Viral myocarditis(VMC)is one of the most common acquired heart diseases in children and teenagers.However,its pathogenesis is still unclear,and effective treatments are lacking.This study aimed to investigate the regulatory pathway by which exosomes alleviate ferroptosis in cardiomyocytes(CMCs)induced by coxsackievirus B3(CVB3).CVB3 was utilized for inducing the VMC mouse model and cellular model.Cardiac echocardiography,left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS)were implemented to assess the cardiac function.In CVB3-induced VMC mice,cardiac insufficiency was observed,as well as the altered levels of ferroptosis-related indicators(glutathione peroxidase 4(GPX4),glutathione(GSH),and malondialdehyde(MDA)).However,exosomes derived from human umbilical cord mesenchymal stem cells(hucMSCs-exo)could restore the changes caused by CVB3 stimulation.Let-7a-5p was enriched in hucMSCs-exo,and the inhibitory effect of hucMSCs-exolet-7a-5p mimic on CVB3-induced ferroptosis was higher than that of hucMSCs-exomimicNC(NC:negative control).Mothers against decapentaplegic homolog 2(SMAD2)increased in the VMC group,while the expression of zinc-finger protein 36(ZFP36)decreased.Let-7a-5p was confirmed to interact with SMAD2 messenger RNA(mRNA),and the SMAD2 protein interacted directly with the ZFP36 protein.Silencing SMAD2 and overexpressing ZFP36 inhibited the expression of ferroptosis-related indicators.Meanwhile,the levels of GPX4,solute carrier family 7,member 11(SLC7A11),and GSH were lower in the SMAD2 overexpression plasmid(oe-SMAD2)+let-7a-5p mimic group than in the oe-NC+let-7a-5p mimic group,while those of MDA,reactive oxygen species(ROS),and Fe2+increased.In conclusion,these data showed that ferroptosis could be regulated by mediating SMAD2 expression.Exo-let-7a-5p derived from hucMSCs could mediate SMAD2 to promote the expression of ZFP36,which further inhibited the ferroptosis of CMCs to alleviate CVB3-induced VMC.

Objective: Kawasaki disease (KD) is the most common autoimmune vasculitis syndrome in children, which supposed be a complex polygenic disorder. Interleukin-17 (IL-17) is a member of the pro-inflammatory cytokine family, which has a strong pro-inflammatory effect and can participate in various acute and chronic inflammatory responses. This study aims to investigate the relationship between the single-nucleotide polymorphism (SNP) locus rs3819025 in the IL-17A gene and the susceptibility to KD. Methods: A total of 120 patients with KD who met the diagnostic criteria (the KD group) and 120 healthy children (the control group) were enrolled retrospectively in this study. Polymerase chain reaction (PCR) and DNA direct sequencing were used to detect the SNPs of children in the 2 groups. Results: The frequencies of GG, GA, and AA genotypes of rs3819025 locus in the IL-17A gene in the KD group were 82.5％, 17.5％, and 0, respectively, and the frequencies of GG, GA, and AA genotypes in the control group were 72.5％, 22.5％, and 5.0％, respectively. There were significant differences in both genotype (χ2=7.524, P=0.023). The allele frequencies G and A of rs3819025 locus in the KD group were 91.25％ and 8.75％, respectively, while those in the control group were 83.75％ and 16.25％, respectively. There was significant difference between the 2 groups (χ2=6.171, P=0.013). The distribution frequencies of GG or GA genotype and G or A allele were 88.46％ or 11.54％ and 94.23％ or 5.77％ in the KD group with coronary artery lesion, respectively. The distribution frequencies of GG or GA genotype and G or A allele were 78.72％ or 21.28％ and 89.36％ or 10.64％ in the KD group without coronary artery lesion, respectively. There were no significant differences in genotype and allele frequencies of rs3819025 between the KD with coronary artery lesion group and the KD group without coronary artery lesion (both P> 0.05). Besides, children with the allele A had a 2.023 times higher risk of KD than those without the allele A (χ2=6.171, P=0.013; OR=2.023, 95％ CI 1.151 to 3.557). Conclusions: The locus rs3819025 in the IL-17A gene is associated with the pathogenesis of KD. The allele A of the locus rs3819025 in the IL-17A gene may be a risk factor for KD.

