Association between TRAF1/C5 Gene Polymorphisms and IgA Vasculitis in Chinese Children.

OBJECTIVE: To investigate the association between loci rs3761847 and rs10818488 of tumor necrosis factor receptor-associated factor 1/complement C5 (TRAF1/C5) gene and the susceptibility to IgAV. METHODS: 100 blood samples of children with IgAV and 100 blood samples of healthy children were collected from the Third Xiangya Hospital of Central South University from June 2017 to June 2019. The target gene fragment was amplified by polymerase chain reaction (PCR), and the single nucleic acid gene polymorphism of the gene loci was detected by PCR sequencing based typing technique. The association between gene polymorphism of each locus and susceptibility to IgAV was analyzed. RESULTS: There were significant differences in both genotype (P < .05) and allele frequencies （P < .05) of rs3761847 of TRAF1/C5 gene between the IgAV group and the control group.Besides, the risks of developing IgAV in children with the TT genotype was 0.495 times and in children with the C allele was 1.627 times of that in children with other genotypes and alleles, respectively (P < .05). For IgAV patients, renal involvement risk in children with CC genotype was 5.859 times of that in children with other genotypes (P < .05). There were no significant differences in genotype (P > .05) and allele frequencies (P > .05) of rs10818488 of TRAF1/C5 gene between the IgAV group and the control group. IgAV patients with TT genotype had a 3.2 times higher risk of renal involvement than those with other genotypes (P < .05). CONCLUSIONS: There is an association between locus rs3761847 of TRAF1/C5 gene single nucleotide polymorphisms and susceptibility to IgAV. The T allele at locus rs3761847 of TRAF1/C5 gene may be a protective factor for IgAV. The C allele at locus rs3761847 and the T allele at locus rs10818488 of TRAF1/C5 gene may be associated with kidney injury in IgAV.

Acetylation of FOXO1 activates Bim expression involved in CVB3 induced cardiomyocyte apoptosis.

Viral myocarditis (VMC) is the major reason for sudden cardiac death among both children and young adults. Of these, coxsackievirus B3 (CVB3) is the most common causative agent of myocarditis. Recently, the role of signaling pathways in the pathogenesis of VMC has been evaluated in several studies, which has provided a new perspective on identifying potential therapeutic targets for this hitherto incurable disease. In the present study, in vivo and in vitro experiments showed that CVB3 infection leads to increased Bim expression and triggers apoptosis. In addition, by knocking down Bim using RNAi, we further confirmed the biological function of Bim in apoptosis induced by CVB3 infection. We additionally found that Bim and forkhead box O1 class (FOXO1) inhibition significantly increased the viability of CVB3-infected cells while blocking viral replication and viral release. Moreover, CVB3-induced Bim expression was directly dependent on FOXO1 acetylation, which is catalyzed by the co-regulation of CBP and SirTs. Furthermore, the acetylation of FOXO1 was an important step in Bim activation and apoptosis induced by CVB3 infection. The findings of this study suggest that CVB3 infection induces apoptosis through the FOXO1 acetylation-Bim pathway, thus providing new insights for developing potential therapeutic targets for enteroviral myocarditis.

The Expression and Role of microRNA-133a in Plasma of Patients with Kawasaki Disease.

Kawasaki disease (KD)), also known as mucocutaneous lymph node syndrome (MCLS), is an autoimmune and systemic vasculitis syndrome. Its etiology and pathogenesis are still unclear. microRNAs (miRNA), a novel class of small non-coding RNAs, regulate the expression of multiple protein-encoding genes at the post-transcriptional level. We intend to study the change of miRNA-133a in the plasma of patients with KD, explore the role of miRNA-133a on HUVEC and define the pathogenesis of vascular dysfunction in KD. miRNA-133a expression and the mRNA and protein expression of protein phosphatase 2 catalytic subunit alpha (PPP2CA) were assessed by RT-qPCR and Western blot, respectively. The PPP2CA mRNA 3'UTR was predicted to be the potential target of miRNA-133a by using the miRNA databases and verified by the luciferase assay. The plasmids of miRNA-133a mimics and inhibitors were transfected into HUVEC cells. The plasma soluble vascular endothelial cadherin (sVE-cadherin, the excised extracellular part of VE-cadherin) levels were investigated by ELISA. The results suggested that miRNA-133a was increased by 3.8 times in the acute KD group and by 2.7 times in the convalescent KD group compared with the control group (both P = .000). PPP2CA is the target gene of miRNA-133a and its expression was inhibited by miRNA-133a acting on PPP2CA mRNA 3'UTR (P = .013). The plasma sVE-cadherin levels in the acute KD groups were increased compared with the control group (P = .024). The ROC curve analysis showed that the expression of miRNA-133a segregate acute KD patients from convalescent KD patients and healthy children. Our results suggest that miRNA-133a might be a new biomarker for KD.

