Objective To study the clinical effect and safety of double filtration plasmapheresis (DFPP) combined with double pulse therapy with methylprednisolone (MP) and cyclophosphamide (CTX) in the treatment of children with severe Henoch-Schönlein purpura nephritis (HSPN). Methods A total of 60 children with severe HSPN who were admitted to the hospital from January 2014 to March 2018 were enrolled and were randomly divided into an observation group and a control group (n=30 each). In addition to routine treatment, the children in the control group were given MP+CTX pulse therapy. Those in the observation group were given DFPP treatment in addition to the treatment in the control group, with three courses of treatment in total. After three courses of treatment, the two groups were compared in terms of 24-hour urinary protein, urinary microproteins, renal function parameters, adverse reactions, and clinical outcome. Results After three courses of treatment, the observation group had significantly greater reductions in 24-hour urinary protein, urinary albumin, urinary immunoglobulin G, urinary β2-microglobulin, serum creatinine, and blood urea nitrogen than the control group (P < 0.05). After the treatment ended, the observation group had a significantly shorter time to achieve remission than the control group (P < 0.05). No serious adverse reactions, such as hemorrhagic cystitis, thrombocytopenia, and hemolysis, were observed, and there was no significant difference in the overall incidence rate of adverse reactions between the two groups (P > 0.05). Conclusions Compared with MP+CTX pulse therapy alone in the treatment of severe HSPN in children, DFPP combined with MP+CTX pulse therapy can further alleviate renal injury and improve clinical outcome and does not increase the incidence rate of adverse reactions.

Objective To study the role of gamma-delta T (γδ T) cells and its subsets in the immunopathogenesis of Henoch-Schönlein purpura (HSP) in children, and to provide new ideas for the treatment of HSP in children from the aspect of γδ T cell regulation. Methods A total of 33 children with HSP were enrolled as the HSP group, and 21 healthy children were enrolled as the healthy control group. The percentages of γδ T cells and its subsets Vδ1⁺T and Vδ2⁺T cells among peripheral blood mononuclear cells (PBMCs) were measured, as well as the apoptosis rate of γδ T cell and plasma level of interleukin-17 (IL-17). Results Compared with the healthy control group, the HSP group had significantly lower percentages of lymphocytes in PBMCs and Vδ2⁺T cells in γδ T cells (P < 0.05). The HSP group had significantly higher percentage of Vδ1⁺T cells in γδ T cells and plasma level of IL-17 than the healthy control group. The HSP group had a significantly higher overall apoptosis rate of γδ T cells than the healthy control group (P < 0.05), especially early apoptosis. The percentage of Vδ2⁺T cells was positively correlated with overall apoptosis rate (r_s=0.615, P < 0.05) and was negatively correlated with IL-17 level (r_s=-0.398, P < 0.05). Conclusions Vδ1+/Vδ2⁺T cell immune imbalance mediated by γδ T cells and over-activation of IL-17 may be involved in the development of HSP, among which the disturbance of immune tolerance induced by Vδ2⁺T cells plays an important role in the pathophysiology of the disease.

Objective To study the role of autophagy in the development of systemic juvenile idiopathic arthritis (sJIA) by analyzing the expression of microtubule-associated protein 1 light chain 3-Ⅱ (LC3-Ⅱ), myeloid differentiation factor 88 (MyD88), and suppressor of T-cell receptor signaling 1 (STS-1) in peripheral blood lymphocytes of children with sJIA. Methods A total of 26 children with sJIA were enrolled as the sJIA group, and 26 healthy children were enrolled as the control group. Western blot was used to measure the protein expression of LC3-Ⅱ, STS-1, and MyD88 in peripheral blood lymphocytes. Immunofluorescence assay was used to measure the expression of LC3-Ⅱ in the cytoplasm of lymphocytes. Pearson correlation analysis was used to assess the correlation between indices. Results Compared with the control group, the sJIA group had significant increases in the expression of LC3-Ⅱ, STS-1, and MyD88 (P < 0.05). In the sJIA group, the expression of LC3-Ⅱ was positively correlated with that of MyD88 (r=0.478, P < 0.05), and the expression of STS-1 was also positively correlated with that of MyD88 (r=0.817, P < 0.05). Conclusions There is high expression of LC3-Ⅱ in peripheral blood lymphocytes of children with sJIA, suggesting that the development of sJIA may be associated with excessive expression of autophagy. STS-1 may induce autophagy by activating some signaling pathways, and MyD88 may participate in autophagy through the Toll-like receptor signaling pathway.

