It has been more than 10 years since chimeric antigen receptor T cells (CAR-T) therapy were first used to treat children with relapsed acute lymphoblastic leukemia, and thousands of patients worldwide have benefited from it. CAR-T treatment has greatly improved the overall prognosis of relapsed and refractory pediatric acute lymphoblastic leukemia patients and is gradually changing the treatment history of relapsed and refractory pediatric hematological tumor patients. Currently, CAR-T treatment for children still faces some challenges, but overall, the prospects are extremely promising.

B cell aplasia (BCA) is a common adverse side effect in pediatric patients with B-acute lymphoblastic leukemia (B-ALL) following CD19-chimeric antigen receptor T-cell (CD19 CAR-T) therapy. The duration of BCA has an impact on the immune status and prognosis of patients. A thorough understanding of BCA helps physicians choose treatment plans in a scientific, normative, and reasonable manner, reducing the risk of infection in pediatric leukemia patients after CAR-T treatment and improving their prognosis and quality of life.

Objective To explore the efficacy and safety of CD19 chimeric antigen receptor T cells (CAR-T) in the treatment of refractory/relapsed B-cell acute lymphoblastic leukemia (B-ALL) in children and adolescents. Methods The clinical data of refractory/relapsed B-ALL patients<25 years old who received CD19 CAR-T therapy from June 2017 to March 2021 were retrospectively analyzed and the efficacy and safety of this therapy was evaluated. Results A total of 64 patients (35 boys and 29 girls) with refractory/relapsed B-ALL were included, and the median age was 8.5 (1.0-17.0) years old. One month following CD19 CAR-T infusion, a short-term effectiveness assessment of all 64 patients showed minimal residual disease (MRD) negative in 62 of them, and complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) in all 64 patients. The incidence rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were 78.1 % and 23.4 %, respectively. Twenty-two patients experienced recurrence after infusion, with a median recurrence time of 10.1 months. The 4-year overall survival (OS) rate was 66.0 %±6.0 %, and the 4-year leukemia free survival (LFS) rate was 63.0 %±6.0 %. Long-term follow-up results demonstrated superior LFS and OS in patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) compared to those who were not bridged to transplantation (4-year LFS: 81.8 %±6.2 % vs. 24.0 %±9.8 %, 4-year OS: 81.4 %±5.9 % vs. 44.4 %±11.2 %; both P<0.01). Conclusions CD19 CAR-T therapy can effectively treat refractory/relapsed B-ALL, and bridging to HSCT after infusion can further improve the long-term survival outcomes in patients.

Objective To investigate the efficacy and safety of modified CLAG regimen (cladribine + cytarabine + granulocyte colony-stimulating factor) with reduced chemotherapy dose in the treatment of children with relapsed/refractory acute myeloid leukemia (R/R-AML). Methods The clinical data of children with R/R-AML treated with the modified CLAG regimen from June 2016 to April 2023 were retrospectively analyzed, and the overall response rate (ORR), incidence of adverse reactions, overall survival (OS) rate, and event-free survival (EFS) rate were calculated. Results Among all the children, 17 had recurrent AML, of them 1 had testicular leukemia recurrence, 3 had secondary recurrence in the bone marrow, and the rest had first recurrence in the bone marrow. Nine patients had refractory AML. All children completed 1 course of chemotherapy with modified CLAG regimen, and hematopoietic stem cell transplantation (HSCT) was bridged in 1 patient with no assessed response to treatment, with an ORR of 84.0 % (21/25) in the remaining 25 children. The ORR was 81.3 % (13/16) in the relapsed children and 88.9 % (8/9) in the refractory children. The ORR was 76.9 % (10/13) in children with low risk cytogenetic stratification and 91.7 % (11/12) in children with moderate and high risk cytogenetic stratification. The 64-month OS and EFS rates of all patients were 69.7 % and 63.3 %, respectively. The 64-month OS and EFS rates of 15 children who responded to treatment and successfully bridged allogeneic HSCT were 92.3 %. The most common adverse reactions were myelosuppression (100 %) and gastrointestinal reactions (100 %), followed by infection (57.7 %), elevated transaminases (34.6 %), and bleeding (19.2 %), and one child abandoned treatment due to grade 4 intracranial hemorrhage. All other adverse reactions were improved after symptomatic treatment. Conclusions The modified CLAG regimen with reduced chemotherapy dose is an effective and safe treatment option for children with R/R-AML.

