Clinical characteristics and risk factors for bronchoscopic airway mucus hypersecretion in childhood pneumonia infected by different pathogens / 中华儿科杂志

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×106 vs. 490 (210, 1 510)×106/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.

Analysis of respiratory syncytial virus nonstructural protein 1 amino acid variation and clinical characteristics / 中华儿科杂志

Objective: To investigate the relationship between amino acid variations of respiratory syncytial virus (RSV) nonstructural protein (NS) 1 and the clinical characteristics. Method: A retrospective case review was conducted. From December 2018 to January 2020, a total of 81 cases of hospitalized children who were tested only positive for RSV by RT-PCR or PCR at the Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University were included in the study. The NS1 genes of RSV subtype A and subtype B were amplified by PCR and sequenced. The amino acid sequences were analyzed. The Chi-square test and Mann-Whitney rank sum test were used to compare the clinical characteristics and type Ⅰ interferon levels of children with or without NS1 variation in the variation and non-variation groups. Results: Among 81 cases, there were 58 males and 23 females. There were 11 cases in the variation group, the age of onset was 2.0 (1.0, 11.0) months, included 4 cases of subtype A (variant sites were: 2 cases for Lys33Gln, one case for Gly2Asp, Pro67Ser, Leu137Phe, respectively) and 7 cases of subtype B (variant sites were: two cases for Val121Ile, one case for Tyr30Cys, Val65Met, Asn85Ser, Ser118Asn, Asp124Asn, respectively). These variant sites all appeared at a very low frequency 0.08 (0.04, 0.29) % in the NCBI PROTEIN database. There were 70 cases in non-variation group, the onset age was 3.5 (1.0, 7.0) months. The proportion of dyspnea in the variation group was higher than that in the non-variation group (10/11 vs. 47% (33/70), χ2=7.31, P<0.01). Conclusions: There are some variant sites in nonstructural protein NS1 of RSV. Children may be prone to have dyspnea with NS1 variations.

Neuro-immune interactions in respiratory diseases / 生理学报

The nervous system and the immune system are relatively independent but interactional, and neuro-immune regulation is very important for the respiratory system to resist external harmful stimuli and to maintain homeostasis. Neuro-immune interaction is involved in the occurrence and development of respiratory diseases, and is essential for monitoring and modulating inflammation and tissue repair. This article summaries the neuro-immune regulation of respiratory system and discusses its role in respiratory diseases, aiming to provide a theoretical basis for further understanding the crosstalk between the nervous and immune systems, to explore the underlying mechanism in respiratory diseases, and to provide new thoughts for the prevention and treatment of respiratory diseases.

Vasoactive intestinal peptide: a potential target for antiviral therapy / 生理学报

Viral infection is clinically common and some viral diseases, such as the ongoing global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have high morbidity and mortality. However, most viral infections are currently lacking in specific therapeutic agents and effective prophylactic vaccines, due to inadequate response, increased rate of drug resistance and severe adverse side effects. Therefore, it is urgent to find new specific therapeutic targets for antiviral defense among which "peptide-based therapeutics" is an emerging field. Peptides may be promising antiviral drugs because of their high efficacy and low toxic side effects. Vasoactive intestinal peptide (VIP) is a prospective antiviral peptide. Since its successful isolation in 1970, VIP has been reported to be involved in infections of SARS-CoV-2, human immune deficiency virus (HIV), vesicular stomatitis virus (VSV), respiratory syncytial virus (RSV), Zika virus (ZIKV) and cytomegalovirus (CMV). Additionally, given that viral attacks sometimes cause severe complications due to overaction of inflammatory and immune responses, the potent anti-inflammatory and immunoregulator properties of VIP facilitate it to be a powerful and promising candidate. This review summarizes the role and mechanisms of VIP in all reported viral infections and suggests its clinical potential as an antiviral therapeutic target.

