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Objective: The GeneXpert MTB/RIF assay (Xpert) is a diagnostic tool that has been shown to significantly improve the accuracy of tuberculosis (TB) detection in clinical settings, with advanced sensitivity and specificity. Early detection of TB can be challenging, but Xpert has improved the efficacy of the diagnostic process. Nevertheless, the accuracy of Xpert varies according to different diagnostic specimens and TB infection sites. Therefore, the selection of adequate specimens is critical when using Xpert to identify suspected TB. As such, we have conducted a meta-analysis to evaluate the effectiveness of Xpert for diagnosis of different TB types using several specimens., Methods: We conducted a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the World Health Organization clinical trials registry center, covering studies published from Jan 2008 to July 2022. Data were extracted using an adapted version of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies. Where appropriate, meta-analysis was performed using random-effects models. The risk of bias and level of evidence was assessed using the Quality in Prognosis Studies tool and a modified version of the Grading of Recommendations Assessment, Development, and Evaluation. RStudio was utilized to analyze the results, employing the meta4diag , robvis , and metafor packages., Results: After excluding duplicates, a total of 2163 studies were identified, and ultimately, 144 studies from 107 articles were included in the meta-analysis based on predetermined inclusion and exclusion criteria. Sensitivity, specificity and diagnostic accuracy were estimated for various specimens and TB types. In the case of pulmonary TB, Xpert using sputum (0.95 95%CI 0.91-0.98) and gastric juice (0.94 95%CI 0.84-0.99) demonstrated similarly high sensitivity, surpassing other specimen types. Additionally, Xpert exhibited high specificity for detecting TB across all specimen types. For bone and joint TB, Xpert, based on both biopsy and joint fluid specimens, demonstrated high accuracy in TB detection. Furthermore, Xpert effectively detected unclassified extrapulmonary TB and tuberculosis lymphadenitis. However, the Xpert accuracy was not satisfactory to distinguish TB meningitis, tuberculous pleuritis and unclassified TB., Conclusions: Xpert has exhibited satisfactory diagnostic accuracy for most TB infections, but the efficacy of detection may vary depending on the specimens analyzed. Therefore, selecting appropriate specimens for Xpert analysis is essential, as using inadequate specimens can reduce the ability to distinguish TB., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=370111, identifier CRD42022370111., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gong, He, Zhou, Hua and Li.)

The "developmental origins of health and disease" (DOHaD) hypothesis posits that early-life environmental exposures have a lasting impact on individual's health and permanently shape growth, structure, and metabolism. This reprogramming, which results from fetal stress, is believed to contribute to the development of adulthood cardiovascular diseases such as hypertension, coronary artery disease, heart failure, and increased susceptibility to ischemic injuries. Recent studies have shown that prenatal exposure to drugs, such as glucocorticoids, antibiotics, antidepressants, antiepileptics, and other toxins, increases the risk of adult-onset cardiovascular diseases. In addition, observational and animal experimental studies have demonstrated the association between prenatal drug exposure and the programming of cardiovascular disease in the offspring. The molecular mechanisms underlying these effects are still being explored but are thought to involve metabolism dysregulation. This review summarizes the current evidence on the relationship between prenatal drug exposure and the risk of adult cardiovascular disorders. Additionally, we present the latest insights into the molecular mechanisms that lead to programmed cardiovascular phenotypes after prenatal drug exposure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Zhou, Hua, Zhang and Li.)

Background: Among all fetal heart block patients, > 50% cases are associated with maternal autoimmune diseases, and such patients should receive treatment. However, nearly half of fetal heart block cases involve a mother with negative results following autoimmune antibody screening. A few studies have reported long QT syndrome (LQTS) can also present as a severe fetal bradycardia, which does not respond to fetal treatment. Herein, we reported a rare case of an infant who presented with high-degree autoimmune-mediated fetal atrioventricular block (AVB) with LQTS induced by a novel KCNH2 variant. This case led us to review our prenatal therapeutic strategy., Case Presentation: A 1-year-old boy presented to our heart center having experienced syncope 5 times in the past year. He had previously presented with fetal bradycardia during the fetal stage from 27 + 3 gestational weeks. The fetal echocardiography demonstrated AVB (2:1 transmission). As the maternal autoimmune antibody results were positive, his mother had received dexamethasone treatment during pregnancy; subsequently, the fetal AVB had changed from 2:1 to 4:3 transmission with elevated ventricular beating rates. However, this patient was identified to have complete AVB after birth. The initial electrocardiogram and Holter measurements at hospital administration showed complete AVB, pleomorphic ventricular tachycardia, a prolonged QT interval (QT = 602 ms, corrected QT = 538 ms), and wide and deep inverted T-waves. Meanwhile, torsades de pointes could be observed in several transit ventricular tachycardias based on Holter monitoring review. Genetic testing revealed KCNH2 c.2483G > A variant-induced LQTS. An implantable cardioverter defibrillator device and permanent pacemaker were both considered as therapeutic alternations; his parents ultimately accepted the implantation of a permanent pacemaker., Conclusions: For fetuses with autoimmune-mediated AVB, intrauterine treatment should still be pursued immediately. However, once the treatment outcomes are deemed unacceptable or unexpected, other genetic variant-related channelopathies should be highly suspected. If the fetus lacks a positive family history, fetal genetic testing should be recommended to improve the prognosis of such patients by introducing integrative therapeutic strategies between the prenatal and postnatal phases., (© 2023. The Author(s).)

Background: Coronary artery aneurysms (CAA) persistence prediction is critical in evaluating Kawasaki disease (KD). This study established a nomogram prediction system based on potential risk factors for assessing the risk of CAA persistence in a contemporary cohort of patients with KD., Methods: This cohort comprised 105 patients with KD who had been diagnosed with CAA during the acute or subacute phase by echocardiography. The follow-up duration was at least 1 year. The clinical and laboratory parameters were compared between the CAA regression and persistence groups. Multivariable logistic regression analysis was used to identify the independent risk factors for CAA persistence, which were subsequently used to build the nomogram predictive model. Decision curve analysis was used to assess the net benefits of different nomogram scores., Results: Of these patients with CAA, 27.6% of patients presented with persistent lesions. The incidences of CAA persistence were 14.1%, 81.3%, and 100.0% in patients with small, medium, and large aneurysms, respectively. The ratio of neutrophils to lymphocytes, γ-GT, and CAA size at diagnosis were considered as the independent risk factors for CAA persistence in patients with KD. The nomogram predictive models yielded a high capability in predicting CAA persistence, based on either univariable or multivariable analyses-identified parameters, compared with using CAA size as a single predictor., Conclusion: The initial ratio of neutrophils to lymphocytes, γ-GT, and CAA size were the independent risk factors for CAA persistence in patients with KD. Nomogram scores could help elevate predictive efficacy in detecting CAA persistence., (© 2023. The Author(s).)

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., (© 2022 Federation of American Societies for Experimental Biology.)

