Pediatric heart failure (PHF) carries a high mortality burden, yet the prognostic value of admission blood pressure (BP) remains poorly defined, and evidence-based thresholds for risk stratification are lacking. This retrospective, multicenter cohort study included 2545 children diagnosed with PHF upon admission across 30 Chinese centers (2013–2022). BP was standardized into age-, sex-, and height-specific percentiles. Associations with in-hospital mortality were analyzed using restricted cubic splines (RCS), machine learning covariate selection, and sensitivity analyses, stratified by sex, age, and etiology. Systolic BP (SBP) percentiles showed a U-shaped association with mortality, with the lowest risk at the 63.8th percentile. Risk increased below the 57th percentile [adjusted hazard ratio (aHR) = 1.86, 95

Background Although heart failure is a well‐known major global public health concern, the general understanding of the clinical status of pediatric heart failure (PHF) is inadequate. Therefore, this study aims to enhance the general understanding of clinical characteristics across different PHF age groups and provide references for improving PHF treatment strategies. Methods This multicenter retrospective cohort study involved patients from 20 Chinese provinces, primarily including hospitalized patients (aged ≤18 years) diagnosed with heart failure between January 2013 and December 2022. The study subjects were categorized into 4 groups: neonatal, infant and toddler, young children, and adolescent. Results Herein, 2903 hospitalized patients with PHF were included. Significant differences were observed across age groups in clinical characteristics, auxiliary examination results, comorbid diagnoses, and hospitalization outcomes. After adjusting for covariates, the odds of in‐hospital death were significantly lower in the infant and toddler (odds ratio [OR], 0.46 [95% CI, 0.25–0.85]), young children (OR, 0.39 [95% CI, 0.18–0.85]), and adolescent (OR, 0.34 [95% CI, 0.13–0.87]) groups compared with the neonatal group. Furthermore, the odds of cardiovascular adverse events were significantly higher in the young children (OR, 1.91 [95% CI, 1.62–2.88]) and adolescent (OR, 2.16 [95% CI, 1.15–4.06]) groups compared with the neonatal group. Additionally, regarding the odds of a bad Ross class, the adolescent group had 1.85 times higher odds (95% CI, 1.11–3.09) compared with the neonatal group, 2.36 times (95% CI, 1.67–3.35) higher odds compared with the infant and toddler group, and 1.45 times (95% CI, 1.05–2.02) higher odds compared with the young children group (P<0.05). Conclusions This study emphasizes the importance of age‐specific stratification in PHF management, revealing distinct clinical and prognostic differences across various developmental stages. Registration URL: https://www.chictr.org.cn. Unique identifier: ChiCTR2300078262.

OBJECTIVE:To explore the clinical characteristics and pathogenic variant in a child with Cantú syndrome (CS). METHODS:A male who was admitted to the Children's Hospital Affiliated to Zhengzhou University on February 23, 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole-exome sequencing (WES). Candidate variant was verified by Sanger sequencing. This study was approved by the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2023-K-087). RESULTS:The child, a 3-year-and-2-month-old male, was born with hirsutism, with heavy hair all over the body and peculiar facial features. Routine echocardiography 1 month before had discovered atrial septal defect. Sequencing revealed that the child has harbored a heterozygous c.2438G>C (p.S813T) variant of the ABCC9 gene, which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2438G>C variant was classified as likely pathogenic (PS2+PM2_Supporting+PP3). CONCLUSION:The heterozygous c.2438G>C variant of the ABCC9 gene probably underlay the pathogenesis of CS in this child.