To explore the efficacy and safety of interleukin-6 receptor monoclonal antibody (tocilizumab) in patients with glucocorticoid-resistant/recurrent massive pericardial effusion after hematopoietic stem cell transplantation. The clinical data, diagnosis, treatments, and outcomes of 2 children with β-thalassemia major complicated by massive pericardial effusion after hematopoietic stem cell transplantation were analyzed retrospectively. One case of pericardial effusion was glucocorticoid-resistant and 1 case was recurrent. The pericardial effusion was resolved rapidly after administration of tocilizumab without significant adverse effects, the course of glucocorticoid therapy was shortened, and there was no recurrence of pericardial effusions during subsequent follow-up. Tocilizumab may be considered as a second-line option for patients with glucocorticoid-resistant or recurrent massive pericardial effusion after hematopoietic stem cell transplantation.

Objective To analyze the clinical characteristics of extremely premature infants conceived by assisted reproductive technology (ART). Methods The clinical data of extremely premature infants admitted to the neonatal intensive care unit from January 2016 to December 2022 were collected. The patients were divided into the ART group and the natural conception (NC) group, and the clinical features between the two groups were compared. Results A total of 478 extremely premature infants were admitted during the study period, including 279 in the NC group and 199 in the ART group. Compared with the NC group, the ART group had lower proportions of male infants and premature rupture of membranes lasting more than 18 hours, but higher proportions of double/multiple births, maternal amniotic fluid abnormalities, gestational diabetes mellitus, periventricular-intraventricular hemorrhage (PIVH), abandonment and death, and the differences were statistically significant (P<0.05). Conclusions The incidence of PIVH in extremely premature infants conceived by ART is higher, and their parents are easy to give up treatment, and the case fatality rate of patients is higher. It is necessary to strengthen the maternal health care during the ART pregnancy and reduce the complications, in order to prevent the occurrence of extremely premature births.

Objective To understand the child-rearing problems and needs of premature/low birth weight (LBW) infants aged 0-3 years in urban areas of China, and to provide a basis for our child health clinicians to carry out targeted child-rearing guidance for high-risk infants. Methods Based on the child-rearing survey data of 1989 children aged 0-3 years and their parents from 15 cities in 14 provinces in China, the child-rearing problems faced by families with either premature/LBW infants or normal infants and their influencing factors were compared and analyzed. Results Among the 151 preterm/LBW infants surveyed in urban areas (7.6 %), 76.8 % of the parents of preterm/LBW infants had experienced at least 3 child-rearing problems in the past 3 months, higher than that of the normal group (66.8 %), and the difference was statistically significant (χ²=6.44, P=0.011). The main child-rearing problems of preterm/LBW infants were feeding or eating (67.6 %), sleep (66.2 %) and behavior (61.6 %). Multivariate logistic regression analysis showed that preterm/LBW infants were risk factors for child-rearing problems in families with infants and young children, and the occurrence of child-rearing problems of premature/LBW infants was related to children's gender, age, main caregivers, family structure and other factors. Conclusions Parents of premature/LBW infants generally have a higher risk of child-rearing problems, and there are specific problems in different age stages, so it is necessary to find child-rearing risk factors in time and provide targeted child-rearing counseling guidance for this group.

Objective To investigate the effects of premature rupture of membranes (PPROM) or oligohydramnios on in-hospital outcomes of preterm infants with gestational age<32 weeks. Methods The clinical data of preterm infants with gestational age<32 weeks who were hospitalized from January 2019 to December 2022 were retrospectively analyzed. The patients were divided into PPROM group and normal group according to the presence or absence of PPROM. PPROM patients combined with oligohydramnios were further included in the oligohydramnios group. The clinical features were compared among the groups. Multivariate logistic regression was used to analyze the effects of PPROM and oligohydramnios on in-hospital outcomes of preterm infants<32 weeks of gestational age. Results A total of 195 preterm infants were included, 83 in the PPROM group, 22 in the oligohydramnios group. There were 112 neonates in the normal group. The median gestational age of PPROM was 29.5 (28.5-30.5) weeks, and the median duration was 48.0 (13.8-85.8) hours. Multivariate logistic regression analysis showed that oligohydramnios was an independent risk factor for death before discharge, hemodynamically significant patent ductus arteriosus (hsPDA) and persistent pulmonary hypertension (PPHN) (P<0.05). The PPROM duration≥168h significantly increased the incidence of PPHN (P<0.05). Compared with the group with only PPROM, the group with both PPROM and oligohydramnios had a longer duration of PPROM, a smaller gestational age at the time of PPROM, and a smaller gestational age at birth, with statistically significant differences (P<0.05). Conclusions The effects of PPROM and oligohydramnios on neonatal prognosis are different. There was no significant correlation between PPROM and premature death and neonatal related diseases. However, PPROM with long duration and oligohydramnios is potentially dangerous for premature infants. Oligohydramnios is closely related to premature death, PPHN and other adverse outcomes.

