Glymphatic System Impairment Contributes to the Formation of Brain Edema After Ischemic Stroke.

BACKGROUND: Blood-brain barrier damage has traditionally been considered to determine the occurrence and development of poststroke brain edema, a devastating and life-threatening complication. However, no treatment strategy targeting blood-brain barrier damage has been proven clinically effective in ameliorating brain edema. METHODS: In mice with stroke models induced by transient middle cerebral artery occlusion (MCAO), the changes in glymphatic system (GS) function impairment were detected by ex vivo fluorescence imaging, 2-photon in vivo imaging, and magnetic resonance imaging within 1 week after MCAO, and the effects of GS impairment and recovery on the formation and resolution of brain edema were evaluated. In addition, in patients with ischemic stroke within 1 week after onset, changes in GS function and brain edema were also observed by magnetic resonance imaging. RESULTS: We found that the extravasation of protein-rich fluids into the brain was not temporally correlated with edema formation after MCAO in mice, as brain edema reabsorption preceded blood-brain barrier closure. Strikingly, the time course of edema progression matched well with the GS dysfunction after MCAO. Pharmacological enhancement of the GS function significantly alleviated brain edema developed on day 2 after MCAO, accompanied by less deposition of Aß (amyloid-ß) and better cognitive function. Conversely, functional suppression of the GS delayed the absorption of brain edema on day 7 after MCAO. Moreover, patients with ischemic stroke revealed a consistent trend of GS dysfunction after reperfusion as MCAO mice, which was correlated with the severity of brain edema and functional outcomes. CONCLUSIONS: GS is a key contributor to the formation of brain edema after ischemic stroke, and targeting the GS may be a promising strategy for treating brain edema in ischemic stroke. REGISTRATION: URL: https://www.chictr.org.cn/showproj.html?proj=162857; Unique identifier: NFEC-2019-189.

Maternal Exposure to Extreme Cold Events and Risk of Congenital Heart Defects: A Large Multicenter Study in China.

Over the past decade, extreme temperature events have become more frequent and longer in duration. Previous studies on the association between extreme cold events (ECEs) and congenital heart defects (CHDs) are few and inconsistent. We conducted a national multicenter study in 1313 hospitals in 26 provinces in China and collected a total of 14 808 high CHD-risk participants from 2013 to 2021. We evaluated the ECEs experienced by each pregnant women during the embryonic period (3-8 weeks). The results indicated that ECEs experienced by pregnant women during the embryonic period were associated with the development of fetal CHD and were more strongly associated with some specific fetal CHD subtypes, such as pulmonary stenosis, pulmonary atresia, and tetralogy of Fallot. Of the CHD burden, 2.21% (95% CI: 1.43, 2.99%)-2.40% (95% CI: 1.26, 3.55%) of fetal CHD cases were attributable to ECEs during the embryonic period. Our findings emphasize the need to pay more attention to pregnant women whose embryonic period falls during the cold season to reduce cold spell detriments to newborns.

Maternal exposure to ambient ozone and fetal conotruncal heart defects in China: A multicenter cohort study.