Objectives This study aimed to describe the genetic and clinical characteristics of paediatric cardiomyopathy in a cohort of Chinese patients.Methods We retrospectively reviewed the clinical history and mutation spectrum of 75 unrelated Chinese paediatric patients who were diagnosed with cardiomyopathy and referred to our hospital between January 2016 and December 2022.Results Seventy-five children with cardiomyopathy were enrolled, including 32 (42.7%) boys and 43 (57.3%) girls. Dilated cardiomyopathy was the most prevalent cardiomyopathy (61.3%) in the patients, followed by hypertrophic cardiomyopathy (17.3%), ventricular non-compaction (14.7%), restrictive cardiomyopathy (5.3%) and arrhythmogenic right ventricular cardiomyopathy (1.3%). Whole-exome sequencing and targeted next-generation sequencing identified 34 pathogenic/likely pathogenic variants and 1 copy number variant in 14 genes related to cardiomyopathy in 30 children, accounting for 40% of all patients. TNNC1 p.Asp65Asn and MYH7 p.Glu500Lys have not been reported previously. The follow-up time ranged from 2 months to 6 years. Twenty-two children died (mortality rate 29%).Conclusions Comprehensive genetic testing was associated with a 40% yield of causal genetic mutations in Chinese cardiomyopathy cases. We found diversity in the mutation profile in different patients, which suggests that the mutational background of cardiomyopathy in China is heterogeneous, and the findings may be helpful to those counselling patients and families.

OBJECTIVE:To analyze the clinical and genetic characteristics of a patient with long QT syndrome type 14 (long QT syndrome-14, LQT14, OMIM # 616247) caused by a de novo CALM1 mutation.METHODS:The clinical data of the patient were collected, next-generation sequencing technology was used to determine the exome gene sequence of the patient, and the suspected pathogenic locus was verified by Sanger sequencing.RESULTS:A 5-year and 9-month-old girl was admitted to the hospital due to a syncopal episode. During the attack, the main symptoms were loss of consciousness, cyanosis of the face and lips, and weakness of limbs. The child had multiple seizures in the past, all of which occurred after emotional excitement and activity. She was diagnosed with epilepsy for more than 3 years, but the effect of antiepileptic treatment was not satisfactory. The electrocardiogram was normal in the past. A month ago, convulsions occurred again after exercise, and the electrocardiogram showed QTc 496 ms. The treadmill test showed a significant prolongation of QTc after exercise, and the genetic results suggested a new heterozygous variant of CALM1, c.395A>G; p. (Asp132Gly). Consequently, she was diagnosed with LQT14 and treated with propranolol. During a follow-up of 15 months, there were no seizures or syncope.CONCLUSIONS:This patient had multiple episodes of convulsions or syncope after emotional stimulation or activity, with intermittent prolongation of the QTc on routine ECG, marked prolongation of the QTc after exercise, and T-wave alternans, which differed from the LQT14 phenotype caused by the previous CALM1 mutation.

OBJECTIVE:To explore the clinical and genetic characteristics of eight children with Primary hypertrophic cardiomyopathy (HCM).METHODS:Eight children with HCM admitted to the Department of Cardiology of Henan Children's Hospital from January 2018 to December 2021 were selected as the study subjects. Clinical data of the children were collected. Whole exome sequencing was carried out on two children, and trio whole exome sequencing was carried out on the remainder 6 children. Sanger sequencing was used to verify the candidate variants in the children and their parents, and the pathogenicity of the variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).RESULTS:The patients had included 5 males and 3 females, with their ages ranging from 5 to 13 years old. The average age of diagnosis was (7.87 ± 4.8) years old, and the cardiac phenotype showed non-obstructive HCM in all of the patients. WES has identified variants of the MYH7 gene in 4 children, including c.2155C>T (p.Arg719Trp), c.1208G>A (p.Arg403Gln), c.1358G>A (p.Arg453His), and c.1498G>A (p.Glu500Lys). Based on the guidelines from the ACMG, the first 3 variants were classified as pathogenic, while c.1498G>A (p.Glu500Lys) was classified as likely pathogenic (PM1+PM2_Supporting+PM6+PP3), which was also unreported previously. The remaining four children had all harbored maternal variants, including MYL2: c.173G>A (p.Arg58Gln; classified as pathogenic), TPM1: c.574G>A (p.Glu192Lys) and ACTC1: c.301G>A (p.Glu101Lys)(both were classified as likely pathogenic), and MYBPC3: c.146T>G (p.Ile49Ser; classified as variant of uncertain significance). Seven children were treated with 0.5 ~ 3 mg/(kg·d) propranolol, and their symptoms had improved significantly. They were followed up until September 30, 2022 without further cardiac event.CONCLUSION:Genetic testing can clarify the molecular basis for unexplained cardiomyopathy and provide a basis for clinical diagnosis and genetic counseling. Discovery of the c.1498G>A (p.Glu500Lys) variant has also expanded the spectrum of MYH7 gene mutations underlying HCM.

