Epstein-Barr virus (EBV) infection is a common pediatric infectious disease. Infectious mononucleosis (IM) and hemophagocytic lymphohistiocytosis (HLH), two major complications of EBV infection, share similar clinical manifestations in the early stage. While IM is typically self-limiting, HLH is life-threatening and requires immediate intervention. Early differentiation between these two conditions is crucial for clinical decision-making; however, reliable prediction models based on readily available laboratory parameters remain scarce. This study aimed to develop and validate a machine learning prediction model using routine blood parameters obtained within 24 h of hospital admission in children with confirmed acute EBV infection to distinguish EBV-associated IM (EBV-IM) from EBV-associated HLH (EBV-HLH). This retrospective cohort study included 4,871 pediatric patients diagnosed with either EBV-IM or EBV-HLH from two campuses of Children’s Hospital of Chongqing Medical University. Demographic information and initial complete blood count (CBC) parameters within 24 h of admission were collected. The cohort was divided into a model development group (Yuzhong Campus, n = 2,848; 70

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition predominantly affecting children, characterized by hyperinflammation and high early mortality. While the HScore criteria, developed by Fardet et al. in 2014, have been widely used to diagnose HLH, recent studies have also explored its potential to predict disease severity in COVID-19 patients, with findings indicating that higher HScore values correlate with increased mortality risk and may identify patients who could benefit from immunomodulatory treatment.However, the potential of HScore-related indicators in predicting early prognosis in patients with HLH has not been reported. This study aimed to investigate the association between HScore scores and related indicators and early mortality in children with Hemophagocytic Lymphohistiocytosis (HLH), and to develop a Cox prediction model for early mortality based on optimized HScore parameters to assist medical professionals in better risk stratification at the time of diagnosis. This retrospective study included 624 children diagnosed with HLH admitted to the Children's Hospital of Chongqing Medical University between January 2006 and December 2022. Five Cox prediction models were developed: Model 1 used HScore values; Model 2 used original HScore grouping criteria; Model 3 used raw HScore parameters; Model 4 grouped HScore parameters by optimal cut-offs; Model 5 combined optimized HScore parameters with common prognostic indicators (total protein, TC, APTT, BUN, ferritin). Model performance was assessed using AUC and calibration curves. An interactive web application was developed using R and Shiny for clinical use. The optimal cut-off value for the HScore was determined to be 223, which stratified children into high-risk and low-risk groups. The estimated 30-day survival rates were 77.9% (95% CI: 73.6%-82.5%) for the low-risk group and 65.8% (95% CI: 60.5%-71.7%) for the high-risk group (P < 0.001). Model 5 demonstrated the highest AUC on both training and validation datasets, with values of 0.881 (95% CI: 0.818-0.942) and 0.813 (95% CI: 0.747-0.881), respectively. Factors associated with increased early mortality risk included hemoglobin levels <61 g/L, platelet counts <31×10^9/L, ferritin levels ≥1318 ng/mL, total protein levels ≥52.3 g/L, AST levels >460 U/L, total cholesterol levels <3.23 mmol/L, APTT levels >60.2s, and bone marrow phagocytosis. To facilitate clinical application, we developed a free online calculator tool (https://ranwyr.shinyapps.io/DynNomapp/) based on the optimal model results. The HScore alone is insufficient for accurately predicting early mortality risk in children with HLH. Our study provides a novel early mortality prediction tool based on optimized HScore parameters, which may aid clinicians in better risk stratification and decision-making at the time of diagnosis.

Background:Post-transplant infections are common complications, and the reasons are pre-transplant conditioning, time required for post-transplant immune reconstitution, and use of immunosuppressive agents. We aimed to analyze the risk factors for Epstein-Barr virus (EBV) reactivation and its progression to post-transplant lymphoproliferative disorder (PTLD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children and to determine the EBV PCR diagnostic threshold for PTLD. Methods:We retrospectively analyzed clinical data of 309 patients who underwent allo-HSCT without engraftment failure at the Children's Hospital of Chongqing Medical University from January 1, 2016, to December 21, 2021. The occurrences of EBV reactivation and PTLD were also recorded. The risk factors for EBV reactivation and progression to PTLD were analyzed, and the diagnostic threshold for PTLD was determined using whole-blood EBV PCR. Results:Among 309 pediatric patients, 256 experienced EBV reactivation within one year and 12 progressed to PTLD. Univariate and multivariate analyses indicated that ATG was the independent risk factor for EBV reactivation. Grade III-IV acute graft-vs.-host disease (aGVHD) was the risk factor for PTLD after EBV reactivation. Conclusions:Post-transplant EBV reactivation is a common complication after allo-HSCT, but rarely progresses to PTLD. Identification of the risk factors for PTLD and regular monitoring of the EBV-DNA load play important roles in prevention and cure of PTLD after HSCT.

