Background:Although randomized controlled trials (RCTs) have confirmed the mucolytic efficacy of ambroxol hydrochloride solution for inhalation (AHSI) in selected cohorts, their stringent exclusion criteria often omit children with comorbidities and complex presentations encountered in routine practice. Consequently, real-world evidence is needed to evaluate the effectiveness and safety of AHSI in a broader, clinically representative pediatric population with acute lower respiratory tract infections (ALRTIs). This study therefore aimed to assess the real-world effectiveness, safety, and nebulizer compatibility of a 7-day AHSI regimen added to standard care in a large, multicenter cohort of hospitalized pediatric patients with ALRTI. Methods:This real-world, multicenter, open-label, single-arm study enrolled hospitalized patients aged ≥6 months with ALRTI (acute bronchitis, bronchiolitis, or pneumonia) and symptom duration <7 days across 62 centers in China (April 2021-April 2022). Key inclusion criteria included a cough score ≥2 (0-4 scale), tenacious sputum, and difficulty expectorating. Major exclusions comprised severe pneumonia, bronchial asthma, interstitial lung disease, significant hepatic or renal dysfunction [alanine aminotransferase (ALT) >1.5× upper limit of normal (ULN), total bilirubin (TBil) or serum creatinine (Scr) > ULN], other severe comorbidities, known hypersensitivity to ambroxol, or recent trial participation. Participants received weight-based doses of nebulized AHSI twice daily for 7 days as add-on to standard care. Follow-up visits occurred at day 4 and day 7 (end of treatment). Primary endpoints were the cough improvement rate (defined by a reduction in cough score) and the overall clinical response rate (investigator-assessed improvement). Secondary endpoints included changes from baseline in cough, throat rales, and pulmonary auscultation scores. Safety assessments comprised monitoring of adverse events (AEs) (coded with MedDRA), vital signs, and laboratory tests (hematology, biochemistry, urinalysis) at baseline and day 7. Results:A total of 2,599 children were enrolled [full analysis set (FAS)]. At baseline, mean age was 3.60±2.50 years, 57.6% were male, and symptom scores were: cough 2.10±0.30, throat sputum 1.65±0.59, lung auscultation 1.44±0.70. In the FAS, the cough improvement rate was 96.73% [95% confidence interval (CI): 96.05-97.41] and the clinical response rate was 94.73% (95% CI: 93.87-95.59). All symptom scores decreased significantly from baseline to day 7 (P<0.001). Drug-related AEs (DRAEs) occurred in 0.39% of patients, predominantly mild-to-moderate rash, transient liver enzyme elevations, and gastrointestinal events; no serious DRAEs were reported. Outcomes were consistent across pneumonia and bronchitis subgroups and across various nebulizer types. Conclusions:This large real-world study demonstrated that a 7-day course of AHSI, added to standard care, was associated with clinically meaningful improvements in respiratory symptoms and a favorable safety profile in children with ALRTI. The consistent effects across disease subtypes and nebulizer devices underscore the practical utility of AHSI in diverse pediatric settings. While the single-arm design limits causal inference, these findings provide robust real-world evidence supporting AHSI as an effective expectorant option. Prospective confirmation through RCTs will further define its role in first-line therapy.

Targeted next-generation sequencing (tNGS) has emerged as a promising tool for pathogen detection in lower respiratory tract infections (LRTIs). Despite its potential, the diagnostic performance and clinical utility of tNGS in the intensive care unit (ICU) setting have not been rigorously defined. This study was designed to evaluate tNGS against conventional microbiological tests (CMT) in this specific patient population. A total of 404 BALF samples from 239 patients underwent parallel tNGS and CMT testing, with orthogonal validation (Sanger sequencing/qRT-PCR) for discrepant results. Using a composite microbiological standard, tNGS demonstrated superior accuracy (80.41% vs. 55.90%) and sensitivity (86.96% vs. 45.45%) but lower specificity (59.90% vs. 88.61%) compared to CMT (all p < 0.05). For bacterial and viral detection, tNGS showed significantly higher accuracy and sensitivity, whereas fungal detection by tNGS was limited by panel design. In terms of concordance with clinical diagnosis, tNGS achieved higher agreement rates than CMT in patients with shock, invasive ventilation, or recent corticosteroid use (all p < 0.05). Multivariable analysis identified shock as an independent predictor of tNGS–clinical concordance (OR = 3.37, p = 0.004). tNGS demonstrated enhanced sensitivity for bacterial and viral detection compared to CMT, albeit with reduced specificity, and fungal accuracy was panel-dependent. Shock independently predicted tNGS agreement with clinical diagnosis and discordance with CMT. From a diagnostic performance perspective, these findings support the preferential use of tNGS for pathogen identification in patients with shock. In other high-risk groups, integrating tNGS with CMT and clinical assessment remains essential to mitigate overdiagnosis. Trial registration: Chinese Clinical Trial Registry, ChiCTR2200060738. Registered 09 June 2022.