Urinary NGAL, IGFBP-7, and TIMP-2: novel biomarkers to predict contrast medium-induced acute kidney injury in children.

BACKGROUND: Serum creatinine (SCr) is unreliable in detecting acute changes in kidney function. Early recognition of contrast-induced acute kidney injury (CI-AKI) can provide better opportunities for preventive interventions. Therefore, the purpose of this study is to examine the value of the combined detection of urinary neutrophil gelatinase-associated lipocalin (NGAL), insulin-like growth factor binding protein-7 (IGFBP-7), and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the early diagnosis of children with CI-AKI. METHODS: A prospective, single-center clinical trial was performed and included 172 children aged 0-18 years. The dynamic changes of urinary NGAL, IGFBP-7, and TIMP-2 levels in children with intravascular injection of contrast medium were investigated to determine whether they can diagnose CI-AKI early. RESULTS: CI-AKI occurred in 20 of 137 enrolled patients, and the incidence was 14.59%. In the CI-AKI group, urinary levels of NGAL, IGFBP-7, TIMP-2, and [IGFBP-7]*[TIMP-2] were significantly increased 2 h after angiography and remained at high levels at 6 h. Using a cutoff value of 36.274 ng/mL, the specificity was 70.0%, and the sensitivity was 68.4% for the prediction of CI-AKI, which was excellent for urinary NGAL. When both urinary IGFBP-7 and TIMP-2 were used together, urinary [IGFBP-7]*[TIMP-2] at 0.417(ng/mL)2/1000 was regarded as the cutoff value. The specificity was 80.0%, and the sensitivity was 81.2%. CONCLUSIONS: NGAL, IGFBP-7, and TIMP-2 concentrations in the urine of children after receiving injections of contrast medium increased faster than SCr and had good clinical value for the early diagnosis of CI-AKI in children. The combination of IGFBP-7 and TIMP-2 was better than either analyte alone.

Association of MnSOD gene polymorphism with susceptibility to Kawasaki disease in Chinese children.

BACKGROUND: Kawasaki disease is a type of acute febrile rash disease that is common in children and is characterised by primary lesions of systemic middle and small vasculitis, which can lead to coronary artery lesions. Manganese superoxide dismutase (MnSOD), one of the most important antioxidases in the human body, plays a key role in maintaining the balance of free radicals in the human body. Two single-nucleotide polymorphisms (SNPS) (rs4880 and rs5746136) in the MnSOD gene were related to oxidative stress disease. The purpose of this study is to explore the possible relationship between MnSOD gene polymorphisms and Kawasaki disease susceptibility. METHODS: This study included 100 Kawasaki disease children and 102 healthy children. Two single-nucleotide polymorphisms (rs4880 and rs5746136) were detected by polymerase chain reaction sequence-based typing. RESULTS: There was a significant difference in both the genotype frequency (χ2 = 10.805, p = 0.005) and the allele frequency (χ2 = 7.948, p = 0.005) of rs5746136 between the Kawasaki disease group and the control group. Children with the A allele had a 0.558 times lower risk of Kawasaki disease than those without the A allele (χ2 = 7.948, p = 0.005, odds ratio = 0.558, 95% confidence interval = 0.371-0.838). There was no significant difference in the genotype and gene frequencies of rs5746136 between the Kawasaki disease-coronary artery lesion and Kawasaki disease-without coronary artery lesion groups (p > 0.05), and there was no significant difference in the rs4880 genotype and allele frequencies between the Kawasaki disease and healthy control groups or between the Kawasaki disease-coronary artery lesion and Kawasaki disease-without coronary artery lesions groups (p > 0.05). CONCLUSION: This study provides evidence supporting an association between MnSOD gene polymorphisms and susceptibility to Kawasaki disease. The genotype AA and the allele A of the MnSOD gene locus rs5746136 were risk factors for Kawasaki disease.