Autoimmune cytopenia (AIC) following pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively rare but it is a challenging complication, and standardized treatment guidelines are lacking. We retrospectively analyzed 436 pediatric patients undergoing allo-HSCT; 37 (8.5%) developed AIC, characterized by autoimmune hemolytic anemia (n = 13), immune thrombocytopenia (n = 11), and Evans syndrome (n = 13). Risk factor analysis revealed that younger age at HSCT, nonmalignant diseases, unrelated donor transplantation, and chronic graft-versus-host disease (cGVHD) were significantly associated with the development of AIC. Through multivariate analysis, cGVHD was identified as an independent risk factor for AIC. In our study, the first-line treatment for AIC involved steroids and/or intravenous immunoglobulin, with a complete remission rate of 48.6%. Additional therapeutic strategies included rituximab, which led to complete remission in 5 of 12 patients we treated, and sirolimus, with 3 of 7 patients achieving complete remission. Three patients achieved partial remission, while 9 patients died due to complications, such as severe infections, extensive GVHD, and multiorgan bleeding. Our findings suggest that cGVHD is an independent risk factor for post-transplant AIC and is typically associated with adverse outcomes, highlighting the critical importance of timely and effective interventions.

Background:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for β-thalassemia major (TM). Currently, TM patients undergoing allo-HSCT achieve a survival rate exceeding 90%, with over 80% attaining disease-free survival following treatment at transplant centers worldwide. Sibling donors constitute the most common graft source, and the immune status of pediatric recipients directly influences transplant approach selection, conditioning regimen design, and prognosis. Children with TM exhibit distinct immune states before and after transplantation, yet research on post-transplant immune reconstitution in these patients remains limited. Therefore, this study aims to explore the characteristics of immune reconstitution following allo-HSCT in TM patients, with the goal of providing additional valuable insights for clinical management. This study aimed to investigate the differences in lymphocyte subset reconstitution within 1 year after allo-HSCT in children with TM, evaluate the efficacy of transplantation, and explore factors influencing post-transplant immune cell reconstitution. Methods:We retrospectively analyzed the clinical data of 74 children with TM who underwent allo-HSCT from September 2014 to December 2020 at the Transplantation Center of the Department of Hematology and Oncology, Children's Hospital of Chongqing Medical University to investigate the factors influencing the reconstitution of immune cells after transplantation in children with TM. Results:(I) The results showed that post-transplant cytomegalovirus (CMV) infection, CD34+ cell content in the graft, and donor type could influence the level of immune cell reconstitution after transplantation in children with TM. (II) The level of post-transplant cell reconstitution was higher in children who did not have anemic heart disease before transplantation, who were compatible human leukocyte antigen (HLA) 10/10 transplants, who were donor-recipient blood group compatibility, and who did not have acute graft-versus-host disease (aGVHD) after transplantation. (III) CMV-infection-positive and Epstein-Barr virus (EBV)-infection-positive children had higher levels of T-cell reconstitution, and CMV-infection-negative children had higher levels of NK-cell and B-cell reconstitution. Conclusions:(I) Post-transplant CMV infection, CD34+ cell content in the graft, and donor type were independent influences on the level of T- and B-cell reconstitution after transplantation in children with TM. (II) No anemic heart disease before transplantation, donor-recipient blood type compatibility, no aGVHD after transplantation, no cGVHD after transplantation, and HLA 10/10 compatible transplantation are favorable for immune cell reconstitution after transplantation. (III) CMV infection and EBV infection after transplantation favored T-cell reconstitution, while CMV infection was detrimental to B-cell reconstitution.

