Predictive performance and analysis of a vancomycin population pharmacokinetic model in Chinese pediatric patients / 药学学报

This study aimed to evaluate the predictive performance of a vancomycin population pharmacokinetic model in 0-10 year Chinese pediatric patients. This study was approved by the Ethics Research Committee of the First Affiliated Hospital of Guangxi Medical University, data from hospitalized children ≤ 10 years of age who receiving vancomycin were collected retrospectively. Individual predictive values (IPRED) were estimated by Bayesian Analysis based on a previous published population pharmacokinetic model, and compared with the observed steady state trough concentration. As results, a total of 371 vancomycin serum concentrations from 191 patients were taken for the external validation. The mean error (ME), the mean relative prediction error (ME%), the mean absolute error (MAE) and the root mean square error (RMSE) in individual prediction method for the total patients were -0.50 mg·L-1, 6.03%, 1.84 mg·L-1, 2.86 mg·L-1 respectively. The correlation coefficient between individual predictions and detection values was 0.95. The stability and the predictive performance of model were accepted by goodness-of-fit, visual predictive check (VPC) and Bland-Altman. The percentage of individual prediction error within ± 30% was 82.75%. The above results suggest that, this Chinese pediatric population pharmacokinetic model in 0-10 years old has a good prediction performance. It can be applied to the design of initial treatment plan and predicting the extent of drug exposure.

Role of programmed death-1 in viral infectious diseases / 中国当代儿科杂志

The research on the immunoregulatory effect of programmed death-1 (PD-1) in infectious diseases mainly focuses on chronic viral infection, but there are few studies on acute viral infection. In chronic viral infection, PD-1 is highly expressed on the surface of CD8T cells, which is a sign of CD8T cell depletion. Recent studies have shown that in chronic viral infection, PD-1 is also highly expressed on the surface of regulatory T cells and binds to programmed death-ligand 1 (PD-L1) on the surface of exhausted CD8T cells, resulting in a stronger inhibitory effect on CD8T cell immunity. Blocking the PD-1/PD-L1 signaling pathway between exhausted CD8T cells and regulatory T cells can significantly reverse the depletion of CD8T cells and greatly improve the antiviral effect of CD8T cells. However, the role of the PD-1/PD-L1 signaling pathway in acute viral infection remains unknown. This article summarizes the latest research on PD-1 in infectious diseases and discusses its role in acute and chronic viral infection.

Advances in application of Jurkat cell model in research on infectious diseases / 中国当代儿科杂志

Infectious diseases can be caused by multiple pathogens, which can produce specific immune response in human body. The immune response produced by T cells is cellular immunity, which plays an important role in the anti-infection process of human body, and can participate in immunological protection and cause immunopathology. The outcome of various infectious diseases is closely related to cellular immune function, especially the function of T cells. Jurkat cells belong to the human acute T lymphocyte leukemia cell line. Jurkat cell model can simulate the function T lymphocytes, so it is widely used in the in vitro studies of T cell signal transduction, cytokines, and receptor expression, and can provide reference and guidance for the treatment of various infectious diseases and the research on their pathogenesis. The Jurkat cell model has been widely used in the in vitro studies of viral diseases and atypical pathogens, but parasitic infection studies using the Jurkat cell model are still rare. This article reviews advances in the application of Jurkat cell model in the research on infectious diseases.

Expression and role of Tc17 cells in mice with neutrophilic asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To determine the proportion of Tc17 cells in the lungs of mice with neutrophilic(NEU) asthma, and to investigate the role of Tc17 cells in the pathogenesis of NEU asthma.</p><p><b>METHODS</b>Thirty-two C57/B6 mice of clean grade were randomly divided into two groups: NEU asthma and control. The mice in the NEU asthma group were sensitized by airway instillation of ovalbumin (OVA) and lipopolysaccharide (LPS), and challenged with an aerosol of OVA, while those in the control group were sensitized and challenged with normal saline. At 24 hours after the final challenge, bronchoalveolar lavage fluid (BALF) was collected, and the total number and differential counts of nucleated cells and percentage of each type were determined. The lung tissues were separated and hematoxylin-eosin staining was performed to observe the pathological changes of lungs; flow cytometry was applied to determine the percentages of Tc17 and Th17 cells in the lung tissues. Enzyme-linked immunosorbent assay was applied to determine the levels of interleukin-6 (IL-6), transforming growth factor β (TGF-β), and interleukin-17 (IL-17) in BALF.</p><p><b>RESULTS</b>The NEU asthma group had a significantly higher total number of nucleated cells, a significantly higher percentage of eosinophils, and a significantly higher percentage of neutrophils in BALF than the control group (P<0.01). The NEU asthma group also had significantly higher percentages of Tc17 and Th17 cells than the control group (P<0.01). In the NEU asthma group, the percentage of Tc17 cells was positively correlated with that of Th17 cells (P<0.05). The NEU asthma group had significantly higher concentrations of IL-6, TGF-β, and IL-17 in BALF than the control group (P<0.05).</p><p><b>CONCLUSIONS</b>The expression of Tc17 cells in the lung tissues increases in mice with NEU asthma, and the increased number of Tc17 cells may be involved in the pathogenesis of NEU asthma. Tc17 cells may play an important role in NEU asthma through IL-17.</p>

Pulmonary surfactant associated gene variants in mixed ethnic population of Han and Zhuang / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the prevalence of pulmonary surfactant associated pathway genes functional variants in Chinese population.</p><p><b>METHOD</b>Using a cohort of 258 mixed ethnic population of Han and Zhuang, we pooled DNA samples from 146 term male infants and 112 term female infants and then used an Ill umina next generation sequencing platform to perform the complete exonic resequencing in 6 target genes:surfactant protein-B (SFTPB), surfactant protein-C (SFTPC), ATP-binding cassette transporter A3 (ABCA3), lysophospholipid acyltransferase 1 (LPCAT1), choline phosphotransferase 1 (CHPT1), phosphate cytidylyltransferase 1, choline, beta (PCYT1B). Collapsing methods was used to determine the functional allele frequency.</p><p><b>RESULT</b>(1) Altogether, 128 variants were found, including 44 synonymous variants, 66 nonsynonymous variants and 18 insertions-deletions. Of these, 28 variants were predicted to alter protein function. Two of these variants were seen twice, the rest variants were only seen once, for a total of 30 functional alleles; (2) ABCA3 had the most functional variants in both male and female groups with the minor allele frequencies of 0.014 (1.4%) and 0.04 (4%), respectively. The total functional allele frequencies of 6 genes were 0.041 (4.1%) and 0.08 (8%) in the two groups, respectively (P = 0.06).</p><p><b>CONCLUSION</b>(1) Functional variants in pulmonary surfactant associated pathway genes are present in the mixed Han-Zhuang population. (2) ABCA3 contained the most functional variants suggesting that ABCA3 could contribute significantly to neonatal respiratory distress syndrome and other lung disease.</p>

Causes of chronic cough in children: an analysis of 111 cases / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the causes of chronic cough in children.</p><p><b>METHODS</b>A prospective cohort study was performed on 111 children with chronic cough who were referred to the First Affiliated Hospital of Guangxi Medical University between December 2008 and January 2011. The causes of chronic cough were investigted.</p><p><b>RESULTS</b>Cough variant asthma (45 cases, 40.5%) was the most common cause of chronic cough, followed by upper airway cough syndrome (34 cases, 30.6%), postinfectious cough (19 cases, 17.1%), allergic cough (5 cases, 4.5%), Tourette's syndrome (4 cases, 3.6%), psychogenic cough (1 case, 0.9%) and endobronchial tuberculosis (1 case, 0.9%). The causes were not identified in 2 cases (1.8%). A single cause for chronic cough was noted in 60 patients (54.1%), and multiple potential causes were noted in 49 patients (44.1%), including two coexisting causes in 47 patients (42.3%) and three in 2 patients (1.8%).</p><p><b>CONCLUSIONS</b>The top three causes of chronic cough in children are cough variant asthma, upper airway cough syndrome and postinfectious cough.</p>

Primary immunodeficiency diseases in children: clinical analysis of 35 cases / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To summarize clinical features of primary immunodeficiency diseases (PID) in children.</p><p><b>METHODS</b>The clinical data of 35 children with PID from September 2005 to December 2008 were studied retrospectively, including illness history, birth history, family history, clinical manifestations, laboratory findings, diagnosis, treatment and outcome.</p><p><b>RESULTS</b>Of the 35 cases of PID, 6 cases were confirmed with combined T- and B-cell immunodeficiency, 4 cases with X-linked agammaglobulinaemia, 22 cases with selective IgG subclass deficiency, 1 case with common variable immunodeficiency and 2 cases with chronic granulomatous disease. All cases had fever and recurrent infections. Respiratory and digestive tract infections were the most common clinical manifestation. Some of the PID cases lagged behind the normal children of the same age in growth and development. Human gamma-globulin transfusion and anti-infection therapy were administered. Two patients discontinued the therapy, one was transferred to the other hospital and the other 32 patients were discharged following improvement in clinical symptoms.</p><p><b>CONCLUSIONS</b>PID should be considered in children who suffer from recurrent infections and autoimmune diseases or do not respond to long-term use of antibiotics. Immunologic tests should be done as early as possible for the children.</p>

Airway neutrophils apoptosis in children with severe asthma / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the changes of neutrophils in airway inflammation in children with severe asthma.</p><p><b>METHOD</b>Children with mild to moderate asthma (n=23), severe asthma (n=16) and healthy control subjects (n=16) underwent lung function tests and sputum induction. The sputum specimens were assayed for cellular differential count, the supernatant and peripheral blood were assayed for the concentrations of IL-8 by "sandwich" enzyme linked immunosorbent assay (ELISA). Sputum supernatant, IL-8 and mifepristone were assessed for their abilities to prolong the in vitro survival of blood-derived neutrophils.</p><p><b>RESULT</b>The percentage of sputum neutrophils was significantly higher in severe asthmatics [59.54 (41.99-74.65)%] than mild-moderate asthmatics [30.03 (15.94-47.71)%] and healthy control subjects [29.72(16.53-45.74)%] (P < 0. 01); the level of IL-8 in sputum was significantly higher in severe asthmatics [2907.78 (331.67 - 3457.93) ng/L] than mild-moderate asthmatics [287.58 (130.75-656.84) ng/L] and healthy control subjects [179.2 (58.55-346.59) ng/L] (P < 0.01); the percentages of neutrophilic apoptosis respectively cultured with LPS [(10.57 +/- 1.97)%], severe asthmatics supernatant [(11.82 +/- 2.96)%], IL-8 [(10.47 +/- 1.93)%], dexamethasone [(9.93 +/- 1.95)%], severe asthma supernatant + mifepristone [(12.15 +/- 2.86)%] in vitro were lower than that cultured with PBS [(17.98 +/- 2.27)%], healthy control supernatant [(17.37 +/- 2.50)%], mild-moderate asthmatics supernatant [(16.35 +/- 3.26)%], mifepristone [(17.89 +/- 2.38)%], and dexamethasone + mifepristone [(17.06 +/- 2.59)%] (P < 0.01).</p><p><b>CONCLUSION</b>Suppression of neutrophilic apoptosis seems to play a potential role in airway neutrophilic inflammation in severe asthmatics, and the level of IL-8 in sputum was significantly higher in patients with severe asthmatics.</p>

Effects of Inhaled Budesonide in Early Phase on Airway Inflammation and Interleukin-6/Signal Transducers and Activators of Transcription 3 Signaling Pathway in Asthmatic Mouse / 实用儿科临床杂志

Objective To observe the effects of inhaled budesonide (BUD) in early phase on the airway inflammation in asthmatic mouse,and its effects on the IL-6/signal transducers and activators of transcription 3(IL-6/STAT3 )signaling pathway in airway,explore the therapeutic target of BUD.Methods Forty Balb/c mice were randomly divided into control group(n=10),asthma group(n=10),BUD group(n=10) and AG490 group(n=10).The mice were sensitized with ovalbumin to establish the asthmatic model.The histological changes were evaluated by HE staining.The levels of IL-4,IL-5 and IL-6 in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay.Lung tissue extracts were analyzed for total STAT3 and phospho-STAT3(p-STAT3) by Western blot.Results 1.The levels of inflammatory cells,EOS%, IL-4,IL-5 and IL-6 levels in the BALF in BUD group were significantly lower than those in asthma group (Pa0.05).Conclusions Inhaled corticosteroid can apparently ameliorate airway inflammation in early phase in asthmatic mouse model,and it can downregulate the expressions of IL-6 and STAT3,inhibit the signal-transduction pathway of STAT3.The IL-6 /STAT3 signaling pathway of airway may be one of the potential therapeutic targets of inhaled corticosteroid.

Study Progress on Change of Small Airway Function in Children with Asthma / 实用儿科临床杂志

Asthma is one kind of chronic respiratory tract inflammatory disease.Recently,it has been discovered that the small airway also participates in asthmatic pathogenesis.The small airway which diameter is less than 2 mm is one of the smallest regions in the lung.Its function may be affected by the small airway disease and related with the airway hyperresponsiveness.Some structural changes in the small airway is the latent reason which aggravates asthma.The change of small airway function in the mild asthma can cause the change of airway hyperresponsiveness.So it is considered that the small airway function is one of the methods to monitor the asthmatic situation.

Study Progress of Low-Grade Inflammation in Pathogenesis of Children with Obesity and Insulin Resistance / 实用儿科临床杂志

Obesity has been a world-wide growing health problem in children and adolescents,insulin resistance plays a pivotal role in the pathogenesis of obesity-associated complications,the mechanism is still unknown.There is growing evidence that obesity is associated with low-grade inflammation in youth.The onset of low-grade inflammation in obesity may be associated with the inflammatory cytokine secreted by adipose tissue,local Monocyte/Macrophage system and role of oxidative stress.The study of inflammatory cytokines in pathogenesis of obesity and insulin resistance will help to develop new treatment strategies to prevent obesity and obesity-associated complications.

Relationships between Plasma Carnitine,Free Fat Acid Levels and Insulin Resisitance in Children with Simple Obesity / 实用儿科临床杂志

Objective To investigate the correlations between plasma levels of carnitine(CT),free fat acid(FFA) and insulin resisitance in children with simple obesity.Methods Fifty-six children diagnosed with simple obesity were enrolled as study group(obesity group),36 healthy children as control group.The concentration of plasma level of insulin was measured by radioimmunoassay(RIA),CT was measured by high performance liquid chromatography(HPLC),FFA and triglyceride(TG) were measured by enzymatic-colorimetric assay.Body mass index(BMI) and waist to hip ratio(WHR) were caculated.Insulin sensitivity index (InSI) and insulin resistance index (InRI) were cacula-ted by homeostasis model assessment of insulin resistance (HOMA-IR).SPSS 13.0 software was used to analyze the data.Results The concentration of CT in plasma was (43.67?12.75) ?mol/L in obesity group,(58.31?21.25) ?mol/L in control group,respectively.There was a significant difference between 2 groups (t=2.566 P

Clinical Feature of Children with Acquired Immunodeficiency Syndrome / 实用儿科临床杂志

Objective To explore the causes,clinical feature,diagnoses and prognosis of children with acquired immunodeficiency syndrome (AIDS) and improve our awareness of this disease.Methods The clinical and laboratory data of 12 children with AIDS were analyszed retrospectively and the clinical feature was summed up.Results Among 12 children with AIDS,9 cases were boys and 3 cases were girls,aged from 45 days to 9 years old.The parents of 11 cases were positive in serological human immunodeficiency virus (HIV) antibody or died of AIDS.The main manifestations were developmental delay and various degree cacotrophia(12 case,100%),the others included abnormity fever,discontinuity cough and hepatosplenomegaly(10 cases,83.3%),recurrent diarrhea and lymphadenopathy (8 cases,66.7%),skin lesion(6 cases,50%),cerebral hypoplasia (4 cases,33.6%),oral candidiasis(3 cases,26.7%),and tympanitis(2 cases,16.7%).Laboratory tests showed:all of 12 cases were positive in serological HIV antibody by test for 2 times.The percent of CD4+ and the ratio of CD4+ to CD8+ were decreasing.One case was dead and the others had bad effect with allopathy.Conclusions Children with AIDS have short clinical latency,diversified clinical manifestation,low cell-mediated immunity function and bad effect with allopathy.To improve our awareness of the di-sease should be helpful for diagnosing and treating it early and prolonging the patients' life.