[Value of galactose-deficient IgA1 in the early diagnosis of Henoch-Schönlein purpura nephritis in children].

OBJECTIVE: To explore the value of galactose-deficient IgA1 (Gd-IgA1) in the early diagnosis of Henoch-Schönlein purpura nephritis (HSPN) in children. METHODS: A total of 67 hospitalized children who were definitely diagnosed with HSPN between January and April 2018 and 58 hospitalized children with Henoch-Schönlein purpura (HSP) were enrolled in the study. Twenty children undergoing routine physical examinations served as controls. The levels of serum and urine Gd-IgA1 were determined using ELISA. The receiver operating characteristic curve was used to analyze the value of serum Gd-IgA1 and urine Gd-IgA1/urine creatinine ratio in the diagnosis of HSPN. RESULTS: The level of serum Gd-IgA1 and urine Gd-IgA1/urine creatinine ratio in children with HSP or HSPN were significantly higher than those in healthy control group (P<0.01), with a significantly greater increase observed in children with HSPN (P<0.01). Serum Gd-IgA1 ≥1 485.57 U/mL and/or urine Gd-IgA1/urine creatinine ratio ≥105.74 were of favorable value in the diagnosis of HSPN. During the six-month follow-up of the 49 children with HSP, the incidence of HSPN was 47% (23/49), which included a 100% incidence in children with serum Gd-IgA1 ≥1 485.57 U/mL and a 73% incidence in children with urine Gd-IgA1/urine creatinine ratio ≥105.74. CONCLUSIONS: Serum and urine Gd-IgA1 is of favorable clinical value in the early diagnosis of HSPN.

Remote ischemic preconditioning upregulates microRNA-21 to protect the kidney in children with congenital heart disease undergoing cardiopulmonary bypass.

BACKGROUND: Acute kidney injury (AKI) is one of the most common emergencies and severe diseases in the clinic. We sought to verify whether remote ischemic preconditioning (RIPC) has a protective effect on the kidney of child with congenital heart disease undergoing cardiopulmonary bypass (CPB) surgery. We hypothesized it may be related to the up-regulation of microRNA-21 (miR-21). METHODS: We performed a prospective randomized clinical study among children with congenital heart disease undergoing CPB surgery between January and December 2016. Children were randomized to an RIPC or control group. Patients in each group were divided into an AKI and a non-AKI group according to the occurrence of AKI at 48 h after surgery. Remote ischemic preconditioning (RIPC) conducted by blood-pressure cuff was performed 12 h before surgery. Serum creatinine (SCr), tumor necrosis factor-α (TNF-α), and miR-21 expression in blood and urine were measured at different time points. RESULTS: A total of 449 cases (200 RIPC; 249 controls) were enrolled. The male/female ratio was 1.18, with a mean age of 37.50 ± 25.31 months. The incidence of AKI in the RIPC group was significantly lower than that in the control group (19.0% vs. 46.2%, P<0.01). In further analysis, at 6 h, 24 h, and 48 h after CPB operation, blood TNF-α levels were significantly lower in the RIPC group than in the control group (P<0.01); at 24 h, 48 h, and 72 h, urine TNF-α levels were significantly lower in the RIPC group than in the control group (P<0.05). Urine and blood miR-21 expression in the RIPC group increased significantly, while there was no obvious change in the control group. CONCLUSIONS: Remote ischemic preconditioning has a protective effect on the kidney in children with congenital heart disease, which may be related with the up-regulation of miR-21 and down-regulating the inflammatory mediator, such as TNF-α.

[Expression and significance of tight junction proteins in the kidney in a mouse model of renal ischemia-reperfusion injury].

