Food allergy is very difficult to diagnose due to their complex pathophysiology, wide range of clinical symptoms, and lack of precise biomarkers. Oral food challenge test is the gold standard for confirming food allergy. The standardized diagnosis and treatment of food allergy requires the clinician to understand the basic knowledge related to allergy, so as to facilitate the correct selection of diagnostic methods and reasonable interpretation of test results.

The clinical management of food allergy primarily involves the avoidance of allergenic foods and symptomatic treatment through multidisciplinary collaboration. Hypoallergenic formula plays a crucial role in providing nutrition for infants with milk protein allergy. It is imperative for doctors to select and standardize hypoallergenic formulas judiciously. Food ladder therapy has been employed in managing mild to moderate non-IgE-mediated food allergies in children. Individualized treatment approaches are the future direction for managing food allergies.

The symptoms of food allergy present nonspecifically, with 60% of children showing digestive system symptoms such as rectal bleeding, diarrhea, constipation, etc. Clinically, it is highly prone to misdiagnosis and missed diagnosis, leading to over-treatment and delayed treatment, exacerbating the condition and affecting the growth and development of affected children. Three criteria should be followed in the diagnosis of food allergies and associated digestive disorders: (1) clinical symptoms; (2) laboratory testing (oral food challenge) to determine allergens; and (3) a direct correlation between food and symptoms. Rectal bleeding is more common in food protein-induced proctocolitis, and in the neonatal period, it needs to be differentiated from infectious diarrhea and necrotizing enterocolitis. In infancy, it needs to be differentiated from anal fissures, intestinal polyps, intussusception, Meckel’s diverticulum, intestinal vascular malformations, very early-onset inflammatory bowel disease and congenital immunodeficiency disease-related diarrhea. Diarrhea is common in food protein-induced enteropathy and food protein-induced enterocolitis syndrome and needs to be differentiated from lactose intolerance, celiac disease, and diarrhea caused by other reasons. Whether food allergy can cause constipation is still debated, and it needs to be differentiated from congenital megacolon and functional constipation.

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 dynamically monitor and analyze the changes of fecal mucin 2 (MUC2) and secretory immunoglobulin A (sIgA) levels during the clinical treatment process of infants with food allergy, and to investigate the usefulness of food allergy’s interaction with sIgA and MUC2. Methods Fifty-two infants diagnosed with food allergy who received outpatient treatment from July 2022 to June 2023 were selected as the food allergy group. Simultaneously, 52 non-allergic diseases infants were chosen as the control group. The levels of fecal MUC2 and sIgA were compared between the two groups. Results There were 23 boys and 29 girls in the food allergy group and 26 boys and 26 girls in the control group. There were no statistically significant differences in age, delivery mode, feeding method, introduction of complementary foods and family history of allergic diseases between the two groups (P>0.05). The levels of fecal MUC2 and sIgA in the food allergy group were higher than those in the control group [(37.81±14.91) μg/mL vs. (25.33±14.29) μg/mL; 182.4(150.2-202.7) μg/mL vs. 147.7(131.4-157.9) μg/mL], and the differences were statistically significant (P<0.001). At the 2nd and 4th week of follow-up, fecal MUC2 level of children with food allergy group gradually decreased, but there was no statistical significance between groups (P>0.05). The level of fecal sIgA increased gradually, and the difference between groups was statistically significant (P<0.05). Binary logistic regression and ROC curve analysis showed that fecal MUC2 and sIgA both had area under the ROC curves above 0.7 (P<0.001), and the combination of the two could increase the diagnosis specificity. Conclusions There were differences in fecal MUC2 and sIgA levels between the two groups. With the improvement of clinical symptoms of children with food allergy, fecal MUC2 levels showed a downward trend and sIgA levels gradually increased, which may serve as potential biomarkers for the diagnosis of food allergy. The two groups' fecal MUC2 and sIgA levels varied from one another. With the improvement of clinical symptoms of children with food allergy, fecal MUC2 level had a downward trend and sIgA level gradually increased, suggesting that these markers could be useful for food allergy diagnosis.

Objective To compare the distribution of gut microbiota in continuously breastfed 12 week-old infants whose mothers were diagnosed with and without gestational diabetes mellitus (GDM), and to further explore the effect of GDM on the gut microbiota of those infants. Methods The mothers enrolled between June 2016 and December 2019 and their breastfed infants who were followed up to 12 weeks of age were selected. The breastfed infants were divided into the GDM group (n=13) and the control group (n=27) according to the results of maternal blood glucose detection during pregnancy. Fecal samples were collected from infants at 12 weeks of age, and 16S rDNA high-throughput sequencing technology was used to detect all fecal samples, and gut microbiota distribution characteristics of the two groups were compared. Spearman correlation analysis was used to analyze the correlation between gut microbiota and blood glucose during pregnancy as well as infant weight. Results A total of 40 pairs of subjects were included, including 13 pairs in the GDM group and 27 pairs in the control group. The gut microbiota in the 2 groups consisted mainly of 3 phyla (Actinobacteria, Firmicutes, and Proteobacteria). The relative abundance of Verrucomicrobia in the GDM group was significantly higher than that in the control group (Z=2.233, P<0.05). At the genus level, the dominant genus in the GDM group came from Actinobacteria and Firmicutes, while in the control group came from Actinobacteria, Firmicutes and Proteobacteria. LEfSe analysis showed that the abundance of Verrucomicrobia, Akkermansia, Lawsonella and Eubacterium hallii were significantly increased in the GDM group, while the abundance of Bacillales, Gemella and Erysipelatoclostridium were significantly increased in the control group (LDA>2). The phylum-level abundance of gut microbiota was not correlated with blood glucose during pregnancy and infant weight at 12 weeks of age (P>0.05). Conclusions GDM during pregnancy had a certain effect on the gut microbiota composition of 12-week-old infants who were continuously breastfed.

Objective To investigate the dynamic changes and distribution of gut microbiota in extremely preterm infants within the first month after birth, and to provide a theoretical basis for early intervention with probiotics. Methods A prospective study was conducted. Extremely preterm infants admitted to our hospital from September 2022 to March 2023 were enrolled. Fecal samples were collected on postnatal days 7, 14, 21 and 28 for high-throughput 16S rRNA sequencing and bioinformatics analysis. Results A total of 35 extremely preterm infants (22 boys and 13 girls) with gestational age of (210±11) days and birth weight of (1419±339) g were enrolled, and 140 fecal samples were collected. At the phylum level, the dominant gut microbiota detected included Firmicutes and Proteobacteria, accounting for more than 80%. At the genus level, the dominant gut microbiota were mainly opportunistic bacteria, including Escherichia, Clostridium, Staphylococcus, Acinetobacter and Klebsiella, while the relative abundance of Bifidobacterium was less than 5%. The difference analysis of key flora showed that the difference in key flora at the phylum and genus level was mainly in Bacteroidetes (P=0.029), Cyanobacteria (P=0.011), Staphylococcus (P=0.010), and Roseobacter (P=0.040). The diversity analysis of gut microbiota showed that there was no significant difference in the Ace and Shannon values of Alpla diversity index at the four time points (P>0.05), while Chao value showed a gradual downward trend (P=0.001). The weighted-unifrac values of beta diversity analysis at the four time points were 0.412 (0.281-0.493), 0.498 (0.214-0.526), 0.428 (0.289-0.490) and 0.143 (0.077-0.423), respectively, and the difference was statistically significant (P<0.001). Conclusions From 7 to 28 days after birth, the dominant gut microbiota of extremely preterm infants gradually changes from Firmicutes to Proteobacteria, with opportunistic bacteria as the main flora. The number of Bifidobacterium colonized is small, and the diversity of gut microbiota shows a downward trend.

Objective To analyze the characteristics of autoantibody expression and prognosis influencing factors in children with immune thrombocytopenia (ITP). Methods The clinical data of 299 children with newly diagnosed ITP hospitalized from September 2020 to September 2021 were retrospectively analyzed. Results A total of 299 children (171 boys and 128 girls) with ITP were included, and the median age was 2.7 (1.0-4.6) years. Among the 296 ITP children who completed autoantibody spectrum detection, 114 (38.5%) showed positive autoantibody spectrum expression. One hundred and fourteen patients (38.5%) of the 296 ITP children who finished autoantibody spectrum detection had positive autoantibody spectrum expression. Among them, 101 patients (88.6%) were positive for anti-nuclear antibody, 59 (51.8%) were positive for anti-SSA /RO52KD antibody, and 52 (45.6%) were positive for anti-SSA /RO60KD antibody. Of 299 children with ITP, 205 were cured. Compared with the cured group, the uncured group had a higher proportion of age ≥ 1 year old, positive antinuclear antibody, anti-SSA/RO52KD antibody, anti-SSA/RO60KD antibody and bleeding score≥3, and a lower proportion of preceding infection and gammaglobulin alone, with statistically significant differences (P<0.05). The binary logistics regression analysis showed that age ≥ 1 year old, positive antinuclear antibody, and bleeding score ≥ 3 were independent risk factors for ITP prognosis (P<0.05), and a history of preceding infection was an independent protective factor for ITP prognosis (P<0.05). Conclusions Autoantibody spectrum antibody expression is common in children with ITP. Age, history of preceding infection, antinuclear antibody and bleeding score are associated with ITP prognosis.

Objective To summarize the clinical features and MRI manifestations of the acute onset of mitochondrial encephalomyopathy (ME) in children, so as to improve the understanding of the disease. Methods The clinical and imaging data of 12 children with confirmed ME from March 2018 to December 2021 were retrospectively analyzed. Results Twelve cases of ME were included, 5 males and 7 females, with a median age of 8 years and 6 months. The main symptoms included stroke-like episodes (8 cases, 66.7%) and headache (7 cases, 58.3%); laboratory tests showed increased serum lactate in 10 cases (83.3%), and genetic testing was positive in 9 cases (75%). 11 cases of cranial MRI scanning detected the lesion, and the lesion areas all showed large patchy T1WI low signal, T2WI/T2-FLAIR high signal, of which nine cases involved cortical and subcortical regions, with the temporoparieto-occipital lobe being the most susceptible area, and the other two cases symmetrically involved the basal ganglia/brainstem and cerebellar hemispheres/brainstem, and six cases were combined with cerebral atrophy; diffusion-weighted imaging (DWI) in seven cases showed that the diffusion of the disease was limited in six cases; magnetic resonance angiography (MRA) in four cases showed that there was an increase in the number of branches of the middle cerebral artery of the affected side; arterial spin labelling (ASL) in three cases showed that the lesion area was highly perfused; and MRS in six cases suggested that the lesion area was highly perfused; and spectroscopy (MRS) suggested that elevated lactate peaks were detected in the lesion area in six cases. Conclusions The most common clinical symptoms of ME in children are stroke-like episodes. Genetic testing may be negative in a few cases, and increased serum lactate is common but not specific; MRI has some characteristic features, including unilateral temporoparieto-occipital cortex and subcortical patchy T2-FLAIR high signals, restricted dispersion and hyperperfusion of the lesion in the acute phase, and increased peaks of lactate in the brain tissue of the lesion, with an increase in the branches of the middle cerebral artery on the affected side.

Objective To summarize the clinical characteristics, diagnosis and treatment and prognosis of acute necrotizing encephalopathy of childhood (ANEC). Methods The clinical data of ANEC patients from June 2016 to December 2022 were retrospectively analyzed. Survivors were followed up through telephone. Survivors' life quality was measured using the pediatric overall performance category scale (POPC). Results A total of 26 children with ANEC were included, with a male to female ratio of 1.6:1 and a median age of 36.0 (23.0-69.0) months. The most common season was summer (42.3%), followed by winter (34.6%). Influenza virus was the most common preceding infection (34.6%), followed by human herpesvirus 6B and SARS-CoV-2. All patients had fever and different degrees of consciousness disorder, and 24 had convulsions. Symmetrical thalamic involvement (100%) was the typical change in imaging, with basal ganglia (50.0%), brainstem (61.5%), cerebellum (26.9%) and other sites involved. Twenty-three patients received methylprednisolone shock therapy, and the in-hospital fatality rate was 23.1% (6/26). The cumulative case fatality rate 6 months after discharge was 30.7% (8/26). The 14 surviving children were followed up regularly for 6 months, and 11 received rehabilitation treatment. One child received two points for the POPC, four received three, six received four, one received five, and two received six. The POPC results of 3 patients with ANEC after SARS-CoV-2 infection at 3 months follow-up were 2 in 2 children and 6 in one child. Conclusions ANEC occurs frequently in summer and winter in South China, and can be induced by SARS-CoV-2 infection. The typical signs of ANEC are fever, convulsion, and disturbance of consciousness, and the typical imaging changes were bilateral thalamic involvement. Early immunotherapy and comprehensive rehabilitation training can reduce the severity of neurological sequelae.

Objective To investigate the clinical features and related influencing factors of newly diagnosed type 1 diabetes mellitus (T1DM) starting with diabetic ketoacidosis (DKA) in children, in order to improve the early identification of high-risk DKA children by clinicians and improve their survival prognosis. Methods The clinical data of 214 newly diagnosed children with T1DM admitted to the hospital from January 1, 2015 to December 31, 2021 were retrospectively analyzed. The patients were divided into DKA group and non-DKA (NDKA) group and the clinical features and laboratory examination were compared between the two groups. The multivariate logistic regression analysis was used to identify the related influencing factors of DKA occurrence in children. Results A total of 214 newly diagnosed T1DM children were included, 110 patients (51.4%) in the DKA group and 104 (48.6%) in the NDKA group. The typical clinical symptoms of diabetes such as polydipsia, polyuria, polyphagia and weight loss were more common in NDKA group, while gastrointestinal symptoms, neuropsychiatric changes and dehydration were more common in DKA group (P<0.05). The variables that were significant in univariate analysis (age, preceding infection, symptom duration, plasma C-peptide and blood glucose) were further included in multivariate logistic regression analysis, and the results showed that preceding infection (OR=7.541, 95%CI: 3.315-17.151), symptom duration (OR=0.989, 95%CI: 0.980-0.999), plasma C-peptide (OR=3.044, 95%CI: 1.571-5.899) and blood glucose (OR=5.652, 95%CI: 2.582-12.373) were independent factors influencing the occurrence of DKA in children. Conclusions Children with newly diagnosed T1DM should be cautious of developing DKA if they have a history of preceding infection, short-term symptoms, low plasma C-peptide, and high blood sugar.

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 investigate the clinical and immunological features of Griscelli syndrome type 2 (GS2) caused by RAB27A gene defect. Methods The clinical data, biochemical examination and pathological biopsy results of 2 children with GS2 in 1 family were collected. Hair was collected for microscopic examination. Peripheral venous blood was extracted for immune-related gene sequencing, and the RAB27A mutation site in the children and their parents was verified by Sanger sequencing. The expression level of RAB27A protein in peripheral blood mononuclear cells was detected by western blot. Flow cytometry was performed to detect CD107a expression in NK and CTL cells, and an age-matched healthy child was used as control. Results The two patients were siblings, and both presented with postnatal hypopigmentation of hair. The main clinical manifestations of both patients were recurrent fever, recurrent respiratory infection combined with hemophagocytic lymphohistiocytosis (HLH), and the younger sister was accompanied by generalized diffuse target-shaped lesions. Accumulation of irregular melanin clusters in the hair were observed in both patients, and the histopathology of the younger sister's lesions showed an irregular distribution of melanocytes in the basal layer of the epidermis. Gene sequencing identified a homozygous frameshift mutation of c.377delC in exon 5 of RAB27A gene, and the parents were consanguineous and both were carriers. Reduced expression of RAB27A protein and defects in the cytotoxicity of NK cells and CTL were observed in peripheral blood mononuclear cells of both patients. Neither patient received chemotherapy or hematopoietic stem cell transplantation (HSCT) and died of HLH successively. Conclusions The definitive diagnosis of GS2 relies on clinical manifestations and genetic testing, immune function testing also contributes to the diagnosis. Currently, allogeneic HSCT is the only method to cure GS2.

To explore the clinical characteristics and mutation spectrum of TRIM8 related pediatric nephrotic syndrome, seizures and developmental retardation in a child and related literature were reviewed. A boy aged 2 years and 6 months was admitted to the hospital due to fever for 5 days and recurrent convulsions for 2 days. The child received rehabilitation training for developmental retardation after birth. Physical examination revealed the child had mild eyelid edema. Laboratory examination showed hypoalbuminaemia (albumin 24.6g/L). Repeated urinalysis indicated massive proteinuria (+++), accompanied by microscopic hematuria. Genetic testing showed the boy carried a de novo heterozygous mutation of c.1375C>T in TRIM8 gene, and his parents were wild-type. TRIM8 gene variants can lead to syndromes with neuro-renal characteristics. Sequencing of the TRIM8 gene should be considered in patients with focal segmental glomerulosclerosis that starts in childhood, especially in patients with neurological abnormalities such as epilepsy and developmental retardation.

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.

Chimeric antigen receptor (CAR)-T cells have become one of the most promising methods for the treatment of malignant tumors due to their specific recognition function and cytotoxicity. However, it also has a series of side effects, especially in children. Toxic reactions can develop rapidly and endanger life in severe cases. In this paper, the side effects of CAR-T cell therapy in children, as well as its clinical manifestations and treatment are summarized, aiming to optimize its application in children.

As an important non-drug treatment for heart failure in adults, cardiac resynchronization therapy (CRT) is gaining more and more interest and application in pediatric heart failure, and it has been preliminarily proved to be effective in heart failure due to some etiologies. This article reviews the application, efficacy, implantation forms and adverse reactions of CRT in children with heart failure caused by different causes such as congenital heart disease and pace-induced cardiomyopathy in recent years, and looks forward to the further development of CRT, in order to provide reference for timely application of CRT in children with heart failure.

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.