Clinical effect of azithromycin adjuvant therapy in children with bronchiolitis: a systematic review and Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To systematically evaluate the clinical effect of azithromycin (AZM) adjuvant therapy in children with bronchiolitis.@*METHODS@#Related databases were searched for randomized controlled trials (RCTs) on AZM adjuvant therapy in children with bronchiolitis published up to February 17, 2019. RevMan 5.3 was used to perform the Meta analysis.@*RESULTS@#A total of 14 RCTs were included, with 667 children in the intervention group and 651 in the control group. The pooled effect size showed that in the children with bronchiolitis, AZM adjuvant therapy did not shorten the length of hospital stay (MD=-0.29, 95%CI: -0.62 to 0.04, P=0.08) or oxygen supply time (MD=-0.33, 95%CI: -0.73 to 0.07, P=0.10), while it significantly shortened the time to the relief of wheezing (MD=-1.00, 95%CI: -1.72 to -0.28, P=0.007) and cough (MD=-0.48, 95%CI: -0.67 to -0.29, P<0.00001). The analysis of bacterial colonization revealed that AZM therapy significantly reduced the detection rates of Streptococcus pneumoniae (OR=0.24, 95%CI: 0.11-0.54, P=0.0006), Haemophilus (OR=0.28, 95%CI: 0.14-0.55, P=0.0002), and Moraxella catarrhalis (OR=0.21, 95%CI: 0.11-0.40, P<0.00001) in the nasopharyngeal region.@*CONCLUSIONS@#AZM adjuvant therapy can reduce the time to the relief of wheezing and cough in children with bronchiolitis, but it has no marked effect on the length of hospital stay and oxygen supply time.

Levels of surfactant proteins A and D in bronchoalveolar lavage fluid of children with pneumonia and their relationships with clinical characteristics / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To observe the levels of pulmonary surfactant proteins A and D (SP-A, SP-D) in bronchoalveolar lavage fluid (BALF) of children with pneumonia, and to explore their relationships with clinical characteristics.</p><p><b>METHODS</b>Thirty-five children with pneumonia were enrolled in this study. Differential cell counts were obtained by Countstar counting board. The levels of SP-A and SP-D in BALF were detected using ELISA.</p><p><b>RESULTS</b>In children with pneumonia, SP-D levels were significantly higher than SP-A levels (P<0.001). SP-D levels were negatively correlated with the neutrophil percentage in BALF (r(s)=-0.5255, P<0.01). SP-D levels in BALF in children with increased blood C-reactive protein levels (>8 mg/L) were significantly lower than in those with a normal level of C-reactive protein (P<0.05). Compared with those in children without wheezing, SP-D levels in children with wheezing were significantly lower (P<0.01). There was no correlation between SP-A levels and clinical characteristics.</p><p><b>CONCLUSIONS</b>SP-D levels in BALF are significantly higher than SP-A levels, and have a certain correlation with clinical characteristics in children with pneumonia. As a protective factor, SP-D plays a more important role than SP-A in regulating the immune and inflammatory responses.</p>

Airway inflammation induced by Poly(I:C) stimulation in the late stage of respiratory syncytial virus infection in mice and its mechanism / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the pathogenic mechanisms of airway inflammation and recurrent wheezing induced by recurrent respiratory virus infection after respiratory syncytial virus (RSV) infection.</p><p><b>METHODS</b>Sixty-four female BALB/c mice (aged 6-8 weeks) were randomly divided into four groups: control, RSV, Poly(I:C), and RSV+Poly(I:C) (n=16 each). The bronchoalveolar lavage fluid (BALF) was collected on the 3rd day after Poly(I:C) administration, and the total cell number and differential counts in BALF were determined. Hematoxylin-eosin staining was used to observe pulmonary pathological changes. The airway responsiveness was detected. ELISA was used to measure the levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-13 (IL-13), matrix metallopeptidase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in BALF.</p><p><b>RESULTS</b>Compared with the other three groups, the RSV+Poly(I:C) group had significant increases in the total number of inflammatory infiltrating cells in the airway, airway responsiveness, and MMP-9 level in BALF (P<0.05). The RSV+Poly(I:C) group showed more severe pulmonary tissue injuries compared with the control and RSV groups (P<0.01). Compared with the RSV group, the RSV+Poly(I:C) group showed significant reductions in the levels of IL-4 and TIMP-1 in BALF (P<0.01).</p><p><b>CONCLUSIONS</b>Viral re-infection in the late stage of RSV infection may cause an imbalance of MMP-9/TIMP-1 expression and thus contribute to aggravated airway inflammation.</p>

Inhibitory effect of chloroquine on airway hyperresponsiveness in asthmatic mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of chloroquine on airway hyperresponsiveness in asthmatic mice and explore the possible mechanism.</p><p><b>METHODS</b>Balb/c mouse models of asthma established using OVA received intraperitoneal injections of chloroquine, dexamethasone, or both prior to OVA challenge. Within 24 h after the final challenge, airway hyper- responsiveness (AHR) of the mice was assessed, and the total cell count and the counts of different cell populations in the bronchoalveolar lavage fluid (BALF) were determined under light microscopy. The severity of lung inflammation was evaluated using HE staining, and the concentrations of IL-6 and PGF2α in the BALF were detected by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Chloroquine pretreatment significantly decreased AHR (P<0.001) in the asthmatic mice and reduced the total cell count (P<0.01), eosinophils (P<0.001), neutrophils (P<0.01), and PGF2α levels in the BALF. Chloroquine combined with low-dose dexamethasone significantly lessened inflammations around the bronchioles (P<0.05) and blood vessels (P<0.01) in the lung tissue, and obviously lowered IL-6 (P<0.05) and PGF2α (P<0.001) in the BALF in the asthmatic mice.</p><p><b>CONCLUSION</b>Chloroquine can inhibit AHR in asthmatic mice and produce better anti-inflammatory effect when combined with dexamethasone for treatment of neutrophilic asthma.</p>

