Role of external signal regulated kinase signal transduction pathway in airway remodeling of rats with asthma and regulation by glucocorticoids / 中华儿科杂志

<p><b>OBJECTIVE</b>Airway remodeling in asthma makes treatment of asthma very difficult, and study of its pathogenesis becomes very important. The present study aimed to explore the role of external signal regulated kinase (ERK) signal transduction pathway in airway remodeling in rats asthma model and regulatory effects of glucocorticoids on ERK signal transduction pathway and airway remodeling.</p><p><b>METHODS</b>Totally 80 male Sprague-Dawlay rats (6-8 weeks old, weighing about 120 g) were randomly divided into control groups (30 rats), asthma groups (30 rats) and treated groups [including a group intervened with dexamethasone (DM group) and budesonide (BUD group), each had 10 rats]. The rats were sensitized for inducing asthma by intraperitoneal injection of ovalbumin and Al (OH)(3) and were repeatedly exposed to aerosolized ovalbumin for 4, 8, or 12 weeks [respectively called 4, 8 or 12 wk asthma group (A4, A8 or A12 group), each had 10 rats]; and correspondingly control rats were intraperitoneally injected with 0.9% NaCl, then were repeatedly exposed to 0.9% NaCl for 4, 8, or 12 weeks [respectively called 4, 8 or 12 wk control group (C4, C8 or C12 group), each had 10 rats]; DM group rats were repeatedly exposed to aerosolized ovalbumin for 8 wk, and BUD group rats for 12 wk. Total bronchial wall thickness (Wat) and smooth muscle thickness (Wam) were measured by an image analysis system. Concentrations of PDGF-AB in serum were measured by sandwich ELISA. Phospho-ERK (P-ERK) and c-Fos were detected by immunohistochemical technique; lung tissue extracts were analyzed for phosphorylation of ERK by Western blotting.</p><p><b>RESULTS</b>Wat and Wam in all asthma groups were significantly higher than those in corresponding control groups (P < 0.01, respectively), those of the treated groups were significantly lower than asthma groups (P < 0.01). The concentrations of PDGF-AB in serum of asthma groups [(228 +/- 18) pg/ml, (293 +/- 77) pg/ml, (225 +/- 66) pg/ml for A4, A8, A12 groups, respectively] were all significantly higher than those of the control groups [(160 +/- 14) pg/ml, (165 +/- 29) pg/ml and (164 +/- 27) pg/ml for C4, C8, C12 group, respectively] (P < 0.01 or P < 0.05); the value of DM group [(157 +/- 46) pg/ml] was significantly lower than that of the group A8 (P < 0.01), no significant difference was found when the values of BUD group [(208 +/- 40) pg/ml] was compared with that of A12 group (P > 0.05). Mean absorbance values (by immunohistochemistry) of P-ERK and c-Fos in asthma groups were significantly higher than those in corresponding control groups (P < 0.01, respectively), DM group had a significantly lower value than group A8 (P < 0.01), BUD group had a significantly lower value than group A12 (P < 0.01); absorbance (by Western blot) of P-ERK in A4, A8, A12 group was significantly higher than that in C4 and C8 group, the value of DM group was significantly lower than that of group A8 (P < 0.01), and that of BUD group (1.8 +/- 0.2) was significantly lower than that of group A12 (P < 0.01).</p><p><b>CONCLUSION</b>Asthmatic rats have higher concentrations of PDGF-AB in serum and phosphorylation of ERK and c-Fos; glucocorticoids inhibit phosphorylation of ERK and c-Fos in asthmatic rats, and to some extent also inhibit Wat and Wam.</p>

Detection of etiologic agents and antibiotic resistance in children with acute lower respiratory tract infection in Wenzhou City / 中国当代儿科杂志

