Background Kawasaki disease (KD) is now the leading cause of acquired heart disease in children in developed countries. Intravenous immunoglobulin (IVIG) and aspirin were considered as the standard initial treatment of KD for decades. However, the optimal dose of aspirin has remained controversial. In recent years, many studies compared the efficacy of low-dose with high-dose aspirin in the acute phase of KD, but the results have not always been consistent. Therefore, we performed this meta-analysis to evaluate the efficacy of low-dose aspirin compared with high-dose for the initial treatment of KD. Methods Studies related to aspirin therapy for KD were selected from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Google scholar through Mar 25 th , 2019. Data were analyzed using STATA Version 15.1. Additionally, publication bias and sensitivity analysis were also performed by STATA version 15.1. Results Six studies were included in our analysis of the rate of coronary artery lesion (CAL), five reports for IVIG-resistant KD (rKD), and four for the duration of fever and hospitalization. However, no significant differences were found between low-dose and high-dose aspirin groups in the incidence of CAL (risk ratio (RR), 0.85; 95%CI (0.63, 1.14); P = 0.28), the risk of rKD (RR, 1.39; 95%CI (1.00, 1.93); P = 0.05), and duration of fever and hospitalization (the mean standard deviation (SMD), 0.03; 95%CI (-0.16, 0.22); P = 0.78). Conclusion Low-dose aspirin (3–5 mg·kg -1 ·d -1 ) may be as effective as the use of high-dose aspirin (≥30 mg·kg -1 ·d -1 ) for the initial treatment of KD. Further well-designed randomized clinical trials are needed to evaluate the efficacy of low-dose aspirin for the initial treatment of KD.

Accumulating evidence has suggested a link between maternal di-(2-ethylhexyl)-phthalate (DEHP) exposure and various developmental abnormalities. However, the evidence regarding the effect of maternal DEHP exposure on fetal cardiac development is scarce. The present study aimed to determine the effect of maternal DEHP exposure on fetal cardiac development in mice and explore the possible involved mechanism preliminarily. The C57BL mice were randomly divided into four groups: the vehicle group (corn oil, n = 10), 250 mg kg DEHP group (n = 15), 500 mg kg DEHP group (n = 20) and 1 g kg DEHP group (n = 20). Pregnant dams in different group received respective intervention by gavage once daily from embryonic day (E)6.5 to E14.5. Maternal weights were monitored every day and samples were collected at E15.5. Hematoxylin and eosin staining was used to examine fetal cardiac malformations. Real-time quantitative polymerase chain reaction and western blot were applied to detect peroxisome proliferator-activated receptor (PPAR)α/PPARγ/Nkx2.5/Gata4/Tbx5/Mef2c/Chf1 mRNA and protein expression, respectively. Maternal DEHP exposure significantly decreased maternal body weight, fetal weight and placental weight, and remarkably elevated fetal cardiac malformations rate. The phenotypes of cardiac anomalies mainly include septal defects, ventricular myocardium noncompaction and cardiac hypoplasia. Higher doses DEHP (500 mg kg and 1 g kg ) could significantly decreased fetal cardiac Gata4/Mef2c/Chf1 expression, while PPARγ expression was upregulated. Maternal exposure to higher doses of DEHP could result in fetal cardiac development malformations in mice and it might have resulted from the inhibition of cardiac GATA4/Mef2c/Chf1 expression via PPARγ activation.

Fetal congenital heart block (CHB) is the most commonly observed type of fetal bradycardia, and is potentially life-threatening. More than 50% of cases of bradycardia are associated with maternal autoimmunity, and these are collectively termed immune-associated bradycardia. Several methods have been used to achieve reliable prenatal diagnoses of CHB. Emerging data and opinions on pathogenesis, prenatal diagnosis, fetal intervention, and the prognosis of fetal immune-associated CHB provide clues for generating a practical protocol for clinical management. The prognosis of fetal immune-associated bradycardia is based on the severity of heart blocks. Morbidity and mortality can occur in severe cases, thus hieratical management is essential in such cases. In this review, we mainly focus on optimal strategies pertaining to autoimmune antibodies related to CHB, although the approaches for managing autoimmune-mediated CHB are still controversial, particularly with regard to whether fetuses benefit from transplacental medication administration. To date there is still no accessible clinical strategy for autoimmune-mediated CHB. This review first discusses integrated prenatal management strategies for the condition. It then provides some advice for clinicians involved in management of fetal cardiovascular disorder.