BackgroundThe number of dialysis patients in China is rapidly increasing, with the proportion of older adults aged ≥ 60 years rising, linked to population aging and longer dialysis duration. This study investigated frailty prevalence in Chinese maintenance hemodialysis (MHD) patients, analyzed its status, risk factors and correlation with long-term survival in older dialysis patients to provide evidence for frailty interventions.MethodsA total of 391 patients were assessed for frailty using the Frailty Screening Scale. Demographic, clinical, and biochemical data were collected, with 24-month follow-up for survival. Multivariate regression and Cox regression models were used for analyses.ResultsThe cohort comprised 222 male patients (56.9%), with a mean age of 61 ± 13.9 years and a median dialysis vintage of 4 (2.0, 8.5) years. Patients aged ≥ 60 years accounted for 57.5% of participants. Frailty assessment showed that 85.3% of older patients had varying degrees of frailty, and 52.7% were in the pre-frail status. Increased age and low albumin level were identified as clinical correlates of frailty. During the 24-month follow-up period, a total of 88 deaths occurred. Regression analysis showed that patients under maintenance hemodialysis with frailty syndrome had a 3–5-fold higher mortality risk compared with non-frail individuals, and this association was more prominent in the elderly population aged over 60 years. Compared with patients with frailty syndrome, individuals in the pre-frail stage had markedly reduced mortality (P = 0.009, P = 0.006).ConclusionFrailty is highly prevalent in older hemodialysis patients and closely correlated with increased mortality. Early frailty screening and risk stratification are essential for older dialysis patients and individuals at high risk of adverse clinical events. This study highlights the clinical value of early identification and standardized management of frailty, which can provide evidence for clinical diagnosis and treatment in this vulnerable population.

Background Traditional auscultation, heavily dependent on the subjective judgment of physicians, can lead to variability in diagnoses. This study aimed to explore the application of machine learning algorithms for analyzing breath sounds in children with asthma, particularly those with asthma in remission and those with cough variant asthma (CVA).Methods Our study collected breath sound data from 50 children with asthma (30 with asthma in remission and 20 with CVA). First, we preprocessed and extracted the breath sound data. Second, machine learning techniques were applied to objectively classify and evaluate the breath sounds of pediatric asthma patients. Then logistic regression, random forest, and support vector machine algorithms were employed to train models and predict outcomes.Results In this study, the support vector machine achieved the best performance in distinguishing between breath sounds from children with asthma in remission and those with CVA. It reached an accuracy of 98.32%, a sensitivity of 96.23%, and an area under the receiver operating characteristic curve of 0.99 in predicting pediatric asthma subtypes.Conclusions Our findings highlight the potential of machine learning models to revolutionize the diagnosis and treatment of pediatric asthma, offering a pathway towards more precise and individualized therapeutic strategies.Trial registration ClinicalTrials.gov number: ChiCTR2300077717 (Registration Date: 2023-11-16).

