ObjectiveTo investigate the predictive efficacy and clinical application value of red blood cell (RBC) parameters (hemoglobin and red blood cell distribution width) and their combined model for sepsis during chemotherapy-induced neutropenia (CIN) in children with acute lymphoblastic leukemia (ALL), based on propensity score matching (PSM) to eliminate confounding bias between groups.MethodsA retrospective cohort design was adopted. A total of 264 children with ALL who received induction remission chemotherapy according to the South China Children's Leukemia Group-ALL-2016 (SCCLG-ALL-2016) protocol and developed CIN between January 2021 and December 2024 in the Affiliated Hospital of Guangdong Medical University and Huizhou Central People's Hospital were included. The patients were divided into a sepsis group and a CIN group according to clinical outcomes. PSM was used to balance baseline characteristics between groups. Univariate and multivariate logistic regression models were used to screen independent influencing factors for sepsis. Receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the predictive efficacy and incremental value of single indicators and the combined model. Decision curve analysis (DCA) was applied to assess clinical net benefit, and Kaplan–Meier curves were plotted to analyze the cumulative incidence of sepsis under different RDW quartiles.ResultsA total of 108 patients were included after PSM matching (75 in the CIN group and 33 in the sepsis group). The RDW levels and pediatric Sequential Organ Failure Assessment (pSOFA) scores in the sepsis group were significantly higher than those in the CIN group, while Hb, RBC, and Hct levels were significantly lower (P < 0.05). Multivariate logistic regression analysis showed that RDW (OR = 1.424, 95% CI: 1.150–1.764, P = 0.001) and pSOFA score (OR = 1.613, 95% CI: 1.102–2.361, P = 0.014) were independent risk factors for sepsis, while Hb (OR = 0.974, 95% CI: 0.943–1.006, P = 0.113) was a protective factor. ROC curve analysis showed that the AUC of the combined model (Hb + RDW) for predicting sepsis was 0.812, which was significantly superior to single Hb (AUC = 0.672), RDW (AUC = 0.701), and pSOFA score (AUC = 0.682). Incremental value analysis showed that compared with single RDW, the IDI of the combined model was 0.068 (P = 0.003). DCA confirmed that the combined model provided better clinical net benefit within the threshold range of 10%–60%. Log-rank test indicated that the cumulative incidence of sepsis in the high RDW level group (Q4) was significantly increased (P = 0.024).ConclusionsRBC parameters (RDW, Hb) are independent predictors of sepsis in children with ALL during CIN. The combined prediction model constructed by Hb and RDW can effectively capture early signals of microcirculatory dysfunction, with predictive efficacy and clinical benefit superior to single indicators.

This study aims to screen key peripheral blood laboratory indicators using machine learning algorithms to develop and validate a prediction model for the 30-day mortality risk following the diagnosis of hemophagocytic lymphohistiocytosis (HLH) in children. This seeks to provide a scientific basis for the early clinical identification of high-risk patients. A retrospective cohort study was conducted, encompassing 133 children diagnosed with HLH at the Children’s Medical Center of the Affiliated Hospital of Guangdong Medical University between January 1, 2015, and December 30, 2024. Based on the survival outcome within 30 days post-diagnosis, the primary observation endpoint was categorized into a mortality group (n = 29) and a survival group (n = 104). Baseline laboratory indicators from the day of diagnosis or within the preceding 24 h were collected. The dataset was randomly partitioned into a training set and a validation set at a 7:3 ratio. Initial screening was performed via univariate analysis, followed by principal component analysis (PCA) and variance inflation factor (VIF) assessments to eliminate redundancy and isolate key predictors. Six machine learning models, including LightGBM, XGBoost, and logistic regression, were constructed using the optimized features. Model performance was evaluated using metrics such as the area under the curve (AUC) and F1 scores. The SHapley Additive exPlanations (SHAP) method was introduced for model interpretation, culminating in the construction of a visual nomogram and an online risk calculator. Five core predictive variables were identified: procalcitonin (PCT), mean corpuscular hemoglobin (MCH), aspartate aminotransferase (AST), C-reactive protein (CRP), and activated partial thromboplastin time (APTT). Among the six evaluated models, LightGBM demonstrated optimal robustness in the feature reduction experiment (validation set AUC = 0.823). SHAP visual analysis revealed that APTT and MCH contributed most significantly to the predictive outcomes; specifically, high elevated levels of APTT, AST, PCT, and CRP, coupled with a low expression level of MCH, were indicative of a high mortality risk. The risk stratification tool derived from this model successfully and significantly distinguished between high-risk and low-risk patients in both the training and validation datasets. A prediction model constructed using PCA feature screening and the LightGBM algorithm can effectively utilize routine peripheral blood indicators to quantitatively assess early mortality risk in pediatric HLH. The developed online calculator demonstrates substantial clinical value for auxiliary decision-making.