OBJECTIVES: To provide clues for further study of the relationship between miRNAs and Kawasaki disease (KD) development, and to provide molecular markers for ultimately improve the rate of early diagnosis for KD. METHODS: We collected acute, recovery KD children's plasma and normal samples, then used the miRNAs Assay Chip to screen the differentially expressed miRNAs in the plasma from KD children. Subsequently, miR-455-5p, which had identified via miRNAs assay chip, was validated by quantitative real-time PCR via independent cohort. RESULTS: According to the results of miRNAs Assay chip, we identified a miRNAs panel including 5 miRNAs significantly up-regulated and 5 miRNAs remarkably down-regulated in the plasma from KD children compared to the normal control; miR-455-5p in both of acute and recovery KD children's plasma was remarkably lower than that in the normal control (<0.001, =0.013, respectively), and miR-455-5p was also significantly lower than that in the recovery of KD children (=0.007) by independent cohort validation. CONCLUSIONS There are significantly differentially expressed circulating miRNAs between the KD children and normal control. We identified 10 miRNAs dysregulation in the KD children's plasma compared with the normal group. Circulating miR-455-5p in both of acute and recovery KD children's plasma is remarkably lower than that in the normal control, and miR-455-5p may considered as a marker to show the recovery process of KD children. Plasma specific circulating miRNAs play an important role in the early diagnosis of KD and become the new molecular marker of KD in the future.
Biomarkers ; Child ; Humans ; MicroRNAs ; genetics ; Mucocutaneous Lymph Node Syndrome ; genetics ; Oligonucleotide Array Sequence Analysis ; Real-Time Polymerase Chain Reaction

Objective:To investigate association between the single nucleotide polymorphisms of endothelial protein C receptor (EPCR) gene and the risk of Kawasaki disease (KD) in a Chinese children.Methods:A total of 103 KD patients including 23 patients with coronary artery lesions (CAL) and 158 controls were recruited.Seven tagging SNPs (rs6088738,rs2069940,rs2069945,rs2069952,rs867186,rs9574,and rs1415774) of EPCR gene were selected for TaqMan allelic discrimination assay.The plasma soluble EPCR (sEPCR) levels of 53 KD and 52 healthy children were detected by ELISA.Results:We found a significant association between rs2069952,rs9574 or rs1415774 and higher probability for the occurrence of KD but not CAL formation.Interestingly,males with these 3 SNPs and rs2069945 SNPs bore a much greater risk of KD than females.The level of plasma sEPCR in children with KD didnot predict the formation of CAL.However,the allele G of rs867186 in EPCR was associated with the increased level of plasma sEPCR in KD patients.Conclusion:The SNPs of EPCR are associated with KD susceptibility in a Chinese Han children.

OBJECTIVETo summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors.

METHODSClinicopathological and follow-up data of 1 165 patients with gastric GIST between January 2000 and December 2013 from 23 tertiary referral hospitals in Shandong Province were collected to establish a database. The risk stratification of all cases was performed according to the National Institutes of Health(NIH) criteria proposed in 2008. Kaplan-Meier method was used to calculate the survival rate. Log-rank test and Cox regression model were used for univariate and multivariate prognostic analyses.

RESULTSAmong 1 165 cases of gastric GIST, 557 were male and 608 were female. The median age of onset was 60 (range 15-89) years. Primary tumors were located in the gastric fundus and cardia in 623 cases(53.5%), gastric body in 346 cases(29.7%), gastric antrum in 196 cases(16.8%). All the cases underwent resection of tumors, including endoscopic resection (n=106), local resection (n=589), subtotal gastrectomy(n=399), and total gastrectomy(n=72). Based on the NIH risk stratification, there were 256 cases (22.0%) at very low risk, 435 (37.3%) at low risk, 251 cases (21.5%) at intermediate risk, and 223 cases (19.1%) at high risk. A total of 1 116 cases(95.8%) were followed up and the median follow-up period was 40 (range, 1-60) months. During the period, 337 patients relapsed and the median time to recurrence was 34 (range 1-60) months. The 1-, 3-, and 5-year survival rates were 98.6%, 86.1% and 73.4%, respectively. The 5-year survival rates of patients at very low, low, intermediate, and high risk were 93.1%, 85.8%, 63.0% and 42.3% respectively, with a statistically significant difference (P=0.000). Multivariate analysis showed that primary tumor site (RR=0.580, 95%CI:0.402-0.835), tumor size (RR=0.450, 95%CI:0.266-0.760), intraoperative tumor rupture(RR=0.557, 95%CI:0.336-0.924), risk classification (RR=0.309, 95%CI:0.164-0.580) and the use of imatinib after surgery (RR=1.993, 95%CI:1.350-2.922) were independent prognostic factors.

CONCLUSIONSThe choice of surgical procedure for gastric GIST patients should be based on tumor size. All the routine procedures including endoscopic resection, local excision, subtotal gastrectomy and total gastrectomy can obtain satisfactory curative outcomes. NIH classification has a high value for the prediction of prognosis. Primary tumor site, tumor size, intraoperative tumor rupture, risk stratification and postoperative use of imatinib are independent prognostic factors in gastric GIST patients.

Recent studies have found that autophagy was not only involved both in the occurrence and development of viral myocarditis (VMC),but also,it plays a key role in anti-viral infections by degradating the viral components,presenting viral antigens and activating the immune response.Meanwhile,the virus can also escape the protective antiviral activity and maintain their own survival and replication by inducing the autophagy of the host cells,becoming the accelerator of the viral infection.The interaction of the virus and the host cell autophagy in VMC is a complex process.Its detailed pathogenesis has yet to be further explored.

Kawasaki disease (KD) is an acute febrile systemic vasculitis,and the cause of KD is not well understood.Based on epidemiologic studies and surveys,several features of KD strongly suggest a genetic component to disease pathogenesis.As a result of their involvement in immune response,human leucocyte antigen (HLA) genes have been extensively studied in association with outcomes of autoimmune and infectious diseases.HLA gene polymorphisms have also been reported to be associated with KD.Now,HLA gene polymorphisms related to KD is focused.

To investigate the association between HbA1C level and severity of coronary artery lesion in non-diabetic patients with coronary heart disease. This study was a retrospective and controlled study in a single center. 302 patients were enrolled. Coronary arterial lesion was confirmed by coronary angiography carried out in Tianjin Chest Hospital between January 2008 and November 2011. The patients enrolled should be non-diabetic with normal fasting blood glucose and HbA1C levels. The patients were divided into 3 groups according to the HbA1C levels, Group 1 (≤5. 5%, n=92),Group 2(5. 6%-5. 8%, n=94),Group 3(5. 9%-6. 4%, n=116), and the SYNTAX scores between the groups were compared. The predictive value of HbA1C in groups with intermediate and high SYNTAX score was identified by Logistic regression analysis while common risk factors such as sex, age, hypertension, lipid, and fasting glucose were adjusted. The SYNTAX score from Group 1 to Group 3 had statistically significantdifference(P<0.01). Simpleregressionwasusedtocalculatethecorrelationcoefficient(r=0.335,P<0. 01). Binary Logistic regression was used to confirm that HbA1C level was also associated with intermediate and high SYNTAX score(OR=5. 089, P<0. 05). In non-diabetic patients, the HbA1C level is associated with the severity of the lesion of coronary artery. The results indicate that a higher level of HbA1C seems to be an independent predictor to the prevalence of complex coronary lesions.

Objective To compare two different revascularization methods in type 2 diabetes mellitus (T2DM) patients with multivessel coronary artery disease treated by percutaneous coronary intervention (PCI) and coronary artery bypass graft ( CABG) .Methods T2DM patients with multivessel disease undergoing success-ful PCI or CABG were enrolled in the study .They were diagnosed by coronary angiography ( CAG) in Tianjin Chest Hospital from May 2009 to May 2010 whose.The patients were followed up for 3 years.The information of patients including physical performance , clinical features , and laboratory examination results were collected .The major ad-verse cardio cerebral events(MACCE)including death, myocardial infarction(MI), revascularization, angina pecto-ris, heart failure, and stroke were collected.Results During the 3 years of follow-up, MACCE(31.58% vs 17.68%, P<0.01), death(4.82%vs 1.10%, P<0.05), MI(4.39%vs 1.10%, P<0.05), angina pectoris (17.27%vs 10.50%, P<0.05)occurred more frequently in PCI group than in CABG group .Conclusion Evi-dences now tend to support CABG for revascularization in T 2DM patients with multivessel disease .

Kawasaki disease (KD) is a systemic vascular inflammatory lesion in children with acute febrile rash illness. The inci-dence rate in recent years is increasing. The traditional treatment in some patients is ineffective, and KD has high incidence of cardiovas-cular complications. Therefore, the selection of an appropriate therapy for KD is an urgent. With the continuous advance of biomedical and pharmacologically research, many biological agents were developed. The traditional treatment has been gradually replaced by the new biological agents which achieved the desired results. Thus this paper reviewed several common biological agents in the clinical treatment of KD.