Incomplete Kawasaki disease complicated with acute abdomen: A case report

Kawasaki disease(KD)is an acute systemic vasculitis characterized by unknown etiology.CASE SUMMARY A 4.5-year-old boy developed an acute abdomen during the onset of incomplete KD.He still had persistent abdominal pain after undergoing exploratory laparotomy and appendectomy.Ultrasound examination at early onset revealed a giant coronary artery aneurysm.The patient developed a myocardial infarction and heart failure accompanied by respiratory and cardiac arrest.He underwent coronary artery revascularization and coronary artery bypass graft using an autologous internal mammary artery.After the operation,the cardiac output increased,and the symptoms of heart failure resolved.Follow-up evaluation at 1 mo after operation showed that the patient's cardiac function had restored to New York Heart Association standard Grade I heart failure,and normal growth was obtained.CONCLUSION Coronary artery revascularization and coronary artery bypass graft is an effective method for treating myocardial ischemia in children with KD complicated with giant coronary artery aneurysm.Nevertheless,some issues still need specific attention.

On the Scalable Fairness and Efficient Active Queue Management of RED

Internet routers generally see packets from a fast flow more often than a slow flow. This suggests that network fairness may be improved without per-flow information. In this paper, we propose a scheme using Most Recently Used List (MRUL)-a list storing statistics of limited active flows that sorted in most recently seen first mode-to improve the fairness of RED. Based on the list, our proposed scheme jointly considers the identification and punish of the fast and unresponsive fast flows, and the protection of slow flows. Its performance improvements are demonstrated with extensive simulations. Different from the previous proposals, the complexity of our proposed scheme is proportional to the size of the MRUL list but not coupled with the queue buffer size or the number of active flows, so it is scalable and suitable for various routers. In addition, another issue we address in this paper is queue management in RED. Specifically, we replace the linear packet dropping function in RED by a judicially designed nonlinear quadratic function, while original RED remains unchanged. We call this new scheme Nonlinear RED, or NLRED. The underlying idea is that, with the proposed nonlinear packet dropping function, packet dropping becomes gentler than RED at light traffic load but more aggressive at heavy load. As a result, at light traffic load, NLRED encourages the router to operate in a range of average queue sizes rather than a fixed one. When the load is heavy and the average queue size approaches the pre-determined maximum threshold (i.e. the queue size may soon get out of control), NLRED allows more aggressive packet dropping to back off from it. Simulations demonstrate that NLRED achieves a higher and more stable throughput than RED and REM. Since NLRED is fully compatible with RED, we can easily upgrade/replace the existing RED implementations by NLRED.

Autoimmune-associated Congenital Heart Block： A New Insight in Fetal Life

Objective： Congenital heart block （CHB） is a rare but life-threatening disorder. More than half of CHB cases are associated with maternal autoimmune, which are termed as autoimmune-associated CHB. This review summarized the recent research findings in understanding autoimmune-associated CHB, discussed the current diagnostic approaches and management strategies, and summarized the problems and future directions for this disorder. Data Sources： We retrieved the articles published in English from the PubMed database up to January 2017, using the keywords including＂Autoimmune-associated＂, ＂Autoimmune-mediated＂, and ＂Congenital heart block＂. Study Selection： Articles about autoimmune-associated CHB were obtained and reviewed. Results： Observational studies consistently reported that transplacental maternal antibodies might recognize fetal or neonatal antigens in various tissues and result in immunological damages, but the molecular mechanisms underlying CHB pathogenesis still need illuminated. Multiple factors were involved in the process of atrioventricular block development and progression. While several susceptibility genes had been successfully defined, how these genes and their protein interact and impact each other remains to be explored. With currently available diagnostic tools, fetal ultrasound cardiography, and fetal magnetocardiography, most of CHB could be successfully diagnosed and comprehensively evaluated prenatally. The efficacy of current approaches for preventing the progression and recurrence of CHB and other autoimmune-mediated damages was still controversial. Conclusions： This review highlighted the relationships between autoimmune injuries and CHB and strengthened the importance of perinatal management and therapy for autoimmune-associated CHB.

Disruption of Planar Cell Polarity Pathway Attributable to Valproic Acid-Induced Congenital Heart Disease through Hdac3 Participation in Mice

Background： Valproic acid （VPA） exposure during pregnancy has been proven to contribute to congenital heart disease （CHD）. Our previous findings implied that disruption of planar cell polarity （PCP） signaling pathway in cardiomyocytes might be a factor for the cardiac teratogenesis of VPA. In addition, the teratogenic ability of VPA is positively correlated to its histone deacetylase （HDAC） inhibition activity. This study aimed to investigate the effect of the VPA on cardiac morphogenesis, HDAC1/2/3, and PCP key genes （Vangl2/Scrib/Rac 1）, subsequently screening out the specific HDACs regulating PCP pathway. Methods： VPA was administered to pregnant C57BL mice at 700 mg/kg intraperitoneally on embryonic day ! 0.5. Dams were sacrificed on E15.5, and death/absorption rates of embryos were evaluated. Embryonic hearts were observed by hematoxylin-eosin staining to identify cardiac abnormalities. H9C2 cells （undifferentiated rat cardiomyoblasts） were transfected with Hdac1/2/3 specific small interfering RNA （siRNA）. Based on the results of siRNA transfection, cells were transfected with Hdac3 expression plasmid and subsequently mock-treated or treated with 8.0 mmol/L VPA. Hdac1/2/3 as well as Vangl2/Scrib/Racl mRNA and protein levels were determined by real-time quantitative polymerase chain reaction and Western blotting, respectively. Total HDAC activity was detected by colorimetric assay.Results： VPA could induce CHD （P 〈 0.001） and inhibit mRNA or protein expression of Hdac1/2/3 as well as Vangl2/Scrib in fetal hearts, in association with total Hdac activity repression （all P 〈 0.05）. In vitro, Hdac3 inhibition could significantly decrease Vangl2/Scrib expression （P 〈 0.01 ）, while knockdown of Hdac 1/2 had no influence （P 〉 0.05）, VPA exposure dramatically decreased the expression of Vanlg2/Scrib together with Hdac activity （P 〈 0.01 ）, while overexpression of Hdac3 could rescue the VPA-induced inhibition （P 〉 0.05）. Conclusion： VPA could inhibit Hdac1/2/3, Vang12/Scrib, or total Hdac activity both in vitro and in vivo and Hdac3 might participate in the process of VPA-induced cardiac developmental anomalies.

Efficacy of prenatal diagnosis of major congenital heart disease on perinatal management and perioperative mortality: a meta-analysis

Background:There is no consensus on the effectiveness of prenatal diagnosis except for hospitalized outcomes.Hence,a meta-analysis of published literature was conducted to assess the effect of prenatal diagnosis.Methods:Literature review has identified relevant studies up to December 2013.A meta-analysis was performed according to the guidelines from the Cochrane review group and the PRISMA statement.Studies were identified by searching PubMed,Embase,the Cochrane Central Register of Controlled Trials and World Health Orgnization clinical trials registry center.Meta-analysis was performed in a fixed/random-effect model using Revman 5.1.1 according to the guidelines from the Cochrane review group and the PRISMA guidelines.Results:The results from 13 cohort studies in 12 articles were analyzed to determine the optimal treatment with the lower rate of perioperative mortality in prenatal diagnosis.The superiority of a prenatal diagnosis has been proven because the surgical procedure could be done in the early neonatal period(95%CI,-0.76,-0.40).The prenatal diagnosis has also remarkably reduced the preoperative and postoperative mortality rates in cases of transposition of the great arteries(95% CI=0.06,0.80;95%CI=0.01,0.82,respectively),as well as the overall results with all subtypes(95% CI=0.18,0.94;95% CI=0.46,0.94,respectively).Conclusions:Prenatal diagnosis is effective in perinatal management with an earlier intervention for major congenital heart disease,but only results in a reduced perioperative mortality in cases of transposition of the great arteries.Further investigations are required to evaluate the effect of prenatal diagnosis on life quality during a long-term follow-up.

Effect of Histone Deacetylase Inhibition on the Expression of Multidrug Resistance-associated Protein 2 in a Human Placental Trophoblast Cell Line

Background： Placental multidrug resistance-associated protein 2 （MRP2）, encoded by ABCC2 gene in human, plays a significant role in regulating drugs＇ transplacental transfer rates. Studies o11 placental MRP2 regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the roles of epigenetic mechanisms in regulating placental drug transporters are still unclear. This study aimed to investigate the effect of histone deacetylases （HDACs） inhibition on MRP2 expression in the placental trophoblast cell line and to explore whether HDAC 1/2/3 are preliminarily involved in this process. Methods： The human choriocarcinoma-derived trophoblast cell line （Bewo cells） was treated with the HDAC inhibitors-trichostatin A （TSA） at different concentration gradients of 0.5, 1.0, 3.0, and 5.0 μmol/L. Cells were harvested after 24 and 48 h treatment. Small interfering RNA （siRNA） specific for HDACI/HDAC2/HDAC3 or control siRNA was transfected into cells. Total HDAC activity was detected by colorimetric assay kits. HDAC 1/2/3/ABCC2 messenger RNA （mRNA） and protein expressions were determined by real-time quantitative polymerase chain reaction and Western-blot analysis, respectively. Immunofluorescence for MRP2 protein expression was visualized and assessed using an immunofluorescence microscopy and ImageJ software, respectively. Results： TSA could inhibit total HDAC activity and HDAC 1/2/3 expression in company with increase ofM RP2 expression in Bewo cells. Reduction of HDAC 1 protein level was noted after 24 h of TSA incubation at 1.0, 3.0, and 5.0 μmol/L （vs. vehicle group, all P 〈 0.001 ）, accompanied with dose-dependent induction of MRP2 expression （P = 0.045 for 1.0 μmol/L, P = 0.001 for 3.0 μmol/L, and P 〈 0.001 for 5.0 μmol/L）, whereas no significant diferences in MRP2 expression were noted after HDAC2/3 silencing. Fluorescent micrograph images of MRP2 protein were expressed on the cell membrane. The fluorescent intensities of MRP2 in the control, HDAC2, and HDAC3 siRNA-transfected cells weir week, and no significant differences were noticed among these three groups （all P 〉 0.05）. However, MRP2 expression was remarkably elevated in H DAC1 siRNA-transfected cells, which displayed an almost 3.19-fold changes in comparison with the control siRNA-transfected cells （P 〈 0.001 ）. Conclusions： HDACs inhibition could up-regulate placental MRP2 expression in ritzy, and HDAC 1 was probably to be involved in this process.