ObjectiveTo screen key peripheral blood indicators based on the Boruta feature selection algorithm, construct a latent class analysis (LCA) model, identify clinically heterogeneous subtypes of pediatric hemophagocytic lymphohistiocytosis (HLH), and evaluate the 30-day mortality risk following diagnosis.MethodsA retrospective cohort study design was employed, enrolling 133 children diagnosed with HLH at the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University between January 1, 2015, and December 30, 2024. Demographic characteristics and laboratory indicators at admission were collected. Patients were categorized into a non-survivor group (29 cases) and a survivor group (104 cases) based on their 30-day survival outcomes after diagnosis. Univariate logistic regression analysis was initially conducted for preliminary variable screening, followed by the Boruta algorithm to eliminate feature noise and identify key predictors. An LCA model was constructed based on the screened variables for subgroup classification, and model fit was evaluated using Akaike information criterion (AIC), Bayesian information criterion (BIC), and entropy, among other metrics. Additionally, Shapley Additive exPlanations (SHAP) analysis, importance scoring, and restricted cubic spline (RCS) models were employed to interpret key variables and explore nonlinear relationships.ResultsAfter dual screening through univariate analysis and the Boruta algorithm, six key predictive variables were identified: activated partial thromboplastin time (APTT), mean corpuscular hemoglobin (MCH), central nervous system (CNS) involvement, cyclosporine treatment, C-reactive protein (CRP), and imaging-confirmed hepatomegaly. LCA modeling demonstrated that the 2-class model exhibited the best fit (AIC = 1,507.750, BIC = 1,573.030, Entropy = 0.702), stratifying patients into a low-risk group (72%) and a high-risk group (28%). Survival analysis revealed a significantly lower 30-day cumulative survival rate in the high-risk group compared to the low-risk group (51.40% vs. 88.50%, Log-rank P < 0.001). Notably, patients in the high-risk group faced a 7.42-fold increased risk of 30-day mortality (HR = 7.4184, 95% CI: 2.6274–20.9205, P < 0.001). SHAP analysis indicated that APTT contributed most to the prediction, while RCS analysis revealed a monotonically increasing relationship between APTT and mortality risk, with elevated MCH levels demonstrating a significant protective trend.ConclusionThe analytical strategy integrating the Boruta algorithm and LCA effectively identifies clinical subtypes of pediatric HLH with distinct mortality risk trajectories based on routine peripheral blood indicators.

Objective:To investigate the joint effect of peripheral blood parameters on the 30-day mortality risk in children with hemophagocytic lymphohistiocytosis (HLH) using weighted quantile sum (WQS) regression, and to elucidate the clinical weights of each feature. Methods:A retrospective cohort design was adopted. A total of 133 pediatric HLH patients diagnosed at the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University between January 1, 2015, and December 30, 2024, were included. The patients were divided into a non-survival group (n = 29) and a survival group (n = 104) based on their 30-day survival outcomes following diagnosis. Baseline peripheral blood parameters within 24 h prior to or on the day of diagnosis were collected. After preliminary screening via univariate logistic regression, a WQS regression model was utilized to evaluate the joint effect of peripheral blood parameters and extract empirical weights. In addition, restricted cubic spline (RCS) analysis was employed to explore the dose-response relationship between core parameters and mortality risk. The predictive efficacy and clinical net benefit of the core parameters and their combined model were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results:Univariate analysis indicated that red blood cell distribution width (RDW), mean corpuscular hemoglobin (MCH), hematocrit (HCT), and hemoglobin (Hb) were significantly associated with early mortality risk. The negative-direction WQS regression model revealed that the overall improvement of peripheral blood parameters had a significant joint protective effect against 30-day mortality risk (β = -0.936, P = 0.012), with MCH (weight 62.6%) and HCT (weight 29.8%) exhibiting the highest relative weights within the evaluated mixture. RCS analysis demonstrated a significant overall association between MCH, HCT, and mortality risk, approximating a linear relationship. The area under the curve (AUC) of the combined predictive model constructed by MCH and HCT improved to 0.728, indicating superior predictive efficacy over single indicators. Moreover, DCA confirmed that the combined predictive model provided a favorable clinical net benefit across a broad range of threshold probabilities compared to single parameters. Conclusion:The analytical strategy incorporating the WQS regression model effectively mitigates collinearity interference among clinical variables. Abnormalities in peripheral blood parameters, primarily driven by HCT and MCH, serve as a exploratory composite indicator for predicting early fatal outcomes in pediatric HLH, offering a potential early warning signal for critical triage in the early stages of the disease.