Calcium mishandling and mitochondrial dysfunction have been increasingly recognized as significant factors involved in the progression procedure of cardiomyopathy. Ca2+ mishandling could cause calcium-triggered arrhythmias, which could enhance force development and ATP consumption. Mitochondrial disorganization and dysfunction in cardiomyopathy could disturb the balance of energy catabolic and anabolic procedure. Close spatial localization and arrangement of structural among T-tubule, sarcoplasmic reticulum, mitochondria are important for Ca2+ handling. So that, we illustrate the regulating network between calcium handling and mitochondrial homeostasis, as well as its intracellular mechanisms in this review, which would be worthy to develop novel therapeutic strategy and restore the function of injured cardiomyocytes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zhou, Liu, Hua, Wang and Li.)

Background: Fetal bradycardia is a common but severe condition. In addition to autoimmune-mediated fetal heart block, several types of channelopathies induce high-degree atrioventricular block (AVB). Long QT syndrome (LQTS) is a major cause of non-autoimmune-mediated fetal heart block. Due to the limitations of prenatal diagnostic technologies, LQTS is seldom identified unless fetal genetic screening is performed. Thus, long-term prenatal dexamethasone (DEX) exposure can become a challenge for these patients. We report on a rare case of a novel KCNH2 variant related to LQTS and associated with high-degree fetal AVB with long-term DEX exposure. This case led us to review our prenatal administration strategy for such patients. Case Presentation: A fetus was identified with high-degree AVB (2:1 transduction at 28 + 2 gestational weeks). Typical tests of immune function in the pregnant woman were conducted including tests for thyroid function, rheumatic screening, autoimmune antibodies (such as anti-Ro/SSA and anti-La/SSB), and anti-nuclear antibodies (anti-ANA). Following the recommended protocol, the pregnant patient received DEX (0.75 mg/day) during pregnancy. Subsequently, the fetal AVB changed from 2:1 to prolonged AV intervals with ventricular tachycardia, which suggested a therapeutic benefit of DEX in some respects. However, a high-degree AVB with a significantly prolonged QTc interval was identified in the neonate following birth. Genetic testing revealed that a KCNH2 c.1868C>A variant induced LQTS. The body length remained approximately -3.2 SD from the reference value after prenatal long-term DEX exposure, which indicated a developmental restriction. Additionally, the functional validation experiments were performed to demonstrate the prolonged duration of calcium transit both in depolarization and repolarization with the KCNH2 c.1868C>A variant. Conclusion: Genetic screening should be recommended in fetuses with autoimmune antibody negative high-degree AVB, especially for 2:1 transduction AVB and in fetuses with changes in fetal heart rhythm following initial DEX treatment. Genetic screening may help identify genetic variant-related channelopathies and avoid unexpected prenatal exposure of DEX and its possible long-term adverse postnatal complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Jing, Wu, Wei, Zhang, Hua, Li, Yu and Zhou.)

Background: An anomalous aortic origin of a coronary artery (AAOCA) has been considered as a dominant cause of sudden cardiac death (SCD) among young age children. Therefore, it is critical to identify AAOCA timely to avoid lethal events. Recently, accumulating cases of right or left coronary arteries originating from inappropriate locations at the sinus of Valsalva have been identified. Here, we report a rare case of AAOCA with an intra-arterial wall course pretending normal migration on imaging screening in a patient who suffered from syncope., Case Summary: A 7-year-old male without a previous history of cardiovascular and cerebrovascular diseases suddenly suffered from sharp chest pain and syncope after intensive exercise. The electrocardiogram showed that the ST segment of multiple leads was depressed by more than 0.05 mV, and biomarkers indicated severe myocardial injuries. The left ventricular ejection fraction (LVEF) decreased dramatically to 23%. Fulminant myocarditis and cardiomyopathy were therefore excluded. However, a relatively normal coronary artery origin, which arose from the left coronary sinus, presented on echocardiography and cardiac CT angiography (CTA). It is difficult to draw an association between severe clinical manifestations and slight malformations on echocardiography and CTA. Furthermore, selective coronary angiography revealed that an anomalous left coronary artery arose from the superior margin of the inappropriate sinus, developed an intramural wall course and finally exits the left sinus of Valsalva and migrated between the aorta and the pulmonary artery, which induced severe myocardial infarction during exercise. Then, the patient received surgical correction with a modified unroofing procedure. After 2 months of intensive treatment, the patient was discharged and remained asymptomatic through 18 months of follow-up., Conclusion: AAOCA, especially anomalous left coronary artery (ALCA), represents a major potential risk of SCD. We reported an atypical manifestation of ALCA arising from the inappropriate sinus of Valsalva and merging into the intra-arterial wall to develop a strange course and then sprout between the aorta and the pulmonary artery. The diversity of AAOCA might present as a relatively normal course under non-invasive radiological imaging scanning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Wang, Wan, Li, Wang, Zhou, Shi, Liu, Fang and Hua.)

Background: Kawasaki disease (KD) is an acute systemic vasculitis and is becoming the leading cause of acquired cardiac disease in Children. Sterile pyuria is a known complication of KD. However, its associations with the inflammatory reaction severity, IVIG resistance as well as coronary artery lesions (CALs) in KD remain elusive., Aims: We aimed to analyze the clinical profiles of sterile pyuria in KD, to determine whether sterile pyuria is an indicator of the disease severity in patients with KD, and to assess the associations between sterile pyuria and IVIG resistance as well as CALs., Methods: We prospectively collected data from 702 patients with KD between January 2015 and June 2020. Profiles of patients with sterile pyuria (group A, n = 63) were compared to those of patients without sterile pyuria (group B, n = 639). The associations between sterile pyuria and IVIG resistance as well as CALs in KD were further determined by univariate and/or multivariate logistic regression analysis., Results: Sterile pyuria was observed in 9.0% of patients with KD, without predominance in age spectrum and gender. The levels of neutrophil percentages, alanine transaminase, total bilirubin, blood urea nitrogen, creatinine, the incidence of initial IVIG resistance, and rate of moderate/giant coronary artery aneurysms (CAAs) were significantly higher in group A than that in group B. Sterile pyuria was identified as an independent risk factor for initial IVIG resistance, yielding high specificity (92.7%) and low sensitivity (18.5%). However, sterile pyuria was not associated with repeated IVIG resistance and persistence of CALs in KD., Conclusion: The incidence of sterile pyuria is relatively low in KD patients. Patients with sterile pyuria in KD exhibited a more severe inflammatory burden and were more likely to develop the initial IVIG resistance and moderate/giant CAAs. The overall prognosis of KD patients with sterile pyuria was satisfactory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Wang, Shao, Zhang, Wu, Liu, Hua, Zhou, Yu, Wang and Wang.)