OBJECTIVE:To explore the clinical phenotype and genetic features of a child with dilated cardiomyopathy (DCM).METHODS:Clinical data of the child who had presented at the Zhengzhou Children's Hospital on April 28, 2020 was collected. Trio-whole exome sequencing (trio-WES) was carried out for the child and her parents, and candidate variants were validated by Sanger sequencing. "FHL2" was taken as the key word to retrieve related literature from January 1, 1997 to October 31, 2021 in the PubMed database and was also searched in the ClinVar database as a supplement to analyze the correlation between genetic variants and clinical features.RESULTS:The patient was a 5-month-old female infant presented with left ventricular enlargement and reduced systolic function. A heterozygous missense variant c.391C>T (p.Arg131Cys) in FHL2 gene was identified through trio-WES. The same variant was not detected in either of her parents. A total of 10 patients with FHL2 gene variants have been reported in the literature, 6 of them had presented with DCM, 2 with hypertrophic cardiomyopathy (HCM), and 2 with sudden unexplained death (SUD). Phenotypic analysis revealed that patients with variants in the LIM 3 domain presented hypertrophic cardiomyopathy and those with variants of the LIM 0~2 and LIM 4 domains had mainly presented DCM. The c.391C>T (p.Arg131Cys) has been identified in a child with DCM, though it has not been validated among the patient's family members. Based on the guidelines of the American College of Medical Genetics and Genomics, the c.391C>T(p.Arg131Cys) variant was re-classified as likely pathogenic (PS2+PM2_Supporting+PP3+PP5).CONCLUSION:The heterozygous missense variant of c.391C>T (p.Arg131Cys) in the FHL2 gene probably predisposed to the DCM in this child, which has highlighted the importance of WES in the clinical diagnosis and genetic counseling.

目的 分析郑州大学附属儿童医院近10年来住院川崎病(Kawasaki disease,KD)病例的临床特点及其变化规律,以提高KD的诊治水平.方法 回顾性分析2010年1月1日至2020年1月1日郑州大学附属儿童医院收治的3 498例KD患儿临床资料,以2015年1月1日为分界点,2015年1月1日后的病例为观察组(2 356例),2015年1月1日前的病例为对照组(1 142例).比较两组流行病学特征(发病月份、年龄、KD类型、性别)、临床表现(手足硬肿、发热、颈部淋巴结肿大、皮疹、结膜充血、肛周及指(趾)端脱皮、口腔黏膜改变)、并发症(包括冠脉损害(CAL)、间质性肺炎、无菌性脑炎、关节炎、肝损害、腮腺炎、无菌性脓尿)、实验室检查指标[白细胞计数(WBC)、血小板计数(PLT)、C反应蛋白(CRP)、血沉(ESR)、谷丙转氨酶(ALT)、降钙素原(PCT)、脑钠肽(BNP)]以及静脉注射丙种球蛋白(Intravenous immunoglobulin,IVIG)不敏感发生率.结果 观察组与对照组间年龄、不完全型KD以及发病月份相比差异有统计学意义(P＜0.05);观察组皮疹、口腔黏膜变化、手足硬肿发生率低于对照组(P＜0.05);两组间实验室指标WBC、PLT、CRP、ESR、ALT、PCT、BNP差异无统计学意义(P＞0.05);观察组合并CAL的发生率13.24％高于对照组8.49％(P＜0.05);观察组IVIG不敏感发生率为19.10％,高于对照组的13.22％(P＜0.05).结论 近10年不完全型KD病例增加,且2015年1月1日后1岁内婴儿KD,冠状动脉损害以及IVIG不敏感发生率增高,临床上应及早作出诊断,及时治疗,减少并发症的发生.