Objective To study the types and characteristics of TUBB1 mutation in children with congenital hypothyroidism (CH) and thyroid dysgenesis (TD) in Shandong, China. Methods Mutations of the whole coding region of the TUBB1 gene were analyzed for 289 children with CH and TD in Shandong. Whole-genome DNA was extracted from peripheral blood leukocytes. PCR multiplication was performed for the whole coding region of the TUBB1 gene. Sanger sequencing was performed for the PCR products, and a biological information analysis was performed. Results Among the 289 children with CH and TD, 4 (1.4%) were found to have a c.952C > T(p.R318W) heterozygous mutation in the TUBB1 gene, resulting in the change of tryptophan into arginine at codon 318 of TUBB1 protein. This mutation was evaluated as "potentially pathogenic" based on the classification criteria and guidelines for genetic variation by American College of Medical Genetics and Genomics. Conclusions A novel mutation is detected in the exon of the TUBB1 gene in children with CH and TD in Shandong, suggesting that the TUBB1 gene may be a candidate pathogenic gene for CH children with TD.

Objective To evaluate the therapeutic effect and safety of letrozole in the treatment of adolescent boys with idiopathic short stature (ISS). Methods A retrospective analysis was performed for the clinical data of 16 adolescent boys with ISS who had a bone age of ≥ 14 years. Among these boys, 8 were initially treated with recombinant human growth hormone (rhGH), followed by rhGH combined with letrozole during a bone age of 14-15.5 years. The other 8 boys were initially treated with rhGH combined with letrozole since their bone age was ≥ 14 years at diagnosis. Of the 16 boys, 16 were treated for not less than 6 months, 12 were treated for not less than 1 year, and 5 were treated for not less than 1.5 years. The increase in bone age, predicted adult height (PAH), final adult height, sex hormones, and adverse reactions after treatment were analyzed. Results After 6 months, 1 year, and 1.5 years of treatment, median bone age was increased by 0 year, 0.5 year, and 0.5 year respectively, which was significantly lower than the increase in age (P < 0.05). There was a significant increase in PAH after treatment (P < 0.05). Seven boys reached final height, which was significantly higher than PAH before treatment (P < 0.05). All the 16 boys had significant increases in luteinizing hormone, follicle-stimulating hormone, and testosterone levels after treatment (P < 0.05), with a significant reduction in the estradiol level and a significant increase in the insulin level at 1 year of treatment (P < 0.05). There was a significant increase in the insulin-like growth factor-1 level at 6 months and 1 year of treatment (P < 0.05). There were no significant changes in blood glucose, blood lipids, uric acid, and the three indices for thyroid function as monitored during treatment (P > 0.05). Conclusions In adolescent boys with ISS and a high bone age, rhGH combined with letrozole can safely and effectively delay the increase in bone age and improve PAH and final adult height, with little adverse effect.

Objective To study the level of circulating Alarin in obese children and its association with various metabolic parameters. Methods A total of 86 obese children with a body mass index (BMI) above the 95th percentile were enrolled as the obesity group, and 82 healthy children, matched for age and sex, with a BMI below the 85th percentile were enrolled as the healthy control group. According to the presence or absence of insulin resistance (IR), the obesity group was further divided into an IR group with 27 children and a non-IR group with 59 children. Related anthropometric parameters, including body height, body weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were measured, and BMI was calculated. Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), fasting insulin (FINS), and fasting blood glucose (FBG) were measured. The area under the receiver operating characteristic curve (AUC) for glucose and insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and whole-body insulin sensitivity index (WBISI) were calculated. ELISA was used to measure the level of circulating Alarin. Results The obesity group had a significantly higher level of circulating Alarin than the healthy control group (P < 0.01). The IR group had a significantly higher level of circulating Alarin than the non-IR group (P < 0.01). Circulating Alarin was positively correlated with BMI, TG, FBG, AUC-glucose, AUC-FINS, and HOMA-IR (P < 0.05) and was negatively correlated with WBISI (P < 0.05). The circulating Alarin level had a linear regression relationship with BMI, FBG, and HOMA-IR, among which HOMA-IR had the greatest influence on the circulating Alarin level (P < 0.05). Conclusions There is a significant increase in the circulating Alarin level in obese children, which may be associated with the development of obesity and IR.