Backgrounds: The traditional treatment of doubly committed subarterial ventricular septal defect (dcVSD) is open-heart surgery. This study aimed to evaluate the feasibility, safety, and outcome of transcatheter closure of small dcVSD using Amplatzer duct occluder-II (ADO-II) in children., Methods: Between January 2016 and April 2021, 24 children (17 male and 7 female patients) with small dcVSD who received transfemoral closure with ADO-II were enrolled retrospectively. All of their available clinical and follow-up data were evaluated., Results: The patients' median age was 3.2 years (1.6-12.6 years, 4.2 ± 3.1 years) and body weight was 13.3 kg (10.0-38.5 kg, 16.5 ± 7.7 kg). Left ventricular angiography showed that the median dcVSD size was 2.0 mm (1.5-3.5 mm, 2.1 ± 0.6 mm). The device was successfully implanted in 23 patients (95.8%), and one patient failed to be closed because of the underestimation of defect size due to preoperative aortic valve prolapse, with 16 patients by the antegrade approach and eight patients by retrograde approach. The diameters of the device used were 3/4, 4/4, and 5/4 mm. The median operative time was 40.0 min (20.0-75.0 min, 41.7 ± 13.7 min), and the median fluoroscopic time was 5.0 min (3.0-25.0 min, 6.8 ± 5.0 min). With a follow-up duration of 1+ to 45+ months, only 1 patient presented with new-onset mild aortic regurgitation (AR)., Conclusion: Transfemoral closure of small dcVSD with ADO-II is technically feasible and safe in the selected children. However, the development or worsening of AR requires long-term follow-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tang, Zhou, Shao, Liu, Li, Hua and Wang.)

Background: Hypertrophic cardiomyopathy (HCM) is the second most common cardiomyopathy in childhood with a life-threatening risk. Implantable cardioverter-defibrillator (ICD) placement is recommended for early prevention if there are two or more clinical risk factors. Pediatric patients with HCM are at a higher risk of sudden cardiac death (SCD), but there are limited reports on indications for ICD implantation in children. Herein we describe the case of Myh7 mutation-induced HCM and cardiac arrest in a patient and evaluated information originating from genetic background to guide ICD administration. Case Presentation: The patient was a girl aged 7 years and 8 months who had been diagnosed with cardiomyopathy in utero 8 years prior. She had had recurrent cardiac arrests within the last 4 years. Electrocardiography indicated abnormalities in conduction, and ST segment changes. Echocardiography indicated significant left ventricular hypertrophy and hypertrophic systolic interventricular septum. Cardiac magnetic resonance imaging depicted general heart enlargement with hypertrophy, and delayed enhancement in myocardium with perfusion defect was also evident. Whole exon sequencing identified a de novo c.2723T>C (p.L908P) heterozygous mutation in the MYH7 gene. MYH7 p.L908P predicted unstable protein structure and impaired function. The patient was scheduled for ICD implantation. There were no complications after ICD implantation, and she was discharged from hospital on the 10th day. Regular oral beta-blockers, amiodarone, spironolactone, and enalapril were administered, and she was required to attend hospital regularly for follow-up. During follow-up there were no cardiac arrests. Literature review of clinical prognoses associated with genetic mutations of MYH7, MYBPC3, TNNI3, TNNT2, and TPM1 in pediatric HCM patients with and without ICD implantation indicated that they were totally differently. Previous reports also indicated that gene mutations predicted earlier onset of cardiac hypertrophy, and increase likelihood of SCD. Conclusion: Variant burden and variant type contribute to the risk of adverse events in pediatric HCM. Early recognition and intervention are vital in children. Gene mutation could be considered an indication for early ICD placement during standard risk stratification of HCM patients. Whether this extends to the majority of pediatric patients requires further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Tang, Li, Lin, Wang, Zhou, Li and Hua.)

Myh7 is a classic biomarker for cardiac remodeling and a potential target to attenuate cardiomyocyte (CM) hypertrophy. This study aimed to identify the dominant function of Myh7 after birth and determine whether its removal would affect CM maturation or contribute to reversal of pathological hypertrophy phenotypes. The CASAAV (CRISPR/Cas9-AAV9-based somatic mutagenesis) technique was used to deplete Myh6 and Myh7, and an AAV dosage of 5 × 10 9 vg/g was used to generate a mosaic CM depletion model to explore the function of Myh7 in adulthood. CM hypertrophy was induced by transverse aortic constriction (TAC) in Rosa26 Cas9-P2A-GFP mice at postnatal day 28 (PND28). Heart function was measured by echocardiography. Isolated CMs and in situ imaging were used to analyze the structure and morphology of CM. We discovered that CASAAV successfully silenced Myh6 and Myh7 in CMs, and early depletion of Myh7 led to mild adulthood lethality. However, the Myh7 PND28-knockout mice had normal heart phenotype and function, with normal cellular size and normal organization of sarcomeres and T-tubules. The TAC mice also received AAV-Myh7-Cre to produce Myh7-knockout CMs, which were also of normal size, and echocardiography demonstrated a reversal of cardiac hypertrophy. In conclusion, Myh7 has a role during the maturation period but rarely functions in adulthood. Thus, the therapeutic time should exceed the period of maturation. These results confirm Myh7 as a potential therapeutic target and indicate that its inhibition could help reverse CM hypertrophy.

Rationale: Left ventricle-right atrium (LV-RA) shunt is a rare case and surgical repair has been the routine procedure to correct this defect. With the rapid development of transcatheter technology, some of the cases can be closed with transcatheter technique. Here, we would like to report a congenital LV-RA case who received transcatheter closure using the Amplazter duct occluder II (ADO II) and the short-term outcomes of this procedure., Patient Concerns: A 2-year-old female presented a systolic murmur between the 2 to 3 sternal rib during the routine examination before kindergarten administration., Diagnosis: The patient denied any cardiac surgery, endocarditis, trauma or cardiomyopathy. The echocardiography confirmed an abnormal shunt between left ventricle and right atrium located in the superior part of ventricular septum which is closed to septal tricuspid valve and anterior mitral valve, and the diameter of this shunt is 2 mm. Besides, the dilation of right atrium (40 mm) has been identified which was not a common clinical manifestation of typical ventricular septal defect. Angiography demonstrated the shunt driven from left ventricle to right atrium., Intervention: An AGA ADO II device had been delivered to close the defect., Outcome: Follow-up kept for 3 months. Echocardiography revealed completed closure of the shunt with normal movement and function valves. And no complication of arrhythmia has been recorded., Lessons: This case report highlighted the administration of ADO II in some ventricular septal defect with superior location, and provided an essential experience of using ADO II to close long tunnel type LV-RA shunt.

MicroRNAs (miRNAs) are important regulators in the process of cardiac hypertrophy and heart failure. Previous studies have shown that miR-199a is upregulated in pressure-overload cardiac hypertrophy and that inhibition of miR-199a attenuates cardiac hypertrophy in vitro . However, the therapeutic role of anti-miR-199a treatment in the cardiac hypertrophy in vivo model is less known. Here, we show an efficient and useful method to treat mouse cardiac hypertrophy and restore cardiac function through injection of adeno-associated virus (AAV)-mediated anti-miR-199a tough decoys (TuDs). RNA-seq transcriptome analysis indicated that genes related to cytoplasmic translation and mitochondrial respiratory chain complex assembly were upregulated in anti-miR-199a-treated recovered hearts. We further validated that PGC-1α is the direct target of miR-199a involved in the therapeutic effect and the regulation of the PGC-1α/ERRα axis and that the downstream pathway of mitochondrial fatty acid oxidation and oxidative phosphorylation constitute the underlying mechanism of the restored mitochondrial structure and function in our anti-miR-199a-treated mice. Our study highlights the important regulatory role of miR-199a in cardiac hypertrophy and the value of the AAV-mediated miRNA delivery system., Competing Interests: The authors declare no competing interests., (© 2020 The Author(s).)

Rationale: Pulmonary hemorrhage is a rare but fatal complication of Henoch-Schönlein purpura (HSP), and more easily ignored in children than in adults due to the absence of clinically evident hemoptysis. Moreover, despite being sporadically reported, given that pulmonary hemorrhage may develop after regression and even disappearance of skin rash, the asynchronous progression of skin and lung lesions poses escalating challenges in the timely diagnosis. We herein presented a delayed diagnosis of late-onset pulmonary hemorrhage in a child with HSP after regression of purpuric rash., Patient Concerns: A 6-year and 3-month child with a history of self-resolved purpuric rash three weeks ago, presented acutely with cough and dyspnea but without fever., Diagnoses: The decreased hemoglobin and diffuse ground-glass opacities of both lungs on CT scan weren't comprehensively evaluated. The child was initially misdiagnosed as pneumonia., Interventions: Antibiotic treatment was initiated. However, no improvement of respiratory status was found following aggressive combination therapy. Bronchoscopy was subsequently performed., Outcomes: An diffuse alveolar hemorrhage with low inflammatory profile was noted after a bronchoscopy. Considering the history of HSP, the diagnosis of HSP-associated pulmonary hemorrhage was ultimately confirmed and the patient received corticosteroids with satisfactory results., Lessons: Pulmonary hemorrhage could occur in children with HSP at late onset of disease after regression of skin rash. New-onset respiratory symptoms in patients with a history of HSP should heighten suspicion for pulmonary hemorrhage, particularly if presenting with lack of fever, sudden drop of hemoglobin, new pulmonary infiltrates and unresponsiveness to antibiotics therapy. Bronchoscopy should be performed early to confirm the diagnosis, specifically for children.

Rationale: To discuss suitable criteria for the application of asymmetric Amplatzer occluders for perimembranous ventricular septal defects (pmVSDs)., Patients Concerns and Diagnoses: We retrospectively studied 18 children with perimembranous VSDs who underwent attempted asymmetric occluder closure between January 2015 and December 2018 in our center., Interventions: Asymmetric Amplatzer occluders were attempted to be placed to all the enrolled patients. We analyzed the diameter of the defects with the receiver operating characteristic curve (ROC) values, the size of the occluders attempted, the presence of aneurysm and the presence of aortic valve prolapse for each patient. Then, for patients who experienced successful device implantation, the therapeutic efficiency was evaluated by follow-up., Outcomes: Only 5 out of a total of 18 patients completed successful device implantation. Compared with failed cases, successful cases demonstrated a significantly smaller VSD size (5.46 ± 1.03 mm vs. 8.73 ± 2.33 mm, P = 0.012) and had a low ratio of aortic valvar prolapse (20% vs. 76.92%, P = 0.026). Four out of 5 successful cases involved arrhythmia complications, but the rhythm of the heart recovered after drug treatment. According to the ROC and Youden analyses, the cut-off value of the defect size for successful asymmetric Amplatzer occluder implantation was no larger than 5.7 mm., Lessons: The application of an asymmetric Amplatzer occluder expands the range of indications for patients with superior localized VSD but is largely limited in cases with aortic valvar prolapse and large VSD sizes. All successful cases recovered from arrhythmia postprocedure.

Rationale: Coronary artery abnormalities are usually of major significance in clinical cardiology and cardiac surgery departments due to associated myocardial ischemia, myocardial infarction, and sudden cardiac death. Among them, anatomical malformations account for most coronary artery abnormalities. However, hypoplasia of the coronary artery is a rare type of coronary artery without any genetic screening information., Patient Concerns: A 10-year-old boy suffered severe chest pain, and a subsequent syncope occurred., Diagnosis and Intervention: The boy complained of significant chest pain with syncope. Computerized tomography (CT) angiography scanning showed that the left coronary artery was dominated by abnormal origins and dramatically narrow artery lesions. Moreover, cardiac magnetic resonance imaging (MRI) confirmed myocardial ischemia. Cardiac catheterization confirmed that this was an extremely rare hypoplastic coronary case. Finally, a mutation was identified in NOTCH1 c.1023C>A for the first time., Outcomes: The boy was discharged after completing all examinations and was forbidden to play any kind of sport activity while waiting for heart transplantation., Lessons: Hypoplastic coronary artery diseases have only been reported within very limited cases. This is the only report that has identified hypoplasia in 3 epicardial major coronary arteries. In addition, this is the first case to provide evidence between NOTCH1 genetic disorder and hypoplastic coronary artery disease in the clinic.

Background: Kawasaki disease (KD) is an acute, self-limiting systemic vasculitis that predominately affects children. Neurological involvement is a known complication of KD, however, its association with KD severity remains elusive. We aimed to systematically describe the general manifestations of neurological involvement in KD, determine whether neurological involvement is a marker of disease severity in patients with KD, and assess the relationship of such involvement with intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs)., Methods: We retrospectively reviewed data from 1582 patients with KD between January 2013 and December 2017. Profiles of patients with neurological symptoms (group A, n = 80) were compared to those of gender- and admission date-matched patients without neurological involvement (group B, n = 512). Multivariate logistic regression analyses were performed to determine whether neurological involvement was significantly associated with IVIG resistance., Results: Neurological involvement was observed in 5.1% (80/1582) of patients with KD. The neurological manifestations were diffuse, presenting as headache (13/80, 16.3%), convulsions (14/80, 17.5%), somnolence (40/80, 50.1%), extreme irritability (21/80, 26.3%), signs of meningeal irritation (15/80, 18.8%), bulging fontanelles (7/80, 8.8%), and facial palsy (1/80, 1.3%). Neurological symptoms represented the initial and/or predominant manifestation in 47.5% (38/80) of patients with KD. The incidence of IVIG resistance and levels of inflammatory markers were higher in group A than in group B. However, neurological involvement was not an independent risk factor for IVIG resistance or CALs., Conclusion: Rates of neurological involvement were relatively low in patients with KD. Neurological involvement was associated with an increased risk of IVIG resistance and severe inflammatory burden. Our results highlight the need for pediatricians to recognize KD with neurological involvement and the importance of standard IVIG therapy., Trial Registration: Retrospectively registered.

The evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for intravenous immunoglobulin resistance prediction was prospectively performed in a large cohort of Kawasaki disease patients. It was found that the predictive values of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, alone or combined, were not good enough although they were identified as independent risk factors for intravenous immunoglobulin resistance.