Eosinophils apoptosis in asthmatic children / 中华儿科杂志

<p><b>UNLABELLED</b>Prominent eosinophil airway inflammation is important in the pathogenesis of asthma. There is increasing evidence that the disorder of eosinophil apoptosis contributes to the mechanism. But most of the studies have been done in vitro or on animal models, very few were done among the adult asthmatics in vivo.</p><p><b>OBJECTIVE</b>The aim of this study was to elucidate the relationship between the apoptotic eosinophils and Bcl-2 in asthmatic children in vivo.</p><p><b>METHODS</b>Eleven mild to moderate asthmatic patients were recruited and the range of age was 7 - 14 years (9 males, 2 females), meanwhile 7 patients with lower respiratory infection were recruited as control and the range of age was 9 - 14 years (5 males, 2 females). Before and after inhaled glucocorticoid (GC) induced sputum, bronchoalveolar lavage (BAL), bronchial mucosa specimens and peripheral blood were obtained for measuring and comparing the changes of apoptotic EG(2)(+) cell by combining the techniques of TUNEL and immunohistochemistry, meanwhile the expression of Bcl-2 in bronchial mucosa specimens was measured by using the immunohistochemical assay.</p><p><b>RESULTS</b>Before the inhalation of GC, the apoptotic EG(2)(+) cells in asthmatics were significantly lower than that in control group (P < 0.01), and the numbers of EG(2)(+) cell in asthmatics group were significantly higher than that in control group (P < 0.001). After the treatment apoptotic EG(2)(+) cells in asthmatics were increased (P < 0.01), and the numbers of EG(2)(+)cell were decreased (P < 0.01, P < 0.05 and P < 0.05, respectively), FEV(1)% was increased (P < 0.05). Before the inhalation of GC, the numbers of Bcl-2(+) cell in asthmatic airway submucosa were higher than that in control group (P < 0.05) but after the treatment the number of Bcl-2(+) cell did not change significantly. (4) Before and after GC treatment the percentages of apoptotic eosinophils of peripheral blood in vivo had no significant changes compared with those of control subjects (P > 0.05). There was a positive correlation between apoptosis of EG(2)(+) cell in sputum, BAL, airway submucosa and FEV(1)% (P < 0.05).</p><p><b>CONCLUSION</b>Apoptosis of EG(2)(+) cell decreased in the airway of asthmatic children and inducing EOS apoptosis is one of the important mechanism of inhaled GC therapy for asthma.</p>

Expression of Signal Transducers and Activator of Transcription 3 in Airway Epithelial Cells of Asthmatic Mouse Model and Its Role in Airway Remodeling / 实用儿科临床杂志

Objective To study the expression of signal transducers and activators of transcription 3(STAT3) in airway epithelial cells of asthmatic mouse model and its association with airway remodeling,explore the role of signal-transduction pathway in airway remodeling.Methods Thirty Balb/c mice were randomly divided into normal control group(n=10),asthma without intervention group(n=10) and AG490 intervention group(n=10).The mice were sensitized with ovalbumin to establish the asthmatic model.The histological changes were evaluated by HE staining,total brochial wall thickness(Wat)and smooth muscle thickness(Wam) were measured by image analysis system,the percentages of collagen deposition were detected by Masson′s trichrome staining,the expression of STAT3 in airway were detected by immunohistochemistry technique;lung tissue extracts were analyzed for phosphorylation of STAT3(p-STAT3)by Western blot.SPSS 13.0 software was used to analyze the data.Results 1.The histological changes including airway thickness,airway smooth cell proliferation and excessive collagen deposition in subepithelial aera were found under light microscope in asthmatic mice.2.The level of STAT3 and p-STAT3 in asthma without intervention group were significantly higher than those in normal control group(Pa

Role of Neutrophilic Inflammation in Severe Asthma in Children / 实用儿科临床杂志

Asthma was considered to be a kind of chronic airway inflammatory diseases mediated by eosinophils(EOS),mast cells,T lymphocytes for a long time,and the typical pathologic features of asthma was airway EOS inflammation.The current study had found out that elevated neutrophils in airway were seen in severe asthma,and this kind of asthma had a poor response to corticosteroids.Impaired neutrophil chemotaxis and apoptosis of airway neutrophilia may be associated with persistent neutrophilic inflammation in the airways of severe asthma.A deep research into the mechanisms of neutrophilic phenotypes asthma would contribute to the new strategy of therapy.This article discusses a range of topics related to the role of neutrophilic inflammation in severe asthma in children,which were organizedas follows.