OBJECTIVE: To study the expression and significance of tight junction proteins (claudin-2, claudin-10, and claudin-17) in a mouse model of renal ischemia-reperfusion injury. METHODS: A total of 152 male C57BL/6 mice were randomly assigned to control group (n=8), sham-operation group (n=72), and model group (n=72). The renal pedicles at both sides were clamped for 30 minutes to establish a mouse model of renal ischemia-reperfusion injury. According to the time points of reperfusion (0, 3, 6, 12, 24, 48, and 72 hours and 5 and 7 days), the sham-operation group and the model group were further divided into 9 subgroups, with 8 mice in each subgroup. RT-PCR and immunohistochemistry were used to measure the mRNA and protein expression of claudin-2, claudin-10, and claudin-17 in renal tissue. RESULTS: The control and sham-operation groups had no significant changes in the mRNA and protein expression of claudin-2, claudin-10, and claudin-17 in renal tissue over the time of reperfusion (P>0.05). Compared with the control and sham-operation groups, the model group had decreased mRNA and protein expression of claudin-2 and claudin-10 after reperfusion, and the expression decreased gradually over the time of reperfusion, with the lowest levels at 24 hours of reperfusion (P<0.05). Compared with the control and sham-operation groups, the model group had increased mRNA and protein expression of claudin-17 after reperfusion, and the expression increased gradually over the time of reperfusion, with the highest mRNA level at 12 hours and the highest protein level at 24 hours of reperfusion (P<0.05). CONCLUSIONS: Renal ischemia-reperfusion injury is closely associated with abnormal expression of tight junction proteins claudin-2, claudin-10, and claudin-17.

Mycophenolate mofetil therapy for steroid-resistant IgA nephropathy with the nephrotic syndrome in children.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) presents as nephrotic syndrome (NS) relatively rarely, and the current treatment experience of IgAN patients with NS is mostly with adults. The objective of our study was to investigate the efficacy of corticosteroids and mycophenolate mofetil (MMF) in treating childhood immunoglobulin A nephropathy (IgAN) with nephrotic syndrome. METHODS: A total of 58 children (39 boys and 19 girls) diagnosed with nephrotic syndrome and primary IgAN were enrolled in the study. All the patients were administered prednisone 2 mg/kg per day for 8 weeks. Steroid-resistant patients were treated with the combined use of MMF (dose of 20 ~ 30 mg/kg per day) and prednisone for 6-12 months. The prednisone dose was reduced stepwise during the combined treatment. RESULTS: Of the 58 children, 14 were steroid-sensitive (M, S, and T variants of the Oxford classification were 0 in most children), and 44 cases who presented serious pathological damage to the kidney were steroid-resistant. The estimated glomerular filtration rate (eGFR) of the steroid-resistant children (86.69 ± 26.85 ml/min/1.73 m(2)) was significantly lower (P < 0.05) than that of the steroid-sensitive children (106.89 ± 26.94 ml/min/1.73 m(2)). After 4 months of combined MMF treatment in 33 steroid-resistant children, complete remission of proteinuria was found in 21 cases, partial remission of proteinuria in 6 cases, and no response was found in 6 cases. Except for the T variant, other variants of the Oxford classification, including M, E, and S morphological variables, was not significantly different among patients complete remission, those with partial remission, and those with no response. The eGFR of children with complete remission of proteinuria (100.04 ± 18.47 ml/min/1.73 m(2)), that of those with partial remission (92.24 ± 27.63 ml/min/1.73 m(2)), and that of those with no response (72.17 ± 27.55 ml/min/1.73 m(2)) were significantly different (P < 0.05). CONCLUSION: Corticosteroid therapy showed satisfactory efficacy in IgAN children with nephrotic syndrome and slight pathological damage. The effect of MMF was good for steroid-resistant IgAN children, but poor for those with tubular atrophy/interstitial fibrosis and renal function impairment.

Clinical and pathological features of acute kidney injury in children.

OBJECTIVE: Based on the diagnostic and staging criteria of acute kidney injury (AKI), we analyze the clinical and pathological characteristics of children at different stages of AKI and explored their clinical significances. METHODS: 165 children with AKI were divided into stage 1, stage 2, and stage 3 groups. Clinical and pathologic characteristics of AKI children were analyzed. RESULTS: The three groups of patients showed significant differences in age, etiology, pathological damage, and the median recovery time of serum creatinine. Of the 165 patients, the incidence and duration of hematuria showed significant differences among the three groups, and the stage 1 group showed longer duration of proteinuria. CONCLUSION: The patients were largely in stage 1 and 3. The children with AKI in stage 1 were largely school-age children and acute glomerulonephritis (AGN) was the main etiology. The AKI children in stage 3 were mainly infants, of which the etiology was mainly drugs and septicemia. The pathological type was mainly acute tubulointerstitial nephritis, and the renal function recovery was slow.

Kocuria species: an underappreciated pathogen in pediatric patients-a single-center retrospective analysis of 10 years' experience in China.