The clinical-genetic characteristics of ETV6-RUNX1-like acute lymphoblastic leukemia (ALL) is still unclear in pediatrics. Therefore, we conducted Fluorescent In Situ Hybridization (FISH), Polymerase Chain Reaction(PCR) and Whole Transcriptome Sequencing (WTS) on 2171 B-lineage ALL cases and identified 49 (2.3%) ETV6-RUNX1-like and 406 (18.7%) ETV6-RUNX1 cases. We found that: i) ETV6-RUNX1-like patients were characterized by ETV6 abnormalities and enrich for PAX5, KRAS, CDKN2A/2B, CRLF2, IKZF1, PTTN11, NRAS, FLT3. ii) Genes affecting of transcription factor regulation, RAS signal pathway, cell cycle regulation, JAK/STAT signal pathway and epigenetic modification were significantly frequent in ETV6-RUNX1-like ALL. iii) Four hub genes, ETV6, CDKN2A, ABL1 and MYC, were identified among ETV6-RUNX1-like ALL. The clinical characteristics highlighted that: i) ETV6-RUNX1-like patients had higher minimal residual disease (MRD) persistence at day 15 (D15 MRD) than ETV6-RUNX1 patients (P = 0.023). ii) 5-year event-free survival (EFS) and overall survival (OS) of ETV6-RUNX1-like patients were both significantly worse than ETV6-RUNX1 patients (65.8 ± 15.4% vs. 95.7 ± 1.0%, P < 0.001 and 91.3 ± 4.2% vs 98.2 ± 0.7%, P = 0.006). iii) ETV6-RUNX1-like positive was the risk factor for EFS (HR 3.25 (95% CI, 1.23–8.61); P = 0.018). Therefore, it is important to discern ETV6-RUNX1-like patients early and opt for more intensive chemotherapy for these patients.

BackgroundHigh-intensity chemotherapy can cause life-threatening complications in pediatric patients. Therefore, this study investigated safety and efficacy of long-acting pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF; Jinyouli®) in children undergoing high-intensity chemotherapy.MethodsTreatment-naive patients received post-chemotherapy PEG-rhG-CSF as primary prophylaxis for two cycles. The primary endpoints were drug-related adverse events (AEs) and bone pain scores. Secondary endpoints included grade 3–4 neutropenia, duration of neutropenia recovery, absolute neutrophil count changes, febrile neutropenia (FN), reduced chemotherapy intensity, antibiotic usage, and AE severity. The cost-effectiveness of PEG-rhG-CSF was compared with that of rhG-CSF (Ruibai®).ResultsHere, 307 and 288 patients underwent one and two PEG-rhG-CSF cycles, respectively. Ninety-one patients experienced drug-related AEs, primarily bone pain (12.7%). Moreover, Grade 3–4 neutropenia and FN were observed. Median FN durations were 3.0 days in both cycles. No drug-related delays were observed during chemotherapy. One patient experienced grade 4 neutropenia-induced reduction in chemotherapy intensity during cycle 2. In total, 138 patients received antibiotics. PEG-rhG-CSF exhibited superior cost-effectiveness compared to rhG-CSF.ConclusionOur findings indicate that PEG-rhG-CSF is safe, efficient, and cost-effective in pediatric patients undergoing high-intensity chemotherapy, providing preliminary evidence warranting further randomized controlled trials.