Background: Patent ductus arteriosus (PDA) is a particularly common problem in preterm infants. Although surgical ligation is rarely performed in many contemporary neonatal intensive care units, it remains a necessary treatment option for preterm infants with a large hemodynamically significant PDA under strict clinical criteria, and it can reduce mortality in preterm infants. However, the optimal timing of surgical ligation is still controversial. We conducted this systematic review and meta-analysis to compare the mortality and morbidity of early and late surgical ligation of PDA in preterm or very-low-birth-weight (VLBW) infants., Methods: This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42019133686). We searched the databases of PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the World Health Organization International Clinical Trials Registry Platform up to May 2019., Results: This review included 6 retrospective studies involving 397 premature or VLBW infants with PDA. Pooled analysis showed that compared with the late ligation group, the early ligation group had a lower fraction of inspired oxygen (FiO2) at 24 hours postoperatively (mean difference [MD] -6.34, 95% confidence interval [CI] -9.45 to -3.22), fewer intubation days (MD -19.69, 95% CI -29.31 to -10.07), earlier date of full oral feeding (MD -22.98, 95% CI -28.63 to -17.34) and heavier body weight at 36 weeks of conceptional age (MD 232.08, 95% CI 57.28 to 406.88). No significant difference in mortality or other complications was found between the early and late groups., Conclusion: Our meta-analysis implies that compared with late surgical ligation, early ligation might have a better respiratory outcome and nutritional status for PDA in preterm or VLBW infants. There was no difference in mortality or postoperative complications between early and late ligation. A randomized prospective clinical trial with a possible large sample size is urgently needed to reinvestigate this conclusion., Prospero Registration Number: CRD42019133686.

Rationale: Although implantation of Amplatzer membranous ventricular septal defect occluder (AVSDO) is an alternation to surgical treatment, the interventional therapy is disapproved by FDA due to high incidence of complete atrioventricular block (cAVB) post closure during early and middle term follow-up. However, long-term outcomes of the accumulating numbers of patients who had received AVSDO in the past decades, still remain an issue of concern and late occurrence of potentially catastrophic heart block long after hospital discharge is especially worrying, but rarely documented. We firstly reported a pediatric case with very late-onset cAVB occurring over ten years following transcatheter closure of PmVSD using AVSDO., Patient Concerns: A 5-year old female received transcatheter closure of PmVSD sized 10-mm on left ventricular angiography with a 14-mm AVSDO owning to a history of recurrent lower respiratory tract infections. Post-procedure echocardiography documented no arrhythmias, residual shunt and aortic regurgitation. All electrocardiogram (ECG) recordings were completely normal and transthoracic echocardiography (TTE) examination showed the device was in the proper position and there was neither residual shunt nor valves regurgitation. Ten years after operation, the patient was re-admitted into our hospital due to recurrent syncope., Diagnoses: A 12-lead ECG showed cAVB with a minimal heart rate of 42 bpm. Device flattening was revealed on 2-dimensional TTE and the occluder appeared to return to its original size and shape. Computed tomography and magnetic resonance imaging of brain did not reveal any intracranial hemorrhages, ischemic changes, or space-occupying lesions. Electroencephalogram detected no epileptiform discharge. Other possible etiologies resulting in cAVB such as myocarditis, hypothyroidism and connective tissue diseases were excluded. Therefore, it was ultimately considered the cAVB was mostly likely to be associated with device closure of PmVSD using AVSDO., Interventions: The child was empirically treated with prednisone (1-2 mg/Kg daily)., Outcomes: Unfortunately, no improvement was observed. A permanent pacemaker was implanted. The following course was uneventful., Lessons: For patients following transcatheter closure of PmVSD using AVSDO, the risk period for developing heart block after device closure appears to be much longer than we speculated. Long-term, perhaps and life-long followed up needs to be considered for this group of patients.

Rationale: Tricuspid regurgitation (TR) is a frequent finding during echocardiography screening in fetal or neonatal life, which reveals a weak association between TR and cardiac malformation. Except for structural abnormalities, dilated cardiomyopathy (DCM) ranks as the top reason for early child morbidity and mortality among all kinds of cardiomyopathy. In the early fetal stage, cardiac abnormalities detected by early fetal genetic testing followed by abnormalities on ultrasound would provide more valuable information for parents and physicians to make a better therapeutic schedule., Patient Concerns: A case of severe TR was found via the fetal ultrasound screening. After birth, this child suffered severe heart dysfunction, and echocardiography confirmed a DCM phenotype within a very short time., Diagnosis and Intervention: A 40-year-old female received routine fetal echocardiographic screening, which demonstrated that the fetus presented severe TR. Six months after birth, the baby experienced severe heart failure, as the EF dropped to 22% with an extremely large LV chamber. The genomic sequence had been determined, and 3 pathogenic gene mutations located in 2 genes, cardiac troponin T (TNNT2) c.548G>A, desmoplakin (DSP) c.3146C>T, and DSP c.5213G>A, were identified. Finally, the patient was diagnosed with DCM. This child received digoxin, hydrochlorothiazide, spironolactone diuresis, captopril, and L-carnitine, and the symptoms of heart failure had been controlled as the patient waited for heart transplantation., Outcomes: During the follow-up, the patient still suffered from poor heart function and an enlarged left ventricle. Concomitantly, the parents placed her on a waiting list for heart transplantation., Lessons: Fetal TR is a common phenomenon, and many studies have indicated that isolated TR is not an appropriate predictor of chromosomal abnormalities or congenital heart defects. However, according to this case, it is urgent to recommend that the mother should take advantage of free fetal DNA analysis in a maternal blood sample to obtain further molecular evidence once fetal echocardiography reveals moderate to severe TR with any maternal high-risk factors for birth defects.

Rationale: Non-significant residual shunt is a relatively common complication after device closure of perimembranous ventricular septal defects (Pm-VSD). Lifelong antibiotic prophylaxis has been recommended in guidelines to avoid infectious endocarditis (IE) if residual shunt remains. Clinicians, however, rarely follow it in their practice and regular follow-up was the most common option since post-procedure IE after transcatheter closure of PmVSD is rarely reported. We firstly described a case of IE after transcatheter closure of PmVSD with modified symmetrical double-disk device with a residual shunt, highlighting the need for reassessing the prognostic implications of post-procedure non-significant residual shunt and the most appropriate treatment strategy., Patient Concerns: A 3-year old female received transcatheter closure of PmVSD sized 5.0 mm on left ventricular angiography with an 8-mm modified symmetric double-disk occluder (SHAMA) owing to a history of recurrent lower respiratory tract infections. Post-procedure echocardiography documented a non-significant residual shunt, but no additional interventions were performed. Two months post procedure, the child was re-admitted into our department with a complaint of persistent fever up to 41°C for 11 days and nonresponse to 1-week course of amoxicillin., Diagnoses: The diagnosis of post procedure IE was established since a vegetation (13 × 9 mm) was found to be attached to the tricuspid valve and the occluder, and Staphylococcus aureus was isolated from all three-blood cultures., Interventions: After 6 weeks of vancomycin treatment, the vegetation disappeared with no sign of valvular dysfunction. Three weeks after discharge, a second device was implanted to abolish persistent residual flow., Outcomes: Unfortunately, the child was ultimately transferred to surgical department due to severe hemolysis after the second device implantation. The occluders were removed and the VSD was closed with a pericardial patch. Tricuspid valvuloplasty was also performed and the following course was uneventful., Lessons: For non-significant residual shunt after device closure of PmVSD, implantation of a second device or surgical repair may be a better and more satisfactory alternative compared with lifelong antibiotic prophylaxis or no interventions, since associated IE can indeed occur despite its rarity and the risk of antibiotic-associated adverse events may outweigh the benefits.

