Table of Content

15 July 2023 Volume 41 Issue 7

  

Original article

Application of single cell sequencing technology in Kawasaki disease research

HUANG Min

Journal of Clinical Pediatrics. 2023, 41(7):  481-485.  doi:10.12372/jcp.2023.23e0436

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Kawasaki disease (KD) is an acute febrile illness which mainly involves the small and medium-sized blood vessels throughout the body, predominantly occurs in children under 5 years old. Coronary artery lesions are its main complication and KD is now the commonest cause of acquired heart disease in children in developed countries. Different from traditional sequencing methods, single-cell sequencing technology can sequence genetic information at single-cell resolution, which can not only solve the problem of cell heterogeneity, but also identify cell subsets, search for biomarkers, and map cell lineages. This commentary will describe the development of single cell sequencing technology and its current application in the field of KD, and provide an outlook on its development.

Clinical diagnosis and treatment of Kawasaki disease-associated macrophage activation syndrome in children

HAO Sheng, HUANG Min

Journal of Clinical Pediatrics. 2023, 41(7):  486-491.  doi:10.12372/jcp.2022.23e0317

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Kawasaki disease is a systemic vasculitis. Macrophage activation syndrome is a severe complication of pediatric rheumatic immune diseases, which is characterized by cytokine storms and has a rapid progression and high mortality rate. Early identification of Kawasaki disease-associated macrophage activation syndrome is difficult, and its main features include persistent fever, splenomegaly, elevated ferritin levels, and decreased platelets. At present, there is no uniform diagnostic criteria for this disease, which mainly refers to the diagnostic criteria of systemic juvenile idiopathic arthritis with macrophage activation syndrome and primary hemophagocytic lymphohistiocytosis. Meanwhile, this disease should be distinguished from Kawasaki disease shock syndrome and childhood multisystem inflammatory syndrome. Glucocorticoids are the main treatment drugs, and patients with poor response can use traditional immunosuppressants such as cyclosporine. Biologic agents and targeted drugs have broad prospects.

Long-term management of severe coronary artery lesions in Kawasaki disease

LIU Fang, LIN Yixiang

Journal of Clinical Pediatrics. 2023, 41(7):  492-497.  doi:10.12372/jcp.2022.23e0331

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Kawasaki disease coronary artery lesions (CAL) has become one of the most common acquired cardiovascular diseases in China. The treatment and long-term management of severe CAL is very challenging. This article summarizes and prospects the management of severe CAL by focusing on diagnosis and evaluation methods, treatment progress and follow-up programs.

Risk factors analysis of coronary artery aneurysm occurrence in children with Kawasaki disease

ZHOU Cuizhen, SONG Sirui, CHEN Liqin, HUANG Min

Journal of Clinical Pediatrics. 2023, 41(7):  498-501.  doi:10.12372/jcp.2023.23e0285

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Objective To investigate the risk factors of coronary artery aneurysm (CAA) occurrence in children with Kawasaki disease (KD). Methods The clinical data of children with KD hospitalized from January 2020 to December 2021 were retrospectively analyzed. According to the presence or absence of CAA, the children were divided into CAA group and non-CAA group, and the clinical characteristics between the two groups were compared. The risk factors affecting the occurrence of CAA and the predictive value of related indicators for KD complicated with CAA were analyzed. Results A total of 557 children with KD (346 boys and 211 girls) were included, and the median age was 25.0 (13.0-45.2) months. CAA was found in 75 patients (13.5%) and intravenous immunoglobulin (IVIG) resistance was observed in 39 (7.0%) patients. Multivariate logistic regression analysis showed that age ≤1 year, IVIG resistance and elevated platelet count (PLT) were independent risk factors for KD complicated with CAA, and elevated albumin (ALB) was a protective factor for KD complicated with CAA (P<0.05). ROC curve analysis showed that the area under ROC curve (AUC) of PLT and ALB predicting KD with CAA was 0.64 (0.57-0.73) and 0.65 (0.58-0.72), respectively. The sensitivity and specificity of PLT>551×10⁹/L for predicting KD with CAA were 63.0% and 67.0%, and the sensitivity and specificity of ALB<36.5U/L for predicting KD with CAA were 68.0% and 56.0%. Conclusions Age≤1 year, IVIG resistance, PLT>551×10⁹/L and ALB<36.5U/L had certain predictive effects on the occurrence of CAA in children with Kawasaki disease.

Effect and predictive value of serum pentraxin-3 level on intravenous immunoglobulin resistance in children with Kawasaki disease

XU Dan, PAN Dongning, LI Yaqin

Journal of Clinical Pediatrics. 2023, 41(7):  502-506.  doi:10.12372/jcp.2023.22e1119

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Objective To explore the effect and predictive value of serum pentraxin-3 (PTX3) level on intravenous immunoglobulin (IVIG) resistance in children with Kawasaki disease (KD). Methods Children with KD diagnosed and treated from January 2017 to July 2022 were selected as the study objects. IVIG resistance was determined according to the IVIG treatment outcome. The relationship between PTX3 and IVIG resistance was analyzed by binary logistic regression. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of PTX3 in predicting IVIG resistance. Results A total of 292 KD children (187 boys and 105 girls) with a median age of 25.0 (10.0-32.0) months were included, and 49 patients (16.8%) showed IVIG resistance. Binary logistic regression analysis showed that the independent risk factors of IVIG resistance were rash, cervical lymph node swelling, increased white blood cell count and CRP, decreased serum sodium, ALT≥33.2 IU/L, creatinine≥42.5 μmol/L, serum ferritin≥180.3 μg/L and PTX3≥19.3 ng/mL. The ROC curve showed that the area under the curve (AUC) of PTX3 for predicting IVIG resistance was 0.77 (95%CI: 0.68~0.85, P<0.001), with moderate accuracy. When the cut-off value was 21.5 ng/mL, the sensitivity, specificity, and Youden index for predicting IVIG resistance were 0.71, 0.69, and 0.40 respectively. Conclusions PTX3 is an independent risk factor for IVIG resistance in KD children, and has a good effect in predicting IVIG esistance.

Clinical features, treatments, and outcomes of neonatal arrhythmia

CHEN Wenwen, DAI Shuzhen, XU Liping

Journal of Clinical Pediatrics. 2023, 41(7):  507-513.  doi:10.12372/jcp.2023.22e0320

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Objective To evaluate the etiology, treatment and outcome of neonatal arrhythmia. Methods The clinical data and short-term follow-up results of neonates diagnosed with arrhythmia from June 2017 to May 2020 were retrospectively analyzed. Results Twenty-three cases with neonatal arrhythmia (11 boys and 12 girls) were included. The mean gestational age was (36.2±2.9) weeks and the mean birth weight was (2784.8±727.7) grams. There were 12 full-term and 11 preterm infants. Abnormal fetal heart rhythm of 8 cases were observed in the prenatal period. There were 9 cases of ectopic beats, 12 cases of tachycardia and 2 cases of conduction block. The main causes of arrhythmia were cardiac structural abnormality, neonatal respiratory distress syndrome and asphyxia at birth. Fourteen cases did not have clear etiology or clinical symptoms. Twelve cases with tachycardia were treated with anti-arrhythmia drugs or electrical cardioversion, while those without clinical symptoms (6 cases of supraventricular premature beats, 3 cases of ventricular premature beats and 1 case of atrioventricular block) did not receive anti-arrhythmia therapy. Four neonates died (17.4%) eventually. Serum levels of creatine kinase, creatine kinase-MB isoenzyme, cardiac troponin T and B-type natriuretic peptide in death group were significantly higher than those in survival group, and the difference was statistically significant (P<0.05). Of the 19 infants who survived until discharge, 11 showed abnormal rhythm on dynamic electrocardiogram, and 2 were treated with oral anti-arrhythmia drug after discharge. By 1 year of age, none of the patients had been readmitted to the hospital for symptomatic arrhythmia. Conclusions Arrhythmia may occur in newborns with underlying diseases, or without clear cause or clinical symptoms. The prognosis of patients with elevated myocardial markers is poor. Rapid arrhythmia should be considered as soon as possible. For those without clear cause or symptoms, those with good heart function, no intervention should be involved, but need to be closely followed.

Influencing factors analysis of the occurrence of small for gestational age in late preterm infants

LIN Yucong, GAO Liang, ZHENG Zhi

Journal of Clinical Pediatrics. 2023, 41(7):  514-518.  doi:10.12372/jcp.2023.22e0473

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Objective To investigate the risk factors of the occurrence of small for gestational age (SGA) in late preterm infants. Methods The clinical data of late preterm infants with gestational age of 34~36⁺⁶ weeks born in Xiamen Maternal and Child Health Hospital and admitted to the neonatal intensive care unit from January 2019 to December 2021 were retrospectively analyzed. According to the gestational age and birth weight, the subjects were divided into SGA group and appropriate gestational age (AGA) group. The propensity score matching function of SPSS software was used to match the two groups with the 1:1 nearest neighbor matching method to obtain the between-group correlation. The clinical features between the two groups were compared. The influencing factors of SGA occurrence in late preterm infants were analyzed by multivariate conditional logistics regression. Results There were 239 patients in SGA group and 239 patients in AGA group, and there were no significant differences in gender and gestational age between the two groups (P>0.05). The proportion of prenatal glucocorticoid therapy, the incidence of gestational hypertension and twin pregnancy in SGA group was higher than that in AGA group, and the incidence of premature rupture of membranes (≥18h) in SGA group was lower than that in AGA group, and the differences were statistically significant (P<0.05). The results of multivariate conditional logistics regression analysis showed that prenatal glucocorticoid therapy, gestational hypertension and twin pregnancy were independent risk factors for SGA occurrence in late preterm infants (P<0.05). Conclusions Reduction of prenatal glucocorticoid treatment, prevention of hypertension during pregnancy, and avoidance of twin pregnancy are the main measures to reduce SGA in late prematureinfants.

Changes of body mass index and its related factors in children and adolescents with type 1 diabetes mellitus

ZHAO Ling, LIU Xiaojing

Journal of Clinical Pediatrics. 2023, 41(7):  519-525.  doi:10.12372/jcp.2023.22e0686

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Objective To compare the body mass index standard deviation scores (BMISDS) at diagnosis and last follow-up in children with type 1 diabetes mellitus (T1DM), and to reveal the related factors affecting the change of BMISDS. Methods The clinical data of children with T1DM initially diagnosed in the endocrinology department from June 2017 to January 2021 were retrospectively analyzed. The correlation between each factor and ΔBMISDS was analyzed. Results Fifty-three children with T1DM (26 boys and 27 girls) were included, and the median course of follow-up was 3.0 (1.5-4.0) years. The median age at diagnosis was 8.0 (5.5-11.0) years, the BMISDS were -1.1 (-1.8-0.6) and 12 patients (22.6%) were overweight and obese. Forty-two patients completed the last follow-up. The median age was 12.0 (8.8-13.3) years, the BMISDS were 0 (-0.6-0.7) and 5 patients (11.9%) were overweight and obese. The BMISDS at the last follow-up were higher than that at diagnosis, the difference was statistically significant (P<0.01). Of the 41 children who were not overweight and obese at the time of diagnosis, 30 completed the last follow-up. The ΔBMISDS of 14 boys and 16 girls were 0.3 (-0.3-1.8) and 1.9 (1.1-2.2), respectively. The ΔBMISDS of girls was higher than that of boys, and the difference was statistically significant (P<0.05). The ΔBMISDS of girls were higher than that of boys in 0~5 years old, 5~10 years old and ≥10 years old groups, and the difference was statistically significant (P<0.05). ΔBMISDS was significantly negatively correlated with BMISDS, fasting C-peptide (FCP), free triiodothyronine (FT₃), free thyroxine (FT₄) and thyrotropin (TSH) at diagnosis (P<0.05), and significantly positively correlated with glycosylated hemoglobin (HbA1c) at diagnosis (P<0.05). In multiple linear regression, ΔBMISDS was still significantly negatively correlated with BMISDS and TSH at diagnosis (P<0.05). Conclusions BMISDS in children with T1DM showed an increasing trend in the course of disease, which was related to gender, BMISDS and TSH at the time of diagnosis. Appropriate intervention measures should be developed to reduce the occurrence of overweight, obesity and its complications.

Clinical analysis of risk factors for recurrence of acute pancreatitis in children

TAN Chunxiu, YANG Ying, WANG Yuanzhen, HUANG Liya

Journal of Clinical Pediatrics. 2023, 41(7):  526-529.  doi:10.12372/jcp.2023.22e1226

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Objective To investigate the risk factors for the recurrence of acute pancreatitis in children. Methods The clinical data of children with acute pancreatitis (AP) admitted to the General Hospital of Ningxia Medical University from December 2010 to December 2020 were analyzed retrospectively. The children were divided into AP group and recurrent acute pancreatitis (RAP) group. The clinical characteristics of the two groups were compared, and the influencing factors of AP recurrence in children were analyzed. Results A total of 90 AP children (55 boys and 35 girls) were included, and the median age was 9.0 (6.0-12.0) years. In the RAP group, 24 patients recurred 6.6 (1.0-11.6) months after the first onset of AP, with a median age of 10.0 (7.0-12.0) years. The common causes of recurrence were idiopathic AP (9 cases, 37.5%), pancreatic anatomical abnormalities (7 cases, 29.2%) and biliary origin (5 cases, 20.8%). Among the 90 children with AP, 15 had severe AP, including 8 in RAP group and 7 in AP group. Among 90 AP children, the incidence of abdominal pain and vomiting were 83.3% and 32.2%. The incidence of pancreatic necrosis and pancreatic pseudocyst was 5.6% and 6.7%. Multivariate logistic regression analysis showed that abnormal pancreatic anatomy and severe AP were independent risk factors for recurrence of AP in children (P<0.05), and idiopathic AP was an independent protective factor for recurrence of AP in children (P<0.05). Conclusions Patients with severe AP and abnormal pancreatic anatomy are prone to recurrence, which should be paid attention to by clinicians.

Genetic characteristics of TRPV4-related congenital skeletal disorder

ZHANG Wenyan, YAO Ziming, ZHANG Xuejun, ZHANG Yaodong, WANG Lingfei, HU Xuyun, HAO Chanjuan

Journal of Clinical Pediatrics. 2023, 41(7):  530-536.  doi:10.12372/jcp.2023.22e1509

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Objective To identify the genetic causes of four patients with different severity of congenital skeletal disorder by genetic diagnosis, and to summarize the clinical characteristics and analyze the genotype-phenotype. Methods The clinical data of four patients were collected. The peripheral blood of the patients and their parents were collected and DNA was extracted. Whole exome sequencing of patients was performed and variants were classified following the interpretation standards and guidelines of the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology. Putative pathogenic variants were verified by Sanger sequencing. Results The four patients all carried TRPV4 heterozygous variants. Two missense variants were inherited from affected parents, and one deletion insertion variant and missense variant were de novo: c.2077G>A (p.Val693Met), c.1199G>A (p.Arg400Gln), c.1657delinsACTA (p.Tyr553delinsThrAsn) and c.259G>A (p.Glu87Lys). None of these variants have been previously reported. Patients 1-3 had varying degrees of short stature, and all 4 had congenital scoliosis and other skeletal deformities. They were diagnosed as mild Metatropic Dysplasia, Autosomal Dominant Brachyomia type 3, Parastremmatic Dysplasia with Metatropic Dysplasia, and classic Metatropic Dysplasia respectively. Their parents with the same variant also had mild bone deformity. Conclusions The phenotypes of congenital skeletal disorders caused by different variants in TRPV4 gene were widely heterogeneous. Patients often present with overlapping skeletal system abnormalities. Therefore, differential diagnosis and clinical intervention can be conducted according to the molecular diagnosis results.

Clinical and genetic characteristics of Kallmann syndrome

TANG Yijun, ZHANG Qianwen, WANG Yirou, CHEN Yao, LI Xin, LI Juan, WANG Jian, WANG Xiumin

Journal of Clinical Pediatrics. 2023, 41(7):  537-542.  doi:10.12372/jcp.2023.22e1053

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Objective To analyze the clinical and genotypic characteristics of children with Kallmann syndrome (KS), and to strengthen clinicians' understanding of the disease. Methods The clinical characteristics, whole-exome gene sequencing results, and treatment outcomes of 20 KS patients were retrospectively analyzed. Results Among the 20 patients, 17 were boys and 3 were girls. The mean age at diagnosis was 13.13 years old. Male children presented micropenis with small testicular size and history of bilateral cryptorchidism, while female patients presented primary amenorrhea and retardation of breast development. The results of Chinese odor recognition test indicated that 93.75% (15/16) children had olfactory disorder. Children with KS may have other systemic manifestations, including neurodevelopmental delay, mental retardation, phalangeal abnormalities, hearing impairment, and congenital cleft lip and palate. Among the 19 patients who underwent whole-exome gene sequencing, 12 variation sites in 6 genes were found, including FGFR1, CHD7, SOX10, KAL1, PROKR2 and SOX2. The molecular diagnosis rate was 63.16% (12/19). Testicular size, penile length, penile girth, T, LH and FSH were significantly improved after receiving pulsatile GnRH pump treatment, and there were no obvious adverse reactions. Conclusions The application of Chinese odor recognition tests can more accurately evaluate olfactory function in children with KS. The whole-exome gene sequencing technology is helpful to improve the molecular diagnosis of the disease, so as to diagnose the children with this rare disease as early as possible. Pulsatile GnRH pump therapy promotes sexual development in children with KS without obvious adverse effects.

The role of ELABELA/Apelin-APJ pathway in cardiovascular development

YANG Junjie, SUN Kun

Journal of Clinical Pediatrics. 2023, 41(7):  543-548.  doi:10.12372/jcp.2023.22e0853

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Congenital heart disease is the commonest birth defect and is closely related to cardiovascular development during the embryonic period. ELABELA/Apelin-APJ pathway mainly contains two peptide ligands, ELABELA and Apelin, as well as their common receptor APJ. It is known that ELABELA/Apelin-APJ pathway is involved in many physiological and pathological processes and is closely related to the occurrence of many disease. In recent years, the relationship between the ELABELA/Apelin-APJ pathway and cardiovascular development has received extensive attention. This article mainly summarizes and compares the powerful regulatory effects of the ELABELA/Apelin-APJ pathway on cardiovascular development, aiming to reveal the role of the two pathways in different stages of cardiac development and the great significance in preventing congenital cardiovascular malformation.

Advances in the pathogenesis of very early onset inflammatory bowel disease

ZHUANG Yan, HUANG Ruiwen

Journal of Clinical Pediatrics. 2023, 41(7):  549-555.  doi:10.12372/jcp.2023.22e0397

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Very early onset inflammatory bowel disease (VEO-IBD) refers to those patients who have developed disease before the age of 6, and their incidence and prevalence have increased rapidly in recent years. With the development of gene sequencing technologies and platforms, the pathogenesis of VEO-IBD has been found to be related to the monogenic variations involved in multiple pathways of immunity. Whether the monogenic variation is the main cause of VEO-IBD is still controversial, but identifying the specific variant type can guide specific treatment to some extent. This paper introduces the possible mechanisms of gene variation and environmental exposure in the pathogenesis of VEO-IBD, focusing on four aspects of monogenic variation associated with VEO-IBD, in order to provide directions for early diagnosis and precise treatment.

Clinical applications of human milk oligosaccharides in infants

JIANG Lu, CAI Wei

Journal of Clinical Pediatrics. 2023, 41(7):  556-560.  doi:10.12372/jcp.2023.23e0465

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Human milk oligosaccharides (HMOs) are unique and abundant complex carbohydrates in breast milk. As the third most abundant component in breast milk, they have gradually received attention from scholars both domestically and internationally. With the rapid development of analytical techniques and multiomics, the research field of HMOs has made great progress and made great breakthroughs in the past few years. However, we are still in the initial stage of revealing the role and mechanisms of HMOs. However, the conclusions are mainly from foreign clinical studies, and need to be further verified by high-quality randomized clinical trials. In addition, we need to consider its effectiveness in different diseases, environment, and populations. Here, we summarize the roles of HMOs in regulating gut microbiome development, intestinal health, immune system development, and brain development in infants. Additionally, we explore the potential future applications of HMOs in infants in China.