Jianhua Zhang

Background: The interplay between gut microbiota and metabolites in the early stages of sepsis-induced acute kidney injury (SA-AKI) is not yet clearly understood. This study explores the characteristics and interactions of gut microbiota, and blood and urinary metabolites in patients with SA-AKI.Methods: Utilizing a prospective observational approach, we conducted comparative analyses of gut microbiota and metabolites via metabolomics and metagenomics in individuals diagnosed with SA-AKI compared to those without AKI (NCT06197828). Pearson correlations were used to identify associations between microbiota, metabolites, and clinical indicators. The Comprehensive Antibiotic Resistance Database was employed to detect antibiotic resistance genes (ARGs), while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways informed on metabolic processes and microbial resistance patterns.Results: Our study included analysis of four patients with SA-AKI and five without AKI. Significant disparities in bacterial composition were observed, illustrated by diversity indices (Shannon index: 2.0 ± 0.4 vs. 1.4 ± 0.6, P = 0.230; Simpson index: 0.8 ± 0.1 vs. 0.6 ± 0.2, P = 0.494) between the SA-AKI group and the non-AKI group. N6, N6, N6-Trimethyl-L-lysine was detected in both blood and urine metabolites, and also showed significant correlations with specific gut microbiota (Campylobacter hominis and Bacteroides caccae, R > 0, P < 0.05). Both blood and urine metabolites were enriched in the lysine degradation pathway. We also identified the citrate cycle (TCA cycle) as a KEGG pathway enriched in sets of differentially expressed ARGs in the gut microbiota, which exhibits an association with lysine degradation.Conclusions: Significant differences in gut microbiota and metabolites were observed between the SA-AKI and non-AKI groups, uncovering potential biomarkers and metabolic changes linked to SA-AKI. The lysine degradation pathway may serve as a crucial link connecting gut microbiota and metabolites.

Background: The COVID-19 pandemic have impacts on the prevalence of other pathogens and people’s social lifestyle. This study aimed to compare the pathogen, allergen and micronutrient characteristics of pediatric inpatients with pneumonia prior to and during the COVID-19 pandemic in a large tertiary hospital in Shanghai, China. Methods: Patients with pneumonia admitted to the Department of Pediatric Pulmonology of Xinhua Hospital between March-August 2019 and March-August 2020 were recruited. And clinical characteristics of the patients in 2019 were compared with those in 2020. Results: Hospitalizations for pneumonia decreased by 74% after the COVID-19 pandemic. For pathogens, virus, mycoplasma pneumoniae (MP) and mixed infection rates were all much lower in 2020 than those in 2019 (P < 0.01). Regarding allergens, compared with 2019, the positive rates of house dust mite, shrimp and crab were significantly higher in 2020 (P < 0.01). And for micronutrients, the levels of vitamin B2, B6, C and 25-hydroxyvitamin D (25(OH)D) in 2020 were observed to be significantly lower than those in 2019 (P < 0.05). For all the study participants, longer hospital stay (OR = 1.521, P = 0.000), milk allergy (OR = 6.552, P = 0.033) and calcium (Ca) insufficiency (OR = 12.048, P = 0.019) were identified as high-risk factors for severe pneumonia by multivariate analysis. Conclusions: The number of children hospitalized with pneumonia and incidence of common pathogen infections were both reduced, and that allergy and micronutrient status in children were also changed after the outbreak of the COVID-19 pandemic.

Background Perfluorooctanoic acid (PFOA) is widely used in daily life, however, research has shown its immune suppression function. Our aim is to investigate the relationship between prenatal exposure to PFOA and allergic diseases in children. Methods A prospective birth cohort study involving 648 pregnant women was conducted. Prenatal information was collected by an interview with the women and from medical records. Fetal umbilical cord blood was collected, and concentration of PFOA and genotype of IL-13 rs20541 were detected. Children were followed at 6, 12 and 24 months and information on the development of allergic diseases was recorded. Multivariate logistic regression analysis was used to examine the association between PFOA and allergic diseases. Stratified analysis was performed based on gender and genotype of IL-13 rs20541. Results In multivariate adjusted models, the highest PFOA quartile is associated with odds of atopic dermatitis (AD) (OR 1.66, 95% CI 1.09–2.55), wheezing (OR 4.06, 95% CI 1.30-12.68), and allergic diseases (OR 1.71, 95% CI 1.15–2.54). Female patients with the highest PFOA quartile have a higher odd of AD (OR 2.25, 95% CI 1.20–4.23) and allergic diseases (OR 1.93, 95% CI 1.07–3.46). Patients with GG genotype of IL-13 rs20541 and the highest PFOA quartile also have a higher odd of AD (OR 2.82, 95% CI 1.41–5.67), wheezing (OR 15.16, 95% CI 1.38-166.59), and allergic diseases (OR 2.42, 95% CI 1.27–4.61). Conclusions Prenatal exposure to PFOA increases the risk of developing allergic diseases in children, especially for the female patients and those with the genotype of IL-13 rs20541 GG.

Background: Asthma is one of the most common chronic diseases affecting children’s health, and recurrent wheezing in infants is closely related to childhood asthma. However, up to now, there is a lack of unified diagnostic criteria and interventions for recurrent wheezing in infants. By analyzing and discussing the risk factors of recurrent wheezing in infants and related intervention measures, we aim to take individualized treatment for different children and reduce the occurrence of recurrent wheezing in infants. Methods: From January 2017 to December 2020, children under 3 years old who were admitted to the Department of Pediatric Respiratory of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine with the chief complaint of wheezing for the first time and were clinically diagnosed with bronchiolitis, asthmatic bronchopneumonia and asthmatic bronchitis were retrospectively analyzed through telephone questionnaires. These children were divided into two groups based on whether the wheezing occurred again after discharge. The demographic characteristics, clinical treatment, imaging characteristics, and related interventions and outcomes after discharge were analyzed in both groups. Results: Among the 523 children under 3 years old who were hospitalized due to wheezing, 264 (50.5%) did not have wheezing after discharge, and 259 (49.5%) still had wheezing after discharge. Both chi-squared test and multivariate analysis showed that male, history of eczema, history of rhinitis, history of wheezing before hospitalization, family smoke exposure, mycoplasma infection and inhalation allergen sensitization were risk factors for recurrent wheezing in infants and young children (PConclusions: (I) Male, with a history of eczema, rhinitis, wheezing before hospitalization, family environment smoke exposure, mycoplasma infection and a history of inhalation allergy are high risk factors for recurrent wheezing in the recurrent wheezing group, and are more likely to have recurrent wheezing after discharge, with shorter days of wheezing control; (II) there was a significant interaction between mycoplasma infection and a history of inhalation allergy in infants with the risk of recurrent wheezing; (III) long-term intervention for children with wheezing for 4 weeks or more after discharge can reduce the probability of recurrent wheezing; (IV) for children of male, with a history of eczema or rhinitis, the most effective intervention to reduce the probability of recurrent wheezing is long-term inhaled corticosteroids (ICS) treatment after discharge.

Music therapy (MT) is a common modality that performs a complementary and integrative role along with standard treatments for many pediatric diseases. This article briefly reviewed the effects of MT on children aged 5– 11 years old and adolescents with asthma from previous studies, specified its functional target towards asthma symptoms, and sorted out the design and investigation of selected research. Medline/PubMed, Embase, SportDis-cus, Cochrane Library, Teacher Reference Centre, Web of Science, Academic Search Complete, PsycARTICLES, and Scopus were queried for experimental and observational studies published between 1990 and 2021. Then, researchers showed that MT lessened patients’ asthma symptoms, improved medication compliance, pulmonary function, and quality of life, and helped children and their parents manage anxiety and depression. This article may serve as a reference for clinical research for pediatric asthma therapies and lay the foundation for future research on MT and its clinical practice.

Background: There is no diagnostic criteria for asthma in children under 6 years of age up to now. Objective: To construct an asthma diagnostic scale for children (< 6 years old) to improve the diagnosis of asthma in China. Methods: Electronic medical record database of a hospital was used to develop the scale. Item pool was established through literature survey and expert opinion, the screening and optimization of items were conducted by using Delphi method, t-test, reactivity analysis, Pearson correlation coefficient, factor analysis, reliability and validity test. The predictive probability of asthma was calculated using the logistic regression, and the receiver operating characteristic (ROC) curve evaluated the diagnostic efficiency of the scale. Another childhood asthma database validated the scale. Results: The asthma diagnostic scale for children (< 6 years old) included five dimensions: dimension 1 (shortness of breath, three concave sign, cyanosis, moist rale, heart rhythm, heart sound and dyspnea), dimension 2 (respiratory sound, cough, sputum), dimension 3 (frequency of wheezing, allergic rhinitis, history of allergy in one or both parents), dimension 4 (gender, wheezing sound, atopic dermatitis), and dimension 5 (reversible airflow, positive in vitroor in vivo allergy test). Cronbach’s α coefficients for the five dimensions were 0.846, 0.459, 0.019, 0.202, and 0.024. The area under the ROC curve (AUC), sensitivity, and specificity were 0.737, 59.1%, and 81.2%. AUC, sensitivity, and specificity of the validation data were 0.614, 76.2%, and 46.7%. Conclusion:The asthma diagnostic scale for children (< 6 years old) had certain reliability, validity, and diagnostic efficiency.

Sepsis most often involves the kidney and is one of the most common causes of acute kidney injury. The prevalence of septic acute kidney injury has increased significantly in recent years. The gut microbiota plays an important role in sepsis. It interacts with the kidney in a complex and multifactorial process, which is not fully understood. Sepsis may lead to gut microbiota alteration, orchestrate gut mucosal injury, and cause gut barrier failure, which further alters the host immunological and metabolic homeostasis. The pattern of gut microbiota alteration also varies with sepsis progression. Changes in intestinal microecology have double-edged effects on renal function, which also affects intestinal homeostasis. This review aimed to clarify the interaction between gut microbiota and renal function during the onset and progression of sepsis. The mechanism of gut–kidney crosstalk may provide potential insights for the development of novel therapeutic strategies for sepsis.

Background A small percentage of asthma patients experience severe and refractory asthma that responds poorly to standard therapy. However, this percentage is increasing and better treatment options are therefore needed. Our previous study showed that cultured human airway smooth muscle cells treated with IL-13 R130Q, a naturally occurring IL-13 variant, displayed enhanced functional activities compared to wild-type (WT) IL-13. The present study aims to determine whether IL-13 R130Q could modulate the ASMC phenotype to further contribute to severe asthma. Methods Human bronchial smooth muscle cells (hBSMCs) were treated with increasing concentrations of IL-13R130Q or WT IL-13 for 24 h. Endogenous expressions of IL-5 and IL-4 were characterized with Enzyme-linked immunosorbent assay analysis. Acetylcholine-induced changes in intracellular calcium concentration were analyzed with the fluorescent probe Fluo-3/AM with flow-cytometric analysis. Cell proliferation was quantified using the CCK-8 kit and cell migration using the Boyden chamber assay. Results IL-13 R130Q induced significantly higher levels of proliferation, migration, and contraction, as well as secretion of IL-4 and IL-5 in hBSMCs compared to WT IL-13. Conclusions Taken all together, our data indicate that IL-13R130Q may contribute to severe asthma through phenotypic modulation of hBSMCs.

Background: IL13, IL4, IL4RA, FCER1BandADRB2are susceptible genes of asthma and atopy. Our previous study has found gene–gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene–gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population.Methods: 989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene–gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods.Results: A four-way gene–gene interaction model (IL13rs20541,IL13rs1800925,IL4rs2243250 andADRB2rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805,P = 9.03 × 10^–4). Among the four SNPs, onlyIL13rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36,P = 3.57 × 10^–3), while the other three had small but synergistic effects. Carriers ofIL13rs20541 TT,IL13rs1800925 CT/TT,IL4rs2243250 TT andADRB2rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14,P = 2.69 × 10^–2). Gene-environment interaction on elevated CBIgE was found betweenIL4rs2243250 and maternal atopy (OR = 1.41,P = 2.65 × 10^–2).Conclusions: Gene–gene interaction betweenIL13rs20541,IL13rs1800925,IL4rs2243250 andADRB2rs1042713, and gene-environment interaction betweenIL4rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.