Objective To investigate the clinical diagnosis of thalassemia intermediate caused by β-thalassemia with α-globin gene triplication. Methods The clinical manifestations of two β-thalassemia heterozygotes were retrospectively analyzed, and the results of β-globin gene sequencing and α-globin gene triplication detection in peripheral blood were also analyzed. Results Case one is a 4 years old girl, and the routine thalassemia gene detection revealed that she was a βCD 41 - 42 heterozygote. Case two was a 13 years old boy, he was a βCD 17 heterozygote detected by routine thalassemia gene sequencing. The clinical manifestations of both cases were moderate to severe anemia with hepatosplenomegaly. No rare mutation was found in β-globin by sequencing. Triplication αααanti4 . 2 fragment was found in case one by Gap-PCR using specific primers. The αααanti3 . 7 fragment was positive in case two by qPCR relative quantification. Conclusion When the result of routine detection indicated beta heterozygote, but with moderate to severe anemia, if there is no rare mutation found by sequencing, the existence of α-globin gene triplication should be considered.

　Objective　To investigate the characteristics and essential points of diagnosis and treatment of double trisomy 47，XXX/48，XXX，+8 combined Behcet disease, a rare inherited immunodeficiency disorder. Methods　The clinical manifestations, karyotype analysis and gene test results of the patients were analyzed, and relevant literatures were reviewed. Results　A 11-year-old girl presented repeated fever for more than 6 years, accompanied with recurrent genital herpes infection and oral apthosis, was clinically diagnosed with Behcet disease. Cytogentic and molecular karyotyping on peripheral lymphocytes demonstrated 47，XXX[12]/48，XXX，+8[18]. Conclusions　Conventional karyotype analysis and chromosomal microarray analysis have a complementary role in the diagnosis of the disease. We conclude that patients with constitutional trisomy 8 and those with trisomy 8 confined to the bone marrow are both at increased risk of developing features of Behcet disease. The mechanism may relate to increased gene dosage of candidate genes for  Behcet’s disease on chromosome 8.

Spinal muscular atrophy (SMA) is a common fatal and disabling neuromuscular disease in infants and young children, caused by the degeneration of spinal anterior horn motor neurons, leading to progressive muscle weakness and atrophy in the limbs. In recent years, the emergence and application of disease-modifying therapies are gradually changing the natural history of SMA. However, the efficacy of these therapies is closely related to factors such as the age at treatment initiation and the pre-treatment disease course. Pre-symptomatic treatment is more promising to enable the affected children to survive and achieve near-normal motor milestones. This consensus was developed by experts from relevant fields, focusing on the following themes: pre-symptomatic SMA diagnosis, treatment decision-making, follow-up management, and key points for parental communication, with the aim of providing standards and guidance for clinical practices of pre-symptomatic treatment of pediatric SMA.

Nocturnal enuresis is a common disease in childhood, which can be harmful to the children’s physical and psychological well-being. Standardized diagnosis and therapeutic approaches are very important for the efficacy and prognosis of enuresis. In recent years, with the accumulation of domestic and foreign clinical research evidence and the application of new diagnostic and therapeutic concepts, it is of great clinical significance to update and improve the consensus on the diagnosis and treatment of enuresis. Therefore, Chinese Cooperative Group for the Management of Pediatric Enuresis Affiliated to Pediatric Nephrology Committee of Chinese Medical Doctor Association has revised and updated the 2014 version of the "Expert Consensus on the Management of Monosymptomatic Nocturnal Enuresis in Chinese Children" based on the latest domestic and international evidence-based rationales and combined with clinical experience. The definition has been revised in accordance with international authoritative guidelines, and the diagnosis process and standardized terminology has been enhanced. The content of medical history collection has been updated to emphasize the differentiation of other diseases and comorbidities, and the recording method of the voiding diary has been revised to improve compliance. For monosymptomatic enuresis, the dosage adjustment and discontinuation plan of desmopressin have been added, and the specific dosage recommendations for second-line drug treatment have been refined. Additionally, a new section on non-monosymptomatic enuresis has been introduced, including treatment strategies and pharmacologic interventions. This consensus recommendations in a problem-oriented manner, delivering more comprehensive and structured guidance for the management of nocturnal enuresis.

Objective To explore the clinical features and prognosis of acute myeloid leukemia (AML) with positive TLS/ERG gene in children. Methods The clinical data of TLS/ERG gene positive AML in 6 children admitted from June 2008 to December 2018 were retrospectively analyzed, and the prognosis data of 62 similar cases of children reported in domestic and foreign literature were summarized and analyzed. Results Six AML children with positive TLS/ERG gene was 1 . 3 % of the AML children from 0 to 18 years admitted in the same period. They were 4 boys and 2 girls with a median age of 9 . 1 years ( 4 . 0 - 14 . 0 years). One case was complicated with central nervous system (CNS) leukemia at the onset. In addition to expressed myeloid markers CD 117 , CD 13 , CD 33 , and CD 34 , immunophenotypic expression of CD 56 was found in 4 ( 66 . 7 %) children. There was no remission after induction chemotherapy in 3 children. Bone marrow recurrence occurred in 3 of 5 children receiving allogeneic hematopoietic stem cell transplantation, and the median recurrence time was 11 . 6 months ( 3 . 0 - 22 . 0 months) after transplantation. After transplantation, one patient relapsed in the form of CNS leukemia, but the bone marrow was in sustained remission. Bone marrow had the sustained remission in 1 case. By summarizing the prognostic data of children with TLS/ERG positive AML reported in the literature, it was found that all patients in the chemotherapy group experienced recurrence, and the recurrence rate in the transplantation group was 69 . 2 %. One of the patients had sustained remission and long-term survival after a second transplant following recurrence. Conclusions The incidence of TLS/ERG positive AML is extremely low, most of its immunophenotypes are associated with CD 56 expression, and the overall prognosis is poor. Hematopoietic stem cell transplantation can improve the prognosis, which is still the recommended treatment for the first remission period, but the recurrence rate after transplantation is still high. It is needed to improve treatment methods and find new treatment options.

Pertussis is an acute respiratory infectious disease caused by Bordetella pertussis, which has a long history and can affect people of all ages. The re-emergence of pertussis has become a global issue of great concern, including in China. Since 2022, the number of whooping cough cases reported in China has increased rapidly. The genotype of the main antigen (pertussis toxin) of the current Bordetella pertussis epidemic strain has changed, and the corresponding antigen is different from the vaccine strain, resulting in immune escape, which is one of the important reasons for the recurrence of pertussis. At present, the resistance of Bordetella pertussis to macrolide antibiotics is an important reason for clinical treatment failure, so it is no longer recommended as the first choice for anti-infection treatment of pertussis. For children over 2 months of age with no contraindications to sulfanilamide, trimethoprim-sulfamethoxazole oral administration is recommended as the preferred anti-infection regimen for pertussis catarrhal stage and spasmodic cough stage. Piperacillin or cefoperazone-sulbactam are recommended for children under 2 months of age or with critical symptoms. The improvement or development of a new generation of pertussis vaccine with the same antigen as the prevalent strain will be a long-term strategy to enhance the immune protection of the susceptible population and control the epidemic of the disease.

Objective To analyze the epidemiological characteristics of common respiratory tract pathogens in children with acute respiratory tract infections (ARTI) in Hainan Province, and to provide reference for the prevention, diagnosis and treatment of ARTI in children. Methods The children with ARTI who were hospitalized in several hospitals in Hainan Province from March 2012 to December 2021 were selected. The serum IgM antibody levels of influenza virus A (FluA), influenza virus B (FluB), respiratory syncytial virus (RSV), adenovirus (ADV), parainfluenza virus (PIV), Mycoplasma pneumoniae (Mp), Chlamydia pneumoniae (Cp), Legionella pneumophila (Lp) and Q fever Rickettsia (COX) were detected by indirect immunofluorescence method. An infection with a pathogen was characterized as having an IgM antibody positive for it. The epidemiological and clinical data of respiratory tract infection cases were analyzed retrospectively. Results In this study, a total of 59312 children were eligible for inclusion, and the IgM positive detection rate of respiratory pathogens was 37.69% (22357/59312). Among the 22 357 IgM positive children, 28255 IgM positive times were found, of them, 35.23% were IgM positive rate for FluA, FluB, RSV, ADV and PIV (9953/28255). The top 3 pathogens were Mp, FluB and PIV, accounting for 86.54% (24451/28255), and the IgM positive rate was 28.58% (16953/59312), 9.50% (5636/59312) and 3.14% (1862/59312), respectively. Dual pathogens were detected in 4039 cases, and the most common combination was Mp and FluB. The detection rates of FluA, FluB, ADV, Cp and Lp were the highest in spring and the lowest in autumn. The detection rates of PIV, Mp and COX were the highest in summer and the lowest in winter. The detection rate of RSV was the highest in summer and the lowest in autumn. The positive detection rate of respiratory pathogen IgM varied between 2012 and 2021, with the highest being in 2013 (78.65%) and the lowest being in 2021 (15.72%). The differences between the years were statistically significant (P<0.001). Conclusions The prevalence of various respiratory pathogens in Hainan region has its seasonality. The corresponding protective measures can be formulated according to their epidemic characteristics to deal with the respiratory infection during the peak incidence season for children.

　Objective　To summarize the treatment experience of refractory systemic juvenile idiopathic arthritis (JIA) by tocilizumab, and to explore the cost-effective treatment. Methods　The clinical data of 6 pediatric patients with refractory systemic JIA treated by tocilizumab from 2014 to June 2016 were retrospectively analyzed in the aspects of course and effectiveness of tocilizumab, steroid reduction, adverse reaction, and growth. Results　The median age of the six patients (3 males and 3 females) was 6 years, and the course of disease were from 16 to 63 months. All patients were treated by other immunosuppressive agents or biological agents in addition to steroid and traditional anti-rheumatic drug therapy. The courses of tocilizumab treatment were from 7 to 26 months and the median time was 9.5 months. All 6 patients responded to tocilizumab and achieved the clinical remission at different time. After the induced remission, the interval of the treatment intervention was increased from 2 weeks up to 4 weeks in 3 cases, and no disease activity was observed. Except one case, another 5 cases reduced and stopped the use of hormones at 5.8 months after tocilizumab treatment. After hormones was reduced and discontinued, the growth was improved. All 6 patients had no serious adverse reactions. Conclusions　Tocilizumab is safe and effective for patients with refractory JIAs. The steroid can be reduced in short time to improve growth. After remission is induced, the interval of the treatment intervention could be prolonged.

Objective To explore the clinical and genetic characteristics of MED 13 L syndrome caused by the mutation of MED 13L gene. Method The clinical data of MED 13 L syndrome in 2 children were retrospectively analyzed. Peripheral blood samples were collected from the children and their parents for gene chip and high-throughput sequencing analysis. The chromosome microdeletions/microduplications were verified by RT-PCR, and gene variations were verified by Sanger sequencing. Results The two patients were boys, aged 2 years 6 months and 4 years 3 months, respectively. Both had special facial features, including oblique head deformity, eyelid ptosis, wide eye distance, flat bridge of nose and sinking corners of mouth. Both had language retardation, motor development retardation, low muscle tension, moderate and mild mental retardation. Case 1 also had ventricular septal defect, and case 2 had polydactyly, autism and dysplasia of corpus callosum, etc. Gene chip analysis results showed that case 1 had a 1 . 42 MB deletion in 12 q 24 . 2 region, and RT-PCR showed no abnormality in the same region of her parents. High throughput sequencing showed that the MED13L gene of in case 2 had heterozygous variation of c.580g > t (p.e 194 x), which had not been reported. Sanger verified that neither parent was abnormal. Conclusion MED 13 L syndrome is characterized by special facial features, retardation in language and, motor, and mental retardation., Sand some MED 13 L syndrome is associated with congenital heart disease, bone abnormalities and behavioral abnormalities. There was a MED 13 L gene abnormality exists and . Aa new mutation which has not been reported has beenis found which has not been reported.

Objective　To investigate the clinical characteristics and pedigree genetics of  neurodegeneration with brain iron accumulation 5. Methods　Clinical features and imaging findings of two patients with neurodegeneration with brain iron accumulation 5 were analyzed, and whole-exome sequencing was used to identify WDR45 gene mutations. Results　A ten month old male infant and a three-year-old female child had history of comprehensive development retardation, the boy had a history of suspected seizures, magnetic resonance imaging (MRI) showed progressive brain atrophy; and the girl had a history of epilepsy, cranial MRI showed slightly hyperintense on T2-weighted images and T2 Flair in the globus pallidus. Whole-exome sequencing identified a novel frameshift mutation c.276-c277insC in exon 6 of WDR45 in the boy  and a reported mutation c.19C> Tin in the girl, which were not found in both parents. Conclusion  The WDR45 gene sequencing combined with medical history and cranial MRI can be used to diagnose neurodegeneration with brain iron accumulation 5 .

Bronchopulmonary dysplasia (BPD) is one of the commonest and most serious complications in premature infants. Severe BPD (sBPD) is defined as premature infants receiving oxygen inhalation for at least 28 days and requiring oxygen concentration >30% or positive pressure ventilation at 36 weeks of corrected gestational age. Infants with sBPD may cause longterm death, cardiopulmonary dysfunction, failure to thrive, impaired cognitive development and motor retardation. With the improvement of survival rate of extremely premature infants in China, the incidence of sBPD has increased gradually. Due to the different pathophysiological mechanisms of different children, the phenotypes of diseases are greatly different, which brings considerable challenges to clinical diagnosis and treatment. In recent years, the diagnosis and treatment consensus at home and abroad has put forward the comprehensive management of the infants with sBPD through multidisciplinary team cooperation. In this review, the mechanism and clinical features of three disease components were introduced, including moderate-severe parenchymal disease, large airway disease and pulmonary hypertension. Respiratory support strategy, tracheostomy and drug treatment of pulmonary hypertension were also described. Neonatologists are expected to further improve the survival rate and prognosis of sBPD patients by strengthening the understanding of key pathophysiological and phenotypic characteristics of sBPD, establishing multidisciplinary team consultation mechanism and adopting targeted treatment strategies.