Objective:Gut acute graft-versus-host disease (aGVHD) is one of serious complication after hematopoietic stem cell transplantation (HSCT). Mucosal-associated invariant T (MAIT) cells are a group of innate T cells that are enriched in the gut. Currently, there is limited research on the role and function of MAIT cells in the development of aGVHD in humans.Our study aim to investigate the effect of MAIT cells on the occurrence of gut aGVHD after HSCT in children, and to developing a new clinical prevention and treatment strategy for gut aGVHD. Methods: We collected peripheral blood(PB)samples from 81 patients 30 days after HSCT. The content of MAIT cells was detected via flow cytometry to investigate the relationship between MAIT cells and gut aGVHD occurrence in children. Results: The count of MAIT cells in the PB of children with gut aGVHD was notably lower than that in those without aGVHD and other types of aGVHD. Conclusion: The PB of patients who develop gut aGVHD after HSCT demonstrates a reduction in MAIT cells. This reduction may be associated with delayed immune reconstitution and a higher risk of gut aGVHD post-transplantation,as well as a potential impact on the host's capacity to defend against intestinal infections.

A boy with primary immunodeficiency, caused by a tyrosine kinase 2 (TYK2) mutation, presented with immune defects and a lifelong history of severe infections. Our aim was to determine whether allogeneic hematopoietic stem cell transplantation (HSCT) could restore the patient's immune defenses and reduce susceptibility to infection. In the absence of a suitable HLA-matched blood relative to act as a donor, the patient received an allogeneic HSCT from unrelated donors. The patient's clinical data were analyzed in the Children's Hospital of Chongqing Medical University (Chongqing, China) before transplantation and during the 4-year follow-up period using a combination of western blotting (e.g., TYK2 and STAT levels), qRT-PCR (e.g., T cell receptor rearrangement excision circles, kappa deletion element recombination circles, and TYK2 transcript levels), and flow cytometry (e.g., lymphocyte subpopulations and CD107α secretion). We found that HSCT significantly reduced the incidence of severe infections, restored normal TKY2 levels, and reversed defects such as impaired JAK/STAT signaling in response to interferon-α or interleukin-10 treatment. Although the patient did not develop acute graft-versus-host disease (GVHD) after transplantation, he did experience chronic GVHD symptoms in a number of organs, which were effectively managed. Our findings suggest that HSCT is a feasible strategy for reconstituting the immune system in TYK2-deficient patients; however, the factors associated with GVHD and autoimmune thyroiditis development in TYK2-deficient patients undergoing HSCT warrant further investigation.

Chronic granulomatous disease (CGD) in children is a rare primary immunodeficiency disorder that can lead to life-threatening infections and inflammatory complications. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly being used to treat severe CGD in children. We conducted a multicenter retrospective analysis of children with CGD who were treated with allo-HSCT at four pediatric hematopoietic stem cell transplant centers in China from September 2005 to December 2019. The study included a total of 171 patients (169 males and 2 females). The median age at the time of transplantation was 6.1 (0-16.4) years. Among them, 154 patients had X-linked recessive inheritance caused by CYBB gene mutations, 12 patients were autosomal recessive, 1 patient had DNAH11 and HYDIN gene mutations, and 4 patients had no gene mutations. The median follow-up period was 36.3 (1.9-79) months. All participating patients were applied to myeloablative conditioning (MAC) regimens. The rates of OS, EFS, and GEFS within three years were 87.5%, 85.3%, and 75.2%, respectively. The total graft failure and the total mortality rate were 5.3% and 11.1%. The cumulative incidence of acute GVHD was 53.8% and the incidence of chronic GVHD was 12.9%, The incidence of chronic GVHD was higher for patients who received unrelated donor cord blood stem cell transplantation (UD-CB) (P = 0.001). Chronic GVHD and coinfections are the risk factors for OS and EFS in patients with CGD after receiving alloHSCT. UD-CB is a risk factor for EFS and the presence of pneumonia before transplantation is a risk factor for OS. In conclusion, through this study, we have demonstrated that allo-HSCT has excellent efficacy in the treatment of CGD in children, especially, RD-haplo is associated with a lower rate of graft failure incidence and mortality than the treatment modalities of other donor type. Therefore, allo-HSCT is strongly recommended when a well-matched donor is available. If a well-matched donor is not available, the HLA-mismatched donor should be carefully evaluated, and the conditioning regimen modified accordingly.