Objective To explore the diagnostic value of matrix metalloproteinase 9 (MMP9) and its related proteins for food allergy (FA) in infants. Methods This nested case-control study enrolled infants with suspected FA from April to October 2023. Infant feces were collected and the infants were divided into FA group and non-FA group according to the results of oral food challenges. The fecal MMP9, tissue inhibitor of metalloproteinase 1(TIMP1) and lipocalin 2(LCN2) were measured by enzyme-linked immunosorbent assay, and the relative content was calculated. The area under the ROC curve (AUC), sensitivity and specificity were used to evaluate the accuracy of the target proteins in the diagnosis of infantile FA. We assessed the diagnose value by area under the curve (AUC), sensitivity and specificity. The predictors of FA were screened by binary logistic regression analysis. Results A total of 69 patients in the FA group and 72 patients in the non-FA group were included. The AUC values of fecal MMP9 and TIMP1 concentrations for the diagnosis of FA were 0.82 and 0.78, respectively, and the AUC values of the relative contents of MMP9 and TIMP1 were increased to 0.85 and 0.83, respectively. The diagnostic value of LCN2 is poor. Binary multivariate logistic regression analysis suggested that fecal MMP9 was the best predictor of FA. Conclusion Fecal MMP9 and TIMP1 are useful diagnostic tools for FA in infants, and can distinguish FA from other similar diseases.

Objective To retrospectively analyze the clinical features and prognosis of immune-related brainstem encephalitis in children. Methods The clinical data, treatment and prognostic follow-up results of children diagnosed with immune-related brainstem encephalitis in the Department of Neurology, from March 2017 to October 2022 were collected. Results A total of 13 children (8 boys and 5 girls) were included. The median age of first onset was 5.0 (1.9-7.1) years old, and 12 had precursor events within 1 month before onset. The common initial neurological symptoms in clinical manifestations were limb movement disorder (69.2 %, 9/13), facial paralysis (46.2 %, 6/13), and decreased consciousness level (46.2 %, 6/13). The common neurological signs during the course of the disease were cranial nerve involvement (76.9 %, 10/13), decreased muscle strength (69.2 %, 9/13) and decreased consciousness level (46.2 %, 6/13). In the acute stage, 30.8 % (4/13) of the children showed protein-cell separation in cerebrospinal fluid, 30.8 % (4/13) of the children had positive serum anti-GQ1b antibody, and 53.8 % (7/13) of the children had abnormal brain stem signals on head MRI. The immunotherapy during acute phase was intravenous methylprednisolone combined with immunoglobulin. Only 1 patient had poor effect, but improved after immunoadsorption therapy. The median follow-up time after discharge was 12 (6-24) months, during which there was no recurrence and only 2 cases of residual sequelae. Conclusions Immune-related brainstem encephalitis in children usually occurs at about 5 years of age with prodromal events. The common neurological symptoms and signs include limb paralysis, cranial nerve paralysis and decreased consciousness level. Most children with first-line immunotherapy have good outcomes and few neurological sequelae.

