简介：AbstractIntroduction:Toxoplasmosis is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). However, for several reasons, clinicians know little about Toxoplasma infection.Case presentation:We report a case of toxoplasmosis that was diagnosed by bone marrow smear and metagenomic next-generation sequencing (mNGS) after HSCT in a boy. Additionally, we summarize the characteristics of toxoplasmosis after pediatric HSCT reported in the literature published in PubMed.Conclusion:Clinicians should increase their awareness of toxoplasmosis in children after HSCT and implement pre-transplant screening and post-transplant monitoring and prevention in future according to the national conditions of our country.

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简介：AbstractBackground:There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.Methods:From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n = 72) or allo-HSCT (n = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.Results:Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P= 0.001), chemotherapy-resistant disease (41% vs. 8%, P= 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).Conclusions:Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.

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简介：AbstractBackground:The impacts of previous cardio-cerebrovascular disease (pre-CCVD) on the outcomes of hematopoietic cell transplantation (HCT) are not well described. Patients with pre-CCVD may often be poor candidates for HCT. This study aimed to investigate the impact of pre-CCVD on transplant outcomes.Methods:A retrospective study was conducted between patients with and without pre-CCVD who consecutively received allogeneic or autologous HCT between November 2013 and January 2020 with a matching of age and disease status. The cardiovascular complications and HCT outcomes of the two groups were evaluated and compared. The primary endpoints were post-transplant cardio-cerebrovascular disease (post-CCVD) and non-relapse mortality (NRM). We used a multivariable Cox proportional hazard model and the Fine-Gray competing risk regressions for analyses to estimate the hazard ratios (HRs).Results:The outcomes of 23 HCT recipients with pre-CCVD were compared with those of 107 patients in the control group. No significant differences were noted in terms of engraftment, overall survival (OS) (67.00% vs. 67.90%, P = 0.983), or relapse (29.78% vs. 28.26%, P = 0.561) between the pre-CCVD group and the control group. The cumulative incidences of 2-year NRM were similar between patients with pre-CCVD and the controls (14.68% vs. 17.08%, P = 0.670). However, pre-CCVD was associated with an increased incidence of post-CCVD (HR: 12.50, 95% confidence interval [CI]: 3.88-40.30, P < 0.001), which was an independent risk factor for increased NRM (HR: 10.29, 95% CI: 3.84-27.62, P < 0.001) and inferior OS (HR: 10.29, 95% CI: 3.84-27.62, P < 0.001).Conclusions:These findings suggest that the existence of pre-CCVD before transplantation might not result in increased mortality directly but superpose the toxicity of the transplantation procedure, leading to a risk of post-CCVD. Post-CCVD was a powerful predictor for high NRM and inferior OS. Further risk stratification of pre-CCVD is needed to reduce NRM in various transplantation settings.

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简介：AbstractBackground: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.

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简介：AbstractChronic obstructive pulmonary disease (COPD), characterized by persistent and not fully reversible airflow restrictions, is currently one of the most widespread chronic lung diseases in the world. The most common symptoms of COPD are cough, expectoration, and exertional dyspnea. Although various strategies have been developed during the last few decades, current medical treatment for COPD only focuses on the relief of symptoms, and the reversal of lung function deterioration and improvement in patient’s quality of life are very limited. Consequently, development of novel effective therapeutic strategies for COPD is urgently needed. Stem cells were known to differentiate into a variety of cell types and used to regenerate lung parenchyma and airway structures. Stem cell therapy is a promising therapeutic strategy that has the potential to restore the lung function and improve the quality of life in patients with COPD. This review summarizes the current state of knowledge regarding the clinical research on the treatment of COPD with mesenchymal stem cells (MSCs) and aims to update the understanding of the role of MSCs in COPD treatment, which may be helpful for developing effective therapeutic strategies in clinical settings.