Indoor Allergen Levels and Household Distributions in Nine Cities Across China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Chinese allergic subjects have high levels of sensitization to house dust mite (HDM) and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households.</p><p><b>METHODS</b>Dust samples were collected from nine cities. Major allergens Der p 1 and Der f 1 from Dermatophagoides pteronyssinus and D. farinae, and specific antigens of Blomia tropicalis, Tyrophagus putrescentiae, Acarus siro, and cockroach species Blattella germanica and Periplaneta americana were measured by ELISA.</p><p><b>RESULTS</b>HDM allergens were found in dust samples from bedding in 95% of the Chinese households. The median levels varied from <0.006 to 9.2 µg/g of dust, depending on the city. The percentages of households having HDM allergen levels associated with the risk of developing allergy sensitization and asthma were 65% and 25%, respectively. Specific antigens of the storage mite and cockroach were only found in samples from the southern and tropical regions of China. Levels of mite allergens were generally higher in samples from bedding compared to samples from the living room, even for storage mites, whereas levels of cockroach antigens were higher in the living room samples.</p><p><b>CONCLUSION</b>HDM allergens are present in bedding dust samples from most Chinese households. Cities in southern and central China have relatively high levels of HDM major allergens compared to cities in northern and western China. Antigens of storage mites and cockroaches are not as common as HDM allergens.</p>

Difference between Nested-polymerase chain reaction and virus isolation in detection of respiratory syncytial virus and their clinical significances / 中华实用儿科临床杂志

Objective To observe the differences between Nested-polymerase chain reaction(N-PCR) and virus isolation methods used for detection of respiratory syncytial virus(RSV),and to reveal the potential clinical features of them.Methods From Jan.2010 to Aug.2012,nasopharyngeal aspirates (NPAs) were collected from the children with respiratory infection in the Department of Respiratory,the Children's Hospital of Chongqing Medical University.Both N-PCR and virus isolation were applied to detect RSV,and clinical data were collected for statistical analysis.Results A total of 1143 specimens were used for RSV detection by N-PCR and virus isolation.The male-female ratio was 2.16 vs 1.00.The age of patients was ranged from 1 month to 165 months(median:7 months).The most common diagnoses were as follows:bronchopneumonia [478 cases (41.8％)],chronic fibrous pneumonia [223 cases (19.5％)],bron-chiolitis [221 cases (19.3％)],bronchitis [71 cases (6.2％)] and upper respiratory infection [21 cases(1.8％)].For N-PCR,458 cases were RSV positive (total positive rate was 40.1％ ; 31.7％ for RSV-A,7.7％ for RSV-B,0.7％ for both RSV-A and RSV-B).With virus isolation method,204 cases were positive (17.8％).Comparison result of N-PCR and virus isolation showed:165 cases were positive (P+ I+) and 646 cases were negative (P-I-) by both methods (identity was 70.1％),and the most difference was N-PCR positive but virus isolation negative group (P+ I-) (293 cases,25.6％).When compared to P-I-group,the clinical features of P+ I-group were as follows:younger,longer hospital stays,remarkable season distribution (with peak in winter and lowest in summer),lower percentage of fever,higher percentage of cough,wheezing,dyspnea,severe pneumonia and respiratory failure,all these differences were statistically significant(all P ＜ 0.05),the ma-nifestations matched the clinical features of RSV infection.When compared to P + I + group,the symptoms in the P + I-group had longer duration before they were admitted to hospital (P =0.005) and lower percentage of wheezing (P =0.009).Conclusions The differences between N-PCR and virus isolation for the detection of RSV existed in duration of symptoms prior to hospitalization.Both the sensibility and specificity of N-PCR are desirable for RSV detection.