Objective To investigate the positive rates of Mycoplasma pneumoniae (MP) and other pathogens in children with acute respiratory infection (ARTI) before, during and after COVID-19 pandemic in Shanghai. Methods The clinical data of children with ARTI who underwent respiratory 5-plex and influenza 3 plex tests in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 1, 2019 to December 30, 2023 were retrospectively analyzed. Results A total of 91825 ARTI cases were included, including 48729 male cases and 43096 female cases, and the median age was 5 (3-8) years old. Before the epidemic, there were 14096 cases, with 5126 positive cases of respiratory pathogens (36.4%); during the epidemic, there were 13366 cases, with 2963 positive cases (22.2%); and after the epidemic, there were 64363 cases, with 33510 positive cases (52.1%). There were significant differences in male proportion, age distribution, and positive rates of various pathogens among the pre-epidemic, epidemic, and post-epidemic groups of ARTI patients (P<0.05). The proportion of children>6 years old was higher in the pre-epidemic and post-epidemic groups, while the proportion of 0-3 years old was higher in the epidemic group (P<0.014). The positive rates of MP in various years and months between 2019 and 2023 showed statistical significance (P<0.05). The positive rate of MP was higher in January, February, and December 2019 (20.3%-37.7%), as well as in January to March 2020 (21.5%-35.3%). In 2021, only the positive rate of MP in December (25.8%) exceeded 20.0%, while all rates in 2022 were below this threshold. From April to June and August to December 2023, the positive rate ranged from 21.5% to 37.2%. The number of MP-positive cases was 23247, and there were statistically significant differences in gender and age distribution among the groups before, during, and after the epidemic (P<0.05). The proportion of MP-positive children>6 years old was higher in the pre- and post-epidemic groups, and the proportion of 0-3 years old in the epidemic group was higher (P<0.014). Conclusions During the period from 2019 to 2023, there have been certain alterations in the epidemiological characteristics of various pathogens associated with ARTI, particularly MP. Moreover, significant changes have occurred in both age distribution and seasonal epidemiological patterns of MP.

Objective To understand the prevalence of respiratory syncytial virus (RSV) and co-positivity of other pathogens before, during and after COVID-19 pandemic, and to provide evidence-based support for improving the prevention and treatment of acute respiratory tract infections (ARTIs) in children. Methods The pathogen detection results of ARTIs children aged ≤16 years who were admitted to the Children's Hospital of Soochow University from January 2016 to May 2024 were retrospectively analyzed. The characteristics of RSV epidemics and mixed positivity for other pathogens in the first year of the COVID-19 epidemic (2020, Stage Ⅰ), the second and third years (2021-2022, Stage Ⅱ) and the post-COVID-19 epidemic (January 2023 to May 2024, Stage Ⅲ) were compared with those in the pre-epidemic period. Results The study included 83356 children with ARTIs, with 11277 (13.5%) testing positive for RSV, 5605 (6.7%) testing positive for RSV alone, and 5672 (6.8%) testing positive for RSV in combination with other respiratory pathogens. In RSV positive children, the detection rates of bacteria, other viral pathogens and atypical pathogens were 39.5%, 13.6% and 5.7%, respectively. RSV test positive rates decreased in 2020 and 2022, while RSV test positive rates increased in 2021, 2023 and 2024 compared with predicted positive rates. There were significant differences in age, epidemic period and season between single RSV positive group and mixed RSV positive group (P<0.001). In stage Ⅲ, the positive rate of RSV mixed with other pathogens was significantly higher than that of single RSV, and the difference was statistically significant (P<0.01). The detection rate of influenza A/B viruses, human parainfluenza virus, adenovirus, human metapneumovirus, Mycoplasma pneumoniae, Chlamydia pneumoniae and Haemophilus influenzae was significantly higher in children with RSV. Conclusions The COVID-19 pandemic had an adverse impact on the prevalence of RSV and the diagnosis and treatment of mixed-positive cases of other pathogens, and the resurgence of mixed-positive RSV and the escalation of infections should be monitored for a long time after COVID-19.

Objective To investigate the relative factors of serum pertussis toxin antibodies (PT-IgG) in children with pertussis.Methods Clinical data of children hospitalized with pertussis from April 1, 2018 to July 31, 2019 were retrospectively analyzed. To analyze the influence of different course of disease, pertussis vaccine dose, onset age and disease severity on PT-IgG level in children with pertussis. Result A total of 638 children were included. In the unvaccinated group, 313 patients (177 boys and 136 girls) had a median age of 78.0 (52.0-125.0) days. In the vaccination group, there were 325 patients (163 boys and 162 girls) with a median age of 232.0 (144.0-483.0) days. There were statistically significant differences in the distribution of PT-IgG levels among different disease course groups at sampling (≤14d, 15-21d, >21d) in the unvaccinated group (P<0.01). The proportion of PT-IgG≥80 IU/mL was higher in patients with disease course >21 days. There was significant difference in PT IgG level between different vaccine groups (P<0.01). The proportion of PT-IgG≥80 IU/mL was higher in patients with disease course of 15~21 days and >21 days. There were statistically significant differences in PT-IgG levels between groups receiving different doses of vaccine (P<0.01). The levels of PT-IgG gradually increased with the increase of vaccine doses. In the unvaccinated group, no matter in the severe group or the normal group, the difference of PT-IgG level among different disease course groups at sampling was statistically significant (P<0.05). In the inoculation group, the difference of PT-IgG levels among different disease course groups at sampling in the normal group was statistically significant (P<0.05).Conclusions The level of PT-IgG in children with acute infection of Bordetella pertussis in China was not high, and 59.9% of them had a PT-IgG level lower than 20IU/mL. PT-IgG levels were affected by the dose of vaccine and the course of disease at the time of sampling.

Objective To investigate the clinical features and long-term prognosis of systemic juvenile idiopathic arthritis (sJIA) complicated with macrophage activation syndrome (MAS). Methods The clinical data of sJIA children complicated with MAS treated from August 2014 to August 2020 were retrospectively analyzed. The sJIA children without MAS diagnosed and treated in the same period were classified as sJIA without MAS group. The clinical manifestations and long-term prognosis were compared between the two groups. Results The median onset age of the 25 patients (11 boys and 14 girls) in sJIA with MAS group was 5.8 (2.6-10.0) years. The median onset age of 38 patients (18 boys and 20 girls) in sJIA without MAS group was 7.0 (5.1-9.0) years. Twenty-one patients had MAS in the early stage of sJIA. Compared with the sJIA without MAS group, the incidence of hepatosplenomegaly, respiratory system involvement, central nervous system involvement and bleeding in the sJIA with MAS group was higher, and the difference was statistically significant (P<0.05). Methemoglobinemia was the most common abnormal laboratory index in sJIA patients with MAS (100%), followed by elevated aspartate aminotransferase (24 cases) and decreased fibrinogen (23 cases). All patients were treated with glucocorticoids, 22 with intravenous immunoglobulin and 22 with cyclosporin A. Tocilizumab was added to 11 patients, 4 of them were treated with tocilizumab within 2 to 3 weeks of MAS activity, and 7 were treated with tocilizumab when sJIA was still in an unstable state after MAS remission. The median follow-up time was 40.0 (26.5-60.5) months. The results of follow-up to August 31, 2022 showed that there were 11 cases of monophasic course, 5 cases of recurrent course, and 9 cases of persistent course in the sJIA with MAS group, and there was no statistically significant difference in long-term prognosis compared with the sJIA without MAS group (P>0.05). Growth retardation occurred in 4 sJIA children with MAS who received glucocorticoid therapy for a long duration. Hormonal cataract occurred in 3 sJIA children with MAS. Conclusions For sJIA children complicated with MAS, if early identification, effective treatment and standardized management can be given in time, the long-term prognosis is similar to that of children without MAS.

Objective To develop a publication check list to improve the quality of rare disease case reporting. Methods Through literature review, 14 sections and 48 items of the alternative publication list for rare disease case reports were formulated. The experts were back-to-back consulted on the items of the alternative publication list. Results A total of 65 consultation sheets for expert opinion were issued by the real-name system, and 52 valid expert opinions were received within a limited period of time. Based on the combined summary of the CARE list and the results of expert opinions, 13 sections and 33 items of publication check list for rare disease case reporting were formed, which were the minimum publication requirements for rare disease case reporting. Conclusions Authors and editors should check this consensus publication check list when reporting rare diseases and pay attention to the scientificity, integrity, and transparency of reports so as to provide readers with more valuable information.