Objective To study the association of Nod-like receptor protein 3 (NLRP3) inflammasome with inflammatory response in the acute stage and coronary artery lesion (CAL) in children with Kawasaki disease (KD). Methods A total of 42 children with KD who were hospitalized from January to October 2017 were enrolled as the KD group, among whom 9 had CAL (CAL group) and 33 had no CAL (NCAL group). Fifteen age-and gendermatched children with pneumonia and pyrexia were enrolled as the pneumonia-pyrexia group. Fifteen healthy children were enrolled as the healthy control group. Real-time PCR was used to measure the mRNA expression of NLRP3 inflammasome (NLRP3, ASC and caspase-1) in peripheral blood mononuclear cells. The Spearman rank correlation test was used to investigate the correlation of NLRP3 mRNA expression with serum levels of C-reactive protein, erythrocyte sedimentation rate, interleukin-6, interleukin-1β, procalcitonin, albumin and prealbumin. Results The KD group had significantly higher mRNA expression of NLRP3, ASC and caspase-1 in the acute stage than the pneumonia-pyrexia and healthy control groups (P < 0.05). The CAL group had significantly higher mRNA expression of NLRP3 than the NCAL group (P < 0.05). NLRP3 mRNA expression was correlated with C-reactive protein, interleukin-6, interleukin-1β, and prealbumin levels in children with KD in the acute stage (r_s=0.449, 0.376, 0.427, and -0.416 respectively; P < 0.05). Conclusions NLRP3 inflammasome may participate in inflammatory response in the acute stage and the development of CAL in children with KD.

Objective To study the effect of different energy feeding patterns on the nutritional status, clinical course, and outcome of children with congenital heart disease (CHD) and severe pneumonia. Methods A total of 43 malnourished infants, aged <6 months, who were diagnosed with ventricular septal defect and severe pneumonia and underwent surgical operation from January 1 to December 30, 2017 were enrolled. They were randomly divided into an observation group with 21 infants and a control group with 22 infants. The infants in the observation group were given calorie-enriched formula milk powder (100 kcal/100 mL) after surgery, and those in the control group were given formula milk powder with normal calories (67 kcal/100 mL). The two groups were observed for 3 months to record physical measurements, laboratory markers and nutritional risk screening results. Nutritional status was evaluated for all infants. The two groups were compared in terms of prognosis and adverse events. Results There were no significant differences between the two groups in physical measurements, laboratory markers, nutritional assessment and nutritional risk screening results on admission (P > 0.05). At discharge and 1 and 3 months after surgery, the control group had significantly higher degree of malnutrition and level of nutritional risk than the observation group (P < 0.05). The analysis of variance with repeated measures showed significant differences in body weight, upper arm circumference, weight-forage Z-score, height-for-age Z-score, weight-for-height Z-score, and albumin level at different time points and between different groups, and there was an interaction between group factors and time factors (P < 0.05). Compared with the control group, the observation group had a significantly lower average daily intake of fluid, a significantly higher average daily intake of energy, and a significantly lower incidence rate of insufficient feeding during hospitalization (P < 0.05). Compared with the control group, the observation group had significantly shorter length of hospital stay, duration of mechanical ventilation, and duration of postoperative pyrexia, as well as significantly lower hospital costs (P < 0.05). No significant adverse reactions were observed in either group. Conclusions An appropriate increase in postoperative energy supply for children with CHD can improve the status of malnutrition and clinical outcome.