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简介：AbstractBackground:Accumulating evidence suggests that lithium influences mesenchymal stem cell (MSC) proliferation and osteogenic differentiation. As decreased bone formation in femoral heads is induced by glucocorticoids (GCs), we hypothesized that lithium has a protective effect on GC-induced osteonecrosis of femoral heads (ONFH).Methods:A rat ONFH model was induced by methylprednisolone (MP) and the effect of lithium chloride on the models was evaluated. Micro-computed tomography (CT)-based angiography and bone scanning were performed to analyze the vessels and bone structure in the femoral heads. Hematoxylin and eosin and immunohistochemical staining were performed to evaluate the trabecular structure and osteocalcin (OCN) expression, respectively. Bone marrow-derived MSCs were isolated from the models, and their proliferative and osteogenic ability was evaluated. Western blotting and quantitative real-time polymerase chain reaction were performed to detect osteogenic-related proteins including Runx2, alkaline phosphatase, and Collagen I.Results:Micro-CT analysis showed a high degree of osteonecrotic changes in the rats that received only MP injection. Treatment with lithium reduced this significantly in rats that received lithium (MP + Li group); while 18/20 of the femoral heads in the MP showed severe osteonecrosis, only 5/20 in the MP + Li showed mild osteonecrotic changes. The MP + Li group also displayed a higher vessel volume than the MP group (0.2193 mm3vs. 0.0811 mm3, P < 0.05), shown by micro-CT-based angiography. Furthermore, histological analysis showed better trabecular structures and more OCN expression in the femoral heads of the MP + Li group compared with the MP group. The ex vivo investigation indicated higher proliferative and osteogenic ability and upregulated osteogenic-related proteins in MSCs extracted from rats in the MP + Li group than that in the MP group.Conclusions:We concluded that lithium chloride has a significant protective effect on GC-induced ONFH in rats and that lithium also enhances MSC proliferation and osteogenic differentiation in rats after GC administration.

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简介：AbstractBackground:Pharmacological factors used to induce insulin resistance (IR) in in vitro models may not mimic the full in vivo features of type 2 diabetes mellitus (T2DM). This study aimed to examine the ability of diabetic serum (DS) to induce IR and investigate whether adipose-derived mesenchymal stem cell conditioned medium (ADMSC-CM) reverses DS-induced IR.Methods:DS was obtained from newly diagnosed T2DM patients. IR was induced in differentiated 3T3-L1 cells by employing dexamethasone, tumor necrosis factor alpha (TNF-α), palmitate and DS. Glucose uptake (2-[N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino]-2-deoxyglucose(2-NBDG) uptake assay), intracellular levels of reactive oxygen species (ROS), and superoxide radicals (O2-) (fluorescence microscopy and fluorometry) were analyzed in control and experimental samples. mRNA expression of key genes involved in glucose transport and inflammation were analyzed by using reverse transcription polymerase chain reaction (RT-PCR). Pro-inflammatory cytokines and phospho-insulin receptor substrate (IRS) (Ser-307) protein expression were analyzed by fluorescence activated cell sorter analysis. Statistical significance was determined by using one-way ANOVA followed by Tukey's multiple comparison tests.Results:ADMSC-CM significantly increased the DS-mediated decrease in 2-NBDG uptake (11.01 ± 0.50 vs. 7.20 ± 0.30, P < 0.01) and reduced DS-driven ROS (fluorescence count, 6.35 ± 0.46 vs. 9.80 ± 0.10, P < 0.01) and O2- (fluorescence count, 3.00 ± 0.10 vs. 4.60 ± 0.09, P < 0.01) production. Further, the ADMSC-CM restored DS-induced down regulation GLUT4 (1.52- fold, P < 0.05) as well as the up-regulation of PPARγ (0.35-fold, P < 0.01), and IKKβ (0.37-fold, P < 0.01) mRNA, and phospho-IRS (Ser-307) protein expression compared to the baseline (median fluorescence intensity, 88,192 ± 2720 vs. 65,450 ± 3111, P < 0.01). DS induced IR, similar to the traditionally used pharmacological factors, namely dexamethasone, TNF-α, and palmitate, which can be attributed to the significantly higher pro-inflammatory cytokines levels (TNF-α (2.28 ± 0.03 pg/mL vs. 2.38 ± 0.03 pg/mL, P < 0.01), interleukin 6 (IL)-6 (1.94 ± 0.02 pg/mL vs. 2.17 ± 0.04 pg/mL, P < 0.01), IL-17 (2.16 ± 0.02 pg/mL vs. 2.22 ± 0.002 pg/mL, P < 0.05), and interferon gamma (IFN-γ) (2.07 ± 0.02 pg/mL vs. 2.15 ± 0.04 pg/mL, P < 0.05)) in DS.Conclusions:DS can be explored as a novel inducer of IR in in vitro studies with further standardization, substituting the conventionally used pharmacological factors. Our findings also affirm the validity of ADMSC-CM as a prospective insulin sensitizer for T2DM therapy.

