Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection. METHODS: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted in China, we enrolled participants 1 to 24 months of age who were hospitalized with RSV infection. Participants were randomly assigned, in a 2:1 ratio, to receive ziresovir (at a dose of 10 to 40 mg, according to body weight) or placebo, administered twice daily, for 5 days. The primary end point was the change from baseline to day 3 (defined as 48 hours after the first administration) in the Wang bronchiolitis clinical score (total scores range from 0 to 12, with higher scores indicating greater severity of signs and symptoms). The intention-to-treat population included all the participants with RSV-confirmed infection who received at least one dose of ziresovir or placebo; the safety population included all the participants who received at least one dose of ziresovir or placebo. RESULTS: The intention-to-treat population included 244 participants, and the safety population included 302. The reduction from baseline in the Wang bronchiolitis clinical score at day 3 was significantly greater with ziresovir than with placebo (-3.4 points [95% confidence interval {CI}, -3.7 to -3.1] vs. -2.7 points [95% CI, -3.1 to -2.2]; difference, -0.8 points [95% CI, -1.3 to -0.3]; P = 0.002). The reduction in the RSV viral load at day 5 was greater in the ziresovir group than in the placebo group (-2.5 vs. -1.9 log10 copies per milliliter; difference, -0.6 log10 copies per milliliter [95% CI, -1.1 to -0.2]). Improvements were observed in prespecified subgroups, including in participants with a baseline bronchiolitis score of at least 8 and in those 6 months of age or younger. The incidence of adverse events related to the drug or placebo was 16% with ziresovir and 13% with placebo. The most common adverse events that were assessed by the investigator as being related to the drug or placebo were diarrhea (in 4% and 2% of the participants, respectively), an elevated liver-enzyme level (in 3% and 3%, respectively), and rash (in 2% and 1%). Resistance-associated mutations were identified in 15 participants (9%) in the ziresovir group. CONCLUSIONS: Ziresovir treatment reduced signs and symptoms of bronchiolitis in infants and young children hospitalized with RSV infection. No safety concerns were identified. (Funded by Shanghai Ark Biopharmaceutical; AIRFLO ClinicalTrials.gov number, NCT04231968.).

Human lung organoid: Models for respiratory biology and diseases.

The human respiratory system, consisting of the airway and alveoli, is one of the most complex organs directly interfaced with the external environment. The diverse epithelial cells lining the surface are usually the first cell barrier that comes into contact with pathogens that could lead to deadly pulmonary disease. There is an urgent need to understand the mechanisms of self-renewal and protection of these epithelial cells against harmful pathogens, such as SARS-CoV-2. Traditional models, including cell lines and mouse models, have extremely limited native phenotypic features. Therefore, in recent years, to mimic the complexity of the lung, airway and alveoli organoid technology has been developed and widely applied. TGF-ß/BMP/SMAD, FGF and Wnt/ß-catenin signaling have been proven to play a key role in lung organoid expansion and differentiation. Thus, we summarize the current novel lung organoid culture strategies and discuss their application for understanding the lung biological features and pathophysiology of pulmonary diseases, especially COVID-19. Lung organoids provide an excellent in vitro model and research platform.

Maternal Exposure to PM2.5 and the Risk of Congenital Heart Defects in 1.4 Million Births: A Nationwide Surveillance-Based Study.

BACKGROUND: Evidence remains limited about the association of maternal exposure to ambient fine particulate matter (airborne particles with an aerodynamic diameter ≤2.5 µm [PM2.5]) with fetal congenital heart defects (CHDs) in highly polluted regions, and few studies have focused on preconception exposure. METHODS: Using a nationwide surveillance-based case-control design in China, we examined the association between maternal exposure to PM2.5 during periconception (defined as 3 months before conception until 3 months into pregnancy) and risk of CHD in offspring. The study included 1 434 998 births involving 7335 CHDs from 2014 through 2017 on the basis of the National Population-Based Birth Defects Surveillance System, covering 30 provinces, municipalities, or municipal districts in China. We assigned maternal PM2.5 exposure during the periconception period to each participant using satellite-based PM2.5 concentrations at 1-km spatial resolution. Multilevel logistic regression models were used to calculate the multivariable-adjusted odds ratio and 95% CI for CHDs in offspring associated with maternal PM2.5 exposure, and the exposure-response association was investigated using restricted cubic spline analysis. Subgroup or sensitivity analyses were conducted to identify factors that may modify the association. RESULTS: The average maternal exposure to PM2.5 levels across all participants was 56.51 µg/m3 (range, 10.95 to 182.13 µg/m3). For each 10 µg/m³ increase in maternal PM2.5 exposure, the risk of CHDs in offspring was increased by 2% (odds ratio, 1.02 [95% CI, 1.00 to 1.05]), and septal defect was the most influenced subtype (odds ratio, 1.04 [95% CI, 1.01 to 1.08]). The effect of PM2.5 on CHD risk was more pronounced during the preconception period. Mothers <35 years of age, those living in northern China, and those living in low-income areas were more susceptible to PM2.5 exposure than their counterparts (all P<0.05). PM2.5 exposure showed a linear association with total CHDs or specific CHD types. CONCLUSIONS: High maternal PM2.5 exposure, especially during the preconception period, increases risk of certain types of CHD in offspring. These findings are useful for CHD prevention and highlight the public health benefits of improving air quality in China and other highly polluted regions.

Analysis of risk factors for acute kidney injury in children with severe wasp stings.

BACKGROUND: Acute kidney injury (AKI) is common in children with sepsis, chronic kidney disease, poisoning or other conditions. Wasp stings are recognized as an important etiology. Several retrospective studies have investigated AKI after wasp stings in adults, but research on children remains limited. METHODS: The study included 48 children with multiple organ dysfunction syndrome after wasp stings. Demographic data, clinical manifestations, laboratory findings, management and clinical outcomes were collected, and analyzed to identify early indicators or risk factors for AKI. RESULTS: 20 children (41.7%) developed AKI, and 28 (58.3%) did not. Serum creatine levels elevated mostly within 24 h from stings in children with AKI (16/20, 80%). Compared with non-AKI group, AKI group exhibited more cases with cola-colored urine, jaundice, and had higher sting numbers/body surface area (BSA) and higher revised sequential organ failure assessment scores (rSOFA) as well as higher levels of C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), lactate dehydrogenase (LDH), troponin (cTnI), creatine kinase (CK), and longer prothrombin time (PT). Both univariable and multivariable logistic regression analysis identified cola-colored urine as a potential early risk factor for AKI. CONCLUSIONS: The AKI group exhibited higher sting numbers/BSA, higher levels of CRP, ALT, AST, TBIL, LDH, cTnI, and CK, as well as longer PT (p < 0.05). Our findings also suggest that cola-colored urine may serve as an early indicator or potential risk factor for AKI after wasp stings in children, which is very easy to identify for first aiders or pediatricians.

Novel compound heterozygous variants in EMC1: Overlapping phenotypes of left ventricular noncompaction and long QT syndrome warranting in-depth exploration.

A couple was referred for prenatal counseling at the gestational age of 35 weeks of a male fetus (II-2) with sinus bradycardia and suspected first degree atrioventricular block with left ventricular noncompaction (LVNC). A previous pregnancy for the couple of a female fetus (II-1) was diagnosed prenatally as sinus bradycardia at the gestational age of 30 weeks. Both fetuses were confirmed to have long QT syndrome (LQTS) with LVNC after birth, and died of heart failure during infancy. The genetic cause of the combined cardiovascular disorders was investigated by trio whole-exome sequencing and Sanger sequencing on DNA extracted from parental blood samples and umbilical cord serum of the proband. Compound heterozygous variants were identified in the endoplasmic reticulum membrane protein complex subunit 1 gene (EMC1, NM_015047.3), including paternally inherited c.245C>T (p. Thr82Met) and maternally inherited c.1459delC (p. Arg487Alafs*49). Pathogenic variants in EMC1 have been associated with a recessive neurodevelopmental disorder, whereas Emc10 knockout mice exhibit cardiovascular issues. The present study shows that EMC1 variation potentially causes the overlapping phenotypes of LVNC and LQTS and may expand the spectrum of diseases caused by EMC1 variation.

Clinical features and risk factors for recurrence of idiopathic pulmonary hemosiderosis in children.

BACKGROUND: This study aims to review the clinical characteristics, therapeutic response and outcome of idiopathic pulmonary hemosiderosis (IPH), and discover the risk factors for recurrence in children with IPH, which will be helpful for the early diagnosis and reasonable treatment of this disease. METHODS: Children with a diagnosis of IPH were enrolled in the study. Clinical data of the children were collected and analysed. RESULTS: A total of 32 patients with regular follow-up after diagnosis were included in this study. Anaemia, cough and haemoptysis constituted the most common initial symptoms of the disease, and the incidences were 90.6%, 75% and 56.2%, respectively. The mean gap between the onset of symptoms and diagnosis was 5 (0.25-36) months. Most of the children experienced remission (complete and partial remission) over the course of 6 months of treatment, but 19 of the children experienced relapse. The causes of disease recurrence included respiratory tract infection (37.5%), corticosteroid (CS) reduction (18.8%), and irregular medication (6.3%). Interestingly, we found that children with history of allergy (HR 4.255, 1.107-16.356) tended to experience disease recurrence (p = 0.01). CONCLUSIONS: Cough and anaemia are the most common symptoms in children with IPH. The recurrence rate of this disease is high, and respiratory tract infection is the most common cause of its recurrence. High-dose CS impluse therapy cannot reduce the recurrence rate of the disease. Allergic history was an import factor associated with disease recurrence. TRIAL REGISTRATION: This study is a retrospective and observational study, which does not involve human specimens or clinical intervention. Therefore, clinical trial registration is not required, and there is no clinical trial number. However, the study was approved by the Institutional Review Board/Ethics Committee affiliated with West China Second University Hospital, Sichuan University (Ethics review number 2022074).

Descriptive epidemiology of gastroschisis in China from 2007 to 2020: a nationwide surveillance-based study.

BACKGROUND: Gastroschisis is a common abdominal wall defect that increases infant mortality risk and health care costs. However, recent epidemiological data on gastroschisis in China is limited. METHODS: Using 2007-2020 data from the Chinese Birth Defects Monitoring Network (CBDMN), we analyzed gastroschisis prevalence rates stratified by birth year, maternal age group, residence area, geographical region, and infant sex. We also examined the temporal variations in prevalence, pregnancy outcomes of affected infants, prenatal diagnoses, and co-occurring anomalies. RESULTS: From 2007 to 2020, a total of 6,813 cases of gastroschisis were identified among 25,909,000 births, comprising 4,675 isolated and 2,138 non-isolated cases. Prevalence rates per 10,000 live and still births were 2.63, 1.80, and 0.83 for the overall, isolated, and non-isolated gastroschisis, respectively, all showing a decreasing trend over the study period. The prevalence of overall gastroschisis varied significantly by maternal age (< 20 years, 9.88/10,000; 20-24 years, 4.17/10,000; 25-29 year, 2.08/10,000; 30-34 years, 1.88/10,000;≥35 years, 2.24/10,000), maternal residence (urban, 2.45/10,000; rural, 2.85/10,000), geographic region (central, 2.54/10,000; east, 2.57/10,000; west, 2.80/10,000), and infant sex (male, 2.13/10,000; female, 1.79/10,000). Non-isolated gastroschisis cases had a higher early neonatal mortality rate than isolated cases (41.91% vs. 28.10%) and frequently co-occurred with musculoskeletal anomalies. CONCLUSIONS: This study highlights a declining trend in gastroschisis prevalence in Chinese population, a contrast to previous studies, and underscores the need for improved perinatal management due to adverse pregnancy outcomes associated with this condition.

The relationship between self-efficacy, resilience, and job burnout in pediatric residents: a cross-sectional study in Western China.

BACKGROUND: Burnout is prevalent among pediatric residents. Self-efficacy and resilience, as concepts of positive psychology, may be protective factors for burnout. However, no current data demonstrates the mechanism of their interaction. OBJECTIVES: To investigate the pediatric residents' status of self-efficacy, resilience, and job burnout in a university-affiliated hospital in western China. To explore relationships among them, especially the mediating effects of resilience. METHODS: The study was conducted with 190 pediatric residents from an A-Class women's and children's hospital in western China. Data included demographic characteristics, status of pediatric residents, measures of burnout (using the Physicians' Career Burnout Questionnaire), self-efficacy (using the General Self-Efficacy Scale) and resilience (using the Connor-Davidson Resilience Scale). Multiple regression analysis and mediation analysis with bootstrapping were used to identify whether resilience mediates the relationship between self-efficacy and burnout. RESULTS: Female pediatric residents exhibited significantly lower self-efficacy (t = 2.53, p<0.05) and higher levels of job burnout (t=-2.64, p<0.01) compared to male residents. Residents in the standardized training stage experienced higher levels of job burnout compared to those who had completed the training, as indicated by t-values of -3.21, -2.13, and - 2.80 (p<0.05). Significant correlations (p ≤ 0.01) were found among self-efficacy, resilience, and burnout. Additionally, our findings indicated that pediatric residents' self-efficacy can positively predict job burnout and its three dimensions through a major mediating effect of resilience. CONCLUSIONS: The findings regarding the mediating effect of resilience on the influence of self-efficacy on burnout, and their association with gender and residency status, have practical implications for interventions aimed at reducing burnout and improving the well-being of pediatric residents.

Chromatin remodeler Znhit1 controls bone morphogenetic protein signaling in embryonic lung tissue branching.

Branching morphogenesis is a key process essential for lung and other organ development in which cellular and tissue architecture branch out to maximize surface area. While this process is known to be regulated by differential gene expression of ligands and receptors, how chromatin remodeling regulates this process remains unclear. Znhit1 (zinc finger HIT-type containing 1), acting as a chromatin remodeler, has previously been shown to control the deposition of the histone variant H2A.Z. Here, we demonstrate that Znhit1 also plays an important role in regulating lung branching. Using Znhit1 conditional KO mice, we show that Znhit1 deficiency in the embryonic lung epithelium leads to failure of branching morphogenesis and neonatal lethality, which is accompanied by reduced cell proliferation and increased cell apoptosis of the epithelium. The results from the transcriptome and the chromatin immunoprecipitation assay reveal that this is partially regulated by the derepression of Bmp4, encoding bone morphogenetic protein (BMP) 4, which is a direct target of H2A.Z. Furthermore, we show that inhibition of BMP signaling by the protein inhibitor Noggin rescues the lung branching defects of Znhit1 mutants ex vivo. Taken together, our study identifies the critical role of Znhit1/H2A.Z in embryonic lung morphogenesis via the regulation of BMP signaling.

Metagenomic analysis reveals distinct changes in the gut microbiome of obese Chinese children.

BACKGROUND: The prevalence of obese children in China is increasing, which poses a great challenge to public health. Gut microbes play an important role in human gut health, and changes in gut status are closely related to obesity. However, how gut microbes contribute to obesity in children remains unclear. In our study, we performed shotgun metagenomic sequencing of feces from 23 obese children, 8 overweight children and 22 control children in Chengdu, Sichuan, China. RESULTS: We observed a distinct difference in the gut microbiome of obese children and that of controls. Compared with the controls, bacterial pathogen Campylobacter rectus was significantly more abundant in obese children. In addition, functional annotation of microbial genes revealed that there might be gut inflammation in obese children. The guts of overweight children might belong to the transition state between obese and control children due to a gradient in relative abundance of differentially abundant species. Finally, we compared the gut metagenomes of obese Chinese children and obese Mexican children and found that Trichuris trichiura was significantly more abundant in the guts of obese Mexican children. CONCLUSIONS: Our results contribute to understanding the changes in the species and function of intestinal microbes in obese Chinese children.

Identification of nonfunctional PABPC1L causing oocyte maturation abnormalities and early embryonic arrest in female primary infertility.

Oocyte maturation arrest, fertilization failure, and early embryonic arrest are important causes of female infertility, whereas the genetic events that contribute to these processes are largely unknown. Loss-of-function of PABPC1L in mice has been suggested to cause female infertility involved in the absence of mature oocytes or embryos in vivo or in vitro. However, the role of PABPC1L in human female reproduction remains largely elusive. In this study, we identified a homozygous missense mutation (c.536G>A, p.R179Q) and a compound heterozygous mutation (c.793C>T, p.R265W; c.1201C>T, p.Q401*) in PABPC1L in two unrelated infertile females characterized by recurrent oocyte maturation abnormalities and early embryonic arrest. These variants resulted in nonfunctional PABPC1L protein and were associated with impaired chromatin configuration and transcriptional silencing in GV oocytes. Moreover, the binding capacity of mutant PABPC1L to mRNAs related to oocyte maturation and early embryonic development was decreased significantly. Our findings revealed novel PABPC1L mutations causing oocyte maturation abnormalities and early embryonic arrest, confirming the essential role of PABPC1L in human female fertility.

Rediscover the predictive capacity of B-type natriuretic peptide applied to neonatal supraventricular tachycardia.

BACKGROUND: Supraventricular tachycardia (SVT) is one of the most common non-benign arrhythmias in neonates, potentially leading to cardiac decompensation. This study investigated the early risk factors of acute heart failure (AHF) secondary to SVT in neonates, and explored their value in guiding the selection of effective anti-arrhythmic treatment. METHODS: A total of 43 newborns diagnosed with and treated for SVT between January 2017 and December 2022 were analyzed. According to the presence of AHF after restoring sinus rhythm in newborns with SVT, they were divided into SVT with AHF group and SVT without AHF group. Clinical data and anti-arrhythmic therapies were analyzed. Risk factors of AHF secondary to SVT in neonates were determined using logistic regression. The cut-off value for predictors of AHF secondary to SVT and demanding of a second-line anti-arrhythmic treatment was determined through receiver operating characteristic (ROC) analysis. RESULTS: Time to initial control of tachycardia > 24 h, hyperkalemia, anemia, and plasma B-type natriuretic peptide (BNP) were identified as risk factors of AHF secondary to SVT in neonates. BNP exhibited AUC of 0.80 in predicting AHF, and BNP > 2460.5pg/ml (OR 2.28, 95% CI 1.27 ~ 45.39, P = 0.03) was an independent predictor, yielding sensitivity of 70.6% and specificity of 84.6%. Neonates with BNP > 2460.5pg/ml (37.5% versus 7.4%, P = 0.04) had a higher demand for a second line anti-arrhythmic treatment to terminate SVT, with sensitivity and specificity for BNP in predicting at 75.0%, 71.4%, respectively. CONCLUSIONS: BNP could be used to predict an incident of AHF secondary to SVT and a demand of second-line anti-arrhythmic treatment to promptly terminate SVT and prevent decompensation in neonates.

A novel ZIC3 mutation in a Chinese family with heterotaxy and multiple types of congenital heart defect.

AIMS: A couple was referred for prenatal counseling at gestational age 21 weeks for revealed situs inversus with levocardia (HP:0,031,592), atrial situs inversus (HP:0,011,538), congenitally corrected transposition of the great arteries (ccTGA, HP:0,011,540) with ventricular septal defect (HP:0,001,629) and right aortic arch (HP:0,012,020). The couple had multiple prior pregnancies with complex congenital heart defects (CHDs, HP:0,001,627) in male fetuses. Testing was initiated to identify any fetal abnormality. The genetic cause of the observed prenatal defects was investigated. MATERIALS AND METHODS: Whole exome sequencing and Sanger sequencing were performed on DNA extracted from parental blood samples and skeletal muscle tissue of the aborted fetuses. RESULTS: A pathogenic hemizygous missense variant in ZIC3 (NM_003413.4: c.895 T > C) associated with X-linked heterotaxy-1 (HTX1) and multiple types of congenital heart defect-1 (CHTD1) (OMIM #306955) was identified, which was inherited from the mother. CONCLUSION: ZIC3 encodes a highly conserved zinc-finger protein that is highly correlated with CHDs. The present study of a Han Chinese family with CHDs expands the mutation spectrum of ZIC3 and provides further evidence that ZIC3 plays important roles in CHDs.

