Targeting iron-metabolism:a potential therapeutic strategy for pulmonary fibrosis.

Iron homeostasisis is integral to normal physiological and biochemical processes of lungs. The maintenance of iron homeostasis involves the process of intake, storage and output, dependening on iron-regulated protein/iron response element system to operate tightly metabolism-related genes, including TFR1, DMT1, Fth, and FPN. Dysregulation of iron can lead to iron overload, which increases the virulence of microbial colonisers and the occurrence of oxidative stress, causing alveolar epithelial cells to undergo necrosis and apoptosis, and form extracellular matrix. Accumulated iron drive iron-dependent ferroptosis to exacerbated pulmonary fibrosis. Notably, the iron chelator deferoxamine and the lipophilic antioxidant ferritin-1 have been shown to attenuate ferroptosis and inhibit lipid peroxidation in pulmonary fibrosis. The paper summarises the regulatory mechanisms of dysregulated iron metabolism and ferroptosis in the development of pulmonary fibrosis. Targeting iron metabolism may be a potential therapeutic strategy for the prevention and treatment of pulmonary fibrosis.

Astragalus polysaccharide protects experimental colitis through an aryl hydrocarbon receptor-dependent autophagy mechanism.

BACKGROUND AND PURPOSE: Disruption of intestinal barriers plays a vital role in the pathogenesis of colitis. The aryl hydrocarbon receptor (AhR) is a recognition sensor that mediates intestinal immune homeostasis and minimizes intestinal inflammation. Astragalus polysaccharide (APS) exerts pharmacological actions in colitis; however, the mechanism has not been elucidated. We investigated whether APS protects through AhR-dependent autophagy. EXPERIMENTAL APPROACH: The symptoms of dextran sulfate sodium (DSS)-induced colitis in mice involving intestinal barrier function and inflammatory injury were evaluated after APS administration. Intestinal-specific Becn1 conditional knockout (Becn1 cKO) mice were constructed and compared with wild-type mice. Autophagy and the effects of APS were investigated after the deactivation of AhRs. The relationship between APS-induced AhRs and autophagic Becn1 was investigated using a dual-luciferase reporter system and chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction assay. Caco-2 cells were used to investigate inflammatory responses and AhR-dependent autophagy. KEY RESULTS: APS improved intestinal barrier function in inflammatory injury in colitis mice. APS triggered autophagic flow; however, knockout of Becn1 in the gut increased susceptibility to colitis, leading to diminished epithelial barrier function and severe intestinal inflammation, impairing the protective effects of APS. Mechanistically, APS-triggered autophagy depends on AhR expression. Activated AhR binds to the promoter Becn1 to operate transcription of genes involved in anti-inflammation and intestinal barrier repair, while deactivation of AhR correlated with intestinal inflammation and the therapeutic function of APS. CONCLUSIONS AND IMPLICATIONS: APS protects colitis mice by targeting autophagy, especially as the AhR stimulates the repair of damaged intestinal barrier functions.

Confusion from prenatal diagnosis: Type C persistent fifth aortic arch or right-side ductus arteriosus.

We described a case of a double aortic arch (DAA) with a subaortic left brachiocephalic vein (LBCV) and right-side ductus arteriosus using high-definition (HD) flow render mode and spatiotemporal image correlation (STIC). We experienced uncertainty regarding this interesting case despite the diagnosis of right-sided ductus arteriosus. The ductus arteriosus originates from the right pulmonary artery (PA) and converges into the descending aorta (DAO), whereas the vessel originated from the PA and converged into the ascending aorta (AAO). Therefore, we assumed that the vessel connecting the PA to AAO may be a type-C persistent fifth aortic arch (PFAA).

Prenatal ultrasound diagnosis of megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome with persistent hyperplastic primary vitreous: a case report.

INTRODUCTION: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a rare autosomal dominant disorder characterised by megalencephaly (i.e. overgrowth of the brain), polymicrogyria and focal hypoplasia of the cerebral cortex and polydactyly. Persistent hyperplastic primary vitreous (PHPV) involves a spectrum of congenital ocular abnormalities that are characterised by the presence of a vascular membrane behind the lens. CASE PRESENTATION: Here, we present a case of foetal MPPH with PHPV that was diagnosed using prenatal ultrasound. Ultrasound revealed the presence of megacephaly, multiple cerebellar gyri and hydrocephalus. Whole-exome sequencing confirmed the mutation of the AKT3 gene, which led to the consideration of MPPH syndrome. Moreover, an echogenic band with an irregular surface was observed between the lens and the posterior wall of the left eye; therefore, MPPH with PHPV was suspected. CONCLUSION: MPPH syndrome with PHPV can be diagnosed prenatally.

Clinical value of prenatal ultrasound in diagnosis and classification of common arterial trunk.

OBJECTIVES: To investigate the clinical value of prenatal ultrasound in the diagnosis of the common arterial trunk (CAT) classification and associated malformations. MATERIALS AND METHODS: The 2D ultrasound images, spatiotemporal image correlations (STICs) and clinical data of 88 fetuses diagnosed with CAT malformations by prenatal ultrasound were retrospectively analyzed and classified. The correlation between different types, fetal malformation and pregnancy outcomes were analyzed. RESULTS: Among the 88 fetuses, there were 39 cases (44.32%) of type A1, 40 cases (45.45%) of type A2, 8 cases (9.09%) of type A3, and 1 case of type A4 (1.14%). There were 16 cases (18.18%) with isolated CAT, 48 cases (54.55%) with complex intra-cardiac structural abnormalities, and 24 cases (27.27%) with intra-cardiac and extra-cardiac structural abnormalities. In extra-cardiac structural malformations, 14 cases were associated with 1 other system abnormality, 4 cases with 2 other system abnormalities, 3 cases with 3 other system abnormalities, while 3 cases were combined with 4 other system abnormalities, among which the facial and physical abnormalities had the highest incidence (39.13%). The STIC images were completely displayed in all 88 cases. There was a statistical difference between isolated CAT and CAT combined with other abnormalities in fetal pregnancy outcomes. CONCLUSIONS: Prenatal ultrasound had a high clinical application value in CAT classification. Pregnancy outcomes were highly correlated with the classification and associated intra-cardiac and extra-cardiac structural malformations. The early evaluation of fetal prognosis before birth has important value for clinical intervention.

Placental micro blood perfusion for isolated single umbilical artery foetuses and VEGF protein expression in the placenta.

Microblood perfusion of isolated single umbilical artery (ISUA) foetus placenta was evaluated using three-dimensional power Doppler ultrasound (3D-PDU). Vascular endothelial growth factor (VEGF) protein expression in the placenta was also semi-quantitative and qualitatively analysed. Differences between ISUA and control groups were compared. 3D-PDU was used to detect placental blood flow parameters, including vascularity index (VI), flow index, and vascularity flow index (VFI), in 58 foetuses in the ISUA group and 77 normal foetuses in the control group. Immunohistochemistry and polymerase chain reaction were employed to analyse the VEGF expression in placental tissues of 26 foetuses in the ISUA group and 26 foetuses in the control group. The control group exhibited higher VI and VFI than the ISUA group (p < 0.05). Meanwhile, the ISUA group showed a higher positivity rate of VEGF protein expression than the control group (χ2=28.013, p˂0.001). The ISUA group also presented a higher VEGF mRNA protein expression than the control group (p˂0.001). 3D-PDU can be used to quantitatively analyse microblood perfusion of the placenta and provide an objective assessment of ISUA foetuses.Impact statementWhat is already known on this subject? Colour Doppler flow can be used to evaluate placental and maternal circulation and remains an ideal method for evaluating high-risk placental function. Three-dimensional power Doppler ultrasound (3D-PDU) can be used to quantify blood vessels and blood flow in placental parenchyma via the measurement of the amplitude of blood vessels and blood flow in normal foetuses, respectively.What do the results of this study add? 3D-PDU can be used to quantitatively analyse micro blood perfusion of the placenta and conduct an objective assessment of isolated single umbilical artery foetuses. The isolated single umbilical artery foetuses exhibited a higher positivity rate of vascular endothelial growth factor (VEGF) protein expression and higher VEGF mRNA protein expression than the normal foetuses.What are the implication of these findings for clinical practice and/or further research? The study provides a reliable basis for maternal-foetal monitoring during pregnancy in the isolated single umbilical artery foetuses. Objective assessment of the occurrence and development of foetuses with isolated single umbilical artery was performed.

Prenatal diagnosis of fetal conotruncal defects by using 2D ultrasound and HD live flow combined with spatiotemporal image correlation.

INTRODUCTION: To explore the diagnostic value of spatiotemporal image correlation (STIC) for different types of fetal conotruncal defects (CTDs). METHODS: The clinical data and STIC images of 174 fetuses with CTDs diagnosed via prenatal ultrasound were analyzed retrospectively. RESULTS: Among the 174 cases of CTDs, 58 were tetralogy of Fallot (TOF); 30, transposition of great arteries (TGA) (D-TGA, 23 cases; cc-TGA, 7 cases); 26, double outlet of the right ventricle (DORV); 32, persistent arterial trunk (PTA) (type A1, 15 cases; type A2, 11 cases; type A3, 5 cases; type A4, 1 case); and 28, pulmonary atresia (PA) (ventricular septal defect, 24 cases; ventricular septal integrity, 4 cases). Among the cases, 156 were complicated with complex congenital intracardiac and extracardiac malformations. The abnormal display rate of the four-chamber view of two-dimensional echocardiography was low. The display rate of the permanent arterial trunk was the highest (90.6%) in STIC imaging. CONCLUSIONS: STIC imaging can be used in the diagnosis of different types of CTDs, especially in persistent arterial trunks, and thus has great value for the clinical treatment and prognosis of these defects.

Prenatal diagnosis of double aortic arch with subaortic left brachiocephalic vein and right-side ductus arteriosus using high-definition flow render mode and spatiotemporal image correlation.

Double aortic arch (DAA) with subaortic left brachiocephalic vein (LBCV) and right-side ductus arteriosus (RDA) was not reported before delivery, only in adults with anatomy course findings. We present a case of fetal DAA with subaortic LBCV and RDA using high-definition (HD) flow render mode and spatiotemporal image correlation (STIC).

Prenatal Ultrasound Diagnosis of Persistent Hyperplastic Primary Vitreous with Retinoblastoma.

INTRODUCTION: Persistent hyperplastic primary vitreous (PHPV) involves a spectrum of congenital ocular abnormalities characterized by the presence of a vascular membrane behind the lens. Retinoblastoma is a life-threatening intraocular malignancy that can cause blindness, eye loss, or even death. PHPV and retinoblastoma are extremely rare prenatal diseases. CASE PRESENTATION: Here, we present a case of fetal PHPV with retinoblastoma diagnosed using prenatal ultrasound. The unilateral lenses were hyperechoic, and irregular echogenic bands between the lenses and posterior eye walls were observed. In cases where the blood flow signal continues in the band-shaped hyperechoic area, PHPV with retinoblastoma should be suspected. CONCLUSION: PHPV with retinoblastoma can be prenatally diagnosed.

Prenatal diagnosis of total anomalous pulmonary venous connection using 2D and HDlive flow combined with spatiotemporal image correlation.

OBJECTIVES: The objective of this study is to examine the application value of two-dimensional (2D) and high-definition live (HDlive) flow combined with spatiotemporal image correlation (STIC) in diagnosing fetal total anomalous pulmonary venous connection (TAPVC). METHODS: Seventeen cases of fetal TAPVC were diagnosed using 2D and HDlive Flow combined with STIC. These cases were then retrospectively analyzed to examine the value of using 2D and HDlive Flow combined with STIC in the diagnosis of TAPVC. RESULTS: 2D and HDlive Flow combined with STIC detected 13 cases of supracardiac TAPVC (two isolated cases, seven cases with right atrial isomerism (RAI), four cases with other complex malformations), one case of isolated intra-cardiac TAPVC, and three cases of cardiac TAPVC (two isolated cases and one case with complex congenital heart anomaly). Small left atrium (LA), the absence of PVs drainage into the LA and the increased retroatrial distance between LA and the descending aorta (DAo) were significant signs that should raise the suspicion of fetal TAPVC. HDlive Flow combined with STIC can dynamically display the TAPVC which may assit the prenatal diagnosis of TAPVC. CONCLUSION: 2D and HDlive Flow combined with STIC can assit the diagnosis of fetal TAPVC abnormalities and has important clinical value.

Prenatal diagnosis of anomalous left brachiocephalic vein courses using high-definition flow render mode and spatiotemporal image correlation.

BACKGROUND: This study aimed to examine the clinical value of high-definition (HD) flow render mode and spatiotemporal image correlation (STIC) to diagnose anomalous left brachiocephalic vein (LBCV) courses in fetuses. METHODS AND RESULTS: Seventeen cases of anomalous LBCV courses were diagnosed using two-dimensional (2D), HD-flow, and HD-flow combined with STIC images and retrospectively analyzed to examine the significance of using HD-flow combined with STIC technology in the diagnosis of anomalous LBCV courses. CONCLUSIONS: HD-flow combined with STIC technology can help in the diagnosis of anomalous fetal LBCV courses, and this technique has important clinical value.

Prenatal diagnosis of fetal inferior vena cava malformation using HDlive flow combined with spatiotemporal image correlation.

OBJECTIVES: This study aimed to examine the application value of high-definition live (HDlive) flow combined with spatiotemporal image correlation (STIC) in the diagnosis of fetal inferior vena cava malformation (IVCM). METHODS: Twenty cases of IVCMs were diagnosed using two-dimensional HDlive flow and HDlive flow combined with STIC and retrospectively analyzed to examine the impact of using HDlive flow combined with STIC in the diagnosis of IVCM. RESULTS: HDlive flow combined with STIC detected one case of duplicated IVC, four cases of left IVC (two cases with complex malformations), and 15 cases of interrupted IVC (two cases of isolated IVC disconnection, five cases with left atrial heterogeneous syndrome, and eight cases with other complex malformations). CONCLUSION: HDlive flow combined with STIC can help in the diagnosis of IVCM, and this technique has important clinical value.

An unusual case of prenatal diagnosis of isolated subaortic left brachiocephalic vein with HDlive flow and spatiotemporal image correlation(STIC).

Subaortic left brachiocephalic vein (LBCV) is rare in prenatal diagnosis. Reported herein is a case of subaortic a LBCV diagnosed using the HDlive flow and spatiotemporal image correlation with postnatal outcomes evaluation in our hospital.

Comparative study of umbilical cord cross-sectional area in foetuses with isolated single umbilical artery and normal umbilical artery.