Objective To study the mRNA level of runt-related transcription factor 3 (RUNX3) in children with bronchiolitis and its clinical significance in bronchiolitis. Methods A total of 54 young children with bronchiolitis were enrolled as the bronchiolitis group, among whom 28 with atopic constitution were enrolled in the atopic bronchiolitis group and 26 with non-atopic constitution were enrolled in the non-atopic bronchiolitis group. A total of 48 healthy young children were enrolled as the healthy control group, among whom 24 with atopic constitution were enrolled in the atopic healthy control group and 24 with non-atopic constitution were enrolled in the non-atopic healthy control group. Quantitative real-time PCR was used to measure the mRNA level of RUNX3 in peripheral blood mononuclear cells. ELISA was used to measure the serum levels of interleukin-4 (IL-4) and interferon gamma (IFN-γ). Results The bronchiolitis group had a significantly lower mRNA level of RUNX3 than the healthy control group, and the atopic bronchiolitis group had a significantly lower mRNA level of RUNX3 than the non-atopic bronchiolitis, atopic healthy control, and non-atopic healthy control groups (P < 0.05). The bronchiolitis group had a significantly higher serum level of IL-4 than the healthy control group, and the atopic bronchiolitis group had a significantly higher serum level of IL-4 than the non-atopic healthy control group (P < 0.05). The bronchiolitis group had a significantly lower serum level of IFN-γ than the healthy control group, and the atopic bronchiolitis group had a significantly lower serum level of IFN-γ than the non-atopic bronchiolitis, atopic healthy control, and non-atopic healthy control groups (P < 0.05). The correlation analysis showed that the mRNA level of RUNX3 was negatively correlated with the serum level of IL-4 and was positively correlated with the serum level of IFN-γ (P < 0.05). Conclusions Measurement of RUNX3 gene expression in peripheral blood mononuclear cells has a certain value in identifying children with atopic constitution at high risk of asthma among children with bronchiolitis.

Objective To study the expression of molecules associated with the Notch signaling pathway in children with tuberculosis, as well as the role of this pathway in the pathogenesis of tuberculosis in children. Methods A total of 62 children who were diagnosed with tuberculosis from June 2017 to December 2018 were enrolled as the case group, and 64 healthy children were enrolled as the healthy control group. Peripheral venous blood samples with a volume of 2 mL were collected, and quantitative real-time PCR was used to measure the mRNA expression levels of the molecules associated with the Notch signaling pathway (receptors Notch1-4, ligands Jagged1/2 and DLL1/3/4, and downstream target genes Hes1 and Hey1) in leukocytes. Results Compared with the healthy control group, the case group had significant increases in the mRNA expression levels of Notch1, Notch2, and DLL4 in leukocytes (P < 0.05), while there were no significant differences in the mRNA expression levels of Notch3/4, Jagged1/2, DLL1/3, Hes1, and Hey1 between the two groups (P > 0.05). Conclusions There are significant increases in the mRNA expression of Notch1/2 and DLL4 in children with tuberculosis, while there are no significant changes in the expression of downstream target genes, suggesting that the Notch signaling pathway, which is activated by the interaction between Notch1/2 and DLL4 after Mycobacterium tuberculosis infection, may play a role in childhood tuberculosis by acting on other target genes, and further studies are needed for clarification.

Objective To study the clinical features and gene mutation spectrum of children with sideroblastic anemia (SA) and the clinical value of targeted next-generation sequencing in the molecular diagnosis of children with SA. Methods Clinical data were collected from 36 children with SA. Targeted next-generation sequencing was used to detect mutations in SA-related pathogenic genes and genes associated with heme synthesis and mitochondrial iron metabolism. The association between genotype and clinical phenotype was analyzed. Results Of the 36 patients, 32 had congenital sideroblastic anemia (CSA) and 4 had myelodysplastic syndrome with ring sideroblasts (MDS-RS). Mutations in CSA-related genes were detected in 19 children (19/36, 53%), among whom 9 (47%) had ALAS2 mutation, 4 (21%) had SLC25A38 mutation, and 6 (32%) had mitochondrial fragment deletion. No pathogenic gene mutation was detected in 4 children with MDS-RS. Among the 19 mutations, 89% (17/19) were known mutations and 11% (2/19) were novel mutations. The novel mutation of the ALAS2 gene c.1153A >T(p.I385F) was rated as "possibly pathogenic" and the novel mutation of the SLC25A38 gene c.175C > T(p.Q59X) was rated as "pathogenic". Conclusions ALAS2 and SLC25A38 gene mutations are commonly seen in children with CSA, but mitochondrial gene fragment deletion also accounts for a relatively high proportion. For children with hypoplastic anemia occurring in infancy, mitochondrial disease should be considered.