Kocuria species are known to be opportunistic pathogens that cause infections in humans, especially immunocompromised hosts. However, reports of pediatric patients are limited. This retrospective study was designed to investigate the spectrum of infections in pediatric patients caused by Kocuria species. Thirty-six patients were enrolled; of these, 29 were infected by Kocuria kristinae, 4 by Kocuria roseus, 2 by Kocuria varians, and 1 by Kocruria rhizophila. Twenty-six patients were diagnosed with bloodstream infection; 6 had ventilator-associated pneumonia; and one each had a catheter-associated urinary tract infection, purulent meningitis, cholangitis, and empyema. Twenty-seven patients were immunocompromised or debilitating, had congenital abnormalities or fitted with indwelling devices. Nine patients were immunocompetent, 4 with early onset before 1 year of age. All Kocuria species were susceptible to lenezolid, vancomycin, and tigecycline; while showing frequent resistance to penicillin and oxacillin. Most cases were cured by administering appropriate antimicrobial agents. To our knowledge, this is the largest case series of pediatric patients with Kocuria species infection. We highlight Kocuria species should be considered as an underappreciated pathogen in pediatric patients.

Association of the clinicopathological characteristics and proteinuria remission of pediatric IgAV with nephrotic-range proteinuria: A retrospective cohort study.

Background: IgA vasculitis (IgAV) combined with nephrotic-range proteinuria is uncommon, and nephrotic-range proteinuria is considered a risk factor for poor prognosis in children with IgAV. There are few clinical studies with large samples. Methods: Children with IgAV and nephrotic-range proteinuria who were hospitalized at the Department of Nephrology, Rheumatology and Immunology, Hunan Children's Hospital, from March 2008 to January 2020 were retrospectively studied; the patients were aged ≤18 years and were followed up for ≥12 months. We analyzed clinical characteristics, pathological changes, treatment responses, and their relationships in patients with IgAV combined with nephrotic-range proteinuria. Results: Two hundred seventy-seven children with an average age at onset of IgAV with nephritis (IgAVN) of 8.0 years (interquartile range (IQR), 6.0-10.0) were enrolled; 65.7% were aged 6-10 years. The male-to-female ratio was 1.35:1. All children had both nephrotic-range proteinuria and hematuria, 49 (17.7%) had hypoalbuminemia, and 9 (3.2%) had estimated glomerular filtration rate < 90 (mL/min/1.73 m2). All included children were followed up for at least 1 year. At 3, 6, and 12 months of follow-up, the remission rates of proteinuria in children with IgAV combined with nephrotic-range proteinuria were 27.8%, 62.1%, and 83.0%, respectively, and the remission rates of hematuria were 1.4%, 8.7%, and 35.7%, respectively. In addition, children with age at onset of IgAV with nephrotic-range proteinuria ≥10 years, who were female, who had proteinuria ≥100 mg/kg/24 h, and who had a pathological grade III or above had lower remission rates of hematuria and proteinuria (P < 0.05). Multivariate factor analysis was performed by logistic regression and showed age at onset of IgAVN ≥ 10 years and crescents to be risk factors for nonremission of proteinuria at 12 months of follow-up (P < 0.05). Conclusions: Age at onset of IgAVN, sex, proteinuria level, pathological grade, and crescents significantly affect proteinuria remission in children with IgAV combined with nephrotic-range proteinuria.

TFRC upregulation promotes ferroptosis in CVB3 infection via nucleus recruitment of Sp1.

CVB3 is a single positive-strand enterovirus, and a common pathogen in myocarditis etiology. Although a number of antiviral candidates are under development, specific targeted therapy is not available for CVB3. Ferroptosis is a new type of regulatory cell death discovered in recent years. In this study, our team provided the first evidence that ferroptosis existed in CVB3 infection in vivo and in vitro by iron overload, and massive accumulation of lipid peroxides. Mechanistically, we construct a classical model of HeLa cells following a time-course infection (6, 12, 24, 36, 48 h) with CVB3 (MOI = 10). We demonstrated that the TFRC gene plays an important role in promoting ferroptosis in CVB3 infection and downregulation of TFRC attenuated the ferroptosis. Interestingly, we observed that TFRC was nuclear translocation induced by the CVB3, which was predominantly localized in the cell membrane, but redistributed to the nucleus during CVB3 infection. Moreover, we found that the transcription factor Sp1 was an essential factor that could bind to the TFRC promoter and upregulate the TFRC transcription. Collectively, these results suggest that the Sp1/TFRC/Fe axis may provide a new target for the development of therapies against CVB3 infection.