Objective:To analyze the clinical efficacy of propafenone combined with Shensong Yangxin capsule in the treatment of premature ventricular contraction (PVC) in children.Methods:A total of 90 children with PVC treated in Children’s Hospital Affiliated of Zhengzhou University from January 2020 to December 2022 were divided into control group A (30 cases), control group B (30 cases) and observation group (30 cases) by random number table method. The control group A was treated with propafenone, the control group B was treated with Shensong Yangxin capsule, and the observation group was treated with propafenone combined with Shensong Yangxin capsule. The treatment efficacy, preoperative and postoperative dynamic electrocardiogram manifestations (24 h PVC frequency and heart rate), and incidence of adverse reactions were compared between the two groups.Results:The total effective rate of the observation group was 96.67% (29/30), higher than that of the control group A (70.00%, 21/30) and the control group B (66.67%, 20/30), P<0.05. Compared with the control group A and the control group B, the 24 h PVC frequency and heart rate in the observation group were lower ( P<0.05). There was no significant difference in the incidence of adverse reactions among the observation group (6.67%, 2/30), the control group A (16.67%, 15/30) and the control group B (13.33%, 4/30), P>0.05. Conclusions:Propafenone combined with Shensong Yangxin capsule is effective in the treatment of children with PVC, which can improve the clinical symptoms of children, and reduce the frequency of PVC and heart rate, without obvious adverse reactions.

Bisphenol A (BPA) is a typical endocrine disruptor, and the use of bisphenol B (BPB) as a substitute is gradually increasing. Some studies have shown that BPB also has endocrine disrupting effects, but its effects on the early stages of fish growth and development have not been reported. In this paper, zebrafish embryos were exposed to different concentrations of BPB until the 6th day post fertilization (dpf), and the toxic effects of BPB on the early development of zebrafish and the possible molecular mechanisms were investigated. The results showed that BPB exposure at 10, 100, and 1000 μg/L induced developmental toxic effects such as early neurotoxicity and cardiovascular toxicity in zebrafish, and the toxic effects were positively correlated with the degree of oxidative damage. These adverse results were ameliorated by the classical antioxidant N-acetyl-L-cysteine (NAC), suggesting the involvement of oxidative stress in BPB-induced early developmental toxicity. The above data suggest that BPB exposure increases oxidative damage and suppresses the expression of genes critical for early neurological and cardiovascular development, ultimately leading to early developmental toxicity in juvenile zebrafish. This study contributes to broadening our understanding of the toxic effects of BPB and provides a basic theoretical basis for the next management support of bisphenol analogs.

OBJECTIVE:To analyze the clinical and genetic characteristics of a child with restricted cardiomyopathy (RCM) and phenylketonuria (PKU), and summarize the clinical characteristics and genetic diversity of RCM in children through a literature review.METHODS:A child with RCM in conjunct with PKU who was admitted to the Children's Hospital Affiliated to Zhengzhou University in June 2020 due to edema of eyelids and lower limbs for 1 year and aggravation for over 1 month was selected as the study subject. Relevant clinical data were collected. Peripheral blood samples of the child and his parents were collected for whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing and bioinformatic analysis. Childhood, TNNI3 gene and restricted cardiomyopathy were used as the keywords to search the Wanfang data knowledge service platform, Chinese Journal Full-text database and PubMed database, and the search period was limited to from the time of establishment till August 2022. Clinical manifestations and characteristics of the TNNI3 gene variants were summarized.RESULTS:The child, a 2-year-old-and-4-month-old male, had normal intelligence, facial features and normal hair and skin color, but his motor and physical development was delayed, in addition with edema of bilateral eyelids and lower limbs. The results of WES and Sanger sequencing revealed that he has harbored compound heterozygous variants of the PAH gene, namely c.331C>T (p.R111X) and c.940C>A (p.P341T), which were inherited from his father and mother, respectively. In addition, he has also harbored a de novo heterozygous variant of c.508C>T (p.R170W) of the TNNI3 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the TNNI3: c.508C>T (p.R170W) was classified as a pathogenic variant (PS2+PS4+PM2_Supporting+PM5), PAH: c.331C>T (p.R111X) as a pathogenic variant (PVS1+PM2_Supporting+PM3+PP4), and c.940C>A (p.P341T) as a likely pathogenic variant (PM2_Supporting+PM3+PM5+PP4). In total 30 children with RCM caused by TNNI3 gene variants were retrieved, with a male-to-female ratio of 1 : 1.55 and manifestations including heart failure, sinus rhythm, bi-atrial enlargement, ST-T wave change, ventricular restricted filling, and decreased ventricular diastolic function. In total 16 variants of the TNNI3 gene were identified, among which c.575G>A was the most common, and all cases had conformed to an autosomal dominant inheritance.CONCLUSION:Phenylalanine hydroxylase deficiency and RCM are rare diseases with complex clinical manifestations. The PAH: c.331C>T (p.R111X)/c.940C>A (p.P341T) and TNNI3: c.508C>T (p.R170W) variants probably underlay the RCM and PKU in this child.

目的:探讨微小RNA-19a-3p(miR-19a-3p)/细胞因子信号抑制物3(SOCS3)信号轴在川崎病(KD)病理发展过程中的调控机制.方法:采集我院川崎病患儿、川崎病治疗后患儿血清,采用实时荧光定量PCR(RT-qPCR)及蛋白质印迹(Western Blot)法检测miR-19a-3p、SOCS3 mRNA及蛋白表达变化.小鼠腹腔注射白色念珠菌水溶物(CAWS)建立川崎病模型,分为正常对照组、模型组、si-miR-19a-3p组、ad-SOCS3组、si-NC组、ad-NC组,每组10只.取小鼠冠状动脉组织,采用酶联免疫吸附实验(ELISA)检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、诱导型一氧化氮合酶(iNOS)、血管内皮素(ET)水平;苏木素-伊红(HE)染色法观察冠状动脉病理变化;免疫组化法检测SOCS3阳性表达水平;RT-qPCR及Western Blot法检测miR-19a-3p、SOCS3 mRNA及蛋白表达变化;Western Blot法检测Janus酪氨酸蛋白激酶2(JAK2)、信号转导和转录激活因子3(STAT3)、磷酸化STAT3(p-STAT3)、核转录因子-κB(NF-κB)、磷酸化NF-κB(p-NF-κB)蛋白表达水平.取人冠状动脉内皮细胞(HCAEC),用川崎病患儿血清培养HCAEC以模拟体外川崎病模型,并分为正常对照组、川崎病组、si-miR-19a-3p组、si-SOCS3组、si-miR-19a-3p+si-SOCS3组、si-NC-1组、si-NC-2组;ELISA法检测细胞上清液炎性因子TNF-α、IL-1β水平;流式细胞术检测细胞凋亡率;管腔形成试验检测管腔形成情况;RT-qPCR法及Western Blot法检测miR-19a-3p、SOCS3 mRNA及蛋白表达变化.结果:川崎病患儿血清中miR-19a-3p表达升高,SOCS3 mRNA及蛋白表达降低(P<0.05);随着川崎病患儿康复,miR-19a-3p、SOCS3 mRNA及蛋白表达均趋于正常.沉默miR-19a-3p及上调SOCS3表达后,川崎病小鼠死亡减少,冠状动脉血管损伤缓解,SOCS3介导的炎性通路相关蛋白表达降低(P<0.05).下调SOCS3表达可逆转miR-19a-3p沉默发挥抑制HCAEC凋亡、管腔形成、炎性因子分泌等作用(P<0.05).结论:miR-19a-3p高表达、SOCS3低表达可能参与川崎病血管炎性损伤过程,沉默miR-19a-3p可靶向上调SOCS3表达,抑制炎症反应,减轻川崎病冠状动脉血管损伤.

目的 报告 1 个罕见的扩张型心肌病(DCM)致病基因突变位点,探讨其基因型与临床表型的关系.方法 对 1 例TNNI3 基因突变致DCM患儿的临床资料进行回顾性分析,采集患儿及其父母外周血基因组 DNA,进行全外显子测序.对DCM相关文献进行复习.结果 患儿,女,1 岁零 6 个月起病,急性期主要表现为纳差、精神萎靡伴少尿,活动量少.心脏彩超提示左心室、左心房明显扩大,左室射血分数 33%,左室缩短率 16%,临床诊断为DCM,无阳性家族史.核心家系全外显子测序结果显示,患儿在TNNI3 基因存在 c.465 G＞A(p.Met155 Ile)杂合错义突变,且为新生突变,其父母均不携带该突变.目前仅 2 例肥厚型心肌病报道过该突变.结论 TNNI3 基因的 c.465 G＞A(p.Met155 Ile)突变为DCM的可能致病突变,可能产生进行性的心衰表型.

患儿 女，2岁6月龄，因“呼吸、心搏骤停后5 h”转入郑州大学附属儿童医院，主要临床表现为心搏骤停、晕厥、无自主呼吸、抽搐。心电图可见单发、成对室性早搏以及多形性室性心动过速，予持续机械通气、抗感染、脑保护、美托洛尔等治疗，遗留有言语和语言障碍、肌无力。基因检测结果提示患儿TRDN基因存在c.326delT（p.Leu109CysfsTer25）纯合变异，确诊为Triadin敲除综合征，后继续予美托洛尔治疗，随访7个月未发生心脏事件。.

OBJECTIVE:To explore the clinical and genetic characteristics of five children with Catecholaminergic polymorphic ventricular tachycardia (CPVT).METHODS:Five children with clinical manifestations consistent with CPVT admitted to the Department of Cardiology of Children's Hospital Affiliated to Zhengzhou University from November 2019 to November 2021 were selected as the study subjects. Their clinical data were collected. Potential variants were detected by whole exome sequencing, and Sanger sequencing was used to verify the candidate variants. All patients were treated with β-blocker propranolol and followed up.RESULTS:All patients had developed the disease during exercise and presented with syncope as the initial clinical manifestation. Electrocardiogram showed sinus bradycardia. The first onset age of the 5 patients were (10.4 ± 2.19) years, and the time of delayed diagnosis was (1.6 ± 2.19) years. All of the children were found to harbor de novo heterozygous missense variants of the RYR2 gene, including c.6916G>A (p.V2306I), c.527G>C (p.R176P), c.12271G>A (p.A4091T), c.506G>T (p.R169L) and c.6817G>A (p.G2273R). Among these, c.527G>C (p.R176P) and c.6817G>A (p.G2273R) were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.527G>C (p.R176P) was classified as a pathogenic variant (PS2+PM1+PM2_Supporting+PM5+PP3+PP4), and the c.6817G>A (p.G2273R) was classified as a likely pathogenic variant (PS2+PM2_Supporting+PP3+PP4). The symptoms of all children were significantly improved with the propranolol treatment, and none has developed syncope during the follow up.CONCLUSION:Discovery of the c.527G>C (p.R176P) and c.6817G>A (p.G2273R) variants has expanded the mutational spectrum of the RYR2 gene. Genetic testing of CPVT patients can clarify the cause of the disease and provide a reference for their genetic counseling.

目的 探讨川崎病(KD)患儿血浆微小核糖核酸-223(miR-223)、FGD5-AS1的表达水平及临床意义.方法 选取收治的KD患儿75例作为KD组,选取同期参加体检的健康儿童60例作为健康对照组,感染发热患儿60例作为发热对照组.根据冠状动脉Z值将KD组患儿分为无冠状动脉损伤组59例和冠状动脉损伤组16例.采用实时荧光定量PCR检测研究对象血浆miR-223、FGD5-AS1表达水平;采用Pearson检验分析KD患儿血浆FGD5-AS1与miR-223表达水平的相关性;使用ROC曲线分析FGD5-AS1、miR-223对KD患儿冠状动脉损伤的诊断价值.结果 KD组、发热对照组患儿血小板计数(PLT)、血沉(ESR)及血浆miR-223、白细胞介素-6(IL-6)、氨基末端脑钠肽前体(NT-proBNP)表达水平均明显高于健康对照组儿童,FGD5-AS1表达水平明显低于健康对照组儿童(P<0.05).KD组患儿PLT、ESR及血浆miR-223、IL-6、NT-proBNP表达水平均明显高于发热对照组患儿,FGD5-AS1表达水平明显低于发热对照组患儿(P<0.05).治疗后KD患儿血浆miR-223表达水平明显降低,FGD5-AS1表达水平明显升高(P<0.05).KD患儿血浆miR-223与FGD5-AS1表达水平呈负相关(P<0.05);miR-223表达水平与血浆IL-6、NT-proBNP表达水平均呈正相关(P<0.05),FGD5-AS1表达水平与血浆IL-6、NT-proBNP表达水平均呈负相关(P<0.05).冠状动脉损伤组患儿PLT、ESR及血浆miR-223、IL-6、NT-proBNP表达水平均明显高于无冠状动脉损伤组患儿,FGD5-AS1表达水平明显低于无冠状动脉损伤组患儿(P<0.05).血浆FGD5-AS1、miR-223水平联合检测对KD患儿冠状动脉损伤诊断的曲线下面积为0.907(95％CI:0.845～0.969),优于二者单独检测.结论 KD患儿血浆FGD5-AS1表达水平明显降低、miR-223表达水平明显升高,二者间可能存在相互作用参与KD进展,可作为评估冠状动脉损伤发生的有效指标.

目的:研究血清脑利尿钠肽(BNP)、血清可溶性肿瘤坏死因子样弱凋亡诱导因子(sTWEAK)水平与扩张型心肌病(DCM)患儿并发心室重构、急性失代偿性心力衰竭(ADHF)的相关性.方法:回顾性选取2018年10月至2020年10月期间河南省儿童医院收治的45例DCM并发心室重构患儿作为本研究的心室重构组;选取同期收治的46例DCM并发ADHF患儿为ADHF组;再选取同期收治的DCM未发生心室重构、ADHF的45例患儿为DCM组.三组患儿均测定血清BNP、sTWEAK水平,ADHF组和DCM组测定左室射血分数(LVEF),心室重构组和DCM组测定左心室舒张末期内径(LVEDD),比较三组患儿血清BNP、sTWEAK水平,分析血清BNP、sTWEAK与LVEDD、LVEF的相关性.并使用受试者工作特征曲线(ROC)分析血清BNP、sTWEAK水平联合诊断DCM并发心室重构、DCM并发ADHF的诊断价值.结果:心室重构组患儿的血清BNP水平明显高于DCM组、ADHF组,sTWEAK水平明显低于DCM组、ADHF组;ADHF组患儿血清BNP水平明显高于DCM组,sTWEAK水平明显低于DCM组,差异均具有统计学意义(P＜0.05).经Pearson相关性分析,LVEF与血清BNP负相关(r=-0.835,P＜0.001),与血清 sTWEAK 正相关(r=0.679,P＜0.001);LVEDD 与血清 BNP 正相关(r=0.899,P＜0.001),与血清sTWEAK负相关(r=-0.712,P＜0.001).ROC曲线分析结果显示,血清BNP、sTWEAK联合诊断DCM并发ADHF以及DCM并发心室重构的效能均高于两者单独诊断.结论:血清BNP、sTWEAK水平与DCM患儿并发心室重构或ADHF存在相关性,二者联合诊断对DCM患儿并发心室重构或ADHF具有较高诊断价值.

目的 分析糖皮质激素联合丙种免疫球蛋白对川崎病患儿的临床效果.方法 选取2019 年 1 月至2022 年 1 月郑州大学附属儿童医院川崎病患儿 195 例为研究对象,按随机数字表法分为观察组(n =98)和对照组(n=97).对照组予以丙种球蛋白,观察组予以联合糖皮质激素.比较两组症状改善时间、住院时间、免疫功能(CD4+、CD8+)、炎症因子[C反应蛋白(CRP)、降钙素原(PCT)]及不良反应.结果 观察组退热时间、皮疹消退时间、黏膜充血消退时间和住院时间均较对照组短(P＜0.05).治疗 14 d后,观察组CD4+水平较对照组低,CD8+水平较对照组高(P＜0.05).治疗 14 d后,观察组CRP、PCT水平较对照组低(P＜0.05).观察组不良反应发生率[10.20％(10/98)]与对照组[16.49％(16/97)]比较,差异未见统计学意义(P＞0.05).结论 糖皮质激素联合丙种免疫球蛋白治疗川崎病患儿,可减轻炎性反应,改善免疫功能,加快症状改善,并具有安全性.

目的 观察病毒性心肌炎(VMC)病儿血浆外泌体微小RNA(miR)-148a的水平并分析其意义.方法 选择2017年9月至2019年6月郑州大学附属儿童医院收治的VMC病儿112例纳入研究组,另选取同期门诊健康体检正常儿童112例为对照组,实时荧光定量PCR(RT-qPCR)检测血浆外泌体miR-148a水平,酶联免疫吸附测定(ELISA)检测血浆外泌体心肌肌钙蛋白I(cTnI),采用自动化生化仪检测血浆外泌体肌酸激酶同工酶(CK-MB)水平、超敏C反应蛋白(hs-CRP)水平.采用Pearson相关性分析检验VMC病儿血浆外泌体miR-148a与cTnI、CK-MB、hs-CRP水平的相关性.绘制受试者工作特征曲线(ROC)分析血浆外泌体miR-148a对VMC的诊断价值.结果 血浆外泌体在透射电镜下呈大小不等、直径约100 nm典型圆形或椭圆形囊泡结构.与对照组比较,研究组血浆外泌体miR-148a水平[(1.01±0.12)比(5.34±1.06)]、血浆cTnI、CK-MB、hs-CRP水平均增加(均P<0.001).VMC病儿血浆外泌体miR-148a与血浆cTnI、CK-MB、hs-CRP水平均呈正相关(r=0.62、0.64、0.49,均P<0.001).血浆外泌体miR-148a及血浆cTnI、CK-MB、hs-CRP诊断早期VMC的曲线下面积(AUC)分别为0.94、0.94、0.83、0.86,截断值分别为1.87、0.19μg/L、56.45 U/L、2.06 mg/L,灵敏度分别为94.60％、92.90％、84.80％、83.90％,特异度分别为92.90％、94.60％、83.90％、83.90％.血浆外泌体miR-148a与血浆cTnI诊断早期VMC的效能一致,均优于血浆CK-MB、hs-CRP.结论 VMC病儿血浆外泌体miR-148a水平上调,可能对VMC有一定诊断价值.

BackgroundDilated cardiomyopathy (DCM), which is a major cause of heart failure, is a primary cardiac muscle disease with high morbidity and mortality rates. DCM is a genetically heritable disease and more than 10 gene ontologies have been implicated in DCM. CDH2 encodes N-cadherin and belongs to a superfamily of transmembrane proteins that mediate cell–cell adhesion in a calcium-dependent manner. Deficiency of CDH2 is associated with arrhythmogenic right ventricular cardiomyopathy (OMIM: 618920) and agenesis of the corpus callosum, cardiac, ocular, and genital syndrome (OMIM: 618929). However, there have been no reports of isolated DCM associated with CDH2 deficiency.MethodsWe performed whole exome sequencing in a 12-year-old girl with non-syndromic DCM and her unaffected parents. Variants in both known DCM-related genes and novel candidate genes were analyzed and pathogenicity confirmation experiments were performed.ResultsNo pathogenic/likely pathogenic variant in known DCM-related genes was identified in the patient. We found a de novo variant in a candidate gene CDH2 in the patient, namely, c.474G>C/p.Lys158Asn (NM_001792.5). This variant has not been reported in the ClinVar or Human Gene Mutation Database (HGMD). CDH2 p.Lys158Asn was found in the conserved domain of N-cadherin, which is associated with the hydrolysis of the precursor segment and interference with adhesiveness. Furthermore, we tested the expression and efficiency of cell–cell adhesion while overexpressing the CDH2 Lys158Asn mutant and two previously reported variants in CDH2 as positive controls. The adhesion efficiency was considerably reduced in the presence of the mutated CDH2 protein compared with wild-type CDH2 protein, which suggested that the mutated CDH2 protein's adhesion capacity was impaired. The variant was probably pathogenic after integrating clinical manifestations, genetic analysis, and functional tests.ConclusionWe identified a CDH2 variant in DCM. We observed a new clinical symptom associated with N-cadherin deficiency and broadened the genetic spectra of DCM.