Objective: To investigate the efficacy of alternative donor (AD) in the treatment of aplastic anemia (AA) in children. Methods: The clinical data of AA children who received AD HSCT in our center from Apr. 2010 to Dec. 2016 were retrospectively analyzed. The overall survival (OS) rate, implant success rate, incidence of acute and chronic graft-versus-host disease (GVHD) were statistically analyzed. Results: A total of 109 children with acquired AA, including 64 severe AA (SAA) , 32 very severe AA (VSAA) and 13 transfusion dependent non-severe AA (NSAA) , were recruited in this retrospective AD HSCT study, the median age was 6 (0.8-18) years old. Of them, 44 patients with 10/10 matched unrelated donor (MUD) , 44 patients with mismatched unrelated donor (MMUD) and 21 patients with mismatched related donor (MMRD) . All patients did not receive ATG before HSCT and the active infection was excluded. Except 3 patients suffered from a second graft failure (2 of them rescued by second HSCT) , 106/109 (97.2%) were engrafted with neutrophil and platelet recovery occurring at a median of 13 days (range, 9-19) and 16 days (range, 10-81) post-transplant. Until day 100 post transplantation, the incidence was 74.3% (81/109) for acute GVHD (aGVHD) and 39.4% (43/109) for grade Ⅱ-Ⅳ aGVHD, 30.7% (31/101) and 9.9% (10/101) for overall chronic GVHD (cGVHD) and moderate cGVHD, respectively, and nobody developed an extend cGVHD. After median follow up of 39 (0.7-103) months for all patients, 13 of 109 patients died. The estimated 5-year overall survival (OS) of the entire cohort was 88.1% (95%CI 81.1%-91.4%) with no difference among the MUD, MMUD and MMRD cohort (93.2%, 84.1% and 85.7%, respectively, P=0.361) . Conclusion These excellent outcomes suggest that unmanipulated AD PBSC is a good HSCT source for children with SAA. It’s reasonable to consider AD HSCT as first line therapy for SAA children without matched sibling donor. Better strategies are required to prevent GVHD.

Objective:To explore the role of activated CD4 + T cells in cardiac remodeling after myocardial infarction (MI). Methods:① Experiment in vitro: naive CD4 + T cells were isolated in mouse spleen, and then stimulated with plate-bound anti-CD3 and anti-CD28 for 48 hours. Exosomes isolated from the supernatant of activated CD4 + T cells were incubated with cardiac fibroblasts (CFs) for 48 hours, and then the ability of CFs proliferation, migration and differentiation were detected by cell counting kit-8 (CCK-8) assay, Transwell assay, and immunofluorescence assay. ② Experiment in vivo: 40 male C57 mice were divided into 4 groups according to random number table method, including control group (Ctrl group), sham operation group (Sham group), MI group, and exosome treatment group (MI+Exo group), with 10 in each group. The mice model of MI was established by ligating the left anterior descending coronary artery. In MI+Exo group, 40 μg/d exosomes were injected intravenously into the tail after modeling. Cardiac function and cardiac fibrosis post-MI were assessed by echocardiography and quantitative polymerase chain reaction (qPCR) at 4th week. Results:① In vitro: exosomes derived from activated CD4 + T cells significantly promote CFs proliferation, migration and differentiation [proliferation ability ( A value): 0.31±0.01 vs. 0.21±0.01, migration capability (cells/MP): 79.20±3.34 vs. 48.80±2.13, differentiation ability (α-smooth muscle actin, α-SMA; fluorescence intensity): 1.56±0.03 vs. 1.00±0.02, all P < 0.05]. ② In vivo: echocardiographic analysis showed that exosomes derived from activated CD4 + T cells aggravated the deterioration of cardiac dysfunction post-MI than MI group, as indicated by left ventricular ejection fraction (LVEF) and fractional shortening (FS) decreased significantly [LVEF: 0.185±0.008 vs. 0.257±0.022, FS: (9.72±1.72)% vs. (14.08±1.08)%, both P < 0.05], left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) increased significantly [LVEDD (mm): 5.43±0.29 vs. 4.62±0.35, LVESD (mm): 4.94±0.12 vs. 3.69±0.29, both P < 0.05]. Additionally, qPCR showed that exosomes derived from activated CD4 + T cells remarkably promoted myocardial fibrosis post-MI than MI group, as indicated by the mRNA expression of α-SMA, collagens (Col1a1, Col3a1) in MI+Exo group was significantly higher than that in MI group [α-SMA (2 -ΔΔCT): 4.72±0.89 vs. 3.58±0.78, Col1a1 (2 -ΔΔCT): 6.59±0.56 vs. 4.23±0.42, Col3a1 (2 -ΔΔCT): 13.40±1.03 vs.4.96±0.36, all P < 0.05]. Conclusion:Activated CD4 + T cells promote cardiac remodeling following MI through transferring exosomes to CFs.

Objective: To evaluate the long-term efficacy and prognostic factors of childhood acute lymphoblastic leukemia (ALL) enrolled in Shanghai Children's Medical Center-Acute Lymphoblastic Leukemia-2005(SCMC-ALL-2005) multicenter study. Methods: Between May 2005 and December 2014, 1 497 newly diagnosed ALL patients were enrolled and treated in 5 hospitals of SCMC-ALL-2005 study group, using risk-stratified SCMC-ALL-2005 protocol. Risk group classification and treatment intensity were based on clinical features, genetic abnormalities, early response to treatment and levels of minimal residual disease (MRD). Kaplan-Meier method was used to generate overall survival (OS) and event-free survival(EFS) curves. Cox proportional hazards models were used for multivariate analyses. Results: The patients were followed up to December 31, 2016, the median follow-up time was 69 months (24-141 months). The 5-year and 10-year OS rates were (80.0±1.0)% and (76.0±2.0)%. The 5-year and 10-year EFS rates were (69.0±1.0)% and (66.0±2.0)%. The 5-year and 10-year relapse rates were (23.0±1.0)% and (25.0±2.0)%. The 5-year OS and EFS for low risk (LR), intermediate risk (IR) and high risk (HR) were (91.1±1.4)% and (83.3±1.8)%, (79.2±1.5)% and (68.9±1.7)%, (52.9±4.4)% and (30.0±3.8)%, respectively. MRD negative status (<0.01%) on day 55 was seen in 792 patients (82.8%) and positive MRD on day 55 was associated with poor prognosis (OR=1.9, 95%CI: 1.3-2.7, P=0.001). Twenty-four HR patients received allogeneic hematopoietic stem cell transplantation and 17(70.8%) of them were alive and in remission. A total of 164 severe adverse events occurred, 46 of them died, treatment-related mortality was 3.1%. Conclusions In this large sample research, the overall outcome for multi-center SCMC-ALL-2005 study was favorable. This helps to promote the standardized treatment of childhood ALL to the whole country. MRD results on day 55 of induction therapy have important prognostic and therapeutic implications.

Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent vascular diseases and alleviate pain. However, the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained, which was associated with mitogen-activated protein kinase (MAPK) signal pathway, hepatic inflammation and fibrotic response. Furthermore, this hypothesis was verified using carbon tetrachloride (CCl

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence