Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection which affects children's health. The intestinal flora play an important regulatory role in host metabolism and immunity and are associated with a variety of diseases. Studies have shown that sepsis and clinical treatments can lead to intestinal flora imbalance in children, which further affects the prognosis of the disease; while healthy intestinal flora can reduce the susceptibility of children to sepsis and improve the survival of sepsis, and ameliorate the damage to the function of organs. This article reviews the related research on intestinal flora and sepsis, in order to contribute to the prevention and treatment of sepsis in children.

Developmental and epileptic encephalopathy (DEE) is a group of heterogeneous disorders characterized by early-onset epilepsy, abnormal electroencephalography and developmental retardation or regression. The etiology of DEE is complex, with high disability rate and fatality rate. With the development of next-generation sequencing technology, more and more genetic causes related to DEE have been discovered, which also deepens the acknowledgement on the pathogenesis of DEE. These researches provide a basis for exploring different treatment methods, especially gene therapy. It is expected that gene therapy will be carried out in the future to improve the prognosis of DEE.

Mechanical ventilation is the main treatment for acute respiratory distress syndrome (ARDS). Proper spontaneous breathing during mechanical ventilation can promote lung recruitment, improve ventilation/perfusion ratio and oxygenation, reduce diaphragm atrophy and improve organ perfusion. However, strong spontaneous breathing may lead to high transpulmonary pressure and increased pulmonary perfusion, thus aggravating lung injury. To establish a better lung protective ventilation strategy in clinical practice, emphasis should be devoted to the regulation of spontaneous breathing and the suitable mechanical ventilation system should be selected. This article reviews the role of regulating spontaneous breathing in the treatment of mechanical ventilation in ARDS patients.

Noninvasive high-frequency oscillatory ventilation(NHFOV) is based on the application of a continuous flow, generating a constant distending positive pressure with superimposed oscillations, delivered all over the spontaneous breathing cycle. NHFOV matches together the advantages of high-frequency ventilation (no need for synchronisation, high efficacy in removing CO₂) and nasal continuous positive airway pressure (NCPAP, non-invasive interface, increase in functional residual capacity allowing oxygenation to improve). As it represents another “brick in the wall” of the non-invasive respiratory support, it has been increasing applied in neonatal intensive care unit (NICU). At present, there is no consensus guidelines on the application of NHFOV, the application of NHFOV is largely based on the local practices and comfort. This article summarizes the physiology of NHFOV, indications, ventilator device, interfaces, parameter settings, and clinical evidence based on a PubMed literature search.

Invasive fungal disease (IFD) is one of the most common types of infection in the treatment of hematologic malignancies and has a significant impact on the prognosis of pediatric patients with hematologic malignancies. In recent years, with the development of pathogen molecular detection techniques and the application of new antifungal drugs, the prognosis of IFD in pediatric patients with hematologic malignancies has been greatly improved. However, challenges such as diagnostic difficulties, complex disease conditions, and the selection of treatment drugs still exist. This article summarizes the current research progress and the latest diagnostic and therapeutic guidelines to elucidate the risk factors, clinical features, treatment strategies, and prognosis of IFD in pediatric patients with hematologic malignancies, aiming to better assist pediatricians in understanding the prevention, management, and treatment of IFD in pediatric patients with hematologic malignancies.

After forty-three years of development, China’s newborn screening program has achieved remarkable success. Professor Chen Ruiguan, not only a pioneer in the field of newborn screening in China but also the founder of this discipline. This article comprehensively reviews the development of newborn screening in China, including the expansion of screened diseases and technological innovations, the promulgation of relevant national policies, the significant achievements of newborn screening, and its impact on families and society. It also looks ahead to future directions, commemorating Professor Chen’s outstanding contributions.

Respiratory syncytial virus (RSV) infection is a global health issue that poses a serious threat to the health of children under the age of 5. This article closely follows the “Chinese expert consensus on the clinical diagnosis and treatment of respiratory syncytial virus infection in children (2023 edition)”, and makes an in-depth interpretation of key issues such as the window period for RSV pathogenic diagnosis, late-onset severe disease of RSV, and supportive treatment of RSV.

The Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder affecting multiple systems, primarily manifesting as retinal lesions, polydactylism (or hyperdactylism), obesity, intellectual diminution, sexual duct development deficiency, and renal abnormalities. To date, 26 disease-causing genes have been identified, all of which are localised to the primary cilia, with the BBS1, BBS2 and BBS10 genes being the most common genetic causes. There is no curative therapy for this disease, and symptomatic supportive treatment is the main focus. This paper reviews the disease from the perspectives of clinical characteristics, diagnostic criteria, causative genes, the current situation of BBS patients in China, and treatment, with a view to providing reference for the clinical diagnosis and treatment of this disease.

Bronchiolitis obliterans syndrome (BOS) is one of the rare and fatal non-infectious pulmonary complications after allogeneic haematopoietic stem cell transplantation (HSCT) in children. Mutiple risk factors such as primary graft dysfunction, graft-versus-host disease (GVHD), lymphocytic bronchiolitis, gastro-oesophageal reflux, and air pollution, particularly in children, have been reported to be the most common contributions to the bronchiolitis obliterans syndromepost-HSCT. An early diagnosis and treatment of BOS following HSCT is challenging due to the lack of obvious early symptoms, high risk of open lung biopsy, irreversible pathophysiological changes, and the failure of steroid treatment in some children. In this review, we summarize research advances in the epidemiology, pathogenesis, diagnosis, and treatment of this lethal noninfectious pulmonary complication, and provide suggestions for further improvement of diagnostic and therapeutic norms applicable to post-HSCT BOS in children.

In recent years, allergic diseases continue to pose a major threat and challenge to the health of a wide range of children, thereby calling for urgent intervention to prevent the progression of the disease. The human gut microbiota is established by the age of 3 years. The imbalance in the gut microbiota occurs due to factors, such as cesarean delivery and antibiotic use before the age of 3 years, is strongly associated with a higher risk of future onset of allergic diseases. Recent advancements in next-generation sequencing methods have revealed the presence of dysbiosis in patients with allergic diseases, which increases attention on the relationship between dysbiosis and the development of allergic diseases. A large number of researchers have conducted in-depth research on the correlation between gut microbiota and allergic diseases, and the research results have revealed that the imbalance of gut microbiota is associated with the high risk of children developing allergic diseases in the future, and the changes in gut microbiota may be used as therapeutic targets for allergic diseases. Therefore, the purpose of this paper is mainly to review the latest research progress of gut microbiota in children with allergic diseases, and try to further promote the treatment and prevention of clinical diseases by comparing the gut microbiota of children with allergic diseases and normal children.

Objective To analyze prenatal diagnosis, genetic counseling and follow-up of five fetuses with isodicentric Y chromosomes and to provide reference for the clinical treatment. Methods From January 2018 to August 2022, 7 347 pregnant women with prenatal diagnostic indications were selected, and fetal amniotic fluid was detected by conventional G-banding karyotype and chromosomal microarray analysis (CMA) simultaneously, and then verified by fluorescence in situ hybridization (FISH). Subsequently, parental karyotypes were analyzed. After genetic counseling, pregnant outcomes were followed up. Results Five fetuses with de novo idic(Y) were detected and all of these Y chromosomes had the same breakpoint in Yq11.2. Among them, four fetuses (cases 2~5) presented with a mosaic 45, X karyotype except the fetus of case 1. Prenatal ultrasonography indicated that all five fetuses were male and no obvious structural abnormalities were found in the other four fetuses except for case 1 with possible bilateral clubfeet. After personalized genetic counseling combined with the ultrasonography results, cases 1~2 chose to continue the pregnancy while cases 3~5 terminated the pregnancy. The child of case 1 was followed up to four years old. The surgical effect of strephenopodia was good, and the mild developmental retardation was improved after rehabilitation training. The child of case 2 was followed up to 2 years old, and no abnormal phenotype was found yet. Case 3 had been pregnant again and had given birth to a healthy baby girl while cases 4 and 5 were still in preparation for pregnancy. Conclusions The combined application of cellular and molecular genetic techniques is helpful for the prenatal diagnosis of the fetuses with idic(Y). Reasonable genetic counseling and long-term follow-up can provide an important reference for subsequent clinical diagnosis and treatment.

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.

Over the past 15 years, the development of antibody detection technology led to the increased awareness of autoimmune encephalitis. However, the innovation has also brought about a certain proportion of misdiagnosis, and some patients have been treated improperly as a result. The main reasons for misdiagnosis include lax implementation of diagnostic criteria, incorrect interpretation of antibody test results, and insufficient differential diagnosis. Compared with adults, the symptoms of children with autoimmune encephalitis are more difficult to identify, and there are antibody spectrum and characteristics that are different from those of adults. The differential diagnosis of the disease involves a wider range, and its diagnosis and treatment face greater challenges. This article will summarize the diagnosis and treatment process of autoimmune encephalitis in children based on the current situation in China. The related pitfalls of diagnosis and treatment are interpreted and analyzed in order to help pediatricians improve accurate diagnosis and treatment of autoimmune encephalitis.

Monogenic lupus is a general term for a class of autoimmune diseases with lupus like symptoms, which is usually diagnosed in childhood. Although it is rare for a single gene variant to cause systemic lupus erythematosus (SLE), understanding its principle is helpful for clinicians to gain a deep understanding of SLE. In recent years, with the widespread application of gene sequencing, many new variations have been discovered. This review is to further understand monogenic lupus from known variations and pathogenic pathways, in order to provide a new development direction for patients with lupus to find more accurate diagnostic markers and formulate more personalized treatments, and also to provide possible targets for the research and development of new drugs for such disease.

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.

ObjectiveTo explore the clinical phenotype and identify genetic variations in Chinese patients with Menke-Hennekam syndrome (MKHK). Methods The clinical and genetic data of seven children with MKHK were retrospectively analyzed. Results All of the seven children are presented with psychomotor developmental delay, variable degree of intellectual disability, short stature, and facial dysmorphism (including short and upslanted palpebral fissures, telecanthi, depressed nasal bridge, short nose, long philtrum, protruding or low-set ears and micrognathia), accompanied by other manifestations (2/7 feeding problems, 4/7 visual impairment, 3/7 hearing impairment, 3/7 cerebral anomaly, 2/7 distal limb malformation). The genetic findings of patientsinvolve six different variants: five missense and one in-frame deletion), all of which arose de novo. c.5218C>T and c.5225T>A (NM_004380.3) variants have not been reported previously in literature. Conclusion MKHK is a rare autosomal dominant genetic disease, most of which are caused by heterozygous missense variation in the end of exon 30 and the beginning of exon 31 of CREBBP. This study revealed six de novo variants of CREBBP, further expanding the genetic spectrum of MKHK.

IgA vasculitis (IgAV) is an autoimmune disease caused by IgA deposition in small blood vessels. It is characterized by non-thrombocytopenic purpura, abdominal pain, joint swelling and pain, hematuria or proteinuria. The disease is self-limited, with only a minority progressing to end-stage renal disease in later life. This paper reviews the clinical features of IgAV in children and the mechanisms of renal involvement, and discusses the treatment and prognosis of the disease.

The high-throughput sequencing technology of genomic DNA has greatly improved the diagnostic efficiency of rare diseases, but currently there are still some patients who have not been diagnosed. In recent years, various detection techniques such as transcriptome, proteomics, metabolomics and lipidomics, and epigenetics have gradually been applied in clinical practice, making it possible to comprehensively diagnose rare disease patients based on these multiomics methods. On the other hand, with the increase of confirmed cases, how to effectively integrate patient clinical data and build rare disease databases to meet the construction needs of high-quality research-oriented patient cohorts has become an increasingly important issue for governments around the world. More importantly, the development of big data models that integrate multiomics information can promote the application of artificial intelligence and machine learning in rare disease research. This will contribute to the clinical evaluation and precise classification of rare disease patients, and effectively improve the research and development efficiency of innovative diagnostic and therapeutic technologies such as gene therapy. Rare disease research has entered the era of digital medicine, which is also a practical need to meet the precise diagnosis and personalized treatment of patients at a higher level.

Based on the theory of the developmental origins of health and disease, Shanghai Birth Cohort and the Early Life Plan have been conducted in Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine. Utilizing professional knowledge and perspectives, we focus on the first 1 000 days of life, paying close attention to the various environmental factors such as the social and physiochemistry environment, nutrition and health status of the mother during pregnancy and babies after birth. This research aims to provide a basis for the prevention, and treatment of developmental diseases.

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.

The healthy life trajectories initiative (HeLTI) is a prospective birth cohort intervention study led by the World Health Organization (WHO), which involves multiple countries including China, Canada, South Africa, and India. The project aims to explore and establish community-family-maternal-child (CFMC) intervention measures that cover multiple stages such as pre-pregnancy, pregnancy, infancy and early childhood by the advantages of HeLTI in personalized health education and authoritative professional health guidance. It aims to implement continuous and multi-level interventions to build an international collaborative research platform, and to achieve the goal of preventing developmental diseases such as obesity from the earliest stage of life. The life tree project (Sino Canadian health life trajectories initiative, SCHeLTI) is jointly funded by the National Natural Science Foundation of China (NSFC) and the Canadian Institutes of Health Research (CIHR). It is led by the International Peace Maternal and Child Health Hospital, and has formed a research team with well-known universities and institutions such as Xinhua Hospital, Fudan University Obstetrics and Gynecology Hospital, and Sherbrooke University in Canada. The project is mainly implemented in 42 community health service centers in Xuhui District, Changning District, Minhang District, Fengxian District, and Songjiang District of Shanghai. The multi-level comprehensive interventions in this project will be promoted in Shanghai and even throughout the whole China, and provide scientific basis for WHO to develop intervention guidelines for childhood obesity.