Single umbilical artery (SUA) is one of the most common prenatal diagnoses in cases of foetal abnormality. This prospective study evaluated 77 foetuses with isolated SUAs and 77 healthy foetuses, both at 22-39 gestational weeks. We categorised gestational age into the second and third trimesters, measured the umbilical arterial blood flow parameters and calculated the umbilical vein (UV) area, umbilical artery (UA) area and UV area/UA area ratio. In the second and third trimesters, a higher UA area was obtained in the isolated SUA group than in the control group (p < .01). Furthermore, the isolated SUA group had a lower UV area/UA area ratio than the control group (p < .01), and a positive linear correlation was found between gestational age and UV area in both groups (p < .01). The presence of isolated SUAs was associated with low birth weight and a high prevalence of small for gestational age.IMPACT STATEMENTWhat is already known on this subject? Single umbilical artery (SUA) is one of the most common prenatally diagnosed foetal abnormalities and approximately 80% foetuses with SUA have isolated SUA, which is a soft indicator of chromosome abnormalities, congenital malformations and premature birth. Umbilical cord cross-sectional area can be evaluated prenatally by ultrasound imaging. Normal values increase with gestational age and foetal size in single pregnancies. Changes in umbilical cord thickness have been associated with complications during pregnancy.What do the results of this study add? The correlation between gestational age and umbilical vein area in the isolated single umbilical artery (SUA) group and control group was better than that between gestational age and umbilical artery area. UA area increased significantly in both groups before 28 weeks but not after 28 weeks, particularly in the isolated SUA group.What are the implications of these findings for clinical practice and/or further research? The study provides a reliable basis for maternal foetal monitoring during pregnancy in the isolated SUA and control groups. Objective assessment of the occurrence and development of foetuses with isolated single umbilical artery was performed.

Prenatal sonographic diagnosis of X-linked hypohidrotic ectodermal dysplasia: An unusual case.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare congenital genetic disorder caused by mutations in the ectodysplasin A gene, resulting in dysplasia or complete absence of teeth, hair, and sweat glands. XLHED is rarely diagnosed prenatally. We describe a case of XLHED diagnosed with prenatal sonography and umbilical cord blood gene testing.

Prenatal diagnosis of complete vascular ring using high-definition flow render mode and spatiotemporal image correlation.

Vascular rings (VRs) are defined as congenital abnormalities of the aortic arch and its branches. VR can form a ring that may compress the esophagus and trachea, which likely result in feeding difficulties and respiratory distress. Physicians performing fetal echocardiography are knowledgeable about VRS and can provide this information to pediatric cardiothoracic surgeons. However, VRs are rare and can be missed. The three vessels and trachea (3VT) view used to diagnose VRs has been reported in the literature multiple times but in a small series. We diagnosed three cases of VRs using high-definition (HD) flow render mode and spatiotemporal image correlation (STIC). The composition of the VRs and vessel connections were shown more intuitively. This article reports our experience of the following related cases. In addition, postnatal imaging features of VRs were also evaluated.

The role of diagnostic magnetic resonance hysterosalpingography in the evaluation of fallopian tubal occlusion of female infertility: A meta-analysis.

OBJECTIVE: To evaluate the diagnostic performance of magnetic resonance hysterosalpingography for fallopian tubal occlusion in the context of female infertility when compared to the diagnostic performance of conditional X-ray hysterosalpingography. METHODS: PubMed, EMBASE, Web of Science, EBSCO, Cochrane Library database, Scopus were searched for studies in which magnetic resonance hysterosalpingography and X-ray hysterosalpingography were used as diagnostic tools for tubal occlusion assessment; databases were searched through April 2020. Two researchers conducted study inclusion assessment, data extraction, a systematic review, and pooled meta-analysis independently. Stata 15.1 software was used to analyze the pooled sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratios, and the area under the summary receiver-operating characteristic curve of magnetic resonance hysterosalpingography. RESULTS: A total of five studies involving 101 patients and 198 fallopian tubes were finally included. Compared with the conditional X-ray hysterosalpingography (the imaging gold standard), the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve of magnetic resonance hysterosalpingography for tubal occlusion were 0.91 (95% CI: 0.48-0.99), 1.00 (95% CI: 0.87-1.00), 230.47 (95% CI: 6.79-7824.72), 0.09 (95% CI: 0.01-0.80), 2676.10 (95% CI: 61.35-120,000), and 1.00 (95% CI: 0.99-1.00), respectively. Subgroup analyses revealed that viscosity of contrast agent (P = 0.024) and test order (P = 0.036) affected the accuracy of MR-HSG to evaluate tubal occlusion. CONCLUSIONS: Our meta-analysis indicated magnetic resonance hysterosalpingography may serve as an alternative for further evaluation of fallopian tubal occlusion of female infertility.