Cardiotoxicity in children is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); therefore, early identification of risk factors can improve patient prognosis. However, there are few data on the clinical characteristics of early-stage cardiotoxicity in children after allo-HSCT. We conducted a retrospective single-center study of pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2016 and December 2022 at the Children's Hospital Affiliated with Chongqing Medical University to evaluate the clinical characteristics of early cardiac events (ECEs) after allo-HSCT and their impact on survival outcomes. We enrolled 444 patients who underwent allo-HSCT—304 males (68

Lipopolysaccharide (LPS)-responsive beige ankyrin (LRBA) gene mutations were first reported as the cause of immunodeficiency syndromes and autoimmunity in 2012. The majority of LRBA patients have multiple organ system involvement and a complex clinical phenotype. Herein we present a comprehensive account on the disease progression and transplantation procedure in a patient with LRBA deficiency who exhibited progressive autoimmune disease symptoms along with recurrent pulmonary infections since the age of 6 years old. Despite receiving abatacept therapy and immunoglobulin replacement treatments to manage the symptoms, but the symptoms still progressed. Therefore, nine years after disease onset, patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). The patient experienced acute and chronic graft-versus-host disease (GVHD) and recurrent infections after transplantation. During one and a half years of follow-up, we found that allogeneic haematopoietic stem cell transplantation can relieve the symptoms of autoimmune disease in patients with LRBA deficiency, and marked clinical improvement and recovery of immune function were observed following stem cell transplantation.

Background: Hemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening disease in children, with a high early mortality rate. This study aimed to construct machine learning model to predict the risk of early death using clinical indicators at the time of HLH diagnosis. Methods: This observational cohort study was conducted at the National Clinical Research Center for Child Health and Disease. Data was collected from pediatric HLH patients diagnosed by the HLH-2004 protocol between January 2006 and December 2022. Six machine learning models were constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) to select key clinical indicators for model construction. Results: The study included 587 pediatric HLH patients, and the early mortality rate was 28.45 %. The logistic and XGBoost model with the best performance after feature screening were selected to predict early death of HLH patients. The logistic model had an AUC of 0.915 and an accuracy of 0.863, while the XGBoost model had an AUC of 0.889 and an accuracy of 0.829. The risk factors most associated with early death were the absence of immunochemotherapy, decreased TC levels, increased BUN and total bilirubin, and prolonged TT. We developed an online calculator tool for predicting the probability of early death in children with HLH. Conclusions: We developed the first web-based early mortality prediction tool for pediatric HLH to assist clinicians in risk stratification at diagnosis and in developing personalized treatment protocols. This study is registered on the China Clinical Trials Registry platform (ChiCTR2200061315).

Objective To investigate similarities and differences in immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD). Method We retrospectively analyzed the lymphocyte subpopulations and the serum level of various immune-related protein or peptide on Days 15, 30, 100, 180 and 360 post-transplantation in 70 children with WAS and 48 children with CGD who underwent allo-HSCT at the Transplantation Center of the Department of Hematology-Oncology, Children’s Hospital of Chongqing Medical University from January 2007 to December 2020, and we analyzed the differences in the immune reconstitution process between the two groups. Results ① The WAS group had higher lymphocyte subpopulation counts than the CGD group. ② Among children aged 1-3 years who underwent transplantation, the WAS group had higher lymphocyte subpopulation counts than the CGD group. ③ Further comparisons were performed between children with non-umbilical cord blood transplantation (non-UCBT) and children with umbilical cord blood transplantation (UCBT) in the WAS group. On Day 15 and 30 post-transplantation, the non-UCBT group had higher B-cell counts than the UCBT group. On the remaining time points post-transplantation, the UCBT group had higher lymphocyte subpopulation counts than the non-UCBT group. ④ Comparisons were performed between children with non-UCBT in the WAS group and in the CGD group, the lymphocyte subpopulation counts were higher in the WAS group compared to the CGD group. ⑤ On Day 100 post-transplantation, the CGD group had higher C3 levels than the WAS group. On Day 360 post-transplantation, the CGD group had higher IgA and C4 levels than the WAS group. Conclusion ① The rate of immunity recovery was faster in children within the WAS group compared to those children within the CGD group, which may be attributed to the difference of percentage undergoing UCBT and primary diseases. ② In the WAS group, the non-UCBT group had higher B-cell counts than the UCBT group at Day 15 and 30 post-transplantation, however, the UCBT group had higher B-cell counts than the non-UCBT group at Day 100 and 180 post-transplantation, suggesting that cord blood has strong B-cell reconstitution potentiality after transplantation.