Objective To investigate the predictive value of urinary CXC motif chemokine ligand 10 (uCXCL10) in the risk of death in critically ill children during their stay in the pediatric intensive care unit (PICU). Methods A total of 323 critically ill children admitted to PICU from September to December 2016 and from December 2017 to January 2018 were selected as the research objects. The patients were divided into survival group (295 cases) and death group (28 cases) according to the outcome during hospitalization in PICU, and the clinical characteristics of the children were compared between the groups. The uCXCL10 levels were serially measured during the first week after PICU admission using an enzyme-linked immunosorbent assay. Stepwise multivariate linear regression analysis were used to determine the correlation between uCXCL10 levels and clinical variables. Multivariate logistic regression analysis were performed to investigate the association of uCXCL10 with mortality after adjusting for confounders. The area under the ROC curve (AUC) was calculated to assess the predictive value of uCXCL10 in mortality of critically ill children. Results The initial and maximum values of uCXCL10 in the death group were significantly higher than those in the survival group (P<0.05). Both stepwise multivariate linear regression and multivariate logistic regression analysis showed that the initial and maximum values of uCXCL10 were significantly associated with mortality (P<0.05). The AUC values of initial and maximum uCXCL10 for predicting death in critically ill children were 0.780 (95%CI: 0.689-0.872, P<0.001) and 0.846 (95%CI: 0.769-0.923, P<0.001), respectively. Conclusion The uCXCL10 is an independent predictor of death in critically ill children.

Objective To explore the clinical, endoscopic, and histopathological characteristics of colorectal polyps in children, as well as the application of different endoscopic treatment methods, so as to provide reference value for the clinical diagnosis and treatment of colorectal polyps in children. Methods The clinical data of 361 children under 14 years of age diagnosed with colorectal polyps and undergoing painless colonoscopy examination and treatment were retrospectively analyzed. Results Colorectal polyps in children are more commonly seen in males (245 cases, 67.87 %) compared to females (116 cases, 32.13 %). The most prevalent age group is the preschool period, accounting for 44.88 % (162/361) of all patients. The most common symptom is hematochezia, observed in 86.70 % (313/361) of cases. There were 288 cases (79.78 %) with a single polyp and 73 cases (20.22 %) with multiple polyps. The polyps in children are mainly located in the left half of the colon (347 cases, 96.12 %). The clinical manifestations and the number of polyps differ significantly across different age groups of children (P<0.05). Endoscopic polypectomy was performed on 459 polyps, all of which were successfully removed. Intraoperative bleeding occurred in 252 cases (69.81 %), and metallic titanium clip closure was the most commonly used hemostasis method (186 cases, 73.81 %). There were 12 patients with recurrence (3.32 %), and the patients with multiple polyps were more likely to relapse (P<0.001). Conclusions Colorectal polyps are more commonly found in male children, with hematochezia being the most frequent clinical symptom. They are prevalent during the preschool age, often located in the left half of the colon, and usually appear as single formations. The predominant morphology is Yamada type IV, with large polyps being the most common. Histopathologically, juvenile polyps are the primary type. Polyps of different shapes and sizes were treated by different endoscopic methods. Micro polyps without a stalk are mainly treated using cold forceps polypectomy; giant polyps and those with a stalk are primarily removed using hot snare polypectomy; small polyps and those without a stalk are mainly treated using endoscopic mucosal resection.

Objective To analyze the clinical features of children with autoinflammatory disease caused by NLRP3 gene variation, and to provide basis for diagnosis and treatment of such children. Methods A retrospective study was conducted on 6 patients diagnosed with autoinflammatory disease caused by NLRP3 gene variation from February 2017 to March 2023. Results A total of 6 children (3 boys and 3 girls) were included. All of the patients developed symptoms in early childhood, with recurrent fever in 5 cases and rash in 6 cases. Before diagnosis, the patients were misdiagnosed as urticaria or atopic dermatitis. One case was misdiagnosed as juvenile idiopathic arthritis due to joint swelling and pain. Four patients were misdiagnosed as suppurative meningitis by lumbar puncture examination and 2 had hearing impairment. One case had obvious multi-organ involvement. Leukocytosis was observed in all 6 cases. C-reactive protein was increased in 5 cases, erythrocyte sedimentation rate was increased in 4 cases, serum amyloid A (SAA) was increased in 4 cases, interleukin-6 (IL-6) was increased in 4 cases, and interleukin-1β (IL-1β) was increased in 2 cases. Five patients had anemia. Four patients were treated with canakinumab by injection every 8 weeks. The patients were followed up for up to 3 years and were generally in good condition. Conclusions NLRP3 gene variations can lead to atypical clinical manifestations of autoinflammatory diseases. Prompt diagnosis and early treatment with IL-1β antagonists like canakinumab supplementation have shown good efficacy in significantly improving clinical symptoms.