Rationale: Hemoptysis is an uncommon chief complaint but a distressing symptom in pediatric patients. Due to the recurrence and mortality in minor patients, an accurate diagnosis of the underlying cause is quite essential for treatment. The etiologies causing hemoptysis in children are similar to that in adults. Isolated unilateral pulmonary vein atresia (PVA), as an unusual cardiovascular anomaly, has rarely been reported to be an etiology of hemoptysis in children., Patient Concerns: A 2-year and 11-month-old boy was admitted into our hospital with a complaint of recurrent hemoptysis for 2 months and the symptom became more aggravated in recent 4 days before admission. Physical examination was only remarkable for slightly diminished breath sounds over the left lung field, pale face, and colorless lip. Series of targeted laboratory evaluation were negative expect for anemia. Due to the identification of asymmetrical transparency of bilateral lung, slight emphysema of right lung, less volume of left lung with ground-glass opacity and reticular opacity, and ipsilateral mediastinal shift on chest CT, and varices of submucosal vessels in the left bronchial tree on the fiber-optic bronchoscope., Diagnoses: It more likely indicated a congenital cardiovascular disease. The diagnosis of left isolated unilateral PVA was ultimately confirmed through chest CT angiography (CTA) with three-dimensional (3D) reconstruction., Interventions: Since the boy did not complain with hemoptysis after admission, respiratory tract infections seldom occurred and no pulmonary hypertension was detected, a conservative approach was chosen with periodic clinical follow-up after discussing with the cardiac surgeons and in accordance to his parents' own wishes., Outcomes: Fortunately, he was doing well after 3 months of clinical observation., Lessons: We firstly reported a rare case of hemoptysis in children secondary to isolated unilateral PVA with no associated congenital heart disease in Chinese population. It is significant to improve the recognition and prompt diagnosis of this rare condition for pediatric clinicians, and widen the etiology spectrum of hemoptysis in children. The diagnosis of unilateral PVA should be considered for a patient with recurrent hemoptysis and imaging findings that indicate hypoplastic lung, ipsilateral mediastinal shift, and smooth margins of left atrium without evidence of rudimentary pulmonary veins.

Introduction: Placental P-glycoprotein (P-gp) plays a significant role in regulating drugs' transplacental transfer rates. Investigations on placental P-gp regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the epigenetic regulation of placental P-gp is rare. Our previous study has demonstrated that HDACs inhibition could up-regulate placental P-gp and HDAC1/2/3 might be involved in this process. The present study was carried out to further explore whether HDAC1/2/3 were indeed involved in the regulation of placental P-gp or not and screen out the subtype engaged in this process., Methods: BeWo and JAR cells were transfected with HDAC1/2/3 specific siRNA. After 48 h of transfection, cells were harvested for real-time quantitative PCR (qRT-PCR), Western blot, immunofluorescence and fluorescent dye efflux assay to evaluate P-gp expression, localization, and efflux activity, respectively. Hdac2 siRNA was intraperitoneally injected to pregnant mice every 48 h from E7.5 to E15.5 and digoxin was administered by gavages 1 h prior to euthanasia at E16.5. Placental Hdac1/2/3 and P-gp expression were determined by qRT-PCR and Western blot. Maternal plasma and fetal-unit digoxin concentrations were detected by enzyme-multiplied immunoassay., Results: In vitro, HDAC2 inhibition could significantly elevate P-gp expression and reduce intracellular accumulation of P-gp substrates (DiOC 2 (3) and Rh 123) both in BeWo and JAR, while knockdown of HDAC1/3 had no influence on P-gp expression and its efflux activity. Additionally, in vivo, Hdac2 silencing in pregnant mice also elevated placental P-gp expression and decreased digoxin transplacental transfer rate., Conclusion: HDAC2 inhibition could result in induction of placental P-gp expression and functionality both in vitro and in vivo., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

microRNAs (miRNAs) belong to a class of non-coding RNAs that regulate post-transcriptional gene expression during development and disease. Growing evidence indicates abundant miRNA expression changes and their important role in cardiac hypertrophy and failure. However, the role of miRNAs in fetal cardiac remodeling is little known. Here, we investigated the altered expression of fifteen miRNAs in rat fetal cardiac remodeling compared with adult cardiac remodeling. Among fifteen tested miRNAs, eleven and five miRNAs (miR-199a-5p, miR-214-3p, miR-155-3p, miR-155-5p and miR-499-5p) are significantly differentially expressed in fetal and adult cardiac remodeling, respectively. After comparison of miRNA expression in fetal and adult cardiac remodeling, we find that miRNA expression returns to the fetal level in adult cardiac failure and is activated in advance of the adult level in fetal failure. The current study highlights the contrary expression pattern between fetal and adult cardiac remodeling and that supports a novel potential therapeutic approach to treating heart failure.