Etiology and clinical features of repeatedly hospitalized children with respiratory virus infection / 中华实用儿科临床杂志

Objective To explore the causative factors of children with respiratory tract infection and their clinical features.Methods Nasopharyngeal aspirate (NPA) was collected from 1746 children with acute respiratory infections (ARIs),aged from 37 days to 3 years,who were admitted to Children's Hospital of Chongqing Medical University between Jun.2009 and May 2011.Fourteen respiratory viruses in NPA were investigated using polymerase chain reactions (PCR) after nucleic acids extracted from the samples and then synthesized cDNA.Sequence analysis was performed to verify the results of each virus from random positive samples.A total of 23 cases were identified with twice or more admissions to hospital.Individual factors,virus detection and clinical characte-ristics were compared between patients with and without repeated hospitalization.Risk factors for repeated hospitalization were investigated.Then these factors were compared in patients with repeated hospitalization between first time and second time.Results The median age was 7 months in patients with repeated hospitalization and 8 months in patients without repeated hospitalization,there were significantly different difference (P ＜ 0.0001).There was no significant difference in virus detection including influenza type A,parainfluenza,respiratory syncytial virus (RSV),adenovirus and human bocavirus between patients with and without repeated hospitalization in the same age group.By comparing clinical features between patients with and without repeated hospitalizatin in the same age group,(69.6％ vs 47.4％,P =O.037) and diarrhea (52.2％vs 29.0％,P =0.017) were found more often in patients with repeated hospitalization.There was no connection between respiratory virus detection and presence of fever,wheeze,cough and diarrhea in patients with repeated hospitalization for the first time of hospitalization.RSV was the most frequently appeared virus in twice hospitalizations,presenting 52.2％ and 30.4％,respectively.One case had twice positive for RSV.In the first hospitalization,there were 16 viruspositive cases and 16 wheeze cases,while in the second hospitalization,there were 12 virus-positive cases (75.0％)and 11 wheeze cases (68.8％),respectively.Conclusions Children with respiratory tract infections suffered repeated hospitalization,mainly occur in children less than 3 years old.Wheeze is an important clinical feature in children with repeated hospitalization.Although causative viruses for patients in each infection are different,RSV is the most common detected viral agent.Virus-positive cases in the first hospitalization present higher viral detection rate during the second hospitalization,with similar trend for wheeze.

Clinical analysis of 28 cases of bronchiolitis obliterans / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical features of bronchiolitis obliterans (BO) in children.</p><p><b>METHODS</b>The clinical data of 28 children with BO between July 2007 and April 2012 was retrospectively reviewed.</p><p><b>RESULTS</b>All patients presented with persistent or repeated cough and wheezing. Twenty-three cases were post-infectious bronchiolitis obliterans (PIBO), among whom the etiology were adenovirus (12 cases), measles (2 cases), influenza virus A (2 cases), mycoplasma pneumoniae (1 case), mycoplasma pneumoniae coinfection with adenovirus (1 case), respiratory syncytial virus coinfection with Parainfluenza type 3 virus (1 case) and pulmonary tuberculosis (1 case). The etiology of 3 cases was not associated with infection. The etiology was unknown in 2 cases. Pulmonary HRCT revealed that decreased density in 25 cases, mosaic perfusion in 21 cases, bronchial wall thickening in 15 cases, bronchiectasis in 12 cases and air retention in 6 cases. Lung function test was performed on 21 cases and demonstrated that obstructive ventilation disorder in all 21 cases. Bronchodilation test was performed on 18 cases and 17 cases showed a negative result. All 28 cases received corticosteroid treatment, and 24 cases were orally administered with low doses of azithromycin. One case died during hospitalization. Eighteen cases were followed up for 4 months to 4 years and seven months. Clinical manifestations were improved in 12 cases and one case died.</p><p><b>CONCLUSIONS</b>Low respiratory infection is the most common cause of pediatric BO and adenovirus is a major pathogen. Persistent wheezing and cough were main clinical manifestations. Pulmonary HRCT imaging is important for diagnosis and follow-up of BO. Lung function test can typically show obstructive ventilation disorder. Corticosteroid and methotrexate may be effective for treatment of BO. Prognosis of this disease is unsatisfactory. Early diagnosis and treatment, and avoidance of repeated respiratory tract infection may be helpful to improve the prognosis.</p>

Etiology of nonspecific chronic cough in children and relationship between TRPV1 gene polymorphisms and nonspecific chronic cough / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the causes of nonspecific chronic cough in children and relationship between transient receptor potential vanilloid 1 (TRPV1) gene polymorphisms and nonspecific chronic cough.</p><p><b>METHODS</b>A total of 195 children with chronic cough were followed up half a month, one month and three months after their first visit to hospital. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine polymorphisms of the TRPV1 gene in the children. A total of 205 healthy or surgical children without chronic cough served as the control group.</p><p><b>RESULTS</b>The etiologic distribution of the 195 children with chronic cough was as follows: 96 (49.2%) cases of cough variant asthma (CVA), 48 (24.6%) cases of CVA complicated by upper airway cough syndrome (UACS), 34 (17.4%) cases of post-infectious cough, and 17 (8.7%) cases of UACS. Three genotypes were identified in both groups at positions rs222747 (CC, GC and GG), rs222748 (CC, TC and TT) and rs8065080 (CC, TC and TT). The frequencies of genotype and allele at position rs222747 did not accord with the law of Hardy-Weinberg. There was no significant difference in frequencies of genotype and allele at positions rs222748 and rs8065080 between the two groups.</p><p><b>CONCLUSIONS</b>CVA, UACS and post-infectious cough are common causes of nonspecific chronic cough in children. TRPV1 gene polymorphisms at positions rs222748 and rs8065080 may be unrelated to nonspecific chronic cough in children.</p>