Risk assessment and prediction model of renal damage in childhood immunoglobulin A vasculitis.

Objectives: To explore the risk factors for renal damage in childhood immunoglobulin A vasculitis (IgAV) within 6 months and construct a clinical model for individual risk prediction. Methods: We retrospectively analyzed the clinical data of 1,007 children in our hospital and 287 children in other hospitals who were diagnosed with IgAV. Approximately 70% of the cases in our hospital were randomly selected using statistical product service soltions (SPSS) software for modeling. The remaining 30% of the cases were selected for internal verification, and the other hospital's cases were reviewed for external verification. A clinical prediction model for renal damage in children with IgAV was constructed by analyzing the modeling data through single-factor and multiple-factor logistic regression analyses. Then, we assessed and verified the degree of discrimination, calibration and clinical usefulness of the model. Finally, the prediction model was rendered in the form of a nomogram. Results: Age, persistent cutaneous purpura, erythrocyte distribution width, complement C3, immunoglobulin G and triglycerides were independent influencing factors of renal damage in IgAV. Based on these factors, the area under the curve (AUC) for the prediction model was 0.772; the calibration curve did not significantly deviate from the ideal curve; and the clinical decision curve was higher than two extreme lines when the prediction probability was ~15-82%. When the internal and external verification datasets were applied to the prediction model, the AUC was 0.729 and 0.750, respectively, and the Z test was compared with the modeling AUC, P > 0.05. The calibration curves fluctuated around the ideal curve, and the clinical decision curve was higher than two extreme lines when the prediction probability was 25~84% and 14~73%, respectively. Conclusion: The prediction model has a good degree of discrimination, calibration and clinical usefulness. Either the internal or external verification has better clinical efficacy, indicating that the model has repeatability and portability. Clinical trial registration: www.chictr.org.cn, identifier ChiCTR2000033435.

Coxsackievirus B3 infection induces glycolysis to facilitate viral replication.

Coxsackievirus B3 (CVB3) is a leading cause of viral myocarditis, but no effective treatment strategy against CVB3 is available. Viruses lack an inherent metabolic system and thus depend on host cellular metabolism for their benefit. In this study, we observed that CVB3 enhanced glycolysis in H9c2 rat cardiomyocytes and HL-1 mouse cardiomyocytes. Therefore, three key glycolytic enzymes, namely, hexokinase 2 (HK2), muscle phosphofructokinase (PFKM), and pyruvate kinase M2 (PKM2), were measured in CVB3-infected H9c2 and HL-1 cells. Expression levels of HK2 and PFKM, but not PKM2, were increased in CVB3-infected H9c2 cells. All three key glycolytic enzymes showed elevated expression in CVB3-infected HL-1 cells. To further investigate this, we used 2 deoxyglucose, sodium citrate, and shikonin as glycolysis inhibitors for HK2, PFKM, and PKM2, respectively. Glycolysis inhibitors significantly reduced CVB3 replication, while the glycolysis enhancer dramatically promoted it. In addition, glycolysis inhibitors decreased autophagy and accelerated autophagosome degradation. The autophagy inducer eliminated partial inhibition effects of glycolysis inhibitors on CVB3 replication. These results demonstrate that CVB3 infection enhances glycolysis and thus benefits viral replication.

Association of miR-181c/d gene locus rs8108402 C/T polymorphism with susceptibility to Kawasaki disease in Chinese children.

Background: Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. The rs8108402 C/T single nucleotide polymorphism (SNP) is located in the promoter region of miR-181-c/d gene and the intron of Nanos3 gene. The miR-181 family contributes to the pathogenesis of cardiovascular and inflammatory disorders, while Nanos3 is involved in DNA transcription regulation and cell proliferation. However, no studies have examined the association between miR-181c/d and Nanos3 polymorphisms and the susceptibility and progression of KD. Objective: The purpose of our study is to examine the association of miR-181c/miR-181d/Nanos3 gene locus rs8108402 C/T polymorphism with KD susceptibility, intravenous immunoglobulin (IVIG) responsiveness, and the development of coronary artery lesions (CAL). Methods: Peripheral blood specimens from 100 children with KD and 100 healthy children were collected. The polymorphism of rs8108402 C/T was detected using polymerase chain reaction-sequencing-based typing technique. Results: There were statistically significant differences in C and T allele frequency distributions between the KD group and healthy controls for the polymorphic site rs8108402 C/T (P = 0.002). The distribution of the genotypes CC, CT, and TT also presented statistical significant difference between the KD and control groups (P = 0.003). Compared to the rs8108402 C allele, the T allele was associated with increased KD susceptibility (OR = 2.080, 95% CI = 1.317∼3.283). However, there were no significant associations discovered between the rs8108402 C/T polymorphism and CAL formation or IVIG unresponsiveness in the study. Conclusion: SNP rs8108402 C/T located in the miR-181c/d promoter and Nanos3 intronic region is associated with susceptibility to Kawasaki disease but not with the development of coronary artery lesions or IVIG unresponsiveness in Chinese children.