A cross-sectional study to explore the correlation between cardiac and hepatic iron overload and its impact on the quality of life in children diagnosed with severe beta-thalassemia major (β-TM). A cohort of 55 pediatric patients with β-TM, diagnosed via genetic testing at the Affiliated Hospital of Guangdong Medical University from January 2015 to January 2022, was included in this study. The assessment of cardiac and hepatic iron overload was conducted using the magnetic resonance imaging T2* technique. The Chinese version of the Pediatric Quality of Life Inventory (PedsQL) 4.0. Pearson correlation analysis was utilized to assess the relationships between the cardiac and hepatic T2* values and between these T2* values and the total scores of PedsQL 4.0. Analysis showed no significant correlation between cardiac and hepatic T2* values. However, a significant relationship was observed between cardiac T2* values and PedsQL 4.0 total scores (r = 0.313, P < .05), indicating that cardiac, but not hepatic, iron overload is associated with the quality of life. This study highlights the absence of correlation between cardiac and hepatic iron overload levels and demonstrates a significant impact of cardiac iron overload on the quality of life in children with β-TM. These findings suggest the need for a focused approach to cardiac health in managing β-TM.

遗传学因素是儿童多发畸形的常见病因.本文报道一例TARP综合征患儿的临床特征与RBM10基因变异情况.患儿临床特征为喂养困难、发育迟缓、肢体抖动、视力障碍、听力缺失、永存左上腔静脉、后颅窝Blake囊肿、舌后坠、小下颌.父母表型无异常.全外显子测序检测+拷贝数变异发现患儿染色体Xp11.23上RBM10基因15～17号外显子半合缺失(chrX:47041146-47041762).经Sanger验证分析,该变异来源于母亲.结合患儿临床表型,诊断为TARP综合征.目前该病尚无特异性治疗,应重视产前检查,必要时需行全外显子组测序检查.对于携带RBM10变异母亲,应做好产前遗传诊断.

Background: Maintenance therapy is an important part of childhood acute lymphoblastic leukemia (ALL). However, the optimal chemotherapy regimen for maintenance therapy is still controversial. We aimed to evaluate the benefits of the continuous use of 6-mercaptopurine(6-MP) and methotrexate (MTX) with pulses of vincristine (VCR) and dexamethasone (DEX) in maintenance therapy for pediatric ALL.Methods: A total of 3,008 pediatric patients with ALL were enrolled in South China (2008-2022) and assigned to one of three maintenance regimens. Randomly selected subjects (n=2406;80%) and the remaining subjects comprised the development and validation groups, respectively. The overall survival (OS) probability was calculated using a predictor-based nomogram to evaluate maintenance regimens impact on OS in relation to baseline characteristics. Nomogram performance was assessed by the area under the receiver operating characteristic curve (AUC) and the calibration curve with 500 bootstrap resample validations. Decision curve analysis (DCA) was performed to evaluate the clinical utility of the nomogram. Then interaction between predicted OS probability and actual overall mortality in different maintenance regimens was tested.Findings: According to the minimum criteria of non-zero coefficients of Lasso and logistic regression screening, elder age, high risk group, T-cell, higher white blood count cell(WBC), lower platelet(PLT), day-15 minimal residual disease(MRD) and d-33 MRD positive were independently associated with a lower OS. A nomogram model for OS was established based on these predictors. The AUC (C statistic) of the nomogram was 0.788 (95% CI: 0.72–0.856) in the development group and 0.746 (95% CI:0.692-0.846) in the validation group. The calibration curves after 1000 bootstraps displayed a good fit between the actual and predicted probabilities in both the development and validation groups. DCA showed that the model in the development and validation groups had a net benefit when the risk thresholds were 0–0.2 and 0–0.25, respectively. This model was used to predict the 5-year OS probability in different maintenance regimens. When the predicted 5-year OS probability between 75% and 95%, the benefit of continuous use of 6-MP and MTX with pulses of VCR and DEX on OM decreased progressively as predicted OS decreased(P<0.05).Interpretation: We have developed a predictive model that can be used to identify pediatric patients with ALL who benefit from continuous use of 6-MP and MTX with pulses of VCR and DEX in terms of OS. Specifically, patients with worse baseline characteristics appear to benefit the most.Trial Registration: The trial is registered at http://www.clinicaltrials.gov with the identifier NCT00846703, and is registered with the Chinese Clinical Trial Registry (Chi-CTR; https://www.chictr.org.cn/;number ChiCTR2000030357).Funding: This work was supported by the Guangzhou Science and Technology Program key projects (No.201803010032), Bethune Medical Scientific Research Fund Project (No.SCE111DS), Guangdong Medical Scientific Research Foundation(A2024057), Guangzhou Basic and Applied Basic Research Foundation (2024A04J4686), Yat-sen Excellent Young Scientists Fund (2024A03J1185) and Sun Yat-sen Pilot Scientific Research Fund (YXQH202205).Declaration of Interest: The authors declare that they have no competing interests.Ethical Approval: Written informed consent with or without assent was obtained from each participant and parent/legal guardian, in accordance with the Declaration of Helsinki. This study was approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, and by ethics committee of other cooperation centers