Objectives The clinical characteristics, risk factors and survival prognosis of pericardial effusion (PE) after haematopoietic stem cell transplantation (HSCT) in children were investigated. Methods Clinical data of children who underwent HSCT at the Children's Hospital Affiliated with Chongqing Medical University from January 2016 to December 2022 were analysed retrospectively. Cox proportional hazards regression and the Kaplan-Meier method were used to analyse the risk factors for post-HSCT PE and its impact on outcomes, respectively. Results We enrolled 452 patients with HSCT: 307 males and 145 females, with a median age of 3.4 (1.8 to 6.5) years at transplantation. Forty-five patients (10%) had PE within a median time of 25 (10.5 to 44) days, 42 (93%) within 100 days. Three patients with large PE were treated with pericardiocentesis and drainage, while the others were treated conservatively. Of the 45 patients with PE, 24 survived, and their PE disappeared after treatment. Graft-versus-host disease (GVHD) grade, abnormal pre-HSCT electrocardiogram, hepatic veno-occlusive disease (HVOD), pulmonary infection and Epstein-Barr virus (EBV) infection were risk factors for PE. The overall survival (OS) rates at 1, 3, and 5 years were 86.0%, 84.2%, and 82.3%, respectively. PE had a significant negative effect on OS after HSCT (P < 0.0001). Particularly, one patient with large PE died of pericardial tamponade. Conclusions Post-HSCT PE usually occurred within 100 days. GVHD grade, abnormal pre-HSCT electrocardiogram, HVOD, pulmonary infection and EBV infection were closely related to PE. PE had a significant negative effect on OS rate.

BACKGROUND:This prospective study aimed to comprehensively understand the changes in intestinal flora at different stages after hematopoietic stem cell transplantation (HSCT) in pediatric patients and to analyze the effect of intestinal flora on acute graft versus host disease (aGVHD), especially on gastrointestinal graft versus host disease (GI GVHD). METHODS:A total of 32 children with primary diseases of primary immunodeficiency disease (PID) and thalassemia were included. 16S sequencing was used to characterize the microbiota layout at three time points peri-transplant including pre-transplant, Day +3, and Day +30. RESULTS:By comparing the intestinal flora of children with GI GVHD and those without GI GVHD, it suggests that in children with GI GVHD, the distribution of intestinal flora after transplantation was more variable and more chaotic (chao1 index, Friedman test, p = .029). Besides, Veillonella and Ruminococcaceae were more abundant before transplantation, Bifidobacteriaceae and Bacillales were more abundant after transplantation. Comparing children with PID and thalassemia, it was found that the destruction of gut microbiota diversity was more significant in children with thalassemia after transplantation. The comparison of children with 0-I° aGVHD and II-III° aGVHD indicates that children with II-III° aGVHD had more Bilophila before transplantation than children with 0-I° aGVHD. Additionally, exploratory analyses to evaluate correlations between clinical characteristics (medications, immune cell recovery, etc.) and microbiome features were also performed. CONCLUSIONS:This study has synthetically shown the distribution of intestinal flora after allo-HSCT, and some characteristic bacteria at different stages that may serve as potential biomarkers were screened out additionally, perhaps providing clues for the prevention and treatment of the disease.

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressive and potentially life-threatening disorder. Identifying risk factors and timely adjustment of the given treatment regimens is critical to reducing the early mortality in HLH patients. Hypocholesterolemia has been reported to be associated with poor prognosis in a variety of critical illnesses. However, serum cholesterol is rarely studied in HLH patients, and its prognostic value is unclear. Methods We conducted a retrospective cohort study at National Clinical Research Center for Child Health and Disorders (Chongqing), identifying pediatric HLH patients diagnosed with the HLH-2004 protocol and treated with immunochemotherapy between January 2008 and December 2020. The patients’ blood lipid levels at initial diagnosis of HLH, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein- cholesterol (LDL-C), were reviewed based on electronic medical records. Both Cox and logistic regression models were used to estimate the effects of blood lipid indicators on early death (within 30 days after diagnosis). Results The observed 30-day mortality rate of the 353 included patients was 19.05% (64/336, 17 were lost to follow-up). The Kaplan-Meier-estimated 3-year survival rate was 61.67% (95% CI, 56.27%-67.59%). Lipid panel was performed in 349 patients: 91.98% (321/349) had TG ≥ 1.80 mmol/L, 92.84% (324/349) had HDL-C ≤ 1.04 mmol/L, 58.74% (205/349) had LDL-C ≤ 1.30 mmol/L and 24.64% (86/349) had TC ≤ 3.11 mmol/L. TC ≤ 3.11 mmol/L and BUN ≥ 7.14 mmol/L were the independent risk factors for 30-day mortality [HR(95%CI): 2.85(1.46, 5.57) and 2.90(1.48, 5.68), respectively]. Compared with the low-risk group (no risk factors present), the patients had a nearly 10-fold increased risk of early death [HR = 9.98, 95%CI: (4.23, 23.56)] in the high-risk group (two risk factors were present) and a 6-fold increased risk of early death [HR = 6.24, 95%CI: (3.18, 12.22)] in the intermediate-risk group (one risk factor was present). Conclusion Severe derangement of lipoproteins is common in children with HLH, and decreased TC is an independent risk factor for early death. More attention needs to be paid to hypocholesterolemia during the management of HLH patients.