BACKGROUND: The relationships between maternal genetic and environmental exposure and conotruncal heart defects (CTDs) have been extensively investigated. Nevertheless, there is limited knowledge regarding the impact of ozone (O3) on the risk of CTDs. OBJECTIVE: To explore the correlation between maternal exposure to O3 and CTDs in China. METHODS: Pregnant women who underwent fetal echocardiography at Beijing Anzhen Hospital between January 2013 and December 2021 were enrolled. Their sociodemographic characteristics and lifestyle information, along with fetal data, were systematically collected. Fetal echocardiography was used to detect CTDs. Maternal exposure to ambient O3 during the embryonic period, the first trimester, the three months preceding the last menstrual period, and the perinatal period was estimated using residential addresses or hospital addresses associated with prenatal visits. The concentration of O3 was divided by quartiles, with the first quartile serving as a reference. Adjusted logistic regression models were employed to examine the associations between every 10 µg/m3 increase or quartile increase in ambient O3 exposure and CTDs. RESULTS: Among 24,278 subjects, 1069 exhibited fetuses with CTDs. Maternal exposure to ambient O3 during three pregnancy periods was associated with increased CTD risk. The adjusted odds ratio (OR) and 95% confidence interval (CI) were 1.271 (1.189-1.360) per 10 µg/m3 increase in O3 during the perinatal period. For each quartile of O3, the risk increased with increasing exposure concentration, particularly during the perinatal period (OR = 2.206 for quartile 2, 2.367 for quartile 3, and 3.378 for quartile 4, all P<0.05). CONCLUSIONS: Elevated maternal exposure to O3 during pregnancy, particularly in the perinatal period, is linked to an increased risk of fetal CTDs. Further longitudinal analyses are needed to validate these results.

Study on the correlation between retrograde ductus arteriosus flow and right ventricular function evaluated by Z-score of tricuspid annular plane systolic excursion in fetuses with Ebstein anomaly.

PURPOSE: To analyze the influence of RV dysfunction evaluated by Free-angle M-mode (FAM) TAPSE Z-score on retrograde ductus arteriosus flow (RDAF) in fetuses with Ebstein anomaly (EA). METHODS: A retrospective cohort study of 30 EA and 60 normal fetuses were enrolled. The EA group was divided into two groups: with RDAF (EA-RDAF group) and without RDAF (EA-NRDAF group). FAM was used to measure TAPSE of EA and normal fetuses, and Z-scores were calculated. The differences of FAM-TAPSE Z-score, gestational week (GW), maternal age (MA), and mitral valve-tricuspid valve distance (MTD) between three groups were compared. The correlation and binary logistic regression between FAM-TAPSE Z-score, GW, MA, MTD, and RDAF were analyzed. RESULTS: FAM-TAPSE Z-score was significantly lower in EA-RDAF group compared to other groups (p < 0.05). FAM-TAPSE Z-score, GW, and MA were negatively correlated with RDAF (p < 0.05), but no correlation was found between TR, MDT, and RDAF (p > 0.05). Multivariate logistic regression showed that FAM-TAPSE Z-score was an independent influencing factor for RDAF (OR = 0.102, p < 0.05). CONCLUSION: RV dysfunction is an independent factor leading to RDAF in EA fetus, which provides a feasible theoretical basis for further study on improvement of RV function through intrauterine treatment to delay and prevent the RDAF, to avoid death cycle and improve live-birth rate.

Association between placental DNA methylation and fetal congenital heart disease.

Congenital heart disease (CHD) is a worldwide problem with high morbidity and mortality. Early diagnosis of congenital heart disease is still a challenge in clinical work. In recent years, few studies indicated that placental methylation may be predictors of CHD. More studies are needed to confirm the association between placental methylation and CHD. The aim of this study was to investigate the association between prenatal placental DNA methylation and CHD. Placental tissues were obtained from four fetuses during the second trimester with isolated, non-syndromic congenital heart disease, including three cases with double outlet right ventricle (DORV) and one case with tetralogy of Fallot (TOF), and four unaffected fetuses as controls. The Illumina Infinium Human Methylation 850K BeadChip assay was employed to identify differential methylation sites (DMSs) and differential methylation regions (DMRs). Differential methylation was evaluated by comparing the ß-values for individual CpG loci in cases vs. controls. In addition, the function of genes was assessed through KEGG enrichment analysis, Gene Ontology (GO) analysis and KEGG pathway analysis. Compared with the control group, we identified 9625 differential methylation genes on 26,202 DMSs (p < 0.05), of which 6997 were hyper-methylation and 2628 were hypo-methylation. The top 30 terms of GO biological process and KEGG enrichment analysis of DMSs were connected with multiple important pathways of heart development and disease. Ten differentially methylated regions and the genes related to DMRs, such as TLL1, CRABP1, FDFT1, and PCK2, were identified. The deformity caused by the loss of function of these genes is remarkably consistent with the clinical phenotype of our cases. The DNA methylation level of placental tissue is closely associated with fetal congenital heart disease.

Associated factors for prenatally diagnosed fetal congenital heart diseases.

OBJECTIVE: Current studies have suggested that fetal congenital heart diseases (CHDs) are caused by various factors. However, few data in this field is available in China. This study aimed to detect associated factors of prenatally diagnosed fetal CHD in a large sample in China. STUDY DESIGN: Pregnant women who underwent fetal echocardiography were recruited in our hospital between May 2018 and September 2019. The maternal sociodemographic and lifestyle characteristics and some fetal factors were obtained. We used forward stepwise logistic regression analysis to assess risk of fetal CHD associated with various factors. RESULTS: A total of 5024 subjects were enrolled, of whom 875 had CHD fetuses. Among the fetal CHD group (N = 875), critical CHDs account for 27%, of which Tetralogy of Fallot is the most (7.1%), followed by coarctation of aorta (4.0%), double-outlet right ventricle (2.9%). The forward stepwise logistic regression models revealed that history of spontaneous abortion (OR = 1.59, 95% CI 1.33-1.91, P = 0.000), upper respiratory tract infection during early pregnancy (OR = 1.30, 95% CI 1.04-1.62, P = 0.020), mental stress during early pregnancy (OR = 2.37, 95% CI 1.15-4.91, P = 0.020), single umbilical artery (OR = 2.30, 95% CI 1.18-4.51, P = 0.015), and paternal smoking (OR = 1.21, 95% CI 1.02-1.44, P = 0.027) are positively associated with an increased risk of fetal CHD. CONCLUSION: We identified several factors positively associated with fetal CHD. These findings suggest that it is important to strengthen healthcare and prenatal counseling for women with these factors.

Uterine hemangiopericytoma with cardiac involvement and pulmonary metastasis: A case report and literature review.

Uterine hemangiopericytoma is extremely rare. This article describes a case of uterine hemangiopericytoma. The tumor involved the parauterine vein; extended into the inferior vena cava, right cardiac cavity, and pulmonary artery; and metastasized to the lungs. It was irregular in shape and exhibited the string-of-beads sign on echocardiography, and it was tightly attached to the right ventricular surface and pulmonary artery wall. The patient underwent tumor resection without adjuvant treatment. A pelvic nodule was found 3 months postoperatively and was considered a recurrent lesion.

[Analysis of MYRF gene variant in a fetus with Cardiac-urogenital syndrome].

OBJECTIVE: To explore the genetic basis for a fetus with Cardiac-urogenital syndrome (CUGS). METHODS: A fetus with congenital heart disease identified at the Maternal Fetal Medical Center for Fetal Heart Disease, Beijing Anzhen Hospital Affiliated to Capital Medical University in January 2019 was selected as the study subject. Clinical data of the fetus was collected. Copy number variation sequencing (CNV-seq) and trio-whole exome sequencing (trio-WES) were carried out for the fetus and its parents. Candidate variants were verified by Sanger sequencing. RESULTS: Detailed fetal echocardiographic examination had revealed hypoplastic aortic arch. The results of trio-WES revealed that the fetus has harbored a de novo splice variant of the MYRF gene (c.1792-2A>C), for which both parents were of the wild-type. Sanger sequencing confirmed the variant to be de novo. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic. CNV-seq has identified no chromosomal anomalies. And the fetus was diagnosed with Cardiac-urogenital syndrome. CONCLUSION: The de novo splice variant of the MYRF gene probably underlay the abnormal phenotype in the fetus. Above finding has enriched the spectrum of MYRF gene variants.

[Clinical and genetic characteristics of 12 cases of Loeys-Dietz syndrome].

OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION: Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.

An Unguarded Tricuspid Valve Orifice Diagnosed by Autopsy.

Introduction: Fetal unguarded tricuspid valve orifice (UTVO) is characterized by a complete or partial absence of the tricuspid valvular tissue or sub-valvular apparatus and only case reports are available at present. We report a UTVO diagnosed by fetal autopsy. Case report: An 18-week fetus was diagnosed by prenatal ultrasound with tricuspid dysplasia with 'to-and-fro' flow across the right-sided heart. Fetal autopsy showed partial agenesis of tricuspid valve instead of valvular dysplasia. This supported a diagnosis of UTVO. Conclusion: Fetal autopsy can differentiate UTVO form other valve abnormalities. The 'to-and-fro' flow pattern across the right atrioventricular orifice could be used to differentiate UTVO from other valve dysplasias on echocardiography.

PLGA-Au-PFH-NPs-based Ultrasound Imaging in Detecting Fetal Spinal Deformities.

The study focused on the performance of ultrasound imaging in detecting fetal spinal deformities. First, the double emulsification method and the carbodiimide method were used to prepare the target Au-loaded nanorod phase-change nano-level contrast agent-PLGA-Au-PFH-NPs. After being characterized for physical and chemical properties, it was used in ultrasound imaging diagnosis. The results showed that the prepared PLGA-Au-PFH-NPs solution was a milky white suspension, the particle size detected by the laser particle sizer was (376.17±20.74) nm, and the Zeta potential was (-4.82±2.88) mV. Under the light microscope, it showed a spherical shape, uniform size distribution, and a very smooth surface. The encapsulation rate measured by the UV spectrophotometer was (80.63±4.82) %, and there was no significant difference in cell survival rate between different concentrations (P>0.05). Prenatal ultrasound in the observation group accurately diagnosed 10 cases with spinal deformities, and the diagnostic accuracy rate was 50%, including 5 cases of meningocele, 3 cases of invisible spina bifida, 1 case of myelomeningocele, and 1 case of hemivertebrae. In the control group, 7 cases were diagnosed correctly by conventional ultrasound, and the diagnosis accuracy rate was 35%, including 3 cases of meningocele, 3 cases of invisible spina bifida, and 1 case of hemivertebra. The diagnostic accuracy of the observation group was higher than that of the control group, and the difference was statistically significant (P<0.05). In conclusion, the prepared PLGA-Au-PFH-NPs had good physical and chemical properties. Ultrasound imaging based on the PLGA-Au-PFH-NPs had high accuracy in diagnosing fetal spinal deformities. To a certain extent, it provides a basis for clinical diagnosis of fetal spinal abnormality and some new ideas for ultrasound imaging diagnosis.

Diagnosis of fetal total anomalous pulmonary venous connection based on the post-left atrium space ratio using artificial intelligence.

OBJECTIVE: To explore whether the post-left atrium space (PLAS) ratio would be useful for prenatal diagnosis of total anomalous pulmonary venous connection (TAPVC) using echocardiography and artificial intelligence. METHODS: We retrospectively included 642 frames of four-chamber views from 319 fetuses (32 with TAPVC and 287 without TAPVC) in end-systolic and end-diastolic periods with multiple apex directions. The average gestational age was 25.6 ± 2.7 weeks. No other cardiac or extracardiac malformations were observed. The dataset was divided into a training set (n = 540; 48 with TAPVC and 492 without TAPVC) and test set (n = 102; 20 with TAPVC and 82 without TAPVC). The PLAS ratio was defined as the ratio of the epicardium-descending aortic distance to the center of the heart-descending aortic distance. Supervised learning was used in DeepLabv3+, FastFCN, PSPNet, and DenseASPP segmentation models. The area under the curve (AUC) was used on the test set. RESULTS: Expert annotations showed that this ratio was not related to the period or apex direction. It was higher in the TAPVC group than in the control group detected by the expert and the four models. The AUC of expert annotations, DeepLabv3+, FastFCN, PSPNet, and DenseASPP were 0.977, 0.941, 0.925, 0.856, and 0.887, respectively. CONCLUSION: Segmentation models achieve good diagnostic accuracy for TAPVC based on the PLAS ratio.