Objective To evaluate left ventricular function and ventricular wall motion disorder by two-dimensional speckle tracking echocardiography (2D-STE) in children with influenza A-related myocarditis. Methods Thirty children with influenza A-related myocarditis were selected as the case group, and 33 children who came in for routine check-ups were used as the normal control group. Routine ultrasonography was performed on both groups, and two-dimensional speckle tracking technology was used to evaluate cardiac function and global longitudinal strain of the left ventricle. Comparative analysis was conducted between the two groups. Results There was no significant difference in age, body surface area, end-diastolic left ventricular diameter (LVIDd), diastolic interventricular septal thickness (IVSd), early diastolic and late diastolic mitral flow velocity ratio (E/A) and CK-MB between the case group and the normal control group (P>0.05). Compared with the normal control group, the heart rate and hsTnI level were higher, and the left ventricular ejection fraction (LVEF), ratio of early diastolic mitral annulus velocity (E/E') and left ventricular global systolic strain peak (GLPS) were lower in the case group, and the differences were statistically significant (P<0.05). GLPS was positively correlated with LVEF and negatively correlated with IVSd, but not significantly correlated with LVIDd, E/A, E/E’, hsTnI, CK-MB and electrocardiographic parameters. The optimal cutoff value of GLPS for the diagnosis of influenza A-related myocarditis in children was -19.9 %. Conclusions Left ventricular long-axis strain of 2D-STE can accurately reflect the changes of left ventricular myocardial mechanical properties in children with myocarditis caused by influenza A virus infection. It can be used as a simple, safe, reliable and practical new means for early diagnosis, follow-up and prognosis evaluation of influenza A-related myocarditis.

Objective To explore the factors influencing the duration of mechanical ventilation after surgery in children with congenital heart disease (CHD). Methods The clinical data of children with CHD aged≤6 months who received surgical treatment at the Pediatric Heart Center of the hospital from October 2020 to December 2023 were retrospectively analyzed. Based on the duration of mechanical ventilation, the patients were divided into a prolonged mechanical ventilation group (≥72 hours) and a control group (<72 hours). Clinical characteristics between the two groups were compared, and the factors influencing the occurrence of prolonged mechanical ventilation after CHD surgery were analyzed. Results A total of 119 children (64 boys and 55 girls) with CHD who received surgery were included and the median age was 47.0 (17.0-81.0) days. There were 54 (45.4 %) children with undernutrition (WAZ<-1). Among them, 33 children had WAZ<-2. There were 29 patients in the prolonged mechanical ventilation group and 90 patients in the control group. Multivariate logistic regression analysis showed that undernutrition and increased risk adjustment for congenital heart surgery-1 (RACHS-1) score were independent risk factors for predicting prolonged mechanical ventilation (P<0.05), and elevated serum albumin was an independent protective factor for predicting prolonged mechanical ventilation (P<0.05). All CHD children recovered and were discharged after treatment. Conclusions In children undergoing surgery for CHD, prolonged mechanical ventilation after surgery should be monitored in patients with preoperative malnutrition, hypoalbuminemia, and high RACHS-1 scores.

X-linked severe combined immunodeficiency (X-SCID) is the most common type of severe combined immunodeficiency disease. The typical immunological feature is the complete absence of mature T cells and NK cells with normal or elevated B cell numbers. The clinical features are recurrent and severe opportunistic infections from early infancy. The patients often have early onset, severe clinical manifestations and poor prognosis. Without prompt diagnosis and treatment, most patients die within the age of two. Hematopoietic stem cell transplantation is the preferred treatment and has a very high survival rate (>90 %) if HLA-matched sibling donors are used. However, when alternative donors are used, the success rate and survival rate are often lower. Gene therapy has been developed as an alternative therapy.

Since the 13th Five-Year Plan, China has made various arrangements in the field of rare diseases, such as actively promoting the clinical research and introduction of rare disease drugs, improving the effectiveness and accessibility of patient clinical treatment. One important task is to carry out the construction of the rare disease registration system. Most rare disease patients develop symptoms at birth or during childhood, with a concentrated demand for clinical treatment. Therefore, it is of great significance to carry out database construction for such patients. This paper summarizes the necessity and importance of the construction of rare disease database in children, strategy selection and challenges encountered at the present stage, aiming to explore the best practice path for the construction of rare disease database in children in China.