　Objective　To explore the clinical features of KBG syndrome and the characteristics of its gnetic mutation. Method　The clinical data and molecular genetic test results of KBG syndrome in a child were retrospectively analyzed, and the relevant literature was reviewed. Results　A boy aged 1 years and 11 months old visited us for psychomotor retardation, deafness and convulsion. He presented a distinctive appearance such as short stature, ptosis, hypertelorism, epicanthal folds, prominent ears and nasal bridge, bulbous nose, long philtrum, macrodontia of the central incisors, clinodactyly and brachydactyly in the hand. Echocardiography showed patent ductus arteriosus. Video-EEG monitoring showed that the epileptic discharge was localized in bilateral parietal and occipital lobes. Genomic sequencing and bioinformatics analysis showed that there was a novel heterozygous mutation of c.316C>T in exon 6 of ANKRD11 gene, leading to premature termination of protein coding (p.R106X). This mutation was predicted to be pathogenic. So the diagnosis of KBG syndrome was confirmed. A total of 28 articles were retrieved. There are about 200 KBG patients reported in the literature, of whom 71% are with ANKRD11 gene mutations and 29% are with 16q24.3 microdeletions, and the ratio of male to female is 1.5:1. The main clinical manifestations of KBGS patients included craniofacial deformity (99%), giant tooth deformity (84%), mental retardation (90%), behavior problems (60%), bone abnormality (75%), short stature (50%) and hearing abnormality (32%). Conclusions　The mutation spectrum of ANKRD11 gene in KBG syndrome has been expanded, and gene detection is helpful for the early diagnosis of KBG syndrome.

Objective To evaluate the efficacy and safety of recombinant human growth hormone (rhGH) for injection in the treatment of prepubertal children with idiopathic short stature (ISS) in China. Methods This study was a randomized, open-label, controlled, multicenter, phase Ⅲ clinical trial of prepubertal ISS from December 27, 2016 to July 30, 2020. Participants were randomly assigned to the high-dose group, low-dose group and control group in a ratio of 3:3:1, and the administration cycle of rhGH was 52 weeks. Changes in height standard deviation scores (ΔHT-SDS) of actual age before and after treatment, annual height velocity (HV) and bone maturity at the end of treatment were observed. At the same time, the rhGH safety during treatment was investigated. Results A total of 150 participants completed the trial. At baseline, there were no significant differences in age, bone age, sex, height, weight, body mass index, HT-SDS, annual HV and insulin-like growth factor 1 levels among all groups (P>0.05). Both full analysis set (FAS) and per protocol set (PPS) analysis found statistically significant differences in ΔHT SDS among the high-dose, low-dose and control groups at week 26, 39 and 52 (P<0.001). Pairwise comparison showed that ΔHT SDS in the high-dose and low-dose groups were higher than those in the control group, and the differences were statistically significant (P<0.05). FAS analysis showed statistically significant differences in HV among the high-dose, low-dose and control groups at week 13, 26, 39, and 52 (P<0.001). Pairwise comparison showed that HV in the high-dose and low-dose groups was higher than that in the control group, and the differences were statistically significant (P<0.05). At week 52, there was no significant difference in bone maturity among all groups (P>0.05). During the study, no serious adverse reaction occurred in each group. Conclusions The rhGH injection is effective in treating ISS, and there is a significant growth in stature after 52 weeks of treatment, but more observation and evaluation of the effect and safety of lifetime height are needed.

Objective To raise the awareness of Pneumocystis jirovecii pneumonia (PCP) in children complicated with severe pertussis, and to enable early diagnosis for improved prognosis. Methods The clinical data of children diagnosed with severe pertussis complicated by PCP from January 1, 2020 to December 31, 2023 were retrospectively analyzed. Results Five cases were enrolled, with one male and four females. The median age was 3.0(2.5-10.0) months, and the median hospital stay was 17.0(7.5-23.5) days, with three deaths recorded. All cases experienced apnea and hypoxemia, with 3 cases presented acute respiratory distress syndrome (ARDS), and 3 cases developed pulmonary hypertension and pertussis encephalopathy. The peak of leucocyte count were 43.8(25.2-87.8)×10⁹/L, which decreased to a post-treatment median of 8.5(5.0-36.5)×10⁹/L, and the median LDH was 942.0(466.5-1837.0) U/L. All 5 cases were treated with azithromycin before diagnosis of PCP, and co-trimoxazole combined with echinocandin were administered additionally for PCP, while 2 survivors were treated within 5 days. Conclusion PCP can occur in severe pertussis children without immunodeficiency, and there is a high risk of death when severe pertussis is complicated by PCP. When the routine treatment for severe pertussis in children has poor efficacy, it is necessary to be alert for Pneumocystis jirovecii infection. Early combined use of co-trimoxazole with echinocandin may improve prognosis.

Objective To investigate the clinical features, imaging manifestations, treatment response and prognosis of children with systemic juvenile idiopathic arthritis associated lung disease (sJIA-LD). Methods The clinical data of 15 children with sJIA-LD were retrospectively analyzed, and the clinical characteristics, laboratory parameters, imaging changes and treatment prognosis were summarized. Results There were 7 boys and 8 girls in current study and the average age was 7 years. The common clinical symptoms were fever (15 cases), joint swelling and pain (12 cases), cough (12 cases), rash (11 cases), lymph node enlargement (9 cases), serositis (8 cases), hepatosplenomegaly (8 cases), shortness of breath (7 cases), chest pain (2 cases) and abdominal pain (1 case). Seven patients were complicated with macrophage activation syndrome (MAS). All the 15 children underwent chest high-resolution CT examination, and the results showed strip or patchy shadow in 15 children, consolidation shadow in 3 children, mesh shadow in 2 children, nodular shadow, calcification shadow and atelectasis in 1 child each. The commonest lesion site was the left lower lobe of the lung (13/15). The imaging findings revealed 9 cases of organizing pneumonia, 5 cases of non-specific interstitial pneumonia, and 1 case of usual interstitial pneumonia. All the 13 patients were treated with non-steroid anti-inflammatory drug and glucocorticoids. In the diagnosis of sJIA-LD, 8 cases were treated with slow-acting antirheumatic drugs, including 3 cases of cyclosporine, 4 cases of methotrexate and 1 case of cyclophosphamide. Eight children were treated with tocilizumab. The condition of 12 children improved, and chest high-resolution CT showed improvement. One patient had lung disease progression and eventually died. Conclusion The early clinical symptoms of sJIA-LD are mild but the mortality is high. The high-resolution CT is helpful for early diagnosis.

Objective　To understand the clinical and pathological features of Epstein-Barr virus (EBV) associated hemophagocytic syndrome.Methods　The clinical data from one deceased pediatric patient of EBV associated hemophagocytic syndrome combined with severe hepatitis were retrospectively analyzed. The relevant literatures were reviewed. Results　The 1 year and 2 months old patient presented with fever, cytopenia, decreased fibrinogen and natural killer cells, elevated serum ferritin and triglycerides. The abnormal lymphocytes accounted for 5% in blood smear. There were 1.39×108 EBV-DNA copies/ml by fluorescence quantitative detection The autopsy results suggest that the cause of death was multiple organ failure. The EB virus encoded RNAs (EBERs) were detected in liver tissues by in situ hybridization. Approximately 30% lymphocytes were EBERs positive and the hepatocytes were EBERs negative. Conclusions　The patient was confirmed to have EBV associated hemophagocytic syndrome involving multiple organs. However the liver damage was not caused by the direct infection of EB virus.