Retrograde flow in aortic isthmus in normal and fetal heart disease by principal component analysis and computational fluid dynamics.

OBJECTIVES: Reverse flow Retrograde flow (RF) of blood in the aortic isthmus can be observed in different types of fetal heart disease (FHD), including abnormalities in heart structure and function. This study sought to investigate the relationship between RF and blood flow parameters, and develop a computational fluid dynamics (CFD) model to understand the mechanisms underlying this observation. MATERIAL AND METHODS: A total of 281 fetuses (gestational age [GA] 26.6±.3 weeks) with FHD and 2803 normal fetuses (GA: 26.1±.1 weeks) by fetal echocardiography collected from May 2016 to December 2018. Principal component analysis (PCA) was performed to find the relationship and the CFD model reconstructed from 3D/4D spatio-temporal image correlation (STIC) images to simulate hemodynamics. RESULTS: There was a significant difference in the percentages of RF between the study (80/201 (39%)) and control (29/2803 (1%)) groups (p < 0.05). The RF occur when the aorta flow rate (left heart) is reduced to 60% by CFD stimulation. Pearson correlation analysis showed significant correlations between flow rate and wall shear stress(WSS) (r = .883, p = 0.047) variables at the AI. CONCLUSION: Volumetric flow rate of AO or left heart was the main component of the cause of RF. The hemodynamics of the cardiovascular system have highly complex behavior hinge on the turbulent nature of circulating blood flow.

Prenatal diagnosis of isolation of aortic brachiocephalic artery.

BACKGROUND: Isolated aortic brachiocephalic artery (IABA) is a rare congenital aortic arch anomaly. It is difficult to diagnose IABA prenatally and the prevalence in the prenatal population is unknown. PURPOSE: To evaluate the echocardiographic characteristics and associations in fetuses with IABA. MATERIAL AND METHODS: We retrospectively analyzed all cases of prenatal diagnosis of IABA from January 2012 to November 2020 and reviewed the follow-up results. Copy Number Variation Sequencing (CNV-Seq) was performed using the biological specimens of the of the fetuses and family members. RESULTS: Ten cases (10/45652, 0.022%) of IABA were identified in our center. The prevalence of the cases with isolated left subclavian artery (ILSCA) in the right aortic arch (RAA) population was 0.98% (6/613). The ILSCA was the most common isolated arch branch. All the isolated branches were on the opposite side of aortic arch in all the cases. The "ice stick" sign in the coronal section could be seen in most cases of IABA. Of the 10 cases, 8 (8/10, 80%) were associated with tetralogy of Fallot (TOF). Two cases of IABA were combined with 22q11.2 deletion syndrome. CONCLUSION: IABA is a rare aortic anomaly. ILSCA was the most common isolated arch branch and TOF was the most common associated intra-cardiac anomaly. The "ice stick" sign in the coronal section could indicate a diagnosis of the IABA.

Fetal atrial appendage aneurysm: Prenatal diagnosis by echocardiography and prognosis.