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a life-threatening malignancy and therapeutic toxicity remains a huge challenge for survival rates. A novel iron-dependent form of cell death, ferroptosis, shows potentials in cancer therapy. This study aimed to identify ferroptosis-associated hub genes within a proteinprotein interaction (PPI) network. Methods: We screened differential expressed genes (DEGs) in GSE46170 dataset and obtained ferroptosis-related genes from FerrDb database. Through overlapping between DEGs and ferroptosis-related genes, ferroptosisassociated DEGs were identified for further PPI network construction. Molecular complex detection (MCODE) algorithm in Cytoscape was employed to determine tightly connected protein clusters. Chord diagram of Gene Ontology (GO) was generated to reveal the potential biological process of hub genes. Through transfection with siRNA of lipocalin 2 (LCN2) into TALL cells, the regulatory role of LCN2 in ferroptosis was investigated. Results: Venn diagram identified a total of 37 ferroptosis-associated DEGs between GSE46170 and ferroptosisassociated genes, which were mainly enriched in ferroptosis and necroptosis. Based on PPI network analysis, 5 hub genes (LCN2, LTF, HP, SLC40A1 and TFRC) were found. These hub genes were involved in iron ion transport and could distinguish T-ALL from normal individuals. Further experimental studies demonstrated that LCN2 was highly expressed in T-ALL, while silencing LCN2 promoted RSL3-induced ferroptotic cell death in TALL cells. Conclusion: This study identified novel ferroptosis-associated hub genes, which shed new insights into the underlying mechanism of ferroptosis in T-ALL and also provide promising therapeutic targets for T-ALL.

目的 总结儿童急性淋巴细胞白血病患儿接受儿童急性淋巴细胞白血病治疗协作组2016方案(SCCLG-ALL-2016方案)治疗过程中严重不良事件(severe adverse events,SAE)的发生情况,并分析发生SAE后死亡的相关危险因素.方法 回顾性分析2017年12月至2021年1月于广东医科大学附属医院儿科确诊并接受SCCLG-ALL-2016方案治疗的82例急性淋巴细胞白血病患儿的临床特点,将化疗过程中发生SAE的患儿(n=21)分为死亡组(n=6)与存活组(n=15),分析化疗过程中发生SAE后导致死亡的相关危险因素.结果 在各治疗阶段中,以诱导缓解治疗阶段(30.9％)记录到的SAE数最多.血液学相关SAE(60.3％)是主要的SAE.在发生的非血液学相关不良事件中,感染相关SAE占比最大(76.1％),其中又以呼吸系统感染事件的发生次数最多.在死亡组的6名患儿中,5名患儿因感染或合并明确感染因素死亡,占死亡原因的83.3％.结论 SCCLG-ALL-2016方案治疗儿童急性淋巴细胞白血病过程中发生的SAE主要发生在诱导缓解治疗阶段,以血液学相关SAE为主;在非血液学相关不良事件中,感染相关SAE占比最高,同时也是化疗期间死亡的重要原因.染色体检查结果阳性可能与死亡结局相关.

目的 探究分层递进的带教模式在儿科住院医师规范化培训中的应用.方法 选取2020年5月—2021年5月在我院儿科培训的住院医师,随机分为试验组25名,对照组25名,观察培训期满后两组住院医师的满意度调查结果和出科考核成绩.结果 试验组住院医师规范化培训学员的出科考核理论知识成绩,临床思维与决策成绩,首次病程记录书写成绩,专科技能操作成绩均显著高于对照组医学生的平均分数,差异有统计学意义(P<0.05);试验组住院医师规范化培训学员对教学方式与教学态度的满意度均高于对照组,差异有统计学意义(P<0.05).结论 分层递进的带教模式在儿科住院医师规范化培训中的应用,可以提高临床医生的专业知识与临床思维决策水平,提升学生对于教学培养的满意度.