This study investigated trimester-specific associations between maternal exposure to fine particulate matter (PM2.5) chemical constituents, precursor gases, and low birth weight (LBW) risk. Using a retrospective cohort of 4,855 singleton live births in Beijing (2017–2018), the study assessed exposure to 8 PM2.5 components and 4 precursor gases across pregnancy stages via logistic regression and quantile g-computation for mixture effects. The LBW prevalence was 3.7

Cough variant asthma (CVA) is a specific asthma phenotype, and wheezing or abnormal breathing sounds are rarely heard in CVA patients during traditional auscultation. This study aimed to use a standardized electronic stethoscope to assess whether there are differences in breath sounds between healthy children and children with CVA. Thirty-five healthy children (476 segments of the inspiratory phase) and nineteen children with CVA (244 segments of the inspiratory phase) participated. A comparative analysis was conducted on the breath sound parameters, including the area under the curve (AUC), the secant slope, and the power of the sound spectrum (decibel, dB), between healthy children and children with CVA. For further comparative analysis, children with CVA were divided into two subgroups based on allergy grades and pulmonary function (PF) statuses: allergy grade < = 2 groups vs. allergy grade > = 3 group, normal PF group vs. abnormal PF group. Statistical analyses were completed using the SPSS software. This study demonstrated that the AUC, the secant slope, and the dB values in children with CVA were higher than those in healthy children. Children with CVA whose allergy grade > = 3 had a higher secant slope value at 700–1700 Hz and higher dB values at 1100 Hz, 1300 Hz, and 1500 Hz. In the abnormal PF group, the dB values at 1300 Hz and 1700 Hz are lower in children with CVA. This study proved that children with CVA have abnormal sounds that traditional auscultation methods cannot identify. Meanwhile, both allergy grade and PF status can affect breath sounds.

Low birth weight is recognized as a risk factor for adult metabolic and cardiovascular diseases. This study investigates whether term low birth weight (TLBW) neonates, who have been exposed to unfavorable settings, demonstrate compromised lipid metabolism. A widely targeted lipidomic analysis was conducted using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) on 59 plasma samples (28 TLBW and 31 term normal birth weight (TNBW) neonates. We conducted univariate and multivariate analyses to identify differential lipids. Spearman's correlation coefficient assessed the association between lipid content at birth and Z-scores for the subsequent physical growth of enrolled children. A total of 1523 lipids in 36 subcategories across 6 major categories were detected. 269 differential lipids were discerned, with 114 up-regulated and 155 down-regulated. In the TLBW group, we observed higher levels of sphingomyelins (including SM(d18:1/16:1), SM(d18:2/23:1), SM(d18:1/22:0), and SM(d18:2/24:1)), Hex3Cer(d18:1/16:0), as well as phosphatidylcholines (PC(O-14:0_20:4) and PC(O-16:0_20:4)), and cholesterol esters (CE (20:4)). In contrast, phosphatidylethanolamines (PE) such as PE (18:2_22:1), PE (18:1_22:1), and triglyceride (TG(10:0_16:2_18:2)) were lower. The KEGG enrichment analysis revealed a consistent alteration in both sphingolipid metabolism and steroid biosynthesis. Moreover, PC(O-16:0_20:4), Hex3Cer(d18:1/16:0), and CE(20:4) exhibited positive correlations with the Z-score of height-for-age at follow-up, while PE(O-18:1_24:4) and PS(20:2_22:4) showed negative correlations with the Z-score of weight-for-age. Our findings reveal novel lipidomic differences between TLBW and TNBW neonates. The observed lipid variations at birth, including sphingomyelins and glycerophospholipids, could affect subsequent growth. Further studies are needed to validate these findings in diverse populations, address confounding factors, and investigate underlying mechanisms.