BACKGROUND: Congenital atrial appendage aneurysm (AAA) is a rare malformation which can coexist with potentially lethal complications. We aimed to summary echocardiographic characteristics and prognosis of fetal AAA. METHODS: We retrospectively analyzed the echocardiographic data of 17 fetuses with AAA，and their outcomes or pathological reports were also collected. RESULTS: Eight fetuses with left AAA (LAAA) and 9 fetuses with right AAA (RAAA) were identified. Five fetuses were diagnosed with other cardiac defects. Two fetuses with RAAA presented with arrhythmias, including atrial premature beats (n = 1) and bradyarrhythmia (n = 1). LAAA could be detected by four-chamber view (50.0%) and short-axis view (100.0%). RAAA could be detected by four-chamber view (100.0%), and view of right ventricular inflow tract (33.3%). There were three cases with mild pericardial effusion. Three cases with complex cardiac defects were selectively terminated, with confirmation of LAAA by autopsy in one case. Fourteen fetuses were born. After following 2 (range, 1-5) years, the AAA disappeared in one case with LAAA and two cases with RAAA. While, 11 cases were still diagnosed with AAA. Atrial premature beats with RAAA, which appeared in prenatal period, still persisted after birth. CONCLUSION: Congenital AAA is a rare abnormality in utero. The short-axis view and the four-chamber view were the most useful views to detect fetal AAA. Fetal AAA may disappear in childhood. Atrial tachyarrhythmias in utero may exist persistently after birth. Patients with AAA should be followed up closely and appropriate intervention should be taken when complications appeared.

A novel intron mutation in FBN-1 gene identified in a pregnant woman with Marfan syndrome.

Marfan syndrome (MFS) is one of the most common hereditary connective tissue diseases, with great individual heterogeneity. We reported a Chinese pregnancy with Clinical diagnosis of MFS, performed whole-exome sequencing, and screened for the genetic abnormality. We also conducted an in vitro mini-gene splicing assay to demonstrate the predicted harmful effects of an intronic variant of FBN-1. Exome sequencing identified a novel intronic variant (c.6497-13 T>A) in intron 53 of the FBN-1 gene (NM_000138.4). It's predicted to insert 11 bp of intron 53 into the mature mRNA. The mini-gene splicing experiment demonstrated that c.6497-13 T>A could result in 11 bp retention in intron 53 to exon 54 (c.6496_6497ins gtttcttgcag) and the use of an alternative donor causing the frameshift p.Asp2166Glyfs*23. According to the results, the pregnant woman chose to continue the pregnancy and gave birth to a healthy baby. This study expands the genetic mutation spectrum of MFS patients and indicates the importance of intron sequencing.

The Differential Diagnosis of Double Aortic Arch and Right Aortic Arch with Mirror-Image Branches in the Fetus: A Potential Novel Method.

The objective of this study was to explore a new method for the differential diagnosis between fetal double aortic arch (DAA) and right aortic arch with mirror-image branches (RAA-MB). Clinical data and prenatal echocardiographic features of the DAA (n = 22) and RAA-MB (n = 65) confirmed by postnatal or autopsy findings were analyzed retrospectively. The angles between the two aortic arches in the DAA group and between the right aortic arch and the mirror branch were measured. The differences between the two groups and differential diagnosis value of the angles were compared and analyzed based on the receiver operating characteristic curve. The proportion of left-sided ductal arteriosus (100%) was higher in the DAA group than that (32.3%) in the RAA-MB group, (P < 0.05). The proportion of conotruncal anomalies is higher in the RAA-MB group (64.6%) than in the DAA group (18.2%) (P < 0.05). There was a significant difference in the angles between the groups (DAA: 50.3° ± 8.3° vs. RAA-MB: 82.9° ± 13.8°) (P < 0.01). When the cutoff value was 62.8°, the sensitivity and specificity of the differential diagnosis were 95.5% and 96.9%, respectively. Distinguishing the angle measurement between DAA and RAA-MB is helpful in prenatal prognosis. We recommend a cutoff value of 62.8°.

Fetal Ultrasonic Evaluation of Bronchial Morphology in Fetuses with Isomerism.