Objective To study the clinical features and etiology of abdominal distension in children with different ages. Methods A retrospective analysis was performed for the clinical data of 1561 children who were admitted due to abdominal distension from January 2013 to October 2016, including clinical manifestations, radiological examination, pathological results, and disease diagnosis. Results Among the 1 561 children, there were 823 neonates (aged < 28 days), 307 infants (aged 28 days to 1 year), 186 toddlers (aged 1-3 years), 120 preschool children (aged 3-6 years), 106 school-aged children (aged 6-12 years), and 19 adolescents (aged 12-17 years). Vomiting was the major associated symptom in neonates, infants, toddlers, and school-aged children, abdominal pain was the major associated symptom in pre-school children, and vomiting and abdominal pain were the major associated symptoms in adolescents. Hypoactive bowel sound was the major accompanying sign in neonates and infants, and abdominal tenderness was the major accompanying sign in the other four age groups. Plain abdominal radiograph showed intestinal inflation in neonates and intestinal inflation with an air-fluid level in the other five age groups. Histopathological examination was performed for 339 children and the pathological results of intestinal tissue showed small, few, or poorly developed submucosal ganglion cells in neonates, intestinal inflammation/bleeding/necrosis in infants, and appendicitis in the other age groups. Necrotizing enterocolitis was the main cause of abdominal distension in neonates (34.4%), and intestinal obstruction was the main cause in infants (36.8%), toddlers (52.2%), pre-school children (51.7%), school-aged children (62.3%), and adolescents (52.6%). Conclusions Vomiting is a common symptom in children with abdominal distension in all age groups. Neonates and infants with abdominal distension often present with hypoactive bowel sounds, and children over 1 year old mainly suffer from abdominal tenderness. Necrotizing enterocolitis is the most common cause of neonatal abdominal distension, and abdominal distension in the other age groups is mainly attributed to intestinal obstruction.

Objective To study the clinical features of neonatal necrotizing enterocolitis (NEC) and risk factors for poor outcomes. Methods A retrospective analysis was performed for the clinical data of 121 preterm infants diagnosed with NEC. According to the treatment method, they were divided into a non-surgical group (n=66) and a surgical group (n=55). According to the outcome, they were divided into a survival group (n=76) and a death group (n=45). Clinical features were compared between these groups. Risk factors for poor outcomes were analyzed by multivariate logistic regression analysis. Results Compared with the non-surgical group, the surgical group had significantly lower corrected gestational age, minimum platelet count, and incidence rate of bloody stool at the onset of NEC (P < 0.05). The maximum C-reactive protein (CRP) and mortality rate in the surgical group were significantly higher than those in the non-surgical group (P < 0.05). Compared with the survival group, the death group had significantly lower gestational age at birth, birth weight, proportion of small-for-gestational-age infants, and corrected gestational age, body weight and minimum platelet count at the onset of NEC (P < 0.05). The incidence of patent ductus arteriosus, rate of use of ibuprofen, maximum CRP and rate of surgical treatment in the death group were significantly higher than those in the survival group (P < 0.05). The multivariate logistic regression analysis showed that ibuprofen treatment was a risk factor for death in infants with NEC (OR=9.149, P < 0.05). Conclusions Ibuprofen treatment increases the risk for death in preterm infants with NEC.