Transcatheter closure has become one of the alternations of surgical treatment since 1988. However, cAVB occurred as a threatening incidence of 6.8% after Amplatzer VSD Occluder closure, which was quite higher than the incidence of 1% to 2% post-surgical closure, which leaded this kind of technique, was not approved by FDA. In this commentary, we reviewed the publications of cAVB following the device closure, and summarized current data of Modified Amplatzer-type Occluder during long-term follow-up, especially introduced the experiences from China, where this kind of treatment became a routine procedure for VSD children. Moreover, we carried our visualized analysis based on scientific literatures using CiteSpace to draw knowledge burst mapping, which revealed the development procedure on this interested topics, and demonstrated the role of China's works to make contributions in the field, and figured out the limitation of our researches, which supplied a basic understanding on why we could not impact the world. Finally, it concluded that transcatheter closure of pmVSD with Modified Amplatzer-type Occluder would be safe and efficient with low incidence of well controlled complications, but it failed to spread our experiences in a more scientific way. And, we hope this kind of therapy could be accepted in a wider region of the world with the increasing evidence from China., (© 2016 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Introductions: Placental P-glycoprotein (P-gp), encoded by ABCB1 gene in human, plays a significant role in regulating drugs' transplacental transfer rates. Investigations on placental P-gp regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the epigenetic control of placental P-gp is rare. This study aimed to investigate the effect of histone deacetylases (HDACs) inhibition on P-gp expression in placental trophoblast cell lines and to explore whether HDAC1/2/3 was involved in this process preliminarily., Methods: Human placental trophoblast cell lines (Bewo and JAR) were treated with two different HDAC inhibitors-suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) at different concentration gradients of 0.5, 1.0, 3.0 and 5.0 μM. Cells were harvested after 24, 48, and 72 h treatment. Total HDAC activity was detected by colorimetric assay Kits. HDAC1/2/3/ABCB1 mRNA and protein expressions were determined by real-time quantitative PCR and western-blot, respectively. Pearson correlation analysis test was performed to explore the relationship between HDAC1/2/3 mRNA and ABCB1 mRNA expression., Results: SAHA and TSA could inhibit total HDAC activity and placental HDAC1/2/3 expression both in Bewo and JAR, but displayed a transient induction of HDAC mRNA or protein level after being treated at low dosage or prolonged exposure to drugs. Discordance in HDAC mRNA and protein expression was also observed. Placental P-gp expression was significantly induced in company with HDACs inhibition. There was a significant negative linear relationship between HDAC1/2 mRNA and ABCB1 mRNA expression., Conclusions: HDACs inhibition could up-regulate placental P-gp expression in trophoblast cells, and HDAC1/2 was most likely to be involved in this process., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Placental P-glycoprotein (P-gp) plays a significant role in controlling transplacental digoxin transfer rate. Investigations on P-gp regulation in placenta of women with different pregnant pathological states are of great significance to individualized transplacental digoxin treatment for fetal heart failure (FHF). This study aimed to explore the effect of 17α-ethynylestradiol induced intrahepatic cholestasis of pregnancy (ICP) on placental P-gp in mice., Methods: ICP model in mice was induced by subcutaneous injection of 17α-ethynylestradiol dissolved in propylene glycol once daily from E12.5 to E16.5. Maternal plasma ALT, AST, TB, DBIL, γ-GT, LDH, ALP and TBA concentrations were measured. HE staining was applied for observation of maternal liver cells degeneration, necrosis and intrahepatic cholestasis. Placental Abcb1a/Abcb1b/HIF-1α mRNA and P-gp/HIF-1α protein expression were determined by real-time quantitative PCR and western-blot. Maternal plasma and fetal-unit digoxin concentrations were detected by a commercial kit assay., Results: The ICP group showed higher levels of maternal plasma ALT, AST, TB, DBIL, γ-GT, LDH, ALP and TBA concentrations, reduction in fetal survival rates, lower placental and fetal weights, and typical liver cells degeneration, necrosis and intrahepatic cholestasis. The placental Abcb1a mRNA and P-gp expression of ICP group were significantly elevated, while transplacental digoxin transfer rates were significantly decreased. Both placental HIF-1α mRNA and protein expression was significantly elevated in the ICP group, and there was a positive correlation between Abcb1a mRNA and HIF-1α mRNA., Conclusions: 17α-ethynylestradiol induced ICP could up-regulate placental P-gp expression and reduce transplacental digoxin transfer rate in mice, which might be partly associated with higher expression of HIF-1α., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To investigate the characteristics of haemodynamically significant patent ductus arteriosus (hsPDA), and the indications of percutaneous transcatheter PDA occlusion., Method: The data of a preterm infant admitted to West China Second Hospital in December. 2013, who finally underwent percutaneous transcatheter PDA occlusion were analyzed With the key words of"preterm""patent ductus arteriosus""transcatheter", Pubmed were searched and potentially relevant reports were retrieved and assessed by manual sorting from 2005 to 2015. Relevant reports in literature were reviewed., Result: A preterm infnat at gestational age of 35 weeks with birth weight of 1 900 g was admitted to our department. Oral ibuprofen for closure of the patent ductus arteriosus failed, and the patient exhibited the features of"ventilator dependent"PDA of premature infants. On the 30th postnatal day, with the body weight of 1 950 g, under basal anesthesia, the infant underwent percutaneous transcatheter PDA occlusion, and the procedure successfully occluded the ductus with Amplatzer duct occluder (ADO). The ventilator was weaned 19 hours post procedure, and the child was discharged 7 days post operation with good recovery, and her growth and development was good. Follow-up for 13 months indicated that the intelligence and physical development evaluated by Bayley scales of infant development test were at the same level of normal age-matched infants. Fifty-two preterm infants treated with percutaneous transcatheter PDA occlusion in 8 reports were enrolled. The preterm infants were born at 23-35 gestational weeks, with PDA diameter of 1-4 mm. The occlusive device included coil, ADO, ADO Ⅱ, ADO Ⅱ AS, AVP Ⅱ and AVP Ⅳ respectively, with body weight of 870-2 610 g on operational days and age of 11-90 postnatal days. All those infants either failed or had contraindications to drug therapy, and exhibited as hsPDA cases. Percutaneous transcatheter PDA occlusions were performed successfully in all 52 cases, and there were no serious procedure-related complications., Conclusion: Percutaneous transcatheter PDA occlusion in preterm infants is feasible and showed positive short-term and long-term effects, which provides an important alternative way for patients with the problem. The indications for transcatheter PDA occlusion include premature infants with hsPDA in whom drug therapy failed or is contraindicated.

Introductions: Placental P-glycoprotein (P-gp) plays a significant role in controlling digoxin transplacental rate. Investigations on P-gp regulation in placenta of women with different pregnant pathology are of great significance to the individualized transplacental digoxin treatment for fetal heart failure (FHF). This study aimed to explore the effect of maternal obesity on the expression and functionality of placental P-gp both in human and in mice., Methods: Placenta tissues from obese and lean women were collected. Female C57BL mice were fed with either a normal chow diet or a high-fat diet for 12 weeks before mating and throughout pregnancy. Maternal plasma glucose, HDL-C, LDL-C, TC, TGs, insulin, IL-1β, IL-6 and TNF-α concentrations was detected. Placental ABCB1/Abcb1a/Abcb1b/IL-1β/IL-6/TNF-α mRNA and P-gp/IL-1β/IL-6/TNF-α protein expression were determined by real-time quantitative PCR and western-blot, respectively. Maternal plasma and fetal-unit digoxin concentrations were detected by a commercial kit assay., Results: Both ABCB1 gene mRNA and protein expression of obesity group was significantly lower than that of control group in human. The high-fat dietary intervention resulted in an overweight phenotype, a significant increased Lee's index, higher levels of plasma glucose, HDL-C, LDL-C, insulin and TGs, increased peri-renal and peri-reproductive gland adipose tissue weight, and larger size of adipose cell. Compared with control group at the same gestational day (E12.5, E15.5, E17.5), placental Abcb1a mRNA and P-gp expression of obese group were significantly decreased in mice, while digoxin transplacental rates were significantly increased. Higher maternal plasma IL-1β/TNF-α concentrations and placental IL-1β/TNF-α expression were observed in obesity groups in comparison with control group at the same gestational age., Conclusions: Maternal obesity could inhibit placental P-gp expression and its functionality both in human and in mice, which might be resulted from a heightened inflammatory response., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Arrhythmias are frequently observed after transcatheter closure of perimembranous ventricular septal defect (pmVSD), especially in the early postprocedure period. Independent risk factors associated with postclosure arrhythmias are still elusive. The current study aimed to identify such risk factors via regression analysis with a long-term follow-up., Methods: A group of 553 patients from June 2003 to December 2010 who received symmetric Amplatzer-type pmVSD occluders for pmVSD in our center were followed for 2-8 years. The complications during the follow-up period were classified as early (within 1 year), continuous (persisted >1 year), or late (recurrent or onset after 1 year). We first evaluated the potential risk factors (age, procedure time, size of the defect, size of the occluder, diameter of the defect, distance of lesion to aortic rim, distance of lesion to tricuspid rim, presence of aneurysm, orifice size on aneurysm, arrhythmia before procedure, procedure time) by comparing complicated and uncomplicated cases using univariate analysis, then logistic analysis for independent risk factors., Results: We identified 90 cases of early, 59 cases of continuous, and 13 cases of late complications. The size of the occluder was identified as an independent risk factor for early, continuous, and late arrhythmias. Preexisting arrhythmias were found to be risk factors for early and late arrhythmias, while the distance between the defect and the tricuspid rim was identified as a risk factor for continuous arrhythmias., Conclusion: The size of the occluder, preexisting arrhythmias, and the distance between the defect and the tricuspid rim were found to be risk factors for arrhythmias after transcatheter closure of pmVSD. Selection of properly sized occluders might be crucial to reduce postclosure complications.