简介：AbstractIn January 2019, the fourth rabies case caused by organ transplantation was noticed in China, with the conditions of one per year for the recent four years. Different from the previous cases, there were no definite epidemiological histories of exposure or rabies-related symptoms from this patient. This case strongly supports the call for the legislation of establishing a national-level management that will incorporate the screening programs on donors prior to the practice of organ transplantation to reduce the risks on rabies caused by organ transplantation.

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简介：AbstractBackground:Investigations of the pathogenic mechanisms in motor neurons (MNs) derived from amyotrophic lateral sclerosis (ALS) disease-specific induced pluripotent stem (iPS) cell lines could improve understanding of the issues affecting MNs. Therefore, in this study we explored mutant superoxide dismutase 1 (SOD1) protein expression in MNs derived from the iPS cell lines of ALS patients carrying different SOD1 mutations.Methods:We generated induced pluripotent stem cell (iPSC) lines from two familial ALS (FALS) patients with SOD1-V14M and SOD1-C111Y mutations, and then differentiated them into MNs. We investigated levels of the SOD1 protein in iPSCs and MNs, the intracellular Ca2+ levels in MNs, and the lactate dehydrogenase (LDH) activity in the process of differentiation into the MNs derived from the controls and ALS patients’ iPSCs.Results:The iPSCs from the two FALS patients were capable of differentiation into MNs carrying different SOD1 mutations and differentially expressed MN markers. We detected high SOD1 protein expression and high intracellular calcium levels in both the MN and iPSCs that were derived from the two SOD1 mutant patients. However, at no time did we observe stronger LDH activity in the patient lines compared with the control lines.Conclusions:MNs derived from patient-specific iPSC lines can recapitulate key aspects of ALS pathogenesis, providing a cell-based disease model to further elucidate disease pathogenesis and explore gene repair coupled with cell-replacement therapy. Incremental mutant expressions of SOD1 in MNs may have disrupted MN function, either causing or contributing to the intracellular calcium disturbances, which could lead to the occurrence and development of the disease.

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简介：AbstractMedulloblastoma is the most common primary pediatric malignancy of the central nervous system. Recurrent and refractory patients account for approximately 30% of them. Immune cells are an important component of the brain tumor microenvironment, including tumor-associated macrophages, T lymphocytes, natural killer cells, dendritic cells, neutrophils and B lymphocytes. Understanding how they behave and interact is important in the investigation of the onset and progression of medulloblastoma. Here, we overview the features and recent advances of each component of immune cells in medulloblastoma. Meanwhile, immunotherapy is a promising but also challenging treatment strategy for medulloblastoma. At present, there are a growing number of immunotherapeutic approaches under investigation including immune checkpoint inhibitors, oncolytic viruses, cancer vaccines, chimeric antigen receptor T cell therapies, and natural killer cells in recurrent and refractory medulloblastoma patients.