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressive and potentially life-threatening disorder. Identifying risk factors and timely adjustment of the given treatment regimens is critical to reducing the early mortality in HLH patients. Hypocholesterolemia has been reported to be associated with poor prognosis in a variety of critical illnesses. However, serum cholesterol is rarely studied in HLH patients, and its prognostic value is unclear. Methods We conducted a retrospective cohort study in National Clinical Research Center for Child Health and Disorders (Chongqing), identifying pediatric HLH patients diagnosed with the HLH-2004 protocol and treated with immunochemotherapy between January 2008 and December 2020. The patients’ blood lipid levels at initial diagnosis of HLH, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein- cholesterol (LDL-C), were reviewed based on electronic medical records. Both Cox and logistic regression models were used to estimate the effects of blood lipid indicators on early death (within 30 days after diagnosis). Results The observed 30-day mortality rate of the 353 included patients was 19.05% (64/336, 17 were lost to follow-up). The Kaplan-Meier-estimated 3-year survival rate was 61.67% (95% CI, 56.27%-67.59%). Lipid panel was performed in 349 patients: 91.98% (321/349) had TG ≥ 1.80 mmol/L, 92.84% (324/349) had HDL-C ≤ 1.04 mmol/L, 58.74% (205/349) had LDL-C ≤ 1.30 mmol/L and 24.64% (86/349) had TC ≤ 3.11 mmol/L. TC ≤ 3.11 mmol/L and BUN ≥ 7.14 mmol/L were the independent risk factors for 30-day mortality [HR(95%CI): 2.85(1.46, 5.57) and 2.90(1.48, 5.68), respectively]. Compared with the low-risk group (no risk factors present), the patients had a nearly 10-fold increased risk of early death [HR = 9.98, 95%CI: (4.23, 23.56)] in the high-risk group (two risk factors were present) and a 6-fold increased risk of early death [HR = 6.24, 95%CI: (3.18, 12.22)] in the intermediate-risk group (one risk factor was present). Conclusion Severe derangement of lipoproteins is common in children with HLH, and decreased TC is an independent risk factor for early death. More attention needs to be paid to hypocholesterolemia during the diagnosis and management of HLH patients.

OBJECTIVE:To investigate the prevalence of respiratory viral infections in patients with primary immunodeficiency disease (PID) during hematopoietic stem cell transplantation.METHODS:108 specimens of nasopharyngeal aspirate were collected from 22 PID patients before and after hematopoietic stem cell transplantation from July 2016 to July 2018 in the Department of Hematology. The TR-PCR was used to detect for respiratory viruses including respiratory syncytial virus(RSV)，human metapneumoviros(hMPV)，coronavirus(CoV) and parainfluenza 1-3 (PIV1-3). And the clinical characteristics and co-infection were analyzed.RESULTS:Among the total 108 specimens, viral pathogens were identified in 41 (37.96%) specimens. Among which the pathogens of highest detection rate was RSV (25.9%). Different types of PID showed different virus infection rates, among which the highest infection rate was severe combined immunodeficiency disease (SCID) patients, with the virus detection rate was 57.9%. The incidence of co-infection with two or more than two viruses was 19.5%.CONCLUSION:Patients with PID who undergo hematopoietic stem cell transplantation are more susceptible to respiratory viruses. RSV is an important respiratory tract virus pathogen after hematopoietic stem cell transplantation.