Molecular switches of myosin isoforms are known to occur in various conditions. Here, we demonstrated the result from fetal heart failure and its potential mechanisms. Fetal and adult heart failure rat models were induced by injections of isoproterenol as previously described, and Go6976 was given to heart failing fetuses. Real-time PCR and Western blot were adopted to measure the expressions of α-MHC, β-MHC and YY-1. Co-immunoprecipitation was performed to analysis whether YY-1 interacts with HDAC5. Besides, histological immunofluorescence assessment was carried out to identify the location of HDAC5. α-MHC was recorded elevated in fetal heart failure which was decreased in adult heart failure. Besides, YY-1 was observed elevated both in fetal and adult failing hearts, but YY-1 could co-immunoprecipitation with HDAC5 only in adult hearts. Nuclear localization of HDAC5 was identified in adult cardiomyocytes, while cytoplasmic localization was identified in fetuses. After Go6976 supplied, HDAC5 shuttled into nucleuses interacted with YY-1. The myosin molecular switches were reversed with worsening cardiac functions and higher mortalities. Regulation of MHC in fetal heart failure was different from adult which provided a better compensation with increased α-MHC. This kind of transition was involved with shuttling of HDAC5 regulating YY-1 function.

Objective: To evaluate the safety of the circular round window and discus anatomic landmarks of posterior wall of internal auditory canal by investigating the microscopic anatomy of internal auditory canal area of the retrosigmold approach, which can provide the anatomical basis for acoustic neutrinomas surgery., Method: Fifteen adult cadaver heads (30 sides) fixed with formalin were used in the study. The retrosigmold approach operations were imitated to dissect the blood vessels and nerves in internal auditory canal area by opening round bony window and removing posterior wall of internal auditory canal., Result: Fifteen specimens of 30 sides circular bone window were opened without injury with transverse sinus and sigmoid sinus. The vertical distance between the highest point of bone window margo superior and the lowest point of transverse sinus margo inferior was (4.02 ± 0.32) mm. The vertical distance from the most anterior point of bone window leading edge to the most posterior point of sigmoid sinus trailing edge was (6.31 ± 0.43) mm. The internal auditory canal tubercle located in the anterior superior position of internal auditory canal. The vertical distance from the highest point of internal auditory canal tubercle to the upper margin of internal auditory canal was (2.31 ± 0.32) mm. To expose the whole internal auditory canal, the length and width of the internal auditory canal posterior wall removal was (7.29 ± 0.32) mm, (4.12 ± 0.29) mm. Within this removal range, no case of cochlea, semicircular canal or venous was injured in 30 specimens., Conclusion: The method of opening round window through retrosigmold approach is simple, practial and convenient. With little variation and easiness of location, the sinternal auditory canal tubercle can be used in the identification of the internal auditory canal. When exposing the whole internal auditory canal, the removal scope of the posterior wall should be paid more attention to, in order to avoid the damage of cochlea, semicircular canal and jugular bulb.

Background: The prognostic implications of clinically silent coronary artery fistula (CAF) and its intermediate/long-term outcomes after transcatheter closure have not been well studied, especially in children., Aims: This study intended to determine the prognostic implications of asymptomatic CAF and to evaluate the intermediate follow-up outcomes following transcatheter occlusion with patent ductus arteriosus (PDA) in children., Methods: Eighteen children with congenital CAF were divided into two groups: the intervention group (n = 14; maximal coronary artery diameter [MCD] ≥5 mm and/or fistulous orifice diameter [FOD] >2 mm), and the non-intervention group (n = 4; MCD <5 mm and FOD ≤2 mm). Patients in the intervention group received percutaneous occlusion with PDA occluder. Clinical outcomes and follow-up data were analyzed and compared between different groups., Results: Patients with clinically silent CAF were followed for 8-130 months. At the mean follow-up of 36 months, patients in the non-intervention group did not show any changes in the measured parameters over time. In contrast, patients in the intervention group showed significant increase of MCD (8.31 ± 2.16 mm to 12.75 ± 3.01 mm; P=.001) and FOD (3.75 ± 3.42 mm to 4.82 ± 1.81 mm; P=.03). In addition, 3 cases of aneurysm formation and 2 cases of mild heart failure were detected before the patients received the attempted transcatheter closure. A total of 14 patients underwent cardiac catheterization with an attempt to close the CAF. Placement of occlusion devices succeeded in 10 patients (71.5%) and failed in 4 patients (28.5%). Ten children with successful transcatheter closure were followed 3-62 months (median, 36 months). At the medial time of 36 months, all patients with closure were in New York Heart Association functional class I and asymptomatic. The MCD decreased from 9.66 ± 3.86 mm to 7.82 ± 3.83 mm (P=.36)., Conclusion: All asymptomatic CAFs in children with MCD ≥5 mm and/or FOD >2 mm should be closed as early as possible to prevent later complications. Transcatheter closure of CAF using the PDA occluder is an effective and safe approach in appropriately selected children and showed favorable intermediate-term follow-up outcomes.

Matrine, one of the Chinese herbal medicine, has anti-tumor activity in a variety of tumor cells. However, its anti-tumor activity in human medulloblastoma remains unclear. The aim of this study was to investigate the presence and mechanism of matrine-induced proliferation and apoptosis in human medulloblastoma D341 cells. D341 cells were divided into experimental groups in which matrine were added at different concentrations and a control group under the same conditions without matrine applied. D341 cell proliferation was analyzed using a cell counting kit-8 assay, apoptosis was detected by annexin-V FITC/PI double-staining, and the expression of Bax, Bcl-2, caspase-3 and caspase-9 was detected by Western blotting. Results showed that matrine significantly inhibited the proliferation of D341 cells. The cells displayed more and larger cytoplasmic vacuoles, and formed apoptotic bodies after matrine treatment. Western blotting analysis showed that expressions of Bax, caspase-3 and caspase-9 increased, while that of Bcl-2 decreased as the drug concentration gradually increased. The study suggests that matrine could induce human medulloblastoma D341 cells apoptosis and inhibit the cells proliferation in vitro by activating Bax, caspase-3 and caspase-9 and reducing Bcl-2 expression.