随着近代以来人类白细胞抗原系统的逐步发现与证实,抗生素使用的广度和深度不断发展,免疫抑制剂及血制品种类等支持治疗的不断完善,造血干细胞移植技术水平得到了快速地提升,是治疗乃至治愈血液病及部分恶性肿瘤疾病的最有效方法.因此,提高对其的认识非常重要,而目前国内外尚无过多关于这方面的系统综述.故本文就目前关于人类白细胞抗原系统的定义及分类、造血干细胞移植技术的分类及特点、移植前的预处理、移植后的继发并发症等作一系统综述,为血液系统疾病及自身免疫疾病、遗传代谢疾病、实体瘤等提供新的治疗思路和手段.

目的 分析梅州地区儿童急性呼吸道感染病原体的流行特征.方法 收集11333例急性呼吸道感染患儿9项呼吸道感染病原体(肺炎支原体、呼吸道合胞病毒、腺病毒、甲型流感病毒、乙型流感病毒、副流感病毒、嗜肺军团菌、Q热立克次体、肺炎衣原体)IgM抗体检测资料,分析病原体感染阳性率与性别、年龄、月份、居住地关系.结果 病原体检测阳性率29.1％,其中肺炎支原体阳性率最高(21.3％),农村高于城镇(P<0.05或0.01).女性患儿肺炎支原体、腺病毒、乙型和甲型流感病毒阳性率高于男性(P<0.01或0.05).肺炎支原体、腺病毒、乙型流感病毒、副流感病毒在1～6岁儿童阳性率较高,而呼吸道合胞病毒在0～1岁较高.肺炎支原体、乙型流感病毒发病高峰分别是11月、4～7月.结论 梅州地区呼吸道病原体与患儿性别、年龄、月份、居住地有关.

Objective: This study aims to explore the toxic effect of PM2.5 on the hematopoietic microenvironment of the bone marrow, and investigate the effect of PM2.5 on oxidative stress injury, the secretion of inflammatory cytokines and the expression of NF-κB p65 and C x 43 in the bone marrow of mice. Methods: A total of 615 mice were treated with normal saline, low dose (0.1 mg/ml) PM2.5 suspension, and high dose (0.2 mg/ml) PM2.5 suspension by intratracheal instillation, respectively. The ROS content, activity of total SOD (T-SOD), DNA injury, and the protein expression levels of IL-1 β, IL-6, TNF-α, NF-κB p65 and Cx43 in bone marrow cells (BMCs) of mice were detected in these three groups. Results: Compared with the normal saline control group, the expression level of reactive oxygen species (ROS) significantly increased in BMCs, while the activity of SOD enzymes significantly decreased in PM2.5 exposed mice. Furthermore, DNA injury significantly increased in PM2.5 exposed mice, and the expression of IL-1 β, IL-6, TNF-α and NF-κB p65 significantly increased, while the protein expression of Cx43 significantly decreased in the PM2.5 exposed mice. The differences were statistically significant ( p < 0.05). There were significant differences in ROS content, T-SOD activity, DNA injury (TL, TD and TM), protein expression of IL-1β, IL-6, TNF-α and Cx43 between the high-dose PM2.5 exposure group and low-dose PM2.5 exposure group ( p < 0.05), but there was no significant difference in the expression of NF-κB p65 between the high-dose and low-dose PM2.5 exposure groups ( p > 0.05). Conclusion: PM2.5 has toxic effects on the bone marrow of mice. Oxidative stress injury, inflammatory reaction and abnormal intercellular communication may be the underlying mechanism .

在过去的几十年中,儿童急性淋巴细胞白血病(ALL)在治疗方面取得了实质性的进展,目前的长期无事件生存率接近80％,但仍有多达20％的患儿复发.复发性ALL是儿童血液肿瘤相关死亡率的重要原因.因此,提高对儿童ALL的相关预后因素的认识非常重要.本文通过对临床特征、分子生物学因素、治疗相关因素、基因多态性这4个方面的预后因素作一系统综述,希望加强对其理解,在临床实践中能够实施更精确的风险分层和制定个性化的治疗计划.

