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.

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.

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.

Prenatal diagnosis of generalized arterial calcification of infancy in the second trimester.

OBJECTIVES: Generalized arterial calcification of infancy (GACI) is a rare autosomal recessive disorder characterized by subintimal fibrous proliferation and deposition of calcium salts in the internal elastic lamina, leading to extensive arterial calcification and stenosis of large and medium-sized arteries. Prenatal diagnosis is usually made in the third trimester by detection of aortic and pulmonary calcification with associated nonimmune hydrops; earlier prenatal diagnosis is rare. This study was performed to examine the prenatal ultrasound and genetic features of fetuses with GACI. METHODS: We retrospectively reviewed the ultrasound findings, their progression in utero, and the clinical features in three fetuses with GACI ascertained using ultrasound in the second trimester. GACI was subsequently confirmed through pathological examination and/or molecular genetic testing. RESULTS: All three fetuses had hyperechogenic valves or annuli as the first detectable manifestation in the second trimester, followed by relatively rapid progression to arterial wall calcification. Three novel mutations of the ENPP1 gene associated with GACI were found in two of the cases (c.26dupG, c.1454A > G, and c.263C > G). CONCLUSIONS: GACI should be suspected when hyperechogenic cardiac valves, annuli, or arterial walls are noted after ruling out other causes of arterial calcification. Genetic testing is important for prenatal and future preimplantation genetic diagnosis.

Can prenatal diagnosis of parachute mitral valve be achieved? A case report of fetal parachute mitral valve.

Parachute mitral valve (PMV) is a common form of congenital mitral stenosis and is difficult to diagnose prenatally. This report describes a fetal case of PMV with coarctation of the aorta that was diagnosed at 25 weeks' gestation by echocardiography and confirmed at autopsy. We describe the ultrasonographic features in this case and present a useful sign for making a prenatal diagnosis of PMV.

[Pulmonary Vascular Remodeling Characteristics of Pulmonary Arterial Hypertension Mouse Model Induced by Left Pneumonectomy and Jugular Vein Injection of Monocrotaline Pyrrole].

Objective: To compare and investigate the differences and characteristics of pulmonary vascular remodeling in three mouse models of pulmonary arterial hypertension (PAH) constructed by left pneumonectomy, jugular vein injection of monocrotaline pyrrole, and left pneumonectomy combined with jugular vein injection of monocrotaline pyrrole, to explore for a PAH animal model that approximates the clinical pathogenesis of PAH, and to create a model that will provide sound basis for thorough investigation into the pathogenesis of severe PAH. Methods: 59 male C57/BL mice (10-12 weeks, 24-30 g) were randomized into four groups, a control group ( n=9), a group that had left pneumonectomy (PE, n=15), a group that had jugular vein injection of monocrotaline pyrrole (MCTP, n=15), and the last group that had left pneumonectomy combined with jugular injection of monocrotaline pyrrole (P+M, n=20). To evaluate the effect of modeling and the characteristics of pulmonary vascular remodeling, hemodynamic and morphological parameters, including right ventricular systolic pressure (RVSP), right ventricle/(left ventricle plus septum) (RV/LV+S), percent of wall thickness in the pulmonary artery (WT%), muscularization of non-muscular arteries, neointima formation, and vascular obstruction score (VOS), were measured in each group. Results: 1) Compared with those of the control group, the RVSP, RV/LV+S, WT%, and the degree of small pulmonary arteries muscularization in the P+M group were significantly increased ( P<0.01). The MCTP group had just slightly higher findings for these indicators ( P<0.05), while no significant change in these indicators was observed in the PE group ( P>0.05). 2) Neointima formation in the acinus pulmonary arteries, which caused obvious stenosis of the lumen, was observed in the P+M group, the VOS being 1.25±0.80 points ( P<0.001). In contrast, neointima formation was not observed in the MCTP group or the PE groups, the VOS being 0 point ( P>0.05). Conclusion: Left pneumonectomy combined with jugular intravenous injection of MCTP could induce severe PAH formation in mouse. The model provides a good simulation of neointima formation, the characteristic pathological change of clinical severe PAH.

Effects of physical therapy on lung function in children with asthma: a systematic review and meta-analysis.

BACKGROUND: Asthma is a common chronic respiratory disease in children. In addition to medications, physical therapy is considered as a treatment strategy for asthma. We conducted this study to investigate the effects of physical therapy on lung function in children with asthma. METHODS: Three databases were searched. We conducted the meta-analysis for the forced expiratory volume in the first second in percent predicted values [FEV1(%pred)], the forced vital capacity in percent predicted values [FVC(%pred)], and the peak expiratory flow in percent predicted values [PEF(%pred)] by using a random effect model. RESULTS: Of the 6474 identified studies, 18 studies (16 in physical training, 2 in breathing exercise or inspiratory muscle training) were included in the systematic review and 11 studies (all in physical training) were included in the meta-analysis. The meta-analysis showed a significantly improved FVC(%pred) in the experimental group. CONCLUSIONS: Physical training improved FVC(%pred) significantly in children with asthma. Further study is needed, especially on the effects of breathing exercise and inspiratory muscle training in children with asthma. IMPACT: Our study reviewed the physical therapies for children with asthma and clarified whether and how these therapies affect them. Our study found that physical training improved the forced vital capacity in percent predicted values [FVC(%pred)] significantly in asthmatic children. Our study provided evidence that physical training could improve lung function in children with asthma, which is not identical to the Global Initiative for Asthma (GINA) guidelines.

Association between maternal exposure to gaseous pollutants and atrial septal defect in China: A nationwide population-based study.

BACKGROUND: The association between maternal exposure to gaseous air pollutants and congenital heart defects (CHD) remains unclear. The concentration-response relationship and the time windows of susceptibility to gaseous pollutants may vary by pollutant species and CHD subtypes. OBJECTIVE: We aimed to examine the relationship between maternal exposures to four species of gaseous pollutants (NO2, O3, SO2, and CO) and atrial septal defect (ASD), which is a common subtype of CHD, and to determine the critical time windows of susceptibility for each gaseous pollutant. METHODS: Among 1,253,633 infants born between October 1, 2013 and December 31, 2016 in China, 1937 newborns were diagnosed with isolated ASD, a prevalence of 1.55‰. Maternal exposures to the gaseous pollutants were estimated by matching the geocoded maternal addresses with the gridded ambient concentrations. The adjusted odds ratios (aOR) between exposures and ASD were quantified by using mixed-effects logistic regression models. RESULTS: We found significantly positive associations between ASD and maternal exposures to NO2, O3, SO2, and CO during entire pregnancy, first-, second-, and third-trimester. However, no statistically significant association was found between maternal exposure to PM2.5, PM2.5-10 and ASD risk (P > 0.05). In the fully adjusted model with respect to average exposure over entire pregnancy, the adjusted odds ratios (aOR) for each 10 µg/m3 increment of NO2, O3, SO2 were 1.33 (95% CI: 1.22-1.45), 1.13 (95% CI: 1.10-1.16), 1.28 (95% CI: 1.20-1.35), respectively; the aOR for each 100 µg/m3 increment of CO was 1.10 (95% CI: 1.06-1.15). The observed concentration-response relationships varied by exposure periods and pollutants, with the strongest association for NO2 during the 1st-8th embryology weeks, for O3 during the third trimester, for SO2 during the second trimester, and for CO without obvious variation. CONCLUSIONS: The findings suggest an increased risk of ASD in association with maternal exposures to four common gaseous pollutants. From the perspective of birth defects prevention and ASD risk mitigation, it is critical to reduce maternal exposure to gaseous pollutants especially during the most susceptible time windows.