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Introduction: Aortic regurgitation (AR) was recognized as a major, but rare complication after device closure for perimembranous ventricular septal defects (PmVSD). Most of them are temporary and non-significant. Infectious endocarditis (IE) is another extremely rare post-procedure complication of PmVSD. Theoretically, AR could increase risk for post-interventional IE. However, no cases have been documented thus far. We firstly described a case of very late-onset IE associated with non-significant AR after transcatheter closure of PmVSD with modified symmetrical double-disk device, underscoring the need for reassessing long-term prognostic implications of non-significant post-procedure AR after PmVSD occlusion and the most appropriate treatment strategy. Patient concerns: A 15-year old male received transcatheter closure of a 6.4 mm sized PmVSD with a 9-mm modified symmetric double-disk occluder (SHAMA) 11 years ago in our hospital. A new-onset mild eccentric AR was noted on transthoracic echocardiography (TTE) examination 1-year post procedure, without progression and heart enlargement. At this time, the child was admitted with a complaint of persistent fever for 16 days and nonresponse to 2-weeks course of amoxicillin and cefoxitin. Diagnosis: The diagnosis of post-procedure IE was established since a vegetation (14 × 4 mm) was found to be attached to the tricuspid valve, an anechoic area (8 × 7 mm) on left upper side of ventricular septum and below right aortic sinus, and severe eccentric AR as well as the isolation of Staphylococcus aureus from all three-blood cultures. Interventions: Treatment with vancomycin was initially adopted. However, surgical interventions including removal of vegetation, abscess and occluder, closure of VSD with a pericardial patch, tricuspid valvuloplasty, and aortic valvuloplasty were ultimately performed because of recurrent fever and a new-onset complete atrioventricular block 12-days later. The child continued with antibiotic therapy up to six weeks post operation. Outcomes: The child's temperature gradually returned to normal with alleviation of AR (mild) and heart block (first degree). The following course was uneventful. Conclusion: Late-onset IE could occur following device closure of PmVSD and be associated with post-procedure AR. For non-significant AR after device closure of PmVSD, early surgical intervention could be an alternative for reducing the aggravation of aortic valve damage and the risk of associated IE.

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Investigations on placental P‐glycoprotein (P‐gp) regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. The role of long noncoding RNA (lncRNA) on placental P‐gp regulation is lacking. The present study was carried out to investigate the regulation and underlying mechanisms of lncRNA urothelial carcinoma associated 1 (UCA1) on P‐gp in Bewo cells. lncRNA UCA1 inhibition or overexpression could decrease or increase ABCB1 mRNA expression, P‐gp expression and its cellular efflux function, respectively. RNA‐FISH revealed that lncRNA UCA1 was mainly located in the cytoplasm of Bewo cells. MicroRNA array was applied and 10 significant miRNAs was identified after lncRNA UCA1 inhibition. Databases of LncTarD, LncRNA2Target, and miRcode were further used to search potential target miRNAs of lncRNA UCA1 and miR‐16‐5p was screened out. Thereafter, we confirmed that miR‐16‐5p expression was significantly upregulated or reduced after lncRNA UCA1 knockdown or overexpression, respectively. Furthermore, we also proved that ABCB1 mRNA expression, P‐gp expression and its cellular efflux function was enhanced or reduced after miR‐16‐5p inhibition or overexpression, respectively. The rescue experiment further indicated that miR‐16‐5p was involved in the positive regulation of lncRNA UCA1 on the expression and function of P‐gp. Lastly, dual‐luciferase reporter system, RNA‐binding protein immunoprecipitation and RNA pull‐down assays were performed to explore the relationships among lncRNA UCA1, miR‐16‐5p, and ABCB1. It was found that lncRNA UCA1(1103–1125) could directly interact with miR‐16‐5p and miR‐16‐5p could directly target ABCB1 coding DNA sequence region (882–907). In conclusion, LncRNA UCA1 could promote the expression and function of P‐gp by sponging miR‐16‐5p in BeWo cells.

Background: The rapid progression from fetal first-degree atrioventricular block (AVB) to third-degree AVB had been reported. However, how to define fetal first-degree AVB with proper technique and the necessity of the treatment in utero for fetal autoimmune-associated first-degree AVB are still controversial.Purpose: To explore the diagnosis and the effect of treatment for fetal first-degree AVB.Cases Presentation: Four pregnant women with positive autoantibodies anti-SSA/Ro were admitted into our hospital with complaints of rapid prolonged atrioventricular (AV) intervals of their fetuses. Fetal AV intervals were re-measured by tissue Doppler imaging (TDI) from the onset of atrial contraction to ventricular systole (Aa-Sa), which were 170 ms (case 1-twin A), 160 ms (case 1-twin B), 163 ms (case 2) and 172 ms (case 3) and 170 ms (case 4), respectively. The histories of medication usage or infection during gestation were denied. Amniotic fluid genetic screenings and virological tests were negative in all cases. No structural cardiac disorders were found and the cardiovascular profile scores were 10 for each fetus. Oral dexamethasone (initial dose of 4.5 mg daily) and hydroxychloroquine (200 mg bid) plus weekly follow-up surveillance were suggested. The dosage of dexamethasone was adjusted according to the changes of the AV intervals and fetal development of biparietal diameters (BPD) and femur lengths (FL). All fetal AV intervals were controlled well. Maternal and fetal adverse effects were noted as diabetes in 1 mother and growth retardation in all fetuses. All fetuses were delivered via cesarean section at 35+4, 37, 38, and 37+1 gestational weeks, with 10 scores of Apgar score. Postnatally, positive anti-SSA/Ro was found in all neonates. However, there were no clinical or laboratory evidence of neonatal lupus syndrome. No abnormal signs were found on postnatal electrocardiogram and echocardiography for all neonates. With a follow-up of 8–53 months, there was no progression of disease and all infants demonstrated normal physical, mental, and motor development.Conclusion: Prenatal treatment for fetal autoimmune-associated first-degree AVB could be an alternative. Strict surveillance and timely adjustment of the treatment according to the conditions of the mother and the fetus are indicated. Further studies are necessary to prove our concept.