Juvenile Idiopathic Arthritis With Epstein-Barr Virus-Associated Smooth Muscle Tumor in a 6-Year-Old Girl: A Rare Case Report.

Herein, we reported a rare case of Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) combined with juvenile idiopathic arthritis (JIA) in a 6-year old girl without HIV, organ transplantation, or congenital immunodeficiency. The patient suffered from pain in the bilateral hip joints, which drastically affected her physical activity. Consequently, she was diagnosed with JIA (September 2019). She was given methotrexate and methylprednisolone pills via oral route and a subcutaneous injection of Recombinant Human Tumor Necrosis Factor-α Receptor II;lgG Fc Fusion Protein for 4 weeks that successfully relieved the pain. In May 2020, the pain reoccurred and was accompanied by occasional headaches. After extensive pathological examination, the patient was diagnosed with EBV-SMT. The imaging examinations after admission showed multiple lesions in the skull, lungs, and vertebral body. Biopsy of the L2 vertebral body was then performed to clarify the diagnosis. Finally, the in-situ hybridization of the tumor of the lumbar vertebrae suggested a non-HIV/transplantation-related EBV-SMT. Consequently, the patient received surgery without chemotherapy and radiotherapy, after which her conditions improved.

Henoch-Schönlein Purpura /IgA Vasculitis Complicated by Coronary Artery Aneurysm: A Case Report and Literature Review.

Henoch-Schönlein purpura (HSP)/ IgA vasculitis (IgAV) is the most common form of systemic vasculitis in children and often involves the skin, gastrointestinal tract, joints, and kidneys, though cardiac involvement rarely occurs. We report on a 6-year-old male child with HSP/IgAV who had renal and cardiac involvement at the initial stage of the disease and in whom we found an extremely rare coronary artery aneurysm. After administration of glucocorticoid combined with mycophenolate mofetil, the renal involvement improved, but the coronary artery aneurysm remained. Pursuant to this case, we retrieved information on other cases of HSP/IgAV complicated with cardiac involvement from the PubMed database, and excluded cases of cardiac involvement accompanied by Kawasaki disease, polyarteritis nodosa, rheumatic fever, Takayasu arteritis, systemic lupus erythematosus, poststreptococcal glomerulonephritis, or sepsis. We then analyzed gender, age, cardiac involvement, renal involvement, treatment, and prognoses. To date, 24 cases of HSP/IgAV complicated with cardiac involvement have been reported. Among them, there were 22 male and 2 female patients, with the onset age ranging from 3 to 71 years old. A total of 10 children (including the child we examined) and 14 adults were identified, and 17 patients (70.8%) had HSP/IgAV complicated with renal involvement. The majority of patients were treated with glucocorticoid and/or immunosuppressants or biological agents, 4 patients died (16.7%), 8 patients were completely relieved (33.3%), and 3 patients had unknown prognoses. This article suggests that HSP/IgAV complicated with cardiac involvement may result in a poor prognosis and early treatment may therefore be essential. Our case revealed that glucocorticoid does not prevent the occurrence of renal and cardiac involvement in HSP/IgAV patients. If HSP/IgAV is complicated with coronary artery dilation, the therapeutic effect of glucocorticoid combined with immunosuppressants is not satisfactory, and early administration of biological agents or IVIG may be an effective therapeutic regimen.

Identification of a novel COL4A5 mutation in the proband initially diagnosed as IgAN from a Chinese family with X-linked Alport syndrome.

Alport syndrome (AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence, the proband was initially diagnosed as IgA nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902delA in COL4A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by IgA nephropathy, which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis.