Clinical analysis of seven pediatric patients with coronavirus disease 2019 (COVID-19) in Jingzhou, Hubei, China: a retrospective study.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) epidemic has spread globally, along with its incidence among children. The purpose of this study was to evaluate the clinical characteristics and outcomes of children infected with COVID-19 and to provide a reference for clinical work. METHODS: The study retrospectively reviewed the clinical characteristics and prognosis of 7 children diagnosed with COVID-19 infection at The First People's Hospital of Jingzhou between January 30 and February 29, 2020. RESULTS: Of the 7 cases, 2 were male and 5 were female, aged 3 months and 14 days to 12 years old (median age 3 years old). There was 1 asymptomatic carrier, 5 cases with mild type infection, which had the main symptoms of cough (4/5) and fever (4/5), and 1 case of moderate type. Among the 7 cases, serum white blood cell count was increased in 1 case, decreased in 1 case, liver transaminase was increased in 1 case, lactate dehydrogenase was increased in 3 cases, creatine kinase MB (CK-MB) was increased in 2 cases, and C-reactive protein was elevated in 2 cases. A total of 4 cases were complicated with mycoplasma pneumoniae and/or influenza B virus infection. A single case of chest computed tomography (CT) showed viral pneumonia. With routine antiviral and symptomatic support therapy, the median time taken for the results of nucleic acid testing by pharyngeal swab to become negative was 14 days (6-26 days) and the median hospital stay was 15 days (8-31 days). All participants were cured and subsequently discharged from hospital. Only 1 case was positive for nucleic acid testing by pharyngeal swab 1 month after being discharged, and the anal swab of 1 case for nucleic acid testing was positive 2 months after being discharged. CONCLUSIONS: All children with COVID-19 who were included in this study in Jingzhou were infected via family clustering, and the laboratory examinations were not specific. Fever and cough were common symptoms, but all cases were mild and had good prognoses.

[Effect of glucocorticoid receptor function on the behavior of rats with attention deficit hyperactivity disorder].

OBJECTIVE: To investigate the ideal animal models for attention deficit hyperactivity disorder (ADHD) subtypes and the effect of glucocorticoid receptor (GR) function on the behavior of ADHD rats by comparing behavioral differences between spontaneously hypertensive rats (SHRs), Wistar Kyoto (WKY) rats, and Sprague-Dawley (SD) rats. METHODS: A total of 24 male SHRs aged 21 days were randomly divided into GR agonist group, GR inhibitor group, and SHR group, with 8 rats in each group. Eight male WKY rats and 8 male SD rats, also aged 21 days, were enrolled as WKY group and SD group respectively. The GR agonist group was treated with intraperitoneal injection of dexamethasone (0.5 mg/kg daily); the GR inhibitor group was treated with intraperitoneal injection of mifepristone (RU486) (54 mg/kg daily); the SHR, WKY, and SD groups were treated with intraperitoneal injection of normal saline (0.5 mL/kg daily). The course of treatment was 14 days for all groups. The open field test and Lat maze test were used to evaluate spontaneous activity and non-selective attention. RESULTS: The open field test showed that before drug intervention the SHR group had significantly higher numbers of line crossings and rearings than the WKY and SD groups (P<0.05); the WKY group had a significantly higher number of line crossings than the SD group (P<0.05); the SD group had a significantly higher number of groomings than the WKY group (P<0.05). After drug intervention, the GR agonist group had significantly lower numbers of line crossings and groomings than the SHR group (P<0.05). The Lat maze test indicated that before drug intervention the SHR group had significantly higher numbers of corner crossings and rearings than the WKY and SD groups (P<0.05); the WKY group had significantly higher numbers of rearings and leanings than the SD group (P<0.05). After drug intervention, the GR agonist group had significantly lower numbers of corner crossings and rearings than the SHR group (P<0.05); the GR inhibitor group had a significantly higher number of rearings than the SHR group (P<0.05); the WKY group had significantly higher numbers of rearings and leanings than the SD group (P<0.05). CONCLUSIONS: SHR is an ideal animal model for mixed subtype ADHD, and further studies are needed to determine whether WKY rats can be used as an animal model for attention-deficit subtype ADHD. GR agonist can effectively improve spontaneous activity and non-selective attention in SHRs.

Glucocorticoids/glucocorticoid receptors effect on dopaminergic neurotransmitters in ADHD rats.

Dexamethaone (DEX, glucocorticoid receptor agonist) and RU486 (glucocorticoid receptor inhibitor) may affect the behavior of attention deficit hyperactivity disorder (ADHD) rats, by changing the level of dopamine and noradrenaline and dopamine transporter in different regions of their brain. In this study, we have investigated the effect and the underlying mechanism of Glucocorticoids/Glucocorticoid receptors on dopaminergic neurotransmitters in ADHD Rats. Thirty male Wistar Kyoto rats (WKY) and 30 male spontaneously hypertensive rats (SHR) were respectively divided into 3 groups randomly as follows: a GR agonist group (DEX), a GR inhibitor group (RU486) and a control group (CON). Open field test and Y maze were performed respectively to assess the behavior of the rats. The levels of dopamine, norepinephrine, and dopamine transporter (DAT) in the prefrontal cortex and striatum were also tested. Our results showed that, the behavior of rats were improved after DEX treatment. We also found that the level of DA and NE increased in DEX group, but decreased significantly in RU486 group. Immunohistochemical assay showed that DAT expression level in DEX group was significantly less than that in RU486 and CON group. In conclusion, by regulation of glucocorticoid receptor, GR agonist can decrease DAT expression, resulting in the increase of DA and NE levels in brain that ameliorate hyperactivity and attention deficit in ADHD rats. Our results suggest that the effects of glucocorticoid receptor on dopaminergic neurotransmitter in the central nervous system may be involved in the pathogenesis of ADHD.

Angiotensin-converting enzyme insertion/deletion polymorphism and susceptibility to Kawasaki disease: a meta-analysis.

BACKGROUND: The angiotensin-converting enzyme (ACE) I/D polymorphism has been reported to be associated with Kawasaki disease (KD), but studies to date present conflicting results. OBJECTIVES: The aim of this study is to derive a more precise estimation of the association between the ACE I/D polymorphism and KD risk. METHODS: PubMed, EMBASE, CNKI and Wangfang databases were retrievaled to identify for relevant studies from inception to May 2017. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using Stata 12.0 software. RESULTS: A total of 6 case-control studies comprising 634 patients and 458 controls were included in the meta-analysis, and we found a significant association between the ACE I/D polymorphism and KD risk (D vs I:OR = 0.81, 95%CI = 0.31-2.11;DD vs II: OR = 1.03, 95%CI = 0.42-2.54; DI vs II: OR = 1.44, 95%CI = 1.09-1.90; dominant model: OR = 1.43, 95%CI = 1.11-1.85; recessive model: OR = 1.21, 95%CI = 0.44-3.29 ). When stratified by sample size>200, this polymorphism is associated with an increased the risk of KD. CONCLUSION: The I/D polymorphism in the ACE gene may be associated with susceptibility to KD.

The report of sustained low-efficiency dialysis (SLED) treatment in fifteen patients of severe snakebite.

To investigate the therapeutic efficacy of sustained low-efficiency dialysis (SLED) in severe snakebite patients. Fifteen patients of severe snakebite was treated with SLED from July 2005 to August 2009 were included in the study. Central venous access was established in all patients. SLED was administered using Dialog(+) dialyzer (B. Braun, Germany). SLED sessions were 6-12 h in duration at a blood flow rate of 200 ml/min and a dialysate flow rate of 300 ml/min. Heparin or low molecular weight heparin was used as anticoagulant. Biochemical indicators, APACHE II scores before and after SLED, and clinical outcomes were evaluated. The levels of serum creatinine, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, creatine kinase isozyme MB, and creatine kinase were significantly lower than the level before SLED (P < 0.05); the level of cholinesterase was significantly higher after SLED (P < 0.01); the APACHE II score before SLED was 14.1 ± 3.8, but decreased significantly to 7.9 ± 1.4, 6.2 ± 1.1, and 4.2 ± 0.8 on days 1, 2, and 7 after SLED, respectively (P < 0.01). Three patients died on days 1, 3, and 4 after SLED, respectively. The remaining twelve patients were either cured or showed improvement at the time of discharge. The survival rate was 80 % where as mortality was 20 %. SLED may be an effective treatment option in severe snakebite patients. It can reduce mortality, thereby, resulting in increased survival rates.

Hepatitis B virus X protein up-regulates tumor necrosis factor-α expression in cultured mesangial cells via ERKs and NF-κB pathways.

OBJECTIVE: To investigate the effects of hepatitis B virus (HBV) X protein (HBx) on the expression of tumor necrosis factor-α (TNF-α) in glomerular mesangial cells (GMCs) and the underlying intracellular signal pathways. METHODS: The plasmid pCI-neo-X that carries the X gene of hepatitis B virus was transfected into cultured GMCs. HBx expression in the transfected GMCs was assessed by Western-blot. TNF-α protein and mRNA were assessed by ELISA and semi-quantitative RT-PCR, respectively. Three kinase inhibitors-U0126, an inhibitor of extracellular signal-regulated kinases (ERKs); lactacystin, an inhibitor of nuclear factor-κB (NF-κB); and SB203580, a selective inhibitor of p38 MAP kinase (p38 MAPK) were used to determine which intracellular signal pathways may underlie the action of HBx on TNF-α expression in transfected GMCs. RESULTS: A significant increase in HBx expression in pCI-neo-X transfected GMCs was detected at 36 h and 48 h, which was not affected by any of those kinase inhibitors mentioned above. A similar increase in the expression of both TNF-α protein and mRNA was also observed at 36 h and 48 h, which was significantly decreased in the presence of U0126 or lactacytin, but not SB203580. CONCLUSIONS: HBx upregulates TNF-α expression in cultured GMCs, possibly through ERKs and NF-κB pathway, but not p38 MAPK pathway.

Comparison of the therapeutic effectiveness of sustained low-efficiency dialysis (SLED) with continuous blood purification (CBP) in critically ill patients.

The differences in therapeutic effectiveness between sustained low-efficiency dialysis (SLED) and continuous blood purification (CBP) were investigated. In order to assess the different treatment methods, 56 critically ill patients were divided into two groups, the CBP group and the SLED group. A comparison was made between all the biochemical indicators, in-hospital duration, hemodynamic parameters, acute physiology and chronic health evaluation (APACHE-II), the survival, and the mortality rates. After treatment, the levels of serum creatine kinase isozyme MB (CK-MB), creatine kinase, creatinine, glutamate-oxalacetate transaminase (AST), glutamate-pyruvate transaminase (ALT), APACHE II score on the 1st, 2nd, and 7th day in both the treatment groups were lower than that before the treatment (P < 0.05). There are no statistical differences in in-hospital duration, biochemical indicators, APACHE II score, hemodynamic parameters, the survival rate and the mortality rate between the two groups (P > 0.05). It was concluded that SLED has similar hemodynamic stability with CBP and the two methods have similar treatment effects in critically ill patients. However, we noticed that SLED can be relatively economical and convenient for critically ill patients in clinical practice.

S gene mutations of HBV in children with HBV-associated glomerulonephritis.

BACKGROUND: Hepatitis B virus-associated glomerulonephritis (HBV-GN) is a kind of immune complex-induced glomerulonephritis. The present study was designed to determine whether mutation of Hepatitis B virus (HBV) S gene is associated with glomerulonephritis in Chinese children. METHODS: Total 53 subjects, including 30 HBV-GN, 5 nephrosis with HBV carriers (control group 1), and 18 HBV carriers (control group 2) were included in this study. Polymerase chain reaction (PCR) was used to detect the HBV-GN S gene mutation. RESULTS: (1) The serotype of HBV was adw in the majority (52/53) of subjects, and was adr in only 1 subject in the control group 2; (2) the genotype of HBV was the type B in 51 subjects, the type E in 1 HBV-GN child, and the type C in 1 HBV carrier; (3) Seventeen point mutations in the S gene of HBV were identified in 21 of 30 (70%) HBV-GN patients. Among them, 16 of 21 (76.2%) mutations may cause amino acid substitutions of the HBV proteins, which occur predominantly (11/16 mutations) at threonine, serine or tyrosine phosphorylation sites of mitogen-activated protein kinase (MAPK) or protein tyrosine kinase (PTK). (4) In addition, single nucleotide mutations without amino acid substitutions (same sense mutation) were found in 2 subjects in each control group and 5 subjects in HBV-GN group. CONCLUSIONS: HBV S gene mutations and the subsequent amino acid substitutions in HBV proteins were found in most children with HBV-GN, suggesting that these mutations may play an important role in the pathogenesis of HBV-GN.

[Mutation of hepatitis B virus S gene in children with hepatitis B virus-associated glomerulonephritis].

OBJECTIVE: Hepatitis B virus-associated glomerulonephritis (HBV-GN) is an immune complex-mediated glomerulonephritis. The present study was conducted to identify HBV S gene mutation in children with HBV-GN. METHODS: Serum HBV DNA was extracted in 53 children, including 30 with HBV-GN, 5 with HBV-carrying nephrosis (control group 1), and 18 HBV carriers (control group 2). HBV S gene sequence was amplified by polymerase chain reaction (PCR). The PCR products were sequenced directly and compared with AY167097.1, an epidemic HBV strain in China. RESULTS: (1) The adw serotype of HBV was found in all the 30 cases with HBV-GN, 5 cases with HBV-carrying nephrosis and 17 HBV carriers except for 1, in whom adr serotype was identified. (2) HBV genotype B was found in 29 children with HBV-GN, 5 cases with HBV-carrying nephrosis and 17 HBV carriers, genotype E was found in a child with HBV-GN, and genotype C in an HBV carrier. (3) A total of 17 kinds of different single nucleotide change in HBV S gene were identified in 21 of 30 (70%) HBV-GN patients. Among them, 16 of 21 (76.2%) nucleotide mutations resulted in amino acid substitution. It was interesting that most (11/16, 68.8%) amino acid substitutions involved threonine, serine and tyrosine, the potential phosphorylation sites of mitogen-activated protein kinase (MAPK) and protein tyrosine kinase (PTK) in HBV protein. Single nucleotide changes which didn not result in amino acid substitution were found in 2 HBV-carrying nephrosis patients, 2 HBV carriers and 5 cases with HBV-GN. CONCLUSION: Single nucleotide changes in HBV S gene were found in most children with HBV-GN. Most mutations in HBsAg resulted in amino acid substitutions involving threonine, serine and tyrosine, which may play a role in the pathogenesis of HBV-GN.

HBV X gene transfection upregulates IL-1beta and IL-6 gene expression and induces rat glomerular mesangial cell proliferation.

The X gene of HBV encodes a 17-kD protein, termed HBx, which has been shown to function as a transcriptional trans-activator of a variety of viral and cellular promoter/enhancer elements. The aim of this study was to investigate the effect of HBx on gene expression of interleukin (IL)-1 and IL-6, and proliferation of rat mesangial cells in vitro. The X gene of HBV was amplified by PCR assay, and inserted into the eukaryotic expression vector pCI-neo. The structure of recombinant pCI-neo-X plasmid was proved by restrict endonuclease digestion and sequencing analysis. pCI-neo-X was transfected into cultured rat mesangial cell line in vitro via liposome. HBx expression in transfected mesangial cells was detected by Western blot. The IL-1beta and IL-6 mRNA expression in those cells was assayed by semiquantitative RT-PCR. Mesangial cell proliferation was tested by MTT. The results showed that HBx was obviously expressed in cultured mesangial cell line at 36th and 48th h after transfection. The expression of IL-1beta and IL-6 mRNA was simultaneously increased. The cell proliferation was also obvious at the same time. It was concluded that HBx gene transfection could induce IL-1beta and IL-6 gene expression and mesangial cell proliferation. HBx may play a critical role in mesangial cell proliferation through upregulation of the IL-1beta and IL-6 gene expression.

HBV X Gene Transfection Upregulates IL-1β and IL-6 Gene Expression and Induces Rat Glomerular Mesangial Cell Proliferation / 华中科技大学学报（医学）（英德文版）

The X gene of HBV encodes a 17-KD protein, termed HBx, which has been shown to function as a transcriptional trans-activator of a variety of viral and cellular promoter/enhancer elements. The aim of this study was to investigate the effect of HBx on gene expression of interleukin (IL)-1β and IL-6, and proliferation of rat mesangial cells in vitro. The X gene of HBV was amplified by PCR assay, and inserted into the eukaryotic expression vector pCI-neo. The structure of recombinant pCI-neo-X plasmid was proved by restrict endonuclease digestion and sequencing analysis. pCI-neo-X was transfected into cultured rat mesangial cell line in vitro via liposome. HBx expression in transfected mesangial cells was detected by Western blot. The IL-1β and IL-6 mRNA expression in those cells was assayed by semiquantitative RT-PCR. Mesangial cell proliferation was tested by MTT. The results showed that HBx was obviously expressed in cultured mesangial cell line at 36th and 48th h after transfection. The expression of IL-1β and IL-6 mRNA was simultaneously increased. The cell proliferation was also obvious at the same time. It was concluded that HBx gene transfection could induce IL-1β and IL-6 gene expression and mesangial cell proliferation. HBx may play a critical role in mesangial cell proliferation through upregulation of the IL-1β and IL-6 gene expression.

[Concentrations of serum iron and transferrin in children with nephrotic syndrome].

OBJECTIVE: Nephrotic syndrome (NS) is characterized by marked urinary excretion of albumin and other intermediated-size plasma proteins such as transferrin. The aim of this study was to determine the changes of serum iron and transferrin and the relationship between the serum and urinary transferrin. METHODS: The indexes related to iron metabolism, including serum iron, ferritin, transferrin, total iron-binding capacity, transferrin saturation and hematological parameters (Hb, MCV, MCH), and urinary transferrin were measured in 37 children with NS before treatment and at the remission stage. Thirty-five age-matched healthy children served as controls. RESULTS: Serum iron levels (18.8 +/- 3.8 micromol/L) in NS patients before treatment were significantly lower than in the healthy controls (22.2 +/-3.8 micromol/L) and those measured at the remission stage (21.0 +/- 3.5 micromol/L) (P < 0.01). Serum transferrin levels in NS patients before therapy (1.9 +/- 0.3 g/L) also decreased compared with those in the healthy controls (3.1 +/- 0.5 g/L) and those measured at the remission stage (2.9 +/- 0.6 g/L) (P < 0.01). In contrast, serum total iron-binding capacity and transferrin saturation were noticeably higher in NS patients before treatment than those in the healthy controls (total iron-binding capacity 56.4 +/- 9.2 micromol/L vs 50.7 +/- 6.8 micromol, P < 0.01; transferrin saturation 55.7 +/- 9.2 % vs 46.4 +/- 8.2%, P < 0.01) and were also higher than those measured at the remission stage (51.9 +/-7.7 micromol/L and 47.4 +/- 13.3%) (P < 0.01). Serum transferrin positively correlated to serum albumin (r = 0.609, P < 0.01) and negatively correlated to urinary transferrin (r = -0.550, P < 0.01) in NS patients before treatment. CONCLUSIONS: Serum iron and transferrin levels markedly decreased in NS patients, which may be partially related to the urinary loss of transferrin.