OBJECTIVE: The aim of the study was to evaluate whether fetal ultrasound could determine bronchial isomerism and distinguish left isomerism from right isomerism. METHODS: We identified 110 healthy fetuses and 28 fetuses with isomerism. The outer angle between the tracheal midline and the inner margin of the bronchus is measured. The bronchial angles and the ratio of left/right bronchial angle were used to differentiate bronchial morphology and confirm the presence of bronchial isomerism in pathological cases. RESULTS: The normal angles of the left and right bronchi were 146.98° (95% CI, 145.15-147.81°) and 167.37° (95% CI, 166.30-168.44°), separately. The cutoff bronchial angle of 156.5° was used to distinguish left bronchus from right bronchus. The bronchial isomerism could be identified in all pathological cases by autopsy and bronchial-atrial concordance occurred in 27 pathological cases (96.4%). In 21 pathological cases, the bilateral bronchial angle was <156.5 versus >156.5 differentiated left from right isomerism, respectively. The ratio of the left/right bronchial angle of >0.935 identified 92.9% (26/28) of all pathological cases, with a sensitivity of 89.7%. CONCLUSIONS: Fetal ultrasound can detect the bronchial morphology and the presence of bronchial isomerism in fetuses with isomerism according to bronchial angles and the ratio of left/right bronchial angle.

NLRP3 inflammasome-mediated microglial pyroptosis is critically involved in the development of post-cardiac arrest brain injury.

BACKGROUND: Brain injury is the leading cause of death and disability in survivors of cardiac arrest, where neuroinflammation is believed to play a pivotal role, but the underlying mechanism remains unclear. Pyroptosis is a pro-inflammatory form of programmed cell death that triggers inflammatory response upon infection or other stimuli. This study aims to understand the role of microglial pyroptosis in post-cardiac arrest brain injury. METHODS: Sprague-Dawley male rats underwent 10-min asphyxial cardiac arrest and cardiopulmonary resuscitation or sham-operation. Flow cytometry analysis, Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), co-immunoprecipitation, and immunofluorescence were used to evaluate activated microglia and CD11b-positive leukocytes after cardiac arrest and assess inflammasome activation and pyroptosis of specific cellular populations. To further explore the underlying mechanism, MCC950 or Ac-YVAD-cmk was administered to block nod-like receptor family protein 3 (NLRP3) or caspase-1, respectively. RESULTS: Our results showed that, in a rat model, successful resuscitation from cardiac arrest resulted in microglial pyroptosis and consequential inflammatory infiltration which was mediated by the activation of NLRP3 inflammasome. Targeting NLRP3 and caspase-1, the executor of pyroptosis, with selective inhibitors MCC950 and Ac-YVAD-cmk treatment significantly prevented microglial pyroptosis, reduced infiltration of leukocytes, improved neurologic outcome, and alleviated neuro-pathological damages after cardiac arrest in modeling rats. CONCLUSIONS: This study demonstrates that microglial pyroptosis mediated by NLRP3 inflammasome is critically involved in the pathogenesis of post-cardiac arrest brain injury and provides a new therapeutic strategy.

Autopsy and postnatal follow-up of prenatally diagnosed ventricular outpouchings.

OBJECTIVES: Prenatal ventricular outpouchings (VOs), which include congenital ventricular aneurysms (CAs) and congenital ventricular diverticula (CD), are very rare. We describe the features and outcomes of prenatal VOs diagnosed over a 4-year period. METHODS: Retrospective cohort study of cases of prenatal diagnoses of CAs and CD at our center between June 2014 and January 2018. The prenatal and postnatal echocardiogram data were reviewed, and telephone follow-up was conducted of liveborn cases. RESULTS: A total of 25 VOs were identified. Two were lost to follow-up, 15 chose termination of pregnancy, and eight resulted in livebirths. Only two cases underwent autopsy: Histopathology showed that the CA wall was substituted by collagen fibers. At follow-up, none of the eight liveborn babies experienced adverse events, and three VOs near the tricuspid annulus almost disappeared, though one was extremely large. CONCLUSIONS: In our center, all liveborn babies with VO had good prognoses. We hypothesize that VOs located near the right ventricular annulus may be caused by prenatally unbalanced pressure, given their decrease in size after birth when the right heart pressure declines.