Objective To investigate the clinical phenotype and genetic characteristics of children with developmental and epileptic encephalopathy(DEE) caused by syntaxin-binding protein 1(STXBP1) gene mutation. Methods The clinical data of 11 patient with STXBP1 gene-related encephalopathy admitted to the Third Affiliated Hospital of Zhengzhou University from October 2015 to May 2022 were retrospectively reviewed, and their clinical phenotypes, gene outcomes, treatment and efficacy were analyzed. Results Of the 11 children, 4 were males and 7 were females, 10 had seizures with developmental delay and 1 showed only developmental delay. The age of onset of epilepsy was 3 days to 1.5 years, with 6 cases starting at less than 3 months, 3 at 3-12 months, and 1 at more than 1 year of age. The common seizure types are epileptic spasm and focal seizure. All the 11 patients had the abnormal interictal electroencephalograms (EEG) including background slowness, multifocal discharge, suppression-burst, and hypsarrhythmia. Two cases had Otahara syndrome in the early stages, which evolved into infantile spasms in the later stages, five cases had infantile spasms, and the rest had epileptic syndromes that could not be typed. Four children had non-specific abnormalities on cranial MRI, including poor development of myelination, and widening of the subarachnoid space in the frontotemporal region.frontotemporal. All children had STXBP1 gene variants, with a total of 11 variant types, including 7 missense variants, 1 frameshift variant, 1 splicing variant, and 2 deletion variants, and the variant loci of the 7 children have not been reported in the literature, which were c.1694T>A, c.1115T>G, C.133_135del, C.1543dupG, exons 6-17 heterozygous deletion, C.429+1G>C, C.855C>G and c.842_843insGGACGACGGCCTGTGGGATAGCACT. During follow-up, 11patients had different degrees of developmental delay, 2 patients had died, and 4 patients had autistic like features. Ten patients with epilepsy were treated with levetiracetam. One patient was seizure free with levetiracetam alone, 5 patients showed partial response, and 4 patients showed no response on multitherapy. 3 patients was seizure free, the remaining 7 patients were drug resistant epilepsy. Conclusion STXBP1 gene-related epilepsy usually occur to infant, and infantile spasm is the most common phenotype. There is significant heterogeneity in the therapeutic effect of epilepsy. Seven unreported mutation sites enriched the gene spectrum of STXBP1 encephalopathy.

Objective To investigate the variation of genes related to neonatal hyperbilirubinemia jaundice and the diseases caused by hyperbilirubinemia jaundice, and its distribution in different degrees of jaundice. Methods A total of 167 neonates diagnosed with hyperbilirubinemia in NICU from July 2022 to July 2023 were selected and divided into severe and non-severe jaundice groups. Gene detection was performed by high-throughput second-generation gene sequencing technology. The jaundice gene variants were rated as pathogenicity, and the positive, carrying and negative rates of jaundice gene variants in children were analyzed, and the distribution of jaundice gene variation and related diseases in the two groups were also analyzed. Results Among 167 children, 18 cases (10.8%) were positive for jaundice gene variation, 55 cases (32.9%) were carriers, and 94 cases (56.3%) were negative. There were 8 genes involved in UGT1A1, ATP7B, HBB, SLC25A13, ATP8B1, SMPD1, G6PD and SLC10A1, among which the mutation frequency of UGT1A1 gene was up to 45.32%, and c.211G>A was the high frequency mutation site. In the group of 31 children with severe jaundice, 16 (51.6%) had positive results for jaundice gene mutations, and all 15 cases of Gilbert syndrome/Crigler-Najjar syndrome had UGT1A1 gene mutations. Among the 136 non-severe jaundice patients, only 2 cases (1.47%) were positive, and 1 case of Gilbert syndrome / Crigler-Najjar syndrome had a variation in UGT1A1 gene. Comparing the rates of positive, carrying and negative of jaundice gene variation between the two groups, the results showed that the positive rate of severe jaundice group was significantly higher than that of non-severe jaundice group, and the negative rate was significantly lower than that of non-severe jaundice group, with statistical significance (P<0.014). Conclusions Jaundice gene variation is closely related to the occurrence and severity of neonatal hyperbilirubinemia. The common cause is UGT1A1 gene variation, and c.211G>A is the high frequency mutation site. It is of great clinical significance to conduct gene detection for children with hyperbilirubinemia, especially severe hyperbilirubinemia.

IgA vasculitis (IgAV) is the most common systemic small vessel vasculitis in children, and it is called IgA vasculitis with nephritis (IgAVN) when it affects the kidneys. Renal damage eventually lead to chronic kidney disease in about 20% children with IgAVN, and accounting for 1%~2% of all childhood end-stage renal disease (ESRD). Therefore, it is important to identify the risk factors for the prognosis of IgAVN in children and give timely and effective intervention for the prognosis of IgAVN. This article reviews the risk factors affecting the prognosis of IgAVN in children, in order to provide reference for clinical decision-making.

Primary care pediatricians often confuse the diagnosis between atopic dermatitis and food allergy. However, allergens are not the sole factor in the onset of atopic dermatitis, and not all patients with atopic dermatitis have food allergies. Consequently, there are pressing issues in contemporary clinical practice that need to be resolved, including a proper knowledge of the role that food allergies play in the pathophysiology of atopic dermatitis, scientific detection and identification of food allergies, and avoiding unreasonable dietary restrictions.