Background and aim:Few studies identified the role of the placenta in birth weight. We aimed to explore the connection between placenta weight, morphology, and term low birth weight (TLBW). Methods:This was a case-control study of neonates born at ≥37 weeks' gestation enrolled in a general hospital from January 2018 to November 2022. Cases (<2,500 g) identified via birth certificates or medical records were matched with controls on the basis of date of birth, gestational age, sex, and maternal age. A nomogram predictive model was constructed based on logistic regression, using placenta parameters and perinatal information. Results:A total of 290 neonates (115 with diagnosed TLBW and 175 controls) were determined. There were no significant differences between the two groups concerning gestational age (265.5 ± 5.4 vs 266.3 ± 5.3 days, P = 0.1397), gender, and maternal age at delivery (32.0 ± 3.5 vs 32.1 ± 3.1 years, P = 0.867). The placenta weight (479.0 ± 80.1 vs 597.1 ± 83.1 cm), length (16.3 ± 2.1 vs 18.8 ± 2.0 cm), width (14.3 ± 2.1 vs 16.9 ± 2.0 cm), and thickness (2.3 ± 0.5 vs 2.4 ± 0.4 cm) in the TLBW group were much lower than those in the control group (all P < 0.001). Univariate predictors of TLBW included smaller placental weight, length, width, thickness, volume, and surface area. When put into a multivariate model, placental weight (aOR for per 10 g increase: 0.89; 95% CI: 0.84-0.94) and width (aOR for per 1 cm increase: 0.69; 95% CI: 0.54-0.88) remained to be independent predictors even after controlling for relevant confounders. The odds of TLBW increased when placental weight was below the 50th percentile (aOR: 5.08, 95% CI: 2.59-9.95). Placental width below the 50th percentile was significantly associated with an increased risk of TLBW (aOR: 6.57, 95% CI: 2.73-15.82). Conclusions:Placental weight and width were found to be associated with TLBW. Further studies focusing on placental function, histology, and pathophysiology are needed to better understand the underlying mechanisms influencing fetal growth and TLBW.

BACKGROUND:Autism spectrum disorder (ASD), a disorder with high heritability, is linked to abnormal cerebral blood flow (CBF) in patients. The present study focuses on exploring the genetic mechanisms behind CBF in ASD. METHODS:A total of 34 children with ASD and 31 typically developing (TD) children were examined to find the inter - group differences in CBF. In combination with the Allen Human Brain Atlas (AHBA), an analysis of transcriptome - neuroimaging spatial association was carried out. This was done to identify genes whose expression was related to CBF changes in ASD, and then gene function characteristics were analyzed. RESULTS:In comparison with TD children, children with ASD had elevated CBF values in the frontal pole, temporal pole, and thalamus, while having lower CBF values in the superior parietal and caudal middle frontal regions. There were 2,759 genes whose expression was spatially correlated with the CBF changes. Functions such as "Inorganic ion transmembrane transport", "adrenergic signaling in cardiomyocytes", and "neuronal system" were significantly enriched. Significantly down - weighted genes had significant correlations with gamma - aminobutyric acid in the AHBA - seq and DrONc - seq databases. CONCLUSION:The transcription - neuroimaging associations arising from cerebral perfusion redistribution in ASD are supplemented in an additional way, which helps in enhancing the understanding of the ASD brain.

IntroductionNearly all global populations (99%) are exposed to air quality levels that exceed the guidelines set by the World Health Organization, posing significant health risks. Concurrently, mental health issues among adolescents are prevalent. However, existing research on the impact of air pollution on mental health has predominantly focused on older age groups, with limited attention to adolescents.MethodsThis study explores the relationship between air pollution and adolescent mental health by utilizing data from the China Family Panel Studies and county-level air pollution statistics. To address potential endogeneity issues, this paper employs the two-stage least squares (2SLS) method for estimations.ResultsThe research reveals a negative impact of air pollution on adolescent mental well-being. Specifically, a one-unit increase in Particulate Matter 2.5 corresponds to a 0.319-point increase in the mental health score, based on an 8-item scale designed to rapidly assess depressive symptoms; higher scores indicate more severe depressive tendencies.DiscussionMechanism discussions show that air pollution adversely affects adolescent mental health by negatively influencing height and weight, increasing the risk of chronic diseases, extending computer use time, reducing the likelihood of walking to school, and disrupting sleep quality. Furthermore, the findings indicate that the impact of air pollution is more pronounced among females, urban students, and those below high school level.