Objective To study the expression levels of glial cell line-derived neurotrophic factor family receptor α-1 (GFRα1) and enhancer of zeste homolog 2 (EZH2) in the intestinal tissue of children with Hirschsprung's disease (HSCR), as well as the role of EZH2 in the regulation of GFRα1 gene expression and the pathogenesis of HSCR. Methods The samples of colon tissue with spasm from 24 children with HSCR after radical treatment of HSCR were selected as the experimental group, and the samples of necrotized colon tissue from 18 children with neonatal necrotizing enterocolitis after surgical resection were selected as the control group. Real-time PCR and Western blot were used to measure the expression levels of GFRα1 and EZH2 in colon tissue in both groups. Human neuroblastoma SH-SY5Y cells were divided into an EZH2 over-expression group and a negative control group. The cells in the EZH2 over-expression group were transfected with pCMV6-EZH2 plasmid, and those in the negative control group were transfected with pCMV6 plasmid. The expression levels of EZH2 and GFRα1 were measured after transfection. Results Compared with the control group, the experimental group had significant reductions in the mRNA and protein expression levels of GFRα1 and EZH2 in colon tissue (P < 0.05), and the protein expression of EZH2 was positively correlated with that of GFRα1 (r=0.606, P=0.002). Compared with the negative control group, the EZH2 over-expression group had significant increases in the expression levels of EZH2 and GFRα1 after SH-SY5Y cells were transfected with EZH2 over-expression plasmid (P < 0.05). Conclusions Low expression of EZH2 in the colon tissue of children with HSCR may be one of the causes of inadequate expression of GFRα1 and onset of HSCR.

Objective To study the clinical features and pathogenic bacteria of late-onset sepsis (LOS) in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants. Methods Among the VLBW/ELBW infants with a gestational age of < 32 weeks who were admitted to the hospital between January 2012 and December 2016, those with LOS were enrolled as the LOS group, and those without sepsis were matched for the infant with LOS in gestational age were enrolled as the control group. According to the presence or absence of in-hospital death, the LOS group was further divided into a death subgroup and a survival subgroup. Risk factors for LOS, clinical features, distribution of pathogenic bacteria, drug resistance, and high-risk factors for LOS-related death were analyzed. Results A total of 513 VLBW/ELBW infants were enrolled, and there were 65 infants in the LOS group and 130 in the control group. The incidence rate of LOS was 12.7%. In the LOS group, 6 infants died and 59 survived. Compared with the control group, the LOS group had a significantly lower birth weight (P < 0.05) and significantly longer indwelling time of peripherally inserted central catheter (PICC), duration of mechanical ventilation, and length of hospital stay (P < 0.05). Compared with the control group, the LOS group had a significantly higher proportion of small-for-gestational-age infants, infants undergoing mechanical ventilation, infants with neonatal necrotizing enterocolitis, or infants who died (P < 0.05). Low birth weight, small-for-gestational-age infant, and long indwelling time of PICC were independent risk factors for LOS in VLBW/ELBW infants (OR=1.396, 2.550, and 1.068 respectively, P < 0.05). Purulent meningitis was an independent risk factor for LOS-related death in VLBW/ELBWIs infants (OR=13.443, P < 0.05). A total of 65 strains of pathogenic bacteria were cultured in the LOS group, among which there were 39 strains (60%) of Gram-negative bacteria, including 15 strains producing extended spectrum beta-lactamases (ESBLs), and antibiotics were applied for 67% (10/15) of the ESBL strains within 2 weeks before the onset of LOS. The rate of antibiotic use for ESBL strains was significantly higher than that for non-resistant strains[67% (10/15) vs 29% (7/24); P < 0.05]. Conclusions Low birth weight, SGA infant, and long indwelling time of PICC are independent risk factors for LOS in VLBW/ELBW infants, and death tends to occur in LOS infants with purulent meningitis. Most pathogenic bacteria of LOS are Gram-negative bacteria, and use of antibiotics within 2 weeks before disease onset may increase the risk of ESBL strain infection.