目的 探究壳寡糖对PM2.5染毒后小鼠骨髓细胞外泌体表达的影响.方法 采用SPF级,6～8周龄的雄性C57BL/6J小鼠32只,按照随机数表法将其分为空白对照组(n=8)、阳性对照组(n=8)、壳寡糖组(n=8)及阴性对照组(n=8).采集2020年5月～2020年12月期间在距离广东省湛江市霞山区人民大道南路段作为采集点,使用QJS-100D型多级颗粒物采集器采集PM2.5,再采用生理盐水将其配制为200μg/ml的悬液.对壳寡糖组及阳性对照组进行PM2.5气管滴注染毒,并对壳寡糖组采用壳寡糖进行灌胃,观察四组小鼠的基本情况,对比四组小鼠骨髓组织病理切片HE染色;采用Western Blot法检测四组小鼠骨髓组织外泌体的CD9、CD63、CD81蛋白表达情况,并检测Wnt/β-catenin下游蛋白(β-catenin、c-myc、Cyclin-D1)的表达水平.结果 空白对照组及阴性对照组的骨髓细胞形态正常,有少量巨核细胞存在,但阳性对照组巨核细胞数量有明显增加,而壳寡糖组巨核细胞少于阳性对照组,多于空白对照组及阴性对照组;壳寡糖组骨髓组织外泌体中CD9、CD63、CD81蛋白的表达水平明显高于阴性和阳性对照组(P<0.05),而壳寡糖组给予壳寡糖后β-catenin、c-myc、Cyclin-D1蛋白的表达水平较阳性对照组有显著下降(P<0.05).结论 对PM2.5染毒后的小鼠采用壳寡糖,可有效缓解其炎性症状,利于降低β-catenin、c-myc、Cyclin-D1蛋白的表达水平,表明壳寡糖可作用Wnt/β-catenin通路,进而改善PM2.5的毒性作用.

目的 探讨壳寡糖对PM2.5染毒后小鼠肺和骨髓中Wnt/β-catenin信号通路相关蛋白表达的影响.方法 32只C57BL/6J小鼠随机分为空白对照组、模型组、壳寡糖组、阴性对照组.通过气管滴注法建立PM2.5染毒模型,壳寡糖(600 mg/kg)或双蒸水每天灌胃2周.HE染色观察肺、股骨及胫骨病理变化,Western blot检测β-catenin、c-myc、Cyclin-D1蛋白表达.结果 壳寡糖组肺及骨髓炎症较模型组改善.模型组肺及骨髓中β-catenin、c-myc、Cyclin-D1表达明显增加(P<0.01),而壳寡糖组这些蛋白表达明显减少(P<0.01).结论 壳寡糖可通过抑制Wnt/β-catenin信号通路改善PM2.5对小鼠肺和骨髓的毒性作用.

Objective Even though childhood acute lymphoblastic leukemia (ALL) has an encouraging survival rate in recent years, some patients are still at risk of relapse or even death. Therefore, we aimed to construct a nomogram to predict event-free survival (EFS) in patients with ALL. Method Children with newly diagnosed ALL between October 2016 and July 2021 from 18 hospitals participating in the South China children’s leukemia Group (SCCLG) were recruited and randomly classified into two subsets in a 7:3 ratio (training set, n=1187; validation set, n=506). Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were adopted to screen independent prognostic factors. Then, a nomogram can be build based on these prognostic factors to predict 1-, 2-, and 3-year EFS. Concordance index (C-index), area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance and clinical utility of nomogram. Result The parameters that predicted EFS were age at diagnosis, white blood cell at diagnosis, immunophenotype, ETV6-RUNX1/TEL-AML1 gene fusion, bone marrow remission at day 15, and minimal residual disease at day 15. The nomogram incorporated the six factors and provided C-index values of 0.811 [95% confidence interval (CI) = 0.792-0.830] and 0.797 (95% CI = 0.769-0.825) in the training and validation set, respectively. The calibration curve and AUC revealed that the nomogram had good ability to predict 1-, 2-, and 3-year EFS. DCA also indicated that our nomogram had good clinical utility. Kaplan–Meier analysis showed that EFS in the different risk groups stratified by the nomogram scores was significant differentiated. Conclusion The nomogram for predicting EFS of children with ALL has good performance and clinical utility. The model could help clinical decision-making.

白血病是我国儿童发病率最高的血液恶性肿瘤,而感染是该类患儿最常见的并发症,严重影响白血病患儿的治疗效果,延长其住院时间,增加其治疗费用及复发率,并且是白血病儿童早期死亡的主要原因.近年来,随着抗菌药物的广泛应用,白血病儿童感染耐药率逐年升高,且多重耐药菌(multi-drug resistant bacteria,MDR)感染常见,对白血病儿童产生极大危害.因此,提高对儿童白血病合并MDR感染的认识非常重要.而 目前国内外尚无关于这方面的系统综述,故本文就目前儿童白血病合并MDR感染的现状、高危因素、机制和防治措施作一系统综述,希望有助于降低其发病率及病死率.