A novel PIEZO2 mutation in a fetus from a Chinese family with Gordon syndrome.

We describe a fetus from a Chinese family whose parents were both healthy but showed multiple malformations, including clubfoot, camptodactyly, micrognathia, and cleft palate. Genomic DNA was extracted from the peripheral blood of the proband's parents and skeletal muscle tissue from the aborted fetus to determine the diagnosis and underlying cause. Whole-exome sequencing revealed that the fetus was heterozygous for a novel variant of uncertain significance in exon 56 (c.8576G>A; p.Trp2859*) of the Piezo-type mechanosensitive ion channel component 2 gene (PIEZO2) (NM_001378183.1). A diagnosis of Gordon syndrome (GS) was made from the presence of this variant and ultrasonic manifestation. Sanger sequencing of the proband's parents resulted in normal chromatograms, suggesting that this was either a de novo variant in the fetus or, less likely, the result of germline mosaicism in the proband's mother or father. This is the first description of GS caused by a PIEZO2 variant in which the fetus was the proband. A prenatal diagnosis of GS can be established by fetal ultrasound examination combined with genetic testing.

A novel NOTCH1 missense variant in two fetuses with a non-syndromic conotruncal heart defect from a single family.

AIMS: We describe two fetuses with conotruncal heart defects (CTDs) (persistent truncus arteriosus and pulmonary atresia/ventricular septal defect, respectively) in a Chinese family whose parents were both healthy. Testing was performed to identify any underlying genetic cause. MATERIALS AND METHODS: Genomic DNA was extracted from the peripheral blood of the proband's parents and the skeletal muscle tissue of the two aborted fetuses for genetic testing. RESULTS: A heterozygous likely pathogenic missense variant, c.1724G〉C (:p.Cys575Ser), in the NOTCH1 gene (NM_017617.5) was detected in the two affected fetuses but not in the parents, and the next generation sequencing test of the proband's father showed a normal result. It is therefore presumed to result from germline mosaicism in the proband's mother or, less likely, is a recurrent de novo variant in the fetuses. CONCLUSION: This is the first description of fetal non-syndromic CTD caused by a variant in NOTCH1. This report not only expands the gene variant spectrum of CTDs, but also emphasizes the importance of NOTCH1 testing when a fetal of CTD is detected.

Epidemiology and prevalence of pulmonary sequestration in Chinese population, 2010-2019.

BACKGROUND: Pulmonary sequestration (PS) is the second common congenital lung malformation and has been known for over 150 years. However, there is a scarcity of epidemiological studies on it. This study aimed to characterize the epidemiology of pulmonary sequestration in Chinese population in the recent decade by using a nationwide database. METHODS: Using data from the Chinese Birth Defects Monitoring Network during 2010-2019, the prevalence rates for PS were calculated by birth year, maternal age, residence area, geographical region, and infant sex. Variations in prevalence and changes over time were further examined. Other variables of interest for analysis included the pregnancy outcomes of affected infants, the prenatal diagnosis, and the co-occurring anomalies of PS cases. RESULTS: During the study period, we identified an average prevalence rate of 0.31, 0.11, and 0.42 per 10,000 live and still births for the isolated, non-isolated, and overall PS, respectively. An upward trend was observed for each category of PS. The prevalence rates varied significantly by maternal age (< 20 years, 0.34/10,000; 20-24 years, 0.33/10,000; 25-29 years, 0.45/10,000; 30-34 years, 0.46/10,000; ≥ 35 years, 0.36/10,000), residence area (urban vs. rural, 0.51/10,000 vs. 0.30/10,000), geographical region (western, 0.33/10,000; eastern, 0.49/10,000; central, 0.43/10,000), and by infant sex (male vs. female, 0.45/10,000 vs. 0.38/10,000). Non-isolated PS cases were more likely born prematurely than isolated cases (15.29% vs. 7.83%). 40.28% and 33.80% of non-isolated cases were accompanied by additional respiratory, and circulatory system malformations, respectively. CONCLUSIONS: The study presents for the first time the prevalence of pulmonary sequestration in Chinese population. The rising prevalence and relatively poor perinatal outcome of affected fetuses or newborns indicate the necessity to improve perinatal management of PS.