Objective To investigate the correlation between peripheral blood myeloid-derived suppressor cells (MDSCs) levels and the severity of necrotizing enterocolitis (NEC), and the biological characteristics of MDSCs in NEC infants. Methods The single-cell sequencing dataset of peripheral blood from NEC patients was downloaded from the GEO database and analysed by quality control, batch correction, clustering dimensionality reduction and cell type annotation. The number and proportion of MDSCs in the peripheral blood of NEC patients at different disease stages were calculated. Subsequently, MDSCs subsets were extracted, differentially expressed genes and enrichment pathways were analysed, and the expression of MDSC immunosuppressive function, apoptosis and chemotaxis related molecules were compared. Results As the severity of NEC increased, the corresponding number and proportion of MDSCs gradually decreased. Compared with stage II NEC patients, upregulated genes in MDSCs of stage III NEC patients were enriched in multiple pathways, such as positive regulation of leukocyte activation and negative regulation of locomotion. And there was no significant difference in immunosuppressive function and apoptotic pathway activation between MDSCs from stage II and III NEC patients, whereas the expression of chemokine receptor CXCR1 was significantly decreased in MDSCs from stage III NEC patients. Conclusion The number of MDSCs in the peripheral blood of NEC patients was inversely correlated with the severity of NEC. And the reduction of MDSCs in stage III NEC patients could be attributed to the downregulated expression of CXCR1.

Objective To investigate the clinical phenotype and genetic variant characteristics of children with Shwachman-Diamond syndrome (SDS). Methods From January 2018 to September 2023, seven children with SDS under long-term follow-up in the Department of Pediatric Endocrine and Genetics were selected as the research objects. The clinical data of children were gathered and peripheral blood samples were collected for exome sequencing (ES), and lineage validation of the variants was performed by Sanger sequencing. Results Among the 7 children with SDS, 3 were boys and 4 were girls. The median age at first diagnosis was 3.0 (0.9-4.0) years. Six patients carried SBDS defects and one case carried EFL1 defect. Among the six patients with SBDS deficiency, five of them carried compound heterozygous variants (two cases with the variants of c.258+2T>C/c.183_184delinsCT, one case with c.258+2T>C/c.40A>G, one case with c.258+2T>C/c.184A>T, one case with c.258+2T>C/ heterozygous deletion of exon 3), and the remaining one patient carried SBDS homozygous variation (c.258+2T>C). Patients with SBDS deficiency were initially diagnosed with short stature (6/6, 100%), and combined with chronic diarrhea (3/6, 50%) and recurrent respiratory infections (1/6, 16.7%). Through examination, all the six patients with SBDS deficiency (100%) were found to have neutropenia and elevated liver enzymes. Four cases had skeletal dysplasia and 3 cases had exocrine pancreatic dysfunction. One SDS patient was confirmed to carry compound heterozygous variants of EFL1 (c.2260C>T/c.316G>A). The main clinical manifestations included short stature and abnormal skeletal development, without pancreatic and blood system involvement. Conclusions Children with SBDS deficiency presented clinical phenotypic heterogeneity. The phenotypic spectrum and variation spectrum of SDS in China were enriched, and an SDS patient with EFL1 variant was reported for the first time in the Chinese population. For children with short stature and symptoms such as neutropenia, exocrine pancreatic dysfunction, and skeletal deformities, genetic testing should be completed to avoid missing the diagnosis of SDS.

Objective To investigate the significance of elevated blood 3-hydroxyisovalerylcarnitine (C5OH) in the diagnosis of inherited metabolic diseases (IMD) and to explore the disease spectrum and genetic characteristics of children with abnormal C5OH in the population of northern China. Methods The data of IMD screening and diagnosis in hospitalized children from November 2012 to October 2021 were retrospectively analyzed, including tandem mass spectrometry (MS/MS) screening of blood metabolites, gas chromatography-mass spectrometry (GC-MS) analysis of urine metabolites and high-throughput sequencing analysis of gene variations. The blood and urine metabolic spectrum and gene variation spectrum of children with abnormal C5OH were analyzed. Results Among 53119 hospitalized children aged 0 to 7 years who underwent MS/MS screening for IMD, 48 (0.090%) children with increased C5OH were detected. Combined with urine GC-MS analysis, 9 (0.017%) children obtained biochemical diagnosis of IMD which verified by gene analysis. Of the 4 children with multiple carboxylase deficiency (MCD), 2 had HLCS gene variation and were confirmed as holocarboxylase synthetase deficiency, while the other 2 had BTD gene variation and were confirmed as biotinidase deficiency. ACAT1 variation was detected in 2 children with β-ketothiolase deficiency, and HMGCL variation was detected in 1 child with 3-hydroxy-3-methyl-glutaricacidemia. In 2 children with suspected MCD or 3-methylcrotonyl coenzyme A carboxylase deficiency that were not classified by biochemical diagnosis, HLCS variation was detected in 1 child, and BTD variation was detected in the other child, and MCD was finally diagnosed. The false positive rate of C5OH detection was 0.073% and the positive predictive value was 18.75%. The false positive rate of C5OH combined with other indicators (C4OH, C3 and C5:1) was 0.009%, and the positive predictive value was 58.33%. There was no false positive in the analysis of C5OH combined with urinary GC-MS, and the positive predictive value was 100%. Conclusions MCD is the main disease type in children with increased C5OH. For C5OH-related IMD, MS/MS combined with GC-MS metabolic analysis has high diagnostic efficiency and clinical value of guiding intervention in advance.

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disorder characterized by progressive muscle weakness and eventual fatality. In recent years, more and more gene therapies have emerged, and comprehensive care throughout the disease course remains crucial for maximizing patient’s survival and quality of life. This consensus, developed through literature review, expert consultations, and clinical experience, provides guidance for managing following aspects of care in non-ambulatory DMD patients, including respiratory, cardiac, rehabilitation, skeletal, nutritional, digestive, dermatological, cognitive, and psychological care. This aims to provide a scientific and practical support for families caring for non-ambulatory DMD patients.

Objective To explore the clinical features of mitochondrial encephalomyopathy (ME) in children in southern China. Methods The clinical data of children diagnosed with ME from January 2015 to August 2022 were retrospectively analyzed. Results Thirty-six children with ME (22 boys and 14 girls) were included, and the onset age was 6.8 (2.1-10.8) years old. The onset symptoms were stroke-like episodes (24 cases), exercise intolerance (7 cases), ptosis (3 cases) and mental retardation (2 cases). Neuromuscular symptoms during the course of the disease included seizures (17 cases), headache (11 cases), paralysis (11 cases), ataxia (10 cases), ptosis of the upper eyelid (7 cases), mental/motor retardation (7 cases), blurred vision (6 cases), disturbance of consciousness (3 cases), and psychobehavioral abnormality (2 cases). Other non-neuromuscular symptoms included fever (7 cases), vomiting (6 cases), slow weight gain (5 cases), abdominal pain (2 cases), urinary retention (1 case), intestinal obstruction (1 case), and respiratory failure after sedation (1 case). The clinical phenotypes included mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) (16 cases), Leigh syndrome (LS) (11 cases), myoclonus epilepsy with ragged-red fibers (MERRF) (3 cases), Kearns-Sayre syndrome (KSS) (2 cases), and unclassifiable types (4 cases). The blood lactic acid of resting phase was increased in 71.4% of the children, and cerebrospinal fluid lactic acid was increased in 95.2% of the children. There was statistically significant difference between blood lactic acid of resting phase and cerebrospinal fluid lactic acid (P<0.05). Abnormal brain MRI was found in 31 children, mostly involving the parietal lobe (15 cases), occipital lobe (14 cases), basal ganglia (13 cases), brainstem (10 cases) and thalamus (8 cases). Long segmental spinal cord abnormal signals were found in 2 cases of LS. Typical broken red fibers were seen by muscle biopsy in 2 children. Genetic examination found mtDNA variations in 81.8% of the children. Conclusions The onset age of ME in children is around the age of 6. Stroke like attack is the commonest onset symptom. MELAS is the commonest clinical phenotype. The levels of resting blood lactic acid and cerebral spinal fluid lactic acid may increase. Head MRI shows that ME often involves the parietal and occipital lobe, basal ganglia, brainstem and thalamus. The results of genetic examination are mainly mtDNA variations.

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 two major treatments for mucopolysaccharidosis type Ⅱ (MPS Ⅱ) are hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). The restoration of central nervous system function is limited by these two therapies, although they are successful in controlling the worsening of physical symptoms. The main limitation is that the blood-brain barrier (BBB) prevents large molecules, including enzymes, from entering the brain, which can affect the effectiveness of treatment. Gene therapy is an emerging therapy for MPS Ⅱ. This article will describe the current preclinical research status and ongoing clinical trials of MPS Ⅱ gene therapy to demonstrate the latest advances in this field.

With the advancement of science and technology, screening and diagnostic techniques for neonatal genetic diseases have made great leaps forward, especially the application of next-generation sequencing (NGS) technology, which has greatly improved the efficiency and accuracy of clinical applications. However, in the face of rapid diagnosis, it has become a new challenge to provide effective treatments to improve the overall prognosis of children.This article will start from the China Neonatal Genome Project, comprehensively and in-depth discuss the current status of newborn genetic disease screening and treatment, focus on the key issues of personalized treatment research and application, and propose efforts for future directions.

Objective To report the clinical and genetic characteristics of three cases of Wiedemann-Steiner syndrome (WDSTS) caused by KMT2A gene mutation, and improve the understanding of the disease and the efficiency of diagnosis and treatment. Methods The clinical data of three cases of WDSTS caused by KMT2A gene mutation in three families diagnosed in Shengjing Hospital of China Medical University from December 2019 to September 2021 were reviewed, and the clinical and genetic characteristics of WDSTS patients reported in the literature were reviewed and summarized. Results All three cases were diagnosed in infancy, with the youngest age of diagnosis of two months old, and the reasons for consultation were growth retardation and anorexia, respectively. Similar to those in previous literature, the clinical manifestations were special facial features, malnutrition (3/3), feeding difficulties, sleep disorders, hirsutism (2/3), and developmental delay (1/3). The clinical manifestations that had not been reported before were umbilical hernia and inguinal hernia. All three cases were de novo frameshift variants, which occurred in exon 3 and 27 in hot spot variants region and exon 11 in non-hot spot variants region, respectively. Conclusions Wiedemann-Steiner syndrome should be considered in children with malnutrition, feeding difficulty and developmental delay, combined with special facial features and specific hirsute. High-throughput exome sequencing should be used to facilitate early diagnosis. De novo frameshift variants of KMT2A gene are common, with hot spots in exon 27 and 3. The three unreported frameshift variants in this study enrich the mutation spectrum of this gene. In addition, patients with variants in the CXXC region of the KMT2A gene may have a more severe clinical phenotype.

Crohn's disease (CD) is a chronic nonspecific gastrointestinal inflammatory disease. The onset of CD in children is insidious, the clinical manifestations are lack of specificity, and early diagnosis is difficult, which leads to the increased complications, surgical rates and disability rates. Early screening and diagnosis, timely intervention can improve the therapeutic effect and prognosis of children, and improve the life quality of children. This article reviews the progress of early screening and diagnosis of CD in children.

Objective To identify KIF12 mutation in an infant with progressive familial intrahepatic cholestasis 8 (PFIC8) and to explore the functional consequences of the mutation. Methods The clinical data of the infant with PFIC8 were analyzed, and whole exome sequencing was conducted on the patient and his parents, and the variation was verified by Sanger sequencing. Immunofluorescence staining, cell phenotyping, qPCR and Western blotting were utilized to investigate the effect of the causative mutations on the gene functions. At the same time, the clinical data and gene variation of 17 reported PFIC8 patients were reviewed. Results The proband, a male infant aged one month and 14 days, exhibited symptoms of fever and jaundice. Whole exome sequencing showed that the KIF12 gene of the patient had a compound heterozygous mutation of c.539G>A+c.928C>T, which had not been reported before. Immunofluorescence staining of liver sections from the patient suggested that the mutation altered the subcellular localization of KIF12 protein within hepatocytes. In 293 T cells, phenotyping of the mutants revealed that c.539A, c.928T and c.539A+c.928T resulted in decreased mRNA levels of KIF12, while c.928T and c.539A+c.928T reduced the protein expression levels of KIF12. A review of the literature revealed seven single site mutations of KIF12 and a compound heterozygous mutation (c.538C>T+c.539G>A) that have been reported. Existing data indicated that the types of KIF12 mutations were not correlated with the extrahepatic clinical phenotypes of PFIC8 patients. Conclusions A novel compound heterozygous mutation was identified in an infant with PFIC8. Among the nine KIF12 mutations identified to date, the mutation types were not associated with the extrahepatic clinical phenotypes of PFIC8.

Objective To summarize the construction plan of the Shanghai Children Rare Diseases Registry Database, and to retrospectively analyze the demographic characteristics and disease spectrum of the patients included in the database. We aim to clarify the distribution characteristics of rare diseases in children, and to provide data support for the construction of a high-level research-based patient cohort and the systematic management of patients with rare disease. Methods Based on the disease catalog from National Rare Diseases Registry System, we build a regional rare disease registration database that can connect to the hospital information system. Descriptive studies were conducted to analyze patient data in the database. Results A total of 6341 cases of rare disease patients diagnosed from 2008 to 2021 were included in the database, covering 109 kinds of diseases. The proportion of outpatients and inpatients was 59.4% (3764 cases) and 40.6% (2577 cases), respectively. The male to female ratio was 1.36∶1. Langerhans cell histiocytosis (11.3%), familial dilated cardiomyopathy (7.9%), hemophilia (5.5%), and neurofibroma (5.4%) accounted for the most cases. With the wide application of high-throughput sequencing technology, the number of pediatric rare disease patients with definite diagnosis has increased year by year, and more than 80% of children can get a clear diagnosis before the ten-year old. Conclusions The present study established a rare disease registry database that includes both outpatients and inpatients. We have described the disease spectrum and demographic characteristics of children with rare diseases, and also reflected the progress in the field of diagnosis of children’s rare diseases in recent years. This study will provide basic data support for further inclusion of more rare diseases and building a higher level database of children's rare diseases in multiple centers.

Birth cohorts are important research tools and resources for exploring the impacts of early life risk factors on offspring’s health throughout their life courses. However, large-scale birth cohorts with long-term follow-up are lack in China. The Born in Guangzhou Cohort Study (BIGCS), a large general-population parent-child prospective cohort, was officially launched in 2012 to conduct long-term longitudinal observation of participating families from pregnancy to offspring. This cohort collected data and biological samples through face-to-face follow-up at multiple time points, including early pregnancy, mid-pregnancy, late pregnancy, delivery, as well as 6 weeks, 6 months, 1 year, 2 years, 3 years, 6 years, and 8.5 years after birth. Cohort children were planned to be followed up to 18 years of age. Up to June 2024, the BIGCS has recruited over 60000 pregnant women and 53000 children, among whom 27000 children are over 6 years old, with over 2.9 million specimens. The aim of this study is to identify the risk factors associated with adverse maternal and children’s health outcomes and explore their potential mechanisms and provide scientific evidences for developing the strategies to improve women and children’s health. This paper will give a brief introduction to the establishment, research progress, and future development of the BIGCS.

Pseudomonas aeruginosa is a common opportunistic pathogen of nosocomial infection, which is widely distributed in the hospital environment and can survive for a long time. Carbapenems antibiotics play an important role in the treatment of serious infections caused by Pseudomonas aeruginosa. However, the outbreak of carbapenems resistant Pseudomonas aeruginosa is particularly prominent in recent years, which has made clinical treatment facing great challenges. This article introduces the main resistance mechanism of Pseudomonas aeruginosa to carbapenems antibiotics and summarizes the application of various clinical treatment schemes, and provides a reference clinical rational use of antibiotics and treatment of carbapenems resistant Pseudomonas aeruginosa infection

Lupus nephritis (LN) is the most common glomerular disease in children, with a more severe onset and progression compared to adults. The prognosis of LN in children is worse than other glomerular diseases and has lifelong effects, although the etiology remains unclear. This article provides an overview of the current diagnosis and treatment status of LN in children, along with a brief description of the treatment for each type of LN based on the latest international guidelines. LN was diagnosed according to the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus. Renal biopsy pathology is an important diagnostic method at present. Treatment for proliferative and non-proliferative LN includes initial therapy and maintenance therapy, following recommendations from adult guidelines. Rational and proactive treatment is crucial for inducing disease remission, preventing relapse, and improving prognosis.

Objective To investigate the variants and clinical characteristics of BRAF gene. Methods The clinical data and types of gene variation in 8 cases of children with BRAF gene variation were retrospectively analyzed. Results Eight children had BRAF gene variations, four of which were derived from germ cells and the other four from somatic cells. The 4 patients with BRAF gene variations from germ cells all showed clinical features of cardio-facio-cutaneous (CFC) syndrome, which is an extremely rare disease. They all have special facial features, developmental retardation, skin and hair abnormalities, and some children also have epilepsy, heart malformation and other manifestations. They were all new variations in the BRAF gene, but the variation sites were different. Of the 4 children whose BRAF gene variations originated from somatic cells, 2 presented with Langerhans cell histiocytosis (LCH), and the other 2 presented with central nervous system malignant tumors. Conclusions When BRAF gene variation occurs in germ cells, children can develop severe developmental disorders that can present as clinical features of CFC syndrome. When BRAF gene variation occurs in somatic cells, it can cause tumors and LCH, etc.

Food for special medical purpose (FSMP) has undergone significant development in China. This paper provides an overview of the evolution of China’s special medical food industry, including its journey from its inception to independent research and development. Furthermore, it discusses the progress made in clinical application, product types, research and development capabilities, as well as regulation and standard management. The challenges and opportunities faced by the special medical food industry in China are also explored. As the domestic and international markets continue to expand and technology advances, FSMP will increasingly play a crucial role in the field of clinical nutrition therapy.

Objective To explore the clinical features, gene variation and follow-up results of children with isovaleric acidemia (IVA), and to provide evidence for early recognition, diagnosis and treatment of IVA. Methods The clinical data of children diagnosed with IVA in the Department of Pediatric Endocrinology from April 2012 to October 2023 were retrospectively analyzed. Results Of the 34 children with IVA (22 boys and 12 girls), 15 had acute neonatal type, 3 had chronic intermittent type, and 16 had asymptomatic type confirmed by neonatal screening. Compared with asymptomatic group, blood isovalerylcarnitine (C5) level, C5/ acetylcarnitine (C2) ratio, C5/ propionylcarnitine (C3) ratio and urine isovalerylglycine level in the group with clinical symptoms (including acute neonatal type and chronic intermittent type) were significantly increased, with statistical significance (P<0.05). A total of 40 mutations were identified in 34 patients, most of which were missense mutations (30/40, 75.0%) and c.1208A>G (n=8) was the most frequent variant. There was no significant correlation between clinical manifestation and type of gene variation. Four patients, all of whom belonged to the acute neonatal type, died during follow-up. Thirty surviving children had considerably lower urinary isovalerylglycine levels at the most recent follow-up, with a statistically significant difference from before therapy (P<0.05). Conclusions Clinical manifestations of IVA lack specificity. Elevated C5, C5/C2 ratio and C5/C3 ratio in plasm and isovalerylglycine in urine are typical hallmarks of IVA. Newborn screening is pivotal for early diagnosis, treatment, and prognosis.

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.

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.