Correlation between ductus venosus spectrum and right ventricular diastolic function in isolated single-umbilical-artery foetus and normal foetus in third trimester.

BACKGROUND: Single umbilical artery (SUA) is the most common umbilical cord malformation in prenatal diagnosis. The presence of an SUA can cause blood circulation disorder in the foetus and functional changes of the foetal heart, affecting foetal circulation. The right ventricular diastolic functions in foetuses with isolated SUA and in normal foetuses in the third trimester were evaluated using the spectral Doppler of blood flow in the foetal ductus venosus (DV). AIM: To evaluate the right ventricular diastolic functions in foetuses with isolated SUA and in normal foetuses in the third trimester. METHODS: Colour Doppler was used to measure the spectrum of foetal DV and tricuspid orifice in 34 foetuses with isolated SUA aged 28-39 wk and in age-matched healthy controls. The DV flow velocities and velocity ratios were measured. The early passive/late active (E/A) ratio at the tricuspid orifice and tissue Doppler Tei index of the foetal right ventricular in the two groups were also measured. RESULTS: During the third trimester, the isolated SUA group showed a lower 'a'-wave peak velocity in the DV than the control group (P < 0.05). The correlations between the velocity ratios and E/A ratio at the tricuspid orifice in the two groups were analysed, and the correlation between the ventricular late diastolic velocity/ventricular diastolic peak flow velocity and E/A ratios was the best (R2 of the isolated SUA group: 0.520; R2 of the control group: 0.358). The correlations between the velocity ratios and tissue Doppler Tei index of foetal right ventricular in the two groups were analysed, and the correlation between the pulsatility index for veins (PIV) and tissue Doppler Tei index ratios was the best (R2 of the isolated SUA group: 0.865; R2 of the control group: 0.627). CONCLUSION: In the isolated SUA group, the atrial systolic peak velocity 'a' decreased, and this finding might be related to the changes in foetal cardiac functions. The ratio of ventricular late diastolic velocity to ventricular diastolic peak flow velocity was closely related to the E/A ratio at the tricuspid valve and can be used to identify changes in the right ventricular diastolic functions of isolated SUA and healthy foetuses. PIV was closely related to the tissue Doppler Tei index of the foetal right ventricular and can be used to identify the right ventricular overall functions of isolated SUA and healthy foetuses.

Prenatal diagnosis of single umbilical artery and postpartum outcome.

OBJECTIVES: To investigate the incidence of the single umbilical artery (SUA) malformation and postpartum outcomes in a retrospective analysis of 781 fetuses. MATERIALS AND METHODS: This retrospective analysis included 781 pregnant women carrying singleton fetuses diagnosed with SUA at Gansu Provincial Maternal and Child-care Hospital between 2013 and 2019. Detailed data on maternal and fetal characteristics and postpartum outcomes were obtained. RESULTS: In total, 624 (79.9 %) fetuses were diagnosed with isolated SUA and 157 (20.1 %) fetuses had SUA together with other structural and/or chromosome abnormalities. The highest incidence of malformation was found in the urinary system, followed by the cardiovascular system and digestive system. The incidence of SUA was 59.1 % on the right side and 40.9 % on the left side. Fetuses with SUA and other abnormalities tended to have a lower mean birth weight (3061 g vs 3201 g, p < 0.01), but no difference in the rate of preterm delivery was noted. CONCLUSIONS: After a diagnosis of SUA, structural observation of the fetus is required. The urinary, cardiovascular and digestive systems should be the focus of observation. If relevant malformations are found, then genetic testing must be performed. With isolated SUA, dynamic monitoring of biological indicators is recommended for lower birth weight, but genetic testing is not recommended.