The rapid development of socio-economics has led to prominent derivative issues such as changes in psychological health, behavioral lifestyles, and environmental quality, which urgently require long-term cohort studies on birth cohorts. These studies should focus on the impact of material and social environmental factors on the health of people in mega-cities and seek the patterns and risk factors of diseases in the new era. The Shanghai Maternal-Child Pairs Cohort (MCPC) adopts a comprehensive and meticulous follow-up approach that integrates "community + obstetric hospitals + schools," conducting 13 follow-ups on 6714 mother-child pairs from early to mid-pregnancy, the delivery period, and the offspring from birth to six years old. MCPC has established a follow-up information database containing millions of data entries, including standardized questionnaires, maternal and child disease diagnosis, child physical growth, body composition, spinal deformities, fingerprint and palmprint, grip strength, physical activity, cognitive ability, and language development level tests, as well as clinical medical records. Additionally, a biobank has been created with 600000 samples from 17 categories, including peripheral blood, umbilical cord blood, finger prick blood, meconium, placenta, urine, feces, buccal mucosa, hair, and nails. Furthermore, 21 standardized SOP documents have been formulated to manage and control the entire process of the sample bank, from collection to cold chain transportation, storage, retrieval, and return. This cohort platform not only provides crucial support for revealing the impact of early-life environmental exposures on population health and multi-omics research but also promotes interdisciplinary innovation.

Objective　To investigate the clinical features of fulminant myocarditis following an influenza A infection, to reduce misdiagnosis, and to improve early treatment and prognosis. Methods　The clinical data of two children with fulminant myocarditis caused by influenza A were retrospectively analyzed. Results　Both of the two cases were presented with acute onset. Patient 1 was a 14-year-old female who had seasonal flu symptoms with heart failure following myocarditis but was otherwise healthy. H3N2 influenza virus infection was detected by molecular analyses of throat and nasal swabs, serum cTnT was 29.5 ng/mL, CK-MB 20.3 ng/mL and Pro-BNP＞35000 pg/mL, with left ventricular dysfunction and ejection fractions 30%. Patient 2 was a 2 years and 10 months old male with the third degree atrioventricular block following myocarditis who had seasonal flu symptoms. H1N1 influenza virus infection was detected by molecular analyses of throat and nasal swabs, with left ventricular dysfunction and ejection fractions of 48%, cTnT 0.35 ng/ml, CK-MB 0.43 ng/ml, Pro-BNP 9740 pg/mL. He was given large doses of steroids and immunoglobulin therapy at the same time, and myocardial nutrition, anti-viral, correcting heart failure, and other comprehensive treatments were also given. He was discharged from hospital in good condition. One month later he developed clinical manifestations of cardiac insufficiency, and the whole 24 hours Holter showed the third degree atrioventricular block, then he was treated with permanent pacemaker implantation. After following-up for 6 months, he was in good condition. Conclusions Influenza A virus infection can cause myocarditis, which comprises a wide spectrum of cardiac involvement from mild myocarditis to cardiogenic shock. Fulminant myocarditis may occur during influenza A virus infection in young individuals, even those with no known predisposing factors. Physicians need to be aware that fulminant myocarditis can be a fatal complication of influenza virus infection in all patients with instable hemodynamics. Early diagnosis and treatment could reduce, in some cases, the risk of severe cardiac events.

Objective To investigate the safety and efficacy of umbilical cord blood transplantation (UCBT) in the treatment of metachromatic leukodystrophy (MLD). Methods The clinical data of 3 MLD children treated with unrelated UCBT from April to September 2019 were retrospectively analyzed. Results All the 3 children showed walking disorder, progressive motor function regression, and 2 of them showed mental retardation. Lysosomal arylsulfatase A (ARSA) decreased in all of them. Head MRI of all the 3 children showed abnormal signals of different degrees in the white matter of the brain and they all had compound heterozygous mutations of ARSA gene. All the 3 children were treated with unrelated UCBT, and the pre-treatment regimen was fludarabine + cyclophosphamide + rabbit anti-human thymocyte immunoglobulin + busulfan, and the prevention of graft-versus-host disease (GVHD) was treated with cyclosporine + mycophenolate mofetil + methotrexate. All the 3 children were successfully implanted, and the whole blood of all children reached complete donor chimerism within 1 month after transplantation. Head MRI showed that the progression of brain parenchymal lesions gradually stopped, and ARSA levels gradually returned to normal. All 3 patients developed infection, 2 developed acute GVHD and 1 developed chronic GVHD. After anti-infection and regulatory immunotherapy, they all improved. The last follow-up was in August 2022, and all 3 patients survived. Long-term efficacy and neurological recovery still require long-term follow-up.Conclusion UCBT is a safe and effective treatment to prevent the progression of MLD.

Objective　To retrospectively analyze the clinical and genetic characteristics of PRRT2-associated paroxysmal diseases in children, and to improve the understanding of genotype-phenotype association of PRRT2 gene. Methods　The clinical data and genetic results of 15 infant epilepsy or paroxysmal dyskinesia patients with PRRT2 mutations were collected from neurology department of Shanghai Children’s Medical Center between May 2016 to July 2018. Results　A total of 15 patients including 8 males and 7 females were collected . The age at onset ranged from 3 months to 13 months and the median age of onset was 6 months. Thirteen patients presented focal seizures with or without secondary generalization, 1 patient presented infant spasms, and 1 patient had seizures at the age of 8 months and presented paroxysmal dyskinesia at the age of 15 years. Twelve patients had familial histories of paroxysmal diseases. Interictal electroencephalograms of 12 patients were normal, interictal electroencephalograms showed epileptiform discharges in 2 cases, atypical peak arrhythmias were observed in 1 patient. MRI tests were normal in 12 patients and showed deepen cerebral sulcus in 2 patients. Fourteen patients were well controlled after using antiepileptic drugs but 1 patient had recurrence after drug withdrawal, and 1 patient was resistant to antiepileptic drugs. All patients had PRRT2 heterozygous mutations, including 9 cases of duplication mutations (c.649dupC, p.Arg217Profs*8） , 2 cases of missense mutations (c.439G>C, p.Asp147His; c.640G>C, p.Ala214Pro; c.962T>C, p.Leu321Pro), 2 cases of deletion mutations (c.649delC, p.Arg217Glufs*12; c.650delG，p.Arg217Glnfs12*), 2 cases of nonsense mutation (c.649C>T, p.Arg217*; c.970G>T, p.Gly324*). Among these mutations, two were novel mutations （c.962T>C and c.970G>T）. In 15 cases, 13 cases inherited mutations from one of parent, 2 cases were de novo mutation. Eleven patients were diagnosed as benign familial infant epilepsy (BFIE), 2 patients were diagnosed as benign infant epilepsy (BIE), 1 patient was diagnosed as paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) and 1 patient was diagnosed as infant spasms. Conclusions　The most common clinical phenotype of PRRT2 gene mutation in pediatrics is BFIE, followed by BIE and PKD/IC. C.649 dupC is the hotspot mutation of PRRT2 gene, and c.962T > C, c.970G > T are likely pathogenic mutations.

Neural tube defects (NTDs) are a class of birth defects that can lead to death or disability. To further guide the prevention, screening, diagnosis, and management of NTDs, the Birth Defects Prevention and Molecular Genetics Branch of the China Maternal and Child Health Association and other organizations convened a panel of multidisciplinary experts for discussion. This panel referenced the latest domestic and international research progress and consensus guidelines, formulating the following expert consensus.