Effects of 1,25-dihydroxyvitamin D3 in rats with experimental autoimmune thyroiditis / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of 1,25(OH)2D3 on thyroid inflammation and Th1/Th2 cells in rats with experimental autoimmune thyroiditis (EAT).</p><p><b>METHODS</b>Forty-eight female Wistar rats were randomly divided into 4 groups, namely the prevention group treated with 1, 25-(OH)2D3 from 0 to the 6th week (n=10), treatment group with 1,25(OH)2D3 treatment from the 2nd to the 8th week (n=10) after immune sensitization, positive control group (n=12) and the negative control group (n=16). All the rats were challenged with porcine thyroglobulin for immune sensitization until the 6th or 8th week except for those in the negative control group. In the prevention group and treatment group, the rats received 1,25(OH)2D3 at 5 microg/kg by intraperitoneal injection every other day, while those in the positive and negative control groups were given peanut oil instead. The thyroid pathologies, serum autoantibody level and cytokine levels were examined after the treatments.</p><p><b>RESULTS</b>The thyroid gland remained structurally intact in the negative control group. In the positive control group, the thyroid showed obvious inflammatory change with structural disruption and even disappearance of the thyroid follicle. The structure of the thyroid gland follicles was intact in the prevention group and treatment group. No significant differences were found in the autoantibody and cytokine levels between the prevention group and negative control group (P>0.05). Compared with the positive control groups, the autoantibody and IFN-gamma and IL-12 levels decreased significantly in the treatment group, but the levels of IL-4 and IL-10 were markedly increased (P<0.05).</p><p><b>CONCLUSION</b>1,25(OH)2D3 given before the establishment of the EAT model helps maintain structural integrity of the thyroid gland and normal levels of the antibodies and cytokines in rats. 1,25(OH)2D3 can ameliorate the pathological changes of the thyroid gland and correct the cytokine disequilibrium in rats with EAT.</p>

Impact of neonatal bacillus Calmette-Guerin vaccination on lung Th17 cells and IL-17 in murine asthma model / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the impact of neonatal bacillus Calmette-Guerin(BCG) vaccination on lung Th17 cells and IL-17 in murine asthma model.</p><p><b>METHODS</b>Neonatal BALB/c mice were divided into three groups: control, OVA and BCG/OVA groups. BCG was administerd in the BCG/OVA group on postnatal day 2 or 3. Except the control group, the mice in the other two groups were sensitized and undergone OVA challenge. Inflammatory cell numbers and morphological identification of leucocytes in bronchoalveolar lavage fluid (BALF) were measured by light microscopy. Cytokine IFN-gamma and IL-17 levels in BALF were measured using ELISA. The percentage of lung Th17 cells were assayed by flow cytometry.</p><p><b>RESULTS</b>There was significantly larger number of total cells, lymphocytes, eosinophils and neutrophils in BALF in the OVA and BCG/OVA groups compared with the control group. The number or percentage of those cells in the BCG/OVA group was lower than that in the OVA group. The level of IL-17 in BALF was significantly higher in the OVA and the BCG/OVA groups compared with the control group, while the level of IFN-gamma was lower. The OVA group had higher level of IL-17 than the BCG/OVA group. The mice in the OVA and the BCG/OVA groups had a higher percentage of Th17 cells in lungs compared with the control group, but there were no significant differences in the percentage of Th17 cells between the OVA and the BCG/OVA groups.</p><p><b>CONCLUSIONS</b>Th17 cells and IL-17 play roles in the pathogenesis of asthma. BCG vaccination can reduce the level of IL-17 in BALF and the reduced IL-17 may be mainly from other IL-17-producing cells in the lungs, not Th17 cells.</p>

Proportion of incidence of etiological agents in children with non-specific chronic cough in Chongqing: a follow-up study / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the proportion of incidence of children with non-specific chronic cough in Chongqing and analyze the characteristics of etiology during the follow-up.</p><p><b>METHOD</b>Diagnostic criteria were defined for children with non-specific chronic cough according to the Guidelines of diagnosis and therapy for children with chronic cough that were formulated by the Subspecialty Group, Society of Pediatrics, Chinese Medical Association and Chinese Journal of Pediatrics in 2008. Totally 266 patients in whom cough was the main or the only symptom,lasting > 4 weeks, presenting to Asthma Center of Children's Hospital, Chongqing Medical University between June 2008 and April 2009 were recruited into this study. Based on the Guidelines, diagnosis was made after taking history, physical examination and assistant examination. After etiological treatment, the patients were followed up during the second week, the fourth week and the twelfth week. Etiological diagnosis was confirmed if cough was resolved after specific therapy. If cough was not resolved,the diagnosis was rechecked and a new therapy was applied.</p><p><b>RESULT</b>Totally 125 (47.0%) patients received final diagnoses of cough variant asthma (CVA), 58 (21.8%) was CVA and upper airway cough syndrome (UACS), 44 (16.5%) was diagnosed postinfection cough, 35 (13.2%) of UACS. In different age groups, the proportion of incidence of etiological agents is statistically distinct. In the ≤ 3 years old group, 35 patients (70.0%) were diagnosed CVA, 10 (20.0%) was postinfection cough; in 3 - 6 years group, 71 patients (50.7%) had CVA; the incidence of UACS was significantly higher in ≥ 6 years group.</p><p><b>CONCLUSION</b>It is concluded that CVA, CVA and UACS, post infection cough, and simple UACS were identified as the three top reasons for children with chronic cough in Chongqing. Children with chronic cough of different age groups had different etiology of cough. The characteristic of each etiology need further study.</p>

Effect of neonatal BCG vaccination on phenotype and function of splenic dendritic cells of BALB/c mice / 中华儿科杂志

<p><b>OBJECTIVE</b>The impact of dendritic cells (DCs) and regulatory T cells (Tr) on the pathogenesis of asthma have been investigated over the past decades. As the professional antigen presenting cells, DCs not only prime immune response directing Th0 cells toward different T subtypes but also induce immune tolerance. As an immunoregulator, Bacillus Calmette-Guerin (BCG) has potential to be applied in allergic diseases such as asthma for prevention. Previous study showed that neonatal BCG vaccination could induce Th1/Tr1 development in mice in vivo. To further identify the mechanism of neonatal BCG vaccination on T cell subsets differentiation, the present study was designed to investigate the impact of BCG vaccination on splenic DCs development in neonatal mice.</p><p><b>METHODS</b>Neonatal specific pathogen free (SPF) BALB/c mice (2-3 days) were divided into intraperitoneal BCG-treated group, subcutaneous BCG-treated group and control group; simultaneously adult SPF BALB/c mice (6-8 weeks) were divided into intraperitoneal BCG-treated and control group. The BCG-treated mice were inoculated with 1 x 10(5) CFU BCG, the mice in control group were not inoculated with any vaccine. Four weeks post BCG vaccination, spleen cells were isolated. With flow cytometry, subtype and maturity of splenic DCs were analysed. Moreover, cells were further separated into mononuclear cell by Ficoll solution. The mononuclear cells were stimulated by 1 microg/ml lipopolysaccharide (LPS) for 18 or 10(5) CFU /ml BCG for 48 hours at 37 degrees C in a humidified atmosphere containing 5% CO2 and cytokines concentration was detected by ELISA.</p><p><b>RESULTS</b>(1) CD11c(+) CD8alpha(+) and CD11c(+) CD8alpha(-) DCs were found in spleen cells of the BALB/c mice. In comparison with the control group, the percent of CD11c(+) CD8alpha(-) DCs in intraperitoneal BCG group significantly declined (P < 0.01) and that of CD11c(+) CD8alpha(+) DCs significantly increased (P < 0.01), there were no significant difference in DC subtypes between intraperitoneal and subcutaneous BCG-vaccinated mice. In contrast, the percent of CD11c(+) CD8alpha(-)DCs markedly increased (P < 0.01) and that of CD11c(+) CD8alpha(+)DCs noticeably reduced (P < 0.01) in adult BCG-vaccinated mice. The percent of CD11c(+)CD8alpha(-)DC was significantly higher and that of CD11c(+) CD8alpha(+)DC was significantly lower in adult-vaccinated BALB/c mice than that of neonatal-vaccinated ones. (2) The expression of costimulatory molecules CD40 on CD11c(+) CD8alpha(-) DCs and CD86 on CD11c(+) CD8alpha(+) DCs in neonatal BCG-treated BALB/c mice was higher than the controls. There were no significant difference in expression of costimulatory molecules on DC between neonatal BCG-vaccinated mice. Compared with the control group, expression of CD40 and MHC-II molecules on CD11c(+) CD8alpha(-) and CD11c(+) CD8alpha(+)DC was significantly higher and that of CD86 was significantly lower in adult BCG-vaccinated mice. The expression of costimulatory molecules on DC had no significant difference between neonatal and adult BCG vaccinated BALB/c mice. (3) As compared with the control mice, concentration of IL-12p70 induced by LPS and IL-10 induced by BCG in vitro from spleen cells culture supernatant was noticeably elevated (P < 0.05) in neonatal BCG-treated BALB/c mice, but that of IL-6 did not change by LPS or BCG stimulation.</p><p><b>CONCLUSION</b>(1) By up-regulating splenic CD8alpha(+)DCs and inducing IL-12p70 and IL-10 production in BALB/c mice, neonatal BCG vaccination promoted Th1/Tr1 development. (2) The effect of BCG vaccination on DC was different between neonates and adult BALB/c mice.</p>