Epidemiology of asthma exacerbation in children before and after the COVID-19 pandemic: a retrospective study in Chengdu, China.

PURPOSE: To examine the numbers and characteristics of children affected by asthma exacerbation in Chengdu, China, before and after the COVID-19 pandemic to inform efforts to manage childhood asthma in the post epidemic era. METHODS: Data were retrospectively collected from children admitted for asthma exacerbation to Chengdu Women and Children's Central Hospital between January 2017 and December 2022. Rates of hospitalization, ages of the affected children, comorbidities and infections, and relationships between hospitalization and seasonal or environmental factors were examined before and after the epidemic. RESULTS: Fewer children were hospitalized for asthma exacerbation, yet more hospitalized children had severe exacerbation after the epidemic than before. Rates of hospitalization varied considerably with time of year, and the timing of peak hospitalizations differed before and after the epidemic. Only before the epidemic, rates of hospitalization for asthma exacerbation were positively correlated with humidity. Infants made up a smaller proportion of hospitalized children after the epidemic than before, with preschool children accounting for most hospitalizations after the epidemic. The proportion of children hospitalized for asthma exacerbation who also had pneumonia was significantly smaller after the epidemic than before. Conversely, the proportion of children hospitalized for asthma exacerbation who also had allergic diseases was significantly greater after the epidemic than before. CONCLUSION: The epidemiology of asthma exacerbation in children changed after the epidemic. Future efforts to manage the condition in the paediatric population should focus on severe asthma exacerbation, prevention and management of allergic diseases, and the influence of meteorological and environmental factors.

Maternal serum CFHR4 protein as a potential non-invasive marker of ventricular septal defects in offspring: evidence from a comparative proteomics study.

BACKGROUND: Despite advances in diagnosis of congenital heart defects, there is no non-invasive biomarker clinically available for the early detection of fetal ventricular septal defects (VSD). METHODS: This study was to profile differentially expressed proteins (DEP) in the first trimester maternal plasma samples that were collected in the 12th-14th week of gestation and identify potential biomarkers for VSD. Maternal plasma samples of ten case-control pairs of women (who had given birth to an isolated VSD infant or not) were selected from a birth cohort biospecimen bank for identifying DEPs by using high-performance liquid chromatography-tandem mass spectrometry-based comparative proteomics. RESULTS: There were 35 proteins with significantly different levels between cases and controls, including 9 upregulated and 26 downregulated proteins. With Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction analyses, most of the DEPs were clustered in pathways related to B cell-mediated immune responses, complement activation, and phagocytosis. Three DEPs were validated using enzyme-linked immunosorbent assay in another set of samples consisting of 31 cases and 33 controls. And CFHR4, a key regulator in complement cascades, was found to be significantly upregulated in cases as compared to controls. CONCLUSIONS: Subsequent logistic regression and receiver operating characteristic analysis suggested maternal serum CFHR4 as a promising biomarker of fetal VSD. Further studies are warranted to verify the findings.

Paclitaxel-Coated versus Uncoated Balloon for Femoropopliteal In-Stent Restenosis: A Systematic Review and Meta-Analysis.