Objective To explore the recovery time and risk factors of coagulopathy caused by rodenticide poisoning through analyzing and following up the confirmed cases,and to provide more useful guidance information for the clinic practice.Methods A total of 96 cases with coagulation dysfunction caused by anticoagulant rodenticide poisoning in Children's Hospital,Chongqing Medical University from January 2014 to December 2016,were analyzed retrospectively.The recovery time of coagulation function and the relationship between recovery time and drug involved way,dysfunction organs and poison concentration were studied respectively.Results (1) A total of 96 patients were hospitalized because of severe coagulopathy caused by the poisoning of second generation anticoagulant rodenticide.Brodifacoum was detected from 33 blood samples and the median concentration was 364 μg,/L (55-4 654 μg/L).Bromadiolone was detected from 7 blood samples and the median concentration was 130 μg/L (18-652 μg/L).Brodifacoum and Bromadiolone were both detected from 8 cases and the median concentration was 741 μg/L (63-6 000 μg/L) and 11 μg/L (3-3 694 μg/L),respectively.(2) A total of 57 cases of the patients were successfully followed up.A total of 18 cases were confirmed with oral poisoning,16 cases with dermal poisoning,while 23 cases denied any involved ways of poisoning,and 7 cases had organs dysfunction.The follow-up time was 12-54 months.All the hospitalized patients were given specific antidote Vitamin K treatment and recovered successfully without any sequelae.(3) The median recovery time of coagulopathy caused by rodenticide poisoning was 2.5 months.(4) The recovery time of coagulation function was positively correlated with the plasma concentration of Brodifacoum(r =0.619,P ＜ 0.01).(5) There was no significant correlation between recovery time and organ dysfunction or drug involved ways of poisoning involvement (all P ＞ 0.05).Conclusions The recovery time of coagulation dysfunction caused by anticoagulant rodenticide in children is much longer.The higher the concentration of Brodifacoum poison is,the longer the recovery time.Enough supplementation course of Vitamin K should be given according to the follow-up of coagulation function.

Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is closely associated with a number of diseases; however, its influence in B-cell acute lymphoblastic leukemia (B-ALL) and the potential molecular mechanisms involved remain unclear. The present study aimed to evaluate the expression of PRPS1 in Chinese children with B-ALL and to investigate the mechanism of action of PRPS1 in this disease. A Cell Counting Kit-8 (CCK-8) assay was performed to examine the proliferation of B-ALL Sup-B15 and Raji cells, and flow cytometric analysis was conducted to determine the cell cycle distribution and rate of apoptosis. The mRNA and protein expression levels of PRPS1, MYC proto-oncogene, bHLH transcription factor, cyclin E1, B-cell lymphoma-2 (Bcl-2), cyclin dependent kinase 2 and caspase-3 were detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Elevated PRPS1 expression was associated with a high-risk stratification and poor prognosis in patients with B-ALL. Furthermore, overexpression of PRPS1 accelerated the growth of and inhibited apoptosis in Sup-B15 and Raji cells as well as increasing the expression of Bcl-2 to induce an anti-apoptotic effect in B-ALL cell lines. The results of the present study indicate that PRPS1 regulates multiple processes in B-ALL and may be an attractive therapeutic target.

OBJECTIVE:To investigate the correlation between the expression level of PRPS1 and the clinical characteristics in children with acute leukemia(AL). METHODS:Real-time quantitative RT-PCR and Western blot were used to detect the level of PRPS1 mRNA and protein expression in bone marrow samples from 176 patients diagnosed as AL (126 cases were newly diagnosed and 50 cases in complete remission), and its relevance with clinical indicators was statistically analyzed. The bone marrow samples from 21 children with non-malignant hematological disease were used as controls. RESULTS:(1)In B-ALL group, the level of PRPS1 mRNA in newly diagnosed patients were significantly higher than that in control and than that in complete remission patients (both P<0.0001). In T-ALL and AML group, differences was only observed between newly diagnosed patients and complete remission patients(both P<0.0001); (2)In B-ALL group, the expression level of PRPS1 increase with along risk enhancement (P<0.01), while no significant difference was observed in T-ALL (P>0.05). In AML patients, expression difference was shown between low risk group and high risk group(P<0.05); (3)High PRPS1 mRNA expression level were associated with high WBC counts and MRD positive in B-ALL patients (P=0.020, P=0.026, respectively); (4)Expression of NT5C2, an essential gene for relapse and drug resistance, was found to be positively correlated with PRPS1 expression in AL samples(P<0.05). CONCLUSION:High expression of PRPS1 is relevant factor of unfavourable prognosis in B-ALL children, which suggest PRPS1 may be a new indicator for prognosis of pediatric B-ALL and an index to guide individualized chemotherapy.