Analysis of 53 cases with bronchoscopically confirmed pediatric tracheobronchomalacia / 中华儿科杂志

<p><b>OBJECTIVE</b>Tracheobronchomalacia is one of the common respiratory tract dysplasia in children. Its symptoms are nonspecific, and routine methods are unreliable in the assessment of tracheobronchomalacia in children. In addition, many physicians are confused about its clinical characteristics, so tracheobronchomalacia is often underdiagnosed. The purpose of this study was to explore the clinical features of tracheobronchomalacia in children and to investigate the diagnostic value of flexible bronchoscopy for children with tracheobronchomalacia.</p><p><b>METHOD</b>For diagnosis and treatment, 229 children out of 4725 patients hospitalized in the division of respiratory disorders were examined by Olympus BF3c-20 flexible bronchoscopy or by Olympus BF-P20 flexible bronchoscopy under general anesthesia with propofol, in Chongqing Children's Hosptial from April 2004 to April 2006. Fifty-three cases were confirmed to have tracheobronchomalacia by bronchoscopy, patients' data including airway lesion, age, sex, clinical characteristics, aided examinations, treatment, final outcomes, were collected and analyzed.</p><p><b>RESULTS</b>(1) Of the 53 children with tracheobronchomalacia, 31 were not suspected for this diagnosis prior to bronchoscopy, who were instead misdiagnosed as refractory pneumonia, difficult-to-control asthma, bronchial foreign body, bronchopulmonary dysplasia and pulmonary atelectasis of unknown origin or bronchiolitis. (2) In the 53 children with tracheobronchomalacia aged one month to eight years, 41 were infants, 6 were younger than two years, 4 were younger than 3 years and the rest 2 cases were older than 3 years. The risk of tracheobronchomalacia related inversely with ages. Ten cases were girls and 43 were boys. (3) Eleven cases had tracheomalacia, 24 bronchomalacia, 18 tracheobronchomalacia; 12 cases had malacia on left lung, 11 on right lung, 19 on both sides; 21 children were mild cases, 25 moderate cases, 7 severe cases. (4) In the 53 children with tracheobronchomalacia, 28 had recurrent or prolonged wheezing, 16 chronic cough, 5 recurrent respiratory infections, 2 atelectasis of unknown origin, and 2 dyspnea.</p><p><b>CONCLUSIONS</b>The infants and toddlers seem to be predisposed more to the bronchomalacia than the older children. Clinical features of children with airway malacia were variable and atypical, expiratory stridor and cough are the most commonly reported symptoms. Flexible bronchoscopy should be regarded as a "golden standard" method for diagnosing TBM.</p>

Clinical characteristics of 12 persistently wheezing children with human bocavirus infection / 中华儿科杂志

<p><b>OBJECTIVE</b>The impact of human bocavirus (HBoV), a newly identified human parvovirus, on childhood persistent wheezing has not been identified. In this study, the clinical features of infantile persistent wheezing induced by HBoV was analyzed.</p><p><b>METHODS</b>Tracheal aspirates were collected by bronchofibroscope or nasopharyngeal (NP) aspirates from April, 2006 to January, 2007. HBoV DNA in the tracheal aspirates of 33 children with persistent wheezing and in NP aspirates of 6 children with persistent wheezing, who had at least or more than four weeks wheezing. RSV was identified by virus isolation in Hep-2 cells and antigen detetion by direct immunofluorescence assay (DIFA) which was also used for diagnosis of adenovirus, influenza A and B, parainfluenza 1, 2, 3 infection.</p><p><b>RESULTS</b>Of the 39 children with persistent wheezing, 12 cases (31%) were positive for HBoV DNA. Age of HBoV-positive patients ranged from 2 month to 1 year. The results of sequencing of PCR products proved that sequences of HBoV DNA from these 12 samples were exactly identical to the those of HBoV stored in GeneBank (accession numbers DQ000495 and DQ000496). Two cases with HBoV infection were found to be co-infected with RSV. Ten of the 12 HBoV-positive samples were collected during the period from winter to spring (1 in November, 4 in December, 2 in January and 3 in April), the other two HBoV-positive samples were collected during the period from summer to autumn (1 in May and the other in July). Seven of the 12 HBoV DNA-positive patients had fever, 5 of them had high fever. Significantly more patients with HBoV infection had fever as compared to patients with RSV infection. All the HBoV positive patients showed abnormal findings on chest X ray such as interstitial infiltrates, lung infiltration and hyperinflation. Abnormal findings on chest X ray were found in higher proportion of HBoV positive patients as compared with RSV positive patients. And other manifestations such as wheezing, cough and respiratory distress had no significant difference between HBoV and RSV infected patients.</p><p><b>CONCLUSIONS</b>This study further demonstrated that HBoV probably is a common pathogen of lower respiratory infection in children and might particularly be associated with persistent wheezing.</p>

Role of Foxp3 expression and CD4+CD25+ regulatory T cells on the pathogenesis of childhood asthma / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the impact of Foxp3 expression and CD(4)(+)CD(25)(+) regulatory T cells on pathogenesis of childhood asthma.</p><p><b>METHODS</b>Totally 15 patients with acute asthma exacerbation, 15 children with asthma remission and 10 children who were hospitalized for skeleton deformity without atopic disorders or history of allergic diseases or respiratory infections within a month as controls were recruited in this study from Sep. 2004 to Mar. 2005. The percentage of CD(4)(+)CD(25)(+) T cells were detected by 2-color flow cytometry. The levels of interleukin (IL)-4, IL-10, interferon (IFN)-gamma, transforming growth factor (TGF)-beta in plasma and supernatant were assayed by ELISA. Both the asthmatic children and the control children were selected to induce sputum by hypertonic saline. Sputum was processed for detecting the expression of Foxp3-mRNA. The expression of Foxp3-mRNA in both sputum and PBMC was detected by semi-quantitative RT-PCR with beta-actin as internal control.</p><p><b>RESULTS</b>The percentage of CD(4)(+)CD(25)(+) regulatory T cells in exacerbation and remission asthmatic children was significantly lower than that of the control children both prestimulation [(10.1 +/- 2.1)% vs. (15.5 +/- 2.7)%, (11.7 +/- 2.5)% vs. (15.5 +/- 2.7)%, P < 0.05] and poststimulation with PHA [(12.4 +/- 2.3)% vs. (26.9 +/- 3.8)%, (17.3 +/- 3.2)% vs. (26.9 +/- 3.8)%, P < 0.05]. The percentage of CD(4)(+)CD(25)(+) regulatory T cells was significantly higher after PHA stimulation in normal children [(15.5 +/- 2.7)% vs. (26.9 +/- 3.8)%, P < 0.01]. The expression of Foxp3-mRNA (Foxp3/beta-actin) in asthmatic children was significantly lower than that in the control children in both PBMC and induced sputum. The expression of Foxp3-mRNA in PBMC was significantly higher after PHA stimulation in the control children (0.77 +/- 0.22 vs. 1.07 +/- 0.21, P < 0.05). However, there was no significant difference in Foxp3-mRNA expression in asthmatic children pre and post PHA stimulation. A significant positive correlation between the Foxp3-mRNA expression and the percentage of CD(4)(+)CD(25)(+) regulatory T cells was detected. The levels of IFN-gamma and TGF-beta were significantly lower in asthmatic children than those in the control children, and the levels of IFN-gamma and TGF-beta correlated positively with Foxp3-mRNA expression and the percentage of CD(4)(+)CD(25)(+) regulatory T cells. The level of IL-4 both in plasma and supernatant was higher in asthmatic children. The levels of IL-10 was higher only in exacerbation than in control children, the levels of IL-4 and IL-10 had no correlation with Foxp3-mRNA expression and the percentage of CD(4)(+)CD(25)(+) regulatory T cells.</p><p><b>CONCLUSION</b>Insufficient secretion of TGF-beta, decreased Foxp3 expression, insufficient number of CD(4)(+)CD(25)(+) regulatory T cells and the defective ability of converting CD(4)(+)CD(25)(-) T cells to CD(4)(+)CD(25)(+) regulatory T cells might play an important role in pathogenesis of asthma.</p>