Background: Several prospective controlled trials to date have assessed the safety and efficacy of paclitaxel-coated balloon angioplasty (PCBA) versus uncoated balloon angioplasty (UCBA) for femoropopliteal (FP) in-stent restenosis (ISR). Therefore, this meta-analysis of prospective controlled trials aimed to summarize the results of these trials and present reliable conclusions. Methods: We systematically searched the PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and CNKI databases for prospective randomized controlled trials (published between January 1, 2008, and July 31, 2021; no language restrictions) comparing PCBA with UCBA in the management of FP ISR. The main endpoints were recurrent restenosis, primary patency, freedom from target lesion revascularization (TLR), clinical improvement, ankle-brachial index (ABI), and major adverse events (MAEs). We assessed the pooled data using a fixed effects model. Results: Of the 206 identified studies, seven were eligible and included in our analysis (N = 593 participants). Compared with UCBA, PCBA yielded a reduction in recurrent restenosis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.13-0.38), a better primary patency (OR, 3.59; 95% CI, 1.72-7.47), an improved likelihood of freedom from TLR (OR, 2.70; 95% CI, 1.36-5.35), greater clinical improvement (OR, 2.38; 95% CI, 1.50-3.79), and a similar mean difference in ABI (0.02; 95% CI, -0.11-0.14) and OR in MAEs (0.71; 95% CI, 0.24-2.14). Conclusions: PCBA as a treatment strategy can achieve better short-term outcomes of FP ISR management, including potent recurrent restenosis-lowering and symptom-improving capacity without increased MAEs. Therefore, it is a promising therapeutic strategy for patients with FP ISR. Systematic Review Registration: This work was registered in PROSPERO, the international prospective register of systematic reviews (number: CRD42021261574).

Human umbilical cord mesenchymal stem cells combined with pirfenidone upregulates the expression of RGS2 in the pulmonary fibrosis in mice.

OBJECTIVE: The therapeutic effect of umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in combination with pirfenidone (PFD) on pulmonary fibrosis in mice and its possible mechanism were investigated. METHODS: C57BL/6 mice were randomly divided into six groups: control group, model group, P10 group, P30 group, P100 group, and P300 group. Modeled by tracheal intubation with 3 mg/kg bleomycin drip, each dose of PFD was administered daily by gavage from day 7 onwards. The mice were observed continuously for 21 days and survival was recorded. Lung tissues were collected on day 21, and hematoxylin-eosin (HE) and Masson staining were performed to assess morphological changes and collagen deposition in the lungs. Collagen content was measured by the Sircol method, and fibrosis marker levels were detected by PCR and Western blot. Another batch of C57BL/6 mice was then randomly divided into five groups: hUC-MSC control group, model group, P100 group, hUC-MSC treatment group, and hUC-MSCs + P30 group. On day 7, 5 × 105 hUC-MSCs were injected into the tail vein, the mice were administered PFD gavage daily from day 7 onwards, and their survival was recorded. Lung tissues were collected on day 21 to detect pathological changes, the collagen content, and the expression of regulator of G protein signaling 2 (RGS2). Pulmonary myofibroblasts (MFBs) were divided into an MFB group and an MFB + hUC-MSCs group; different doses of PFD were administered to each group, and the levels of RGS2, intracellular Ca2+, and fibrosis markers were recorded for each group. RESULTS: Compared with other PFD group doses, the P100 group had significantly improved mouse survival and lung pathology and significantly reduced collagen and fibrosis marker levels (p < 0.05). The hUC-MSCs + P30 group had significantly improved mouse survival and lung pathology, significantly reduced collagen content and fibrosis marker levels (p < 0.05), and the efficacy was better than that of the P100 and hUC-MSCs groups (p < 0.05). RGS2 expression was significantly higher in the MSCs + P30 group compared with the P100 and hUC-MSCs groups (p < 0.05). PFD increased RGS2 expression in MFBs (p < 0.05) in a dose-dependent manner. Compared with PFD and hUC-MSCs treatment alone, combination of hUC-MSCs and PFD increased RGS2 protein levels, significantly decreased intracellular Ca2+ concentration, and significantly reduced fibrosis markers. CONCLUSION: The findings suggest that hUC-MSCs combined with low-dose PFD have a therapeutic effect better than that of the two treatments used separately. Its effect on attenuating bleomycin-induced pulmonary fibrosis in mice is related to the increase of RGS2.