Objectives While low birth weight (LBW) is a recognized risk factor for adult metabolic syndrome, the unique lipid metabolic phenotype of late preterm low birth weight (LPTB-LBW) neonates—who experience dual exposures to shortened gestation and intrauterine growth restriction—remains uncharacterized. This study specifically examines whether the convergence of prematurity and growth restriction synergistically disrupts lipid metabolic programming. Methods Using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we compared lipidomic profiles of 88 plasma samples: 45 LPTB-LBW (340/7-366/7 weeks, <2,500 g) and 43 later preterm birth-normal birth weight (LPTB-NBW, 340/7-366/7 weeks, 2,500–4,000 g) controls. Multivariate orthogonal partial least squares-discriminant analysis and univariate modeling identified discriminant lipids. Maternal-neonatal lipid continuity was assessed through Spearman’s correlation analysis. Result A total of 1,173 lipids were identified, categorized into five major lipid classes, with 349 significantly different lipids detected (324 upregulated and 25 downregulated) in the LPTB-LBW group. All glycerolipids were upregulated, accounting for 50% (162/324) of the upregulated lipids. Long-chain polyunsaturated triglycerides (TG) showed extreme elevations, such as TG (18:2_18:3_18:4) and TG (18:2_20:4_20:5). Monoglycerides, including MG (18:2) and MG (18:1), were also significantly elevated. Among glycerophospholipids (GP), 76 species were upregulated, with notable increases in phosphatidylethanolamines such as PE (O-18:0_22:3) and PE (18:2_22:1), while PG (20:4_22:6) was significantly reduced. All differentially expressed ceramides, including Cer (d26:3/33:1(2OH)), Cer (d29:2/30:2(2OH)), and Cer (d28:3/31:1(2OH)), were upregulated, whereas sphingosines were downregulated. Cholesterol esters were decreased, while bile acids, free fatty acids and acylcarnitines were elevated. KEGG pathway enrichment analysis highlighted significant perturbations in cholesterol, glycerolipid, and sphingolipid metabolism. Maternal high-density lipoprotein cholesterol (HDLC) levels during early pregnancy showed exclusive negative correlations with neonatal lipids, particularly triacylglycerol TG (16:0_18:2_18:2) (r = − 0.33, p = 0.002), diacylglycerols, and ceramides, whereas no associations were observed for maternal low density lipoprotein (LDLC), TC, or TG. Conclusions LPTB-LBW neonates exhibit a unique lipidomic phenotype marked by hyperaccumulation of glycerolipids (e.g., long-chain polyunsaturated TGs), elevated ceramides, and altered phospholipid species (increased PE, decreased PG). Maternal HDLC levels negatively correlated with specific neonatal lipids. These findings highlight early-life lipid alterations in LPTB-LBW infants and the need for further investigation into their clinical implications.

Purpose:Sepsis is a life-threatening condition, and early detection remains a challenge. While bile acids have been implicated in various diseases, their role as biomarkers for sepsis is underexplored. This study aims to identify metabolites associated with sepsis and assess the potential of bile acids for early diagnosis and prognosis of pediatric sepsis. Methods:We enrolled 100 participants in the discovery phase and 141 participants in the validation phase. Non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomics analyses were performed to identify differential metabolites between sepsis patients and healthy controls. Targeted quantitative analysis of 12 plasma bile acids (BA) was conducted to assess their concentrations. Machine learning algorithms, including Recursive Feature Elimination (RFE), Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), Support Vector Machine-RFE (SVM-RFE), and Gradient Boosting Decision Tree (GBDT), were employed to identify key BAs for sepsis diagnosis. Results:Untargeted metabolomics revealed bile acid pathway dysregulation, validated by targeted quantification showing elevated primary bile acids-cholic acid (CA), glycocholic acid (GCA), taurocholic acid (TCA), glycochenodeoxycholic acid (GCDCA), taurochenodeoxycholic acid (TCDCA)-and taurine-conjugated secondary bile acid TDCA (p<0.05). Conversely, secondary bile acids deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), ursodeoxycholic acid (UDCA), glycoursodeoxycholic acid (GUDCA), and lithocholic acid (LCA) were significantly reduced (p<0.05). Univariate logistic regression identified TCA, TDCA, GCA, TCDCA, GCDCA, and TDCA/DCA as risk factors for sepsis, while LCA, DCA, UDCA, GUDCA, and DCA/CA were protective factors. Five machine learning models identified four bile acid indicators-UDCA, GUDCA, GCA, DCA-as key predictors for sepsis diagnosis, with a combined model area under the curve (AUC) of 0.880. Additionally, DCA/CA and GCDCA were important predictors for septic shock, with risks increasing by 4.5% (OR = 1.045, 95% CI: 1.009-1.081) and 30% (OR = 0.700, 95% CI: 0.526-0.932), respectively. LCA was a risk factor for respiratory failure in sepsis, with an OR of 2.154 (95% CI: 1.022-4.540). Conclusion:Our results highlight the potential of bile acid profiling as a diagnostic and prognostic biomarker for pediatric sepsis. These findings suggest a path toward early intervention, improving patient outcomes by enabling timely detection and treatment.