Faltering growth is an important clinical signs for early identification of nutritional problems, and early identification and intervention of faltering growth in infants and young children is of great significance for improving their short-term and long-term health outcomes. Previous published guidelines and expert consensus lack a unified definition of faltering growth, which affects clinical identification, evaluation and standardized management. In March 2023, the Journal of Pediatric Gastroenterology and Nutrition published an article titled 'Catch-up growth in infants and young children with faltering growth: expert opinion to guide general clinicians'. It not only expounds the importance of catch-up growth, but also formulates practical consensus recommendations on how to properly define, evaluate and manage faltering growth, which has practical guiding value for clinicians. Based on the current situation of clinical practice in China, this paper interprets the recommendations in order to provide guidance and reference for clinicians to manage infants and young children with faltering growth in China.

The Caspase activation and recruitment domain 11 (CARD 11 ) encodes a scaffold protein which plays an important role in multiple signaling pathways participated by antigen recognition receptors of T cells and B cells, including nuclear transcription factors, c-Jun N-terminal kinase and mammalian rapamycin target protein signaling pathway. The germline variation of CARD11 causes three different primary immunodeficiency diseases, including profound combined immunodeficiency (biallelic loss-of-function mutations), B-cell expansion with nuclear factor κB and T cell anergy (heterozygous, gain-of-function mutations) and severe atopic disease with diverse immunologic phenotypes (heterozygous, dominant negative mutations). Since the clinical manifestations of diseases caused by different CARD 11 germline variations are diverse, it is necessary to conduct functional verification experiments on rare variations to determine their pathogenicity. This article reviews the genotypes, clinical and immunophenotypes, and treatments of CARD11 variant-related diseases.

Benign epilepsy of childhood with centrotemporal spikes (BECT) is the commonest focal epilepsy syndrome in children. The pathogenesis of BECTS involves the interaction of complex polygenes and environmental factors, presenting a pattern of multifactorial inheritance. BECTS can evolve into atypical BECTS, both of which can be combined with electrical status epilepticus during slow wave sleep (ESES). The treatment of BECTS requires consideration of multiple factors and individualized risk-benefit assessment to determine the best treatment regimen. Early recognition and diagnosis of BECTS comorbid cognitive impairment should be emphasized. Attention deficit hyperactivity disorder (ADHD) is the commonest childhood psychobehavioral comorbidity of BECTS. Formal treatment of BECTS comorbid ADHD should be initiated as soon as possible. There are still many problems and challenges in the clinical diagnosis and treatment of BECTS. This article will review the recent progress in the diagnosis and treatment of BECTS, aiming to provide reference for the clinical diagnosis and treatment of BECTS and improve the life quality of children with BECTS.

Objective To study the clinical features and prognosis of adenovirus pneumonia complicated with plastic bronchitis in children. Methods The clinical data and follow-up results of 11 children with adenovirus pneumonia complicated with plastic bronchitis diagnosed in hospital from January 2018 to December 2022 were retrospectively analyzed. Results The median age of the 11 patients (7 boys and 4 girls) was 6.0 years old. All of them had fever and cough, 3 children were accompanied by wheezing, 6 had shortness of breath, and 7 had decreased breathing sounds. The mean duration of fever was (7.55±3.59) days, the mean peak of temperature was (39.95±0.79) ℃. There were 7 children with toxic encephalopathy and 8 with liver function impairment. The LDH, IL-6 and PCT levels were increased to different degrees in all patients, and CRP>30mg/L was found in 7 patients. Chest CT+3D reconstruction showed that lung consolidation was the main lesion, including atelectasis in 6 cases and pleural effusion in 4 cases. Six patients were administered with intravenous immunoglobulin, and 9 patients received methylprednisolone. Five patients received facial mask oxygen inhalation. One child received mechanical ventilation, and then changed to V-V-ECMO. All children underwent bronchoscopy and plastic body removal. Among them, 7 patients received bronchoscopy once and 4 received bronchoscopy twice. One child died and the others were discharged after improvement. During follow-up, 1 child had recurrent cough and wheezing, and the others had good prognosis. Conclusions Adenovirus pneumonia with plastic bronchitis is usually characterized by persistent high fever, shortness of breath, hypoxia, reduced breath sound, and significantly increased levels of CRP, PCT and LDH. Most of the imaging findings show atelectasis and lung consolidation, which are easy to combine with other organ injuries. Active anti-inflammatory therapy and bronchoscopy should be performed as soon as possible. Most of patients have a well prognosis, while a few may have poor prognosis such as recurrent cough and wheezing.

Immune thrombocytopenia (ITP) is the most common bleeding disorde characterized by isolated thrombocytopenia in children. It is mediated by a variety of autoimmune mechanisms. Children with ITP usually have acute onset. A considerable proportion of patients can be traced back to the history of precursor infection or vaccination, which can make them immune intolerant, resulting in the occurrence of ITP. There is strong heterogeneity of ITP in children. At present, more and more children tend to relapse. The first-line treatment is not effective, and the protracted treatment leads to chronic ITP. Clinicians should make corresponding individualized treatment and give reasonable management according to the characteristics of each child to reduce treatment-related complications and improve the quality of life of children.

Protracted bacterial bronchitis (PBB) is a persistent infectious disease of the bronchial intima caused by bacteria. PBB is the leading cause of chronic cough in children at home and abroad. At present, it has been included in the guidelines for chronic cough in many countries and has been improved and updated. The diagnosis of PBB includes clinical diagnostic criteria and microbiology-based diagnostic criteria. Currently, amoxicillin-clavulanate potassium is recommended as the first choice for the treatment of PBB. When children are allergic to penicillin or resistant to amoxicillin-clavulanate potassium, cephalosporins or macrolides can be selected. Although cough relief after 2 weeks of appropriate antibiotic treatment is a critical part of the diagnosis of PBB, there is currently no consensus on the optimal course of antibiotics treatment. The prognosis of PBB is generally good, but frequent recurrence and repeated antibiotic use are common. There is also a risk of progression to bronchiectasis if PBB is recurrent and associated with Haemophilus influenzae infection. Up to now, the understanding of PBB in China started relatively late, and there are still deficiencies in diagnosis and treatment. In order to standardize PBB diagnosis and therapy, this article primarily presents the current state of PBB diagnosis and treatment and highlights issues that still need to be resolved in this area.

Objective　To explore the clinical characteristics and growth pattern in patients with 1p36 deletion syndrome. Methods　Chromosomal microarray analysis (CMA) was used to detect genetic changes in two children with growth and developmental delay. Long-term follow-up of one subject was conducted to track the trend of height and weight change. Results Two subjects (one girl and one boy) were reported, both presenting characteristic face, obesity, short stature and intellectual disability (especially delay in language development). CMA identified 1p36.33-p36.32 deletion in both subjects. The girl harbors a 1757 kb heterozygous deletion, and the boy harbors a 2533 kb heterozygous deletion. Both were diagnosed as 1p36 deletion syndrome. Long-term follow-up on this subject from 7 years old and onwards revealed decelerated growth from 12 years old. Conclusions　1p36 deletion syndrome has varied clinical manifestations including typical facial characteristics, developmental delay, and other abnormalities. Females with this syndrome can present decelerated growth in middle adolescence, which eventually leads to short stature. CMA can facilitate the diagnosis of 1p36 deletion syndrome.

Objective To investigate the correlation between functional constipation (FC) and the formation of fecaliths in the appendix cavity in children with acute appendicitis (AA). Methods The clinical data of children diagnosed with AA from August 2022 to June 2023 were retrospectively analyzed. According to the presence or absence of fecaliths in the appendix cavity, the patients were divided into the AA group with fecaliths and the AA group without fecaliths. The clinical characteristics of FC between the two groups were compared, and the factors affecting the formation of fecaliths in the appendix cavity of children with AA were analyzed. Results A total of 192 children (114 boys and 78 girls) with AA were included and the median age was 6.0 (4.0-9.0) years old. There were 72 children in the AA group with fecaliths and 120 in the AA group without fecaliths. Compared with the AA group without fecaliths, the AA group with fecaliths had a higher incidence of fecal retention (≥ 4 years old), higher prevalence of FC, longer average constipation time, and higher incidence of dietary bias, and the difference was statistically significant (P<0.05). Binary logistic regression analysis showed that prolonged constipation duration and dietary bias were independent risk factors for the formation of fecaliths in the appendix cavity of children with AA (P<0.05). Conclusions Long-term constipation and dietary bias have a certain correlation with fecaliths formation in the appendix cavity of children with AA.

Objective To analyze the clinical characteristics and genetic variations in 8 children with metachromatic leukodystrophy (MLD), and to explore the correlation between genotype and clinical phenotype as well as the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods The study collected data from children diagnosed between 2013 and 2024, confirmed through whole exome sequencing, and found that all children had symptoms such as developmental delay, with ages at diagnosis ranging from 1 year and 3 months to 9 years and 6 months. Results Based on the age of onset and clinical manifestations, 4 cases were late infantile type, with 2 deaths; 4 cases were juvenile type, with a survival rate of 100%. Genetic sequencing revealed compound heterozygous variations in the ARSA gene, a total of 15 mutations, of which 3 were newly reported and all were deleterious variations. Three children received allo-HSCT treatment and all survived but with progression of symptoms. Conclusion MLD mainly manifests as central nervous system damage, and diagnosis should be confirmed in combination with clinical manifestations, ARSA enzyme activity, and genetic testing. Early diagnosis and treatment are crucial for improving prognosis, and allo-HSCT can increase survival rates, but the therapeutic effect is limited.

Hemorrhagic cystitis (HC) is one of the common complications of allogeneic hematopoietic stem cell transplantation, which is the key point of transplantation prevention and treatment. This article introduces the etiology, pathogenesis, prevention and treatment of HC. The occurrence of HC is often related to the toxicity of high-dose radiotherapy and chemotherapy before transplantation, gene polymorphism of drug metabolism enzyme, viral infection, graft-versus-host disease, patient age, sex, donor type and transplantation method. Diagnosis of HC is not difficult, based on the history, typical clinical manifestations, and necessary auxiliary tests. Effective preventive measures are adequate hydration and alkalization of urine, diuresis and the application of Mesna. The treatment mainly includes antiviral therapy, immunotherapy, bladder irrigation, bladder perfusion, hyperbaric oxygen therapy and surgical treatment.

Objective To explore the clinical and gene characteristics of Coffin-Siris syndrome caused by ARID 1 B mutation. Methods The clinical data and molecular genetic test results of Coffin-Siris syndrome caused by ARID 1 B gene mutation in a child were retrospectively analyzed, and the relevant literature was reviewed. Results A 2 -year- and 8 -month-old was brought to clinic for psychomotor retardation. He had difficulties in feeding and poor weight gain after birth. He presented a distinctive facial appearance including sparse scalp hair, low frontal hairline, arched shaggy eyebrows, long eyelashes, broad nasal tip, flat nasal bridge, thin upper lip, a thick and everted lower lip and thick lip hair. He had hypotonia and small toenails in right foot. A heterozygous missense mutation of c. 6257 T>C (p.Leu 2086 Pro) in ARID 1 B gene was found in the child by whole exome sequencing, which was not found in his parents and was a new variant. A total of 86 reported cases of Coffin-Siris syndrome caused by ARID1 B gene mutation were retrieved through literature search. The clinical characteristics of the patients were basically consistent with the reported cases. Conclusion Coffin-Siris syndrome is a rare autosomal dominant genetic disease that can involve multiple systems, and genetic testing can help diagnose.

Objective To explore the related factors of treatment failure in children with acute lymphoblastic leukemia (ALL). Methods The clinical data of 124 newly diagnosed ALL children with treatment failure admitted from January 2013 to December 2017 were retrospective analyzed. The association of different clinical features with recurrence time and sites was compared and the possible risk factors for treatment failure was analyzed. Results By April 15, 2020, the median follow-up time was 24.0 (14.0-43.5) months. Among the 124 children who failed treatment, 82 were boys and 42 were girls. The median age at first diagnosis was 8.0 (3.3-13.0) years. The reasons for treatment failure included recurrence (104 cases), non-recurrent death (19 cases) and secondary tumor (1 case). Totally 104 ALL children relapsed, whose median recurrence time was 17.7 (3.0-57.2) months. Very early recurrence (52 cases) was the commonest recurrence time, and bone marrow (84 cases) was the commonest recurrence site. The recurrence time was correlated with initial white blood cell count, immunophenotyping, different fusion genes and risk stratifications (P<0.05). The recurrence site was correlated with initial white blood cell count and immunophenotyping (P<0.05). MRD level on day 33 was an independent risk factor for treatment failure survival rate (TFS) and overall survival (OS) rate (P<0.05). Conclusions Recurrence is the main cause of treatment failure in children with ALL. Close monitoring of early treatment response, active prevention and treatment of very early recurrence can reduce the incidence of treatment failure and improve the OS rate of children with ALL.

Objective To investigate the clinical features and gene mutation of patients diagnosed with ZTTK syndrome (Zhu-Tokita-Takenouchi-Kim syndrome). Method The clinical data of three cases of ZTTK syndrome were retrospectively analyzed. Whole exome sequencing was applied to analyze the patients' genetic variants, and Sanger sequencing was used to verify the variant loci. Results In this study, 3 patients, aged from 10 months to 3 years and 8 months, had clinical phenotypes of facial dysmorphism, developmental delay, intellectual disability, microcephaly and abnormal muscle tone, abnormal hand joint or foot valgus, pyelonephritis, cryptorchidism and premature closure of cranial suture. In two cases, sulcus widening and cerebral dysplasia were observed on brain MRI. We found de novo variation in SON gene in all three children, c.3020G>A (p.R1007H), c.1195delG (p.V399fsTer1) and c.5753_5756delTTAG (p.V1918EfsTer87). Conclusion This study reports three cases of ZTTK syndrome due to SON gene abnormalities, which expands the mutation spectrum of SON gene. In this paper, we report three cases of ZTTK syndrome, extending the spectrum of mutations in this gene. The clinical manifestations of ZTTK syndrome are of multisystem involvement; whole exome sequencing may help to make a clear clinical diagnosis.

Objective To explore the risk factors of death from influenza A (H1N1)-associated encephalopathy (IAE) in children, and to provide evidence for early clinical diagnosis and intervention. Methods The clinical data of children with H1N1 IAE admitted to the hospital from January 2014 to December 2020 were retrospectively analyzed, and they were divided into the survival group and the death group according to prognosis. The risk factors associated with death in children with H1N1 IAE were analyzed by binary logistic regression. Results A total of 59 children (39 boys and 20 girls) with H1N1 IAE were included. The median age was 42 (21-73) months, and 66.1% (39/59) of the children were <5 years old. The median time between the onset of neurological symptoms and fever was 1 (0.5-2) days. Thirty-three patients (55.9%) had severe pneumonia and respiratory failure, and 1 of them had plastic bronchitis. Fifty-eight children were treated with oseltamivir. The median time from onset to use of anti-influenza drugs was 2 (1-4) days. Forty-eight patients were discharged from hospital with improvement and 11 died (18.6%). The median time from admission to death was 3 (1-5) days. Compared with the survival group, the death group presented higher incidences of consciousness disorder, respiratory failure, and brain herniation, a greater proportion of cases requiring mechanical ventilation treatment, a higher neutrophil count, elevated levels of procalcitonin, blood glucose, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, a longer prothrombin time, a higher ratio of abnormal head CT findings, and a lower monocyte count. All the differences were statistically significant (P<0.05). The results of binary logistic regression analysis revealed that elevated neutrophil count and lactate dehydrogenase levels might be associated with the occurrence of death in children with H1N1 IAE (P<0.05). Conclusions For children with H1N1 IAE, the risk of death may increase with elevated neutrophil counts and lactate dehydrogenase levels.

Objective To analyze the clinical efficacy of hematopoietic stem cell transplantation (HSCT) in the treatment of hematological neoplastic diseases in children. Methods The clinical data of 86 children with hematological neoplastic diseases who underwent HSCT in the Affiliated Hospital of Xuzhou Medical University from March 2016 to August 2020 were retrospectively analyzed. Results Eighty-six children (50 boys and 36 girls) with HSCT were included, and the median age was 11 (9-14) years. There were 27 cases of acute lymphoblastic leukemia (ALL), 28 cases of acute myeloid leukemia (AML), 16 cases of aplastic anemia (AA), 5 cases of lymphoma, 4 cases of chronic myeloid leukemia (CML), 3 cases of myelodysplastic syndrome (MDS), 1 case of neuroblastoma (NB), 1 case of systemic neosclerosis (SSC) and 1 case of adrenoleukodystrophy (ALD). There were 7 cases of autologous transplantation, 4 cases of umbilical cord blood transplantation and 75 cases of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median follow-up time of 86 patients was 29.5 (17.6-44.0) months. A total of 84 patients were successfully implanted, and 1 patient failed autologous transplantation and 1 failed allo-HSCT. Fourteen patients relapsed, including 4 patients with autologous transplantation and 10 patients with allo-HSCT. Six patients developed grade Ⅲ/Ⅳ GVHD, all of whom were allo-HSCT. Twenty patients died, including 4 patients with autologous transplantation and 16 patients with allo-HSCT. Fisher's exact test showed that there was significant difference in the occurrence of grade Ⅰ/ⅡGVHD among the four groups of autologous transplantation, cord blood transplantation, SIB homozygous and half homozygous (P<0.001). Conclusions HSCT is an effective method to treat a variety of malignant diseases in children, but recurrence and severe GVHD after transplantation are important factors affecting the prognosis. Preventing recurrence and controlling rejection are very important in children's HSCT.

Spinal muscular atrophy (SMA), a devastating hereditary neuromuscular disease, is often complicated by scoliosis. While scoliosis correction surgery is frequently indicated to correct spinal deformities, it is not without significant risks, including the potential for infection, hemorrhage, and neurological damage. Consequently, the management of perioperative medications is of paramount importance for the prevention and control of these complications, as well as for facilitating patient recovery. However, the distinctive physiological and pathological characteristics of SMA, coupled with the lack of standardized protocols, present considerable challenges in perioperative medication management. This review article offers an in-depth examination of the perioperative medication therapy management for patients with SMA undergoing scoliosis surgery. It aims to establish an evidence-based framework and provide a reference for the judicious use of drugs in clinical settings.

Department of nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, Beijing 100020 , China)

Objective　To explore the clinical characteristics of chromosome 6p25 deficiency syndrome. Method The clinical data of chromosome 6p25 deficiency syndrome in 1 child were retrospectively analyzed and the relevant literature was reviewed. Results　The boy, aged 2 years and 9 months old, presented with language retardation, recurrent respiratory infections, special facial features and hypoplasia of teeth. Ophthalmoscopy revealed changes of AxenfeldRieger syndrome in the anterior segment. Cranial MR suggested right temporal pole arachnoid cyst, dysplasia of corpus callosum, and third and fourth ventricle dilatation. The hearing test was normal, and the brainstem auditory evoked potential indicated poor bilateral waveform differentiation. Genetic testing revealed a heterozygosis deletion of 2.833Mb in the region p25.3-p25.2 of chromosome 6 (chr6:393140-3226909) in the child, so he was diagnosed with chromosome 6p25 deletion syndrome. No case report of chromosome 6p25 deletion syndrome in children was found in the Chinese database. Conclusion　The clinical manifestations of chromosome 6p25 deletion syndrome are diverse, and the main pathogenic genes are FOXC1, SERPINB6, TUBB2A, TUBB2B, and so on.

Objective　To analyze the genotype and clinical characteristics of Alport syndrome in children. Methods Clinical manifestation and genetic test results of 1 Chinese boy with Alport syndrome were retrospectively analyzed. Results The 11-year-old male patient presented with unexplained hematuria and proteinuria with mild renal dysfunction 4 years ago and progressed to the uremia stage of chronic kidney disease due to poor treatment compliance. There was no high-frequency hearing impairment and ocular fundus pathology. Renal biopsy showed chronic sclerosing glomerular disease and diffuse tubular atrophy (atrophy area over 80%). Immunofluorescence staining of basement membrane of alpha 3 and alpha 5 (IV) were positive. Gene sequencing identified a hemizygous mutation of c.2631dupA (insertion) in COL4A5 gene, resulted in amino acid changes of p.G878Rfs*20 (prematurely termination of protein translation after 20 amino acids). It was identified as a de novo mutation. According to ACMG guidelines. This variant is classified as pathogenic. It has not been reported in the HGMDpro database. Conclusion　Gene sequencing is helpful for the diagnosis of Alport syndrome and the discovery of novel variant of COL4A5 gene.

Febrile infection-related epilepsy syndrome (FIRES) is a rare and catastrophic epileptic encephalopathy that predominantly affects school-aged children.Characterized by a biphasic clinical course, FIRES manifests as rapid progression to refractory status epilepticus following a preceding febrile infection. The prognosis of FIRES is dismal: the acute-phase mortality rate is approximately 10%, and survivors often develop chronic refractory epilepsy and cognitive impairment. The pathogenesis of FIRES remains unclear, but neuroinflammation involving cytokines such as IL-6 may play a key role. Tocilizumab, a humanized monoclonal antibody targeting the IL-6 receptor, exerts anti-inflammatory effects by blocking IL-6 signaling. For FIRES patients unresponsive to conventional anti-seizure medications (ASMs), first-line immunotherapies, or ketogenic diet, tocilizumab is currently recommended as a second-line immunotherapeutic option. This review summarizes the background, mechanisms, clinical applications, safety profile, and challenges associated with tocilizumab in FIRES management, aiming to update clinicians on the latest advances in this field..

Mycoplasma pneumoniae (MP) is one of the main pathogens of community-acquired pneumonia, which can cause respiratory symptoms and other extrapulmonary complications. Macrolide antibiotics are the first choice for the treatment of MP infection. In recent years, with the increase of MP infection rate and the wide application of antibiotics, the situation of macrolide drug resistance is becoming more and more serious. Vaccine is the best scientific method to prevent and control the prevalence, infection and pathogenicity of germs. At present, animal MP vaccine has been marketed at home and abroad and achieved good protective effects, while MP vaccine for human is still in the research stage. Based on this, the MP related vaccine is reviewed in order to provide some reference for the development of human MP vaccine in the future.