<p><b>OBJECTIVE</b>The etiology of acute lower respiratory tract infection (LRTI) in children in Wenzhou City remains poorly defined. This study investigated the etiological agents responsible for acute LRTI and patterns of the antibiotic resistant bacterial pathogens in children with acute LRTI from Wenzhou City.</p><p><b>METHODS</b>Lower respiratory tract secretions were obtained from 454 children with acute LRTI (aged 1 month to 10 years, median age 6 months) within 24 hrs after admission for bacterial culture. Meanwhile respiratory viruses were detected by the Direct immunofluorescence (DIF) assay. The K-B method was applied for the drug susceptibility test.</p><p><b>RESULTS</b>Etiological agents were identified in 297 cases out of 454 patients (65.4%. Viral pathogens were identified in 229 cases (50.4%), bacteria in 135 cases (29.7%) and mixed viral-bacterial infections in 67 cases (14.8%). The isolating rate of Respiratory syncytial virus (RSV) was the highest (180 cases, 39.6%) in all of the samples. The isolating rates of other viral pathogens were as follows: Parainfluenza virus 3 type (PIV3) (6.6%), Adenovirus (2.2%), Influenza A (0.9%) and Influenza B (0.7%). Of the 135 strains of bacterial pathogens, 19 kinds of bacterial pathogens were isolated. The predominant isolate was Klebsiella pneumoniae (K. pneumoniae) (9.9%), followed by Escherichia coli (E.coli) (4.4%), Streptococcus pneumoniae (S. pneumoniae) (4.2%) and Staphylococcus aureus (S. aureus) (4.2%). The isolating rates of K. pneumoniae and E.coli with extended-spectrum beta-lactamases strains (ESBLs) positive were 42.2% and 65.0%, respectively. The pathogens isolated of the first 5 places in children with acute LRTI under six months were RSV, K. pneumoniae, PIV3, E.coli and S. aureus in turn. RSV, PIV3, S. pneumoniae, K. pneumoniae and E.coli were found to be the pathogens of the first 5 places in children with acute LRTI between six months and three years. The resistant rates of K. pneumoniae and E.coli to ampicillin were 97.8% and 75.0%, respectively. K. pneumoniae and E.coli with positive ESBLs were resistant to cephalosporin. The resistant rates of S. pneumoniae to erythromycin and penicilin were 100% and 68.4%, respectively. The resistant rates of S. aureus to erythromycin and penicillin were 94.7% and 89.5%, respectively.</p><p><b>CONCLUSIONS</b>RSV is the most common pathogen responsible for acute LRTI in children in Wenzhou City, followed by K. pneumoniae and PIV3. The rate of antibiotic resistance of common bacteria and the isolating rate of Gram-negative bacillus with ESBLs positive are high.</p>

Expression of signal transducer and activator of transcription 6 in rat asthma model and the modulatory effect of dexamethasone / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the expression of signal transducer and activator of transcription 6 and its mRNA in rat asthma model and the modulatory effect of dexamethasone (DXM).</p><p><b>METHODS</b>Thirty male SD rats were randomly divided into three groups: the control group, asthma group and DXM group. The rats in each group were sacrificed 24 h after the last challenge. In the experiment, the rat model of asthma was established by ovalbumin (OVA) challenge method. The lung tissue was taken from the left lung, and bronchoalveolar lavage fluid (BALF) was collected from the right lung. The total cell numbers, eosinophils (EOS) count and differentiated cell counts in BALF were performed on different count fluids. The concentrations of IL-4 in serum and BALF were measured by using sandwich ELISA. The protein expressions of STAT6 were detected with immunohistochemical techniques. The mRNA expressions of STAT6 were detected with in situ hybridization.</p><p><b>RESULTS</b>(1) The total cell counts in BALF, the absolute counts of EOS, and the ratios of eosinophils to the total cell numbers (EOS%) of asthma group were all significantly higher than those of the control group (P < 0.01). The total cell counts in BALF, the absolute counts of EOS, and EOS% of DXM group were all significantly lower than those of asthma group (P < 0.01). (2) The concentrations of IL-4 in BALF and serum of asthma group [(25.7 +/- 7.4) ng/L, (34.2 +/- 10.5) ng/L] were significantly higher than those of control group [(8.6 +/- 3.0) ng/L, (12.1 +/- 2.9) ng/L] (P < 0.01). The concentrations of IL-4 in BALF and serum of DXM group were significantly lower than those of asthma group. (3) Immunohistochemistry showed that the protein content of STAT6 around the bronchus of asthma group (0.171 +/- 0.025) was significantly higher than that of the control group (0.082 +/- 0.022) (P < 0.01), while that of DXM group (0.114 +/- 0.013) was significantly lower than that of asthma group. The epithelial cells were the cells. In situ hybridization showed that the mRNA expression of STAT6 around the bronchus of asthma group (0.180 +/- 0.013) was significantly higher than that of the control group (0.091 +/- 0.012) (P < 0.01), while that of DXM group (0.114 +/- 0.010) was significantly lower than that of asthma group. (4) There was a significant correlation between the concentration of IL-4 in BALF, the content of STAT6 and STAT6 mRNA, respectively, in the epithelial cells of bronchus. There was a significant correlation between the absolute numbers of EOS and EOS% in BALF, the content of STAT6 and STAT6 mRNA, respectively, in the epithelial cells of bronchus.</p><p><b>CONCLUSIONS</b>STAT6 protein and STAT6 mRNA were found strongly expressed in rat asthma model and the epithelial cells were the chief expressing cells. Dexamethasone had an inhibitory effect on airway inflammatory cells infiltration. It significantly depressed STAT6 and mRNA expression. Which may be a key process in modulatory mechanism of asthma.</p>