AIM:In this study, we aimed to provide a comprehensive analysis of real-world implications for the therapeutic efficacy and safety of baloxavir marboxil, oseltamivir phosphate capsules and oseltamivir phosphate granules in the treatment of 160 Chinese children with influenza A. METHODS:This retrospective study included children aged 10-16 with influenza A treated at a hospital in Beijing between January 2023 and August 2024. Participants were categorised into three groups: oseltamivir capsule group (n = 56), oseltamivir granule group (n = 55) and baloxavir group (n = 49). Clinical characteristics, epidemiology, therapeutic effects (e.g., fever clearance time, total illness duration and curative rate), drug costs and adverse reactions were compared among groups. RESULTS:No significant differences were found in demographics or initial symptoms (p > 0.05). Fever clearance time and total illness duration were significantly shorter in the baloxavir group compared to the oseltamivir capsule group (both p < 0.01) and the oseltamivir granule group (p < 0.01, p < 0.05) mainly in children with high fever. While the total effective rates were similar across groups, baloxavir showed a notably higher curative rate (84%, 41/49) than oseltamivir capsules (45%, 25/56) and granules (49%, 27/55) (p < 0.01). Cost analysis indicated that oseltamivir capsules were the least expensive, with baloxavir being slightly less costly than oseltamivir granules (p < 0.01). CONCLUSIONS:Baloxavir marboxil exhibited superior efficacy in reducing fever and shortening the illness duration. Its single-dose regimen enhances compliance with antiviral therapy, although it remains a relatively more expensive option. In contrast, oseltamivir granules enabled more accurate dosing, while oseltamivir capsules were the most cost-effective treatment.

Although previous studies have explored many risk factors associated with childhood asthma worldwide, limited studies have examined whether these risk factors differ in different regions. Our study aims to investigate whether there are differences in the factors influencing childhood asthma in Northern and Southern China and to explore possible reasons for this. A cross-sectional analysis of 12,771 urban children aged 4-14 in China, we first applied a group Least Absolute Shrinkage and Selection Operator (LASSO) to influencing factors associated with childhood asthma, using cross-validation as the criterion. Then, we used logistic regression to calculate further the results. The Area Under the curve value used to evaluate model performance. In Northern China, risk factors for childhood asthma include boys, previously hospitalized with eczema/dermatitis or asthmatic bronchitis or chronic cough, history of infected with viral, bacterial or mycoplasma, testing positive for allergens, having conjunctivitis or two or more allergy problems, paternal or maternal with asthma or conjunctivitis or eczema/dermatitis, autumn and winter and house decoration less than 1 year before move in; Older than 11 years and the frequency of airing the quilt are protective factor against asthma. In Southern China, risk factors include antibiotic use in neonates, previously hospitalized with asthmatic bronchitis, history of infected with viral, testing positive for allergens, having conjunctivitis, summer or winter, screen time more than 4 h per day and paternal or maternal with rhinitis. Our findings suggested that risk or protective factors contributing to childhood asthma differ significantly between Northern and Southern China.

