in superior antileukemia effects of haplo-SCT compared with MSDT.

Association of Persistent Minimal Residual Disease with Poor Outcomes of Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Background: Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo?HSCT). Methods: We retrospectively analyzed 145 consecutive AML patients undergoing allo?HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre?HSCT. Results: In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ2 = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ2 = 8.759, P = 0.003) or pre?HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ2 = 5.547, P = 0.019). In haploidentical SCT (haplo?SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre?HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo?SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo?SCT, those without persistent MRD underwent haplo?SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ2 = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200–2.382, P = 0.003), worse leukemia?free survival (HR = 1.812, 95% CI: 1.168–2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528–3.627, P < 0.001). Conclusion: Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo?SCT settings.

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation

Background:For patients with B cell acute lymphocytic leukemia(B-ALL)who underwent allogeneic stem cell transplantation(allo-SCT),many variables have been demonstrated to be associated with leukemia relapse.In this study,we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.Methods:A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People’s Hospital from December 2010 to December 2015 were enrolled in this retrospective study.We aimed to evaluate the factors associated with transplant outcomes after allo-SCT,and establish a risk score to identify patients with different probabilities of relapse.The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.Results:All patients achieved neutrophil engraftment,and 95.4%of patients achieved platelet engraftment.The 5-year cumulative incidence of relapse(CIR),overall survival(OS),leukemia-free survival(LFS),and non-relapse mortality were 20.7%,70.4%,65.6%,and 13.9%,respectively.Multivariate analysis showed that patients with positive post-transplantation minimal residual disease(MRD),transplanted beyond the first complete remission(≥CR2),and without chronic graft-versus-host disease(cGVHD)had higher CIR(P<0.001,P=0.004,and P<0.001,respectively)and worse LFS(P<0.001,P=0.017,and P<0.001,respectively),and OS(P<0.001,P=0.009,and P<0.001,respectively)than patients without MRD after transplantation,transplanted in CR1,and with cGVHD.A risk score for predicting relapse was formulated with the three above variables.The 5-year relapse rates were 6.3%,16.6%,55.9%,and 81.8%for patients with scores of 0,1,2,and 3(P<0.001),respectively,while the 5-year LFS and OS values decreased with increasing risk score.Conclusion:This new risk score system might stratify patients with different risks of relapse,which could guide treatment.

Successful hematopoietic stem cell transplantation with haploidentical donors and non-irradiation conditioning in patients with Fanconi anemia

To the Editor:Allogeneic hematopoietic stem cell transplantation(HSCT)is the only curative option for bone marrow(BM)abnormalities in Fanconi anemia(FA).However,patients with FA cannot tolerate the toxicity of the therapeutic regimen for acquired aplastic anemia,which mainly contains 200 mg/kg cyclophosphamide(CTX),and low-dose CTX regimens are considered more suitable.Some centers have also added different doses of irradiation to the conditioning regimen.[1]Due to their side effects on growth and development and the possibility of developing a secondary malignant disease,some trials have replaced the irradiation with fludarabine.Moreover,data on transplants from haploidentical donors are scarce.