Effect of macrophage inflammatory protein-1alpha and its mRNA on airway inflammation of mouse asthma model / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the effect of macrophage inflammatory protein-1alpha(MIP-1alpha) and its mRNA on airway inflammation of mouse with induced asthma.</p><p><b>METHODS</b>Seventy male BALB/C mice were randomly divided into the control group and asthma group (including 7 subgroups, 10 mice each). The control group included group A(24) (the lavaging subgroup was sacrificed 24 h after the last challenge) and group A(0) (the non-lavaging subgroup was sacrificed from 18 h to 24 h after the last challenge); asthma group included group B(3) (the lavaging subgroup was sacrificed 3 h after the last challenge), group B(8) (the lavaging subgroup was sacrificed 8 h after the last challenge), group B(24) (the lavaging subgroup was sacrificed 24 h after the last challenge), group B(36) (the lavaging subgroup was sacrificed 36 h after the last challenge) and group B(0) (the non-lavaging subgroup was sacrificed from 18 h to 24 h after the last challenge). In the experiment, the mice model of asthma was established by the ovalbumin (OVA) challenge methods. Eosinophils (EOS) numbers and differentiated cell numbers in bronchoalveolar lavage fluid (BALF) were counted; the concentrations of MIP-1alpha in serum and BALF were measured by sandwich enzyme-linked immunosorbent assay (sandwich ELISA); the protein expressions of MIP-1alpha were detected by immunohistochemical techniques; the mRNA expressions of MIP-1alpha were determined by in situ hybridization technique.</p><p><b>RESULTS</b>(1) The concentrations of MIP-1alpha in BALF and serum of group B(3) [(30.2 +/- 4.2) pg/ml, (30.8 +/- 4.6) pg/ml], group B(8) [(35.3 +/- 4.9) pg/ml, (34.9 +/- 5.1) pg/ml], group B(24) [(42.9 +/- 5.8) pg/ml, (41.7 +/- 6.3) pg/ml] and group B(36) [(37.8 +/- 4.7) pg/ml, (35.7 +/- 4.9) pg/ml] were significantly higher than those of group A(24) [(20.9 +/- 3.8) pg/ml, (22.4 +/- 4.3) pg/ml] (P < 0.01); the concentrations of MIP-1alpha in BALF and serum went up at 3 h, reached peak at 24 h, and had descended at 36 h. (2) Immunohistochemistry showed that the protein expressions of MIP-1alpha around the bronchus of group B(0) [(26.4 +/- 6.2)%] were significantly elevated as compared to those of group A(0) [(10.3 +/- 2.5)%] (P < 0.01), the epithelial cell was the chief expression cell. (3) In situ hybridization showed that the mRNA expressions of MIP-1alpha around the bronchus of group B(0) [(23.9 +/- 4.2)%] were significantly increased when compared to those of group A(0) [(8.7 +/- 1.8)%] (P < 0.01), the epithelial cell was the chief expression cell. (4) There was a significant correlation between the concentrations of MIP-1alpha and the numbers of EOS in BALF and between the concentrations of MIP-1alpha and the percentage of EOS numbers in the total cell numbers (EOS%) in BALF.</p><p><b>CONCLUSIONS</b>MIP-1alpha protein and MIP-1alpha mRNA were found strongly expressed in mouse asthma model, the epithelial cell was the chief expression cell; the kinetic characteristic of MIP-1alpha showed that its level increased at 3 h, reached peak at 24 h and declined at 36 h; MIP-1alpha and EOS gathering had a significant correlation.</p>

Diagnostic study on children's diaphragmatic fatigue / 中华儿科杂志

<p><b>OBJECTIVE</b>In the recent twenty years, the diaphragmatic contraction, relaxation functions and electric activity have been explored through electromyography (EMG) and transdiaphragmatic pressure (Pdi) determination. But these techniques required some complex and expensive instruments, so the diagnosis and treatment of children's diaphragmatic fatigue have not been well evaluated. The present study explored the diagnosis of children's diaphragmatic fatigue through measuring ribcage-abdomen motion and analyzed its asynchrony.</p><p><b>METHODS</b>Fifty-three children (male 37, female 16, and age rage from 1 months to 9 years) with respiratory rate > 30 breaths/min, heart rate > 110 beats/min, and respiratory dysfunction had asynchronized ribcage-abdomen motion showed by impedance respirograph (IRG). The authors observed whether ribcage-abdomen motion was synchronic and calculated M levels (staggered peak time/total duration of the breathing cycle). The ribcage and abdomen outputs were displayed on vertical (for rib cage) and horizontal (for abdomen) axes of X-Y instrument. In addition, the change of respiratory frequency and heart rate was observed and arterial blood-gas analysis was also performed.</p><p><b>RESULTS</b>(1) M levels in one-dimensional IRG were positively correlated with alpha angle in two-dimensional IRG (r = 0.956, P < 0.001). Asynchronized respiratory motions could be divided into three types. type I showed completely contra-directional movements of respiration, M levels for (48.1 +/- 4.4)%, an irregularly clockwise loop in the two dimensional IRG, and alpha angle for (138.3 +/- 15.0) degrees. In type II, one dimensional IRG showed displaced peak of the chest and abdomen motion curves, M levels were (16.5 +/- 4.7)%, two dimensional IRG was displaced in a counterclockwise direction, and alpha angle was (55.3 +/- 10.8) degrees. In type III, abdominal motion curve of one dimensional IRG had double peaks, M levels were 0, two dimensional IRG was presented as 8-shaped double circles, alpha angle was (41.3 +/- 3.8) degrees; (2) pH levels in the patients with type I and type II diaphragmatic fatigue were significantly lower, and PCO(2) levels were significantly higher than those with type III or in the normal subjects (P < 0.001 for all), but there was no statistically significant difference between type III and the normal subjects (P > 0.05); (3) Both of respiratory rate and heart rate in type I, type II and type III were higher than those in the normal subjects (all P < 0.001), and the differences among the three types were significant (P < 0.001 for all); (4) Both M levels and alpha angle were negatively correlated with pH levels (r = -0.514, P < 0.001 and r = -0.497, P < 0.001), while positively correlated with PCO(2) levels (r = 0.672, P < 0.001 and r = 0.625, P = 0.01).</p><p><b>CONCLUSIONS</b>(1) IRG can be reliably used to diagnose children's diaphragmatic fatigue. This technique is simple and easy to perform and non-invasive. It is therefore worthy of recommending for further clinical investigations. (2) According to the characteristics of IRG, diaphragmatic fatigue can be divided into three types. (3) The development of children's diaphragmatic fatigue has a series of characteristic changes. (4) To avoid the patients suffering from respiratory failure, it is the key time to adopt the policies of prevention and treatment when IRG shows signs of type III diaphragmatic fatigue.</p>

Eosinophils apoptosis, fas mRNA and bcl-2 mRNA expressions in asthma model of young rat and effects of achyranthes bidentata polysaccharides / 中华儿科杂志

<p><