Objective To study the clinical features and prognosis of bacterial meningitis in full-term and preterm infants. Methods A retrospective analysis was performed for the clinical data of 102 neonates with bacterial meningitis. According to the gestational age, they were divided into a preterm group (n=46) and a full-term group (n=56). The two groups were compared in terms of clinical manifestations, laboratory markers, imaging findings, and clinical outcomes. Results Poor response and apnea were the major clinical manifestations in the preterm group (P < 0.05), while pyrexia and convulsions were more common in the full-term group (P < 0.05). The full-term group had a significantly higher glucose level in cerebrospinal fluid (CSF) than the preterm group (P < 0.05). Compared with the full-term group, the preterm group had significantly higher C-reactive protein level, positive rate of blood culture, and incidence rate of poor prognosis (P < 0.05). There were no significant differences between the two groups in leukocyte count in peripheral blood, levels of leukocytes and protein in CSF, and positive rate of CSF culture (P > 0.05). Conclusions There are certain differences in the clinical manifestations between full-term and preterm infants with bacterial meningitis. Preterm infants tend to have a higher incidence rate of poor prognosis.

No abstract available

No abstract available

No abstract available

Objective To study the changes and significance of apoptosis signal-regulating kinase 1 (ASK1) in left ventricular remodeling in FVB/N mice. Methods A total of 54 FVB/N mice were randomly divided into 4 groups:0 d group with 8 mice, 7 d group with 10 mice, 14 d group with 16 mice, and 21 d group with 20 mice. A model of cardiac remodeling was established by intraperitoneal injection of isoproterenol (ISO) at a daily dose of 30 mg/kg, and the 7 d, 14 d, and 21 d groups were injected for 7, 14, and 21 consecutive days respectively. The 0 d group was given intraperitoneal injection of an equal volume of normal saline. Echocardiography was used to measure left ventricular posterior wall thickness at end diastole (dLVPW) and the ratio of heart weight to tibia length (HW/TL) was measured. Hematoxylin-eosin staining was used to measure left ventricular myocardial fiber diameter. Picric-Sirius red staining was used to measure myocardial collagen deposition area in the left ventricle. Quantitative real-time PCR was used to measure the mRNA expression of ASK1, type I collagen (collagen I), and B-type natriuretic peptide (BNP). The mortality rate was observed for each group. Results There were gradual increases in HW/TL, myocardial fiber diameter, and dLVPW after 0, 7, and 14 days of ISO injection (P < 0.05). There were no significant changes in HW/TL ratio and dLVPW from days 14 to 21 of ISO injection (P > 0.05), while there was a significant reduction in myocardial fiber diameter (P < 0.05), which was similar to the value on day 7 (P > 0.05). There were significant increases in myocardial collagen deposition area and the mRNA expression of collagen I, ASK1, and BNP after 0, 7, 14, and 21 days of ISO injection, which reached the peaks on day 21 (P < 0.01). The mRNA expression of ASK1 was positively correlated with myocardial collagen deposition area and the mRNA expression of collagen I and BNP and had a weak correlation with HW/TL, myocardial fiber diameter, and dLVPW. There was a significant increase in the mortality rate of the mice over the time of ISO injection. Conclusions The expression of ASK1 in the myocardium is closely associated with left ventricular remodeling. The increase of ASK1 expression may lead to the aggravation of left ventricular remodeling, and the mechanism of which needs further study.

In recent years, the concept of "augmented renal clearance" (ARC) has been proposed in the field of critical illness and is defined as enhanced renal clearance of drugs. ARC is considered when the creatinine clearance rate exceeds 130 mL/(min·1.73 m²). An increasing number of evidence has shown that ARC is commonly seen in critically ill adults and children. In critically ill children, low drug concentration due to ARC may lead to treatment failure. Unfortunately, ARC is often neglected due to the lack of reliable tools to assess renal function in critically ill children. Therefore, with reference to the articles on ARC in critically ill children, this article reviews the concept of ARC, the pathogenesis of ARC, the influencing factors for ARC, the identification tools for ARC, and the influence of ARC on pharmacokinetics/pharmacodynamics of antibacterial agents and clinical outcome, in order to provide a reference for clinical medication.