The prevalence of childhood overweight and obesity in China has been rapidly increasing in recent years. The purposes of this study were to investigate the prevalence of infant overweight in Beijing and to explore the influencing factors using a generalized estimating equation (GEE) model. This is a birth cohort study from January 2022 to December 2022 in Beijing, involving 2,008 newborns from local residents. Four times of follow-up visits were conducted at 2, 5, 8, and 12 months of age for physical measurements and health information collection. Multiple exposures were considered, including demographic characteristics of infants, maternal pregnancy information, feeding pattern and outdoor activities of infants. The GEE model was utilized to identify influencing factors for infant overweight while adjusting for potential confounders. The prevalence of overweight for 2-, 5-, 8-, and 12-month-old infants were 14.4

IntroductionThe pathological mechanism of sepsis-related acute lung injury (ALI) is closely linked to mitochondrial dysfunction and pyroptosis. Although low-dose extracorporeal shock wave (SW) therapy has been widely utilized in tissue and organ injury repair, its role in sepsis-related ALI remains unclear. This study aimed to elucidate the regulatory mechanisms of SW on mitochondrial pyroptosis crosstalk in septic ALI.MethodsThe sepsis-related ALI mouse model was induced by tail vein injection of LPS. In vitro, LPS and ATP induced a pyroptosis model in type II alveolar epithelial (AT2) cells. The levels of inflammatory factors and oxidative stress were detected. The ultrastructure of lung mitochondria was observed by transmission electron microscope. Moreover, the mitochondrial membrane potential, ATP content, and the level of mtDNA were determined in cells and tissues. Western blot was used to detect mitochondrial oxidative stress and dysfunction, as well as the expression of pyroptosis-related proteins mediated by NLRP3 inflammasome.ResultsSW significantly reduced the secretion levels of inflammatory factors TNF-α, IL-1β, IL-6, and IL-8 in serum, alveolar lavage fluid (BALF), and cell supernatant, inhibited oxidative stress markers (ROS, MDA, MPO), and upregulated antioxidant index (SOD, GSH). Pathological evidence indicates that SW can alleviate the pathological changes of lung injury and restore the mitochondrial ultrastructure of AT2 cells. The mechanism study shows that SW can enhance mitochondrial membrane potential and ATP production, inhibit mtDNA migration and p65 nuclear translocation, and down-regulate the expression of mitochondrial coding genes (MT-ND2, MT-ND4) and iNOS. At the same time, SW inhibited the NLRP3/ASC/Caspase-1 signaling axis, thereby disrupting pyroptosis cascades.ConclusionThis study reveals that SW attenuates septic ALI by targeting mitochondrial-pyroptosis crosstalk, offering a novel non-invasive therapeutic strategy for clinical applications.

BACKGROUND:During the COVID-19 pandemic, prolonged nonpharmaceutical interventions (NPIs) reduced the circulation of respiratory pathogens. The effects of NPIs on "immunity debt" in children are unclear, especially after almost 3 years of NPIs in China. METHODS:Between November 2021 and October 2023, a cross-sectional study of 235 children (age 9 months-5 years) was conducted at the China-Japan Friendship Hospital, Beijing. Serum IgG antibodies against 10 respiratory pathogens, including influenza A, influenza B, respiratory syncytial virus (RSV), parainfluenza virus, adenovirus (types 7 and 55), Mycoplasma pneumoniae, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, were measured using a novel antigen-specific detection platform. Antibody levels were compared between the following three periods: during NPIs (2021-2022), after NPIs (January-June 2023), and during the Mycoplasma pneumoniae epidemic (July-October 2023). In parallel, hospital-based nucleic acid surveillance from 2017 to 2023 was analyzed. FINDINGS:IgG levels exhibited pathogen-specific patterns. Antibody titers against M. pneumoniae and influenza A declined significantly during NPIs and rebounded after the restrictions were lifted, coinciding with increased clinical detection of these two pathogens. In contrast, the antibody levels for influenza B, RSV, parainfluenza virus, and adenovirus were stable across all periods. SARS-CoV-2 antibody titers rose after December 2022, reflecting the introduction of this new pathogen. INTERPRETATION:Our results provide the first multi-pathogen serological evidence that prolonged NPIs led to pathogen-specific immunity debt in young children in China. The effects were most pronounced for pathogens with high pre-pandemic circulation or rapid antigenic drift. Sustained serological surveillance and pathogen-targeted vaccination strategies can mitigate epidemic rebounds after periods of reduced exposure.

ObjectivesTo investigate the epidemiological and clinical characteristics of children infected with the Omicron variant of SARS-CoV-2 during the early outbreak in Beijing, with particular attention to symptom profiles, clinical management, and persistent symptoms at 12 weeks post-infection.MethodsThis prospective study enrolled children under 18 years of age with confirmed or suspected Omicron infection in Beijing between December 2022 and January 2023. Data were collected via an online questionnaire targeting both community-managed and outpatient children. A follow-up survey was conducted at 12 weeks post-infection to assess long-term symptoms.ResultsA total of 1,610 children aged 15 days to 18 years were included (median age: 3.00 years; 51.4% boys). Fever (96.4%) was the most common symptom, with a mean peak temperature of 39°C (range: 37.6–41°C). Other frequent symptoms included cough (59.1%), runny nose (43.7%), and fatigue (22.1%). The mean duration of fever was 2.05 ± 1.09 days, and the mean duration of all symptoms was 5.89 ± 4.35 days, with both showing significant differences across age groups (p < 0.001). By one week post-infection, symptoms had resolved in 34.2% of cases. At 12 weeks, 2.9% (43/1,471) of children still reported persistent symptoms. The most common were cough (1.4%), nasal congestion (1.1%), dry throat and exertional dyspnea (each 0.7%), and fatigue (0.6%).ConclusionsOmicron infection affected children across all age groups, with a higher prevalence in younger children. Fever and cough were the predominant acute symptoms, while a small subset reported mild persistent symptoms 12 weeks post-infection.

To characterize local functional connectivity (FC) differences in children with autism spectrum disorder (ASD) compared to typically developed (TD) children, and to analyze the correlation between local FC and the atypical behavior in autistic children. Thirty children with ASD and 25 TD children were recruited. Participants underwent rs-fMRI scans, and regional homogeneity (ReHo) of specific brain regions was measured. Performance was assessed using the Autism Behavior Checklist (ABC) and the Gesell Development Diagnosis Scale (GDDS). Children with ASD demonstrated reduced ReHo in the right occipital lobe lingual, left postcentral, and left precuneus compared with TD children. Within the ASD group, the ABC total score was negatively related to ReHo values in both the left postcentral and left precuneus. The ReHo value in the left postcentral was negatively correlated with ABC scores related to sensory and body/object use, while the ReHo value in the left precuneus was negatively correlated with scores related to social skills and self-help. The mean Developmental Quotient (DQ) of GDDS was positively correlated with the ReHo value in the right occipital lobe lingual. Besides, the ReHo value in this region was positively correlated with the DQ of adaptive behavior. The ReHo value in the left postcentral was positively correlated with the DQ of fine motor skills (p < 0.05 for all). Children with ASD exhibit reduced local FC in specific brain regions, which are associated with specific performances in autism. These findings may provide a novel insight into the pathophysiological mechanisms of ASD.

Immunocompromised patients face higher risks of Severe Acute Respiratory Syndrome Coronavirus 2 infection and co-infections, leading to a possibility of high disease severity and poor outcomes. Conversely, immunosuppression can mitigate the excessive inflammatory response induced by the virus, potentially reducing disease severity. This study aims to investigate the prognostic differences and early inflammatory response characteristics in various types of immunocompromised patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care unit (ICU), summarize their clinical features, and explore potential mechanisms. A retrospective analysis was conducted on critically ill COVID-19 patients admitted to the ICU of 59 medical centers in mainland China during the Omicron outbreak from November 2022 to February 2023. Patients were categorized into two groups based on their immunosuppression status: immunocompromised and immunocompetent. Immunocompromised patients were further subdivided by etiology into cancer patients, solid organ transplant (SOT) patients, and other immunocompromised groups, with immunocompetent patients serving as controls. The mortality rates, respiratory support, complications, and early inflammatory cytokine dynamics upon ICU admission among different populations were analyzed. A total of 2030 critically ill COVID-19 patients admitted to ICU were included, with 242 in the immunocompromised group and 1788 in the immunocompetent group. Cancer patients had a higher median age of 69 years (IQR 59, 77), while SOT patients were generally younger and had less severe illness upon ICU admission, with a median APACHE II score of 12.0 (IQR 8.0, 20.0). Cancer patients had a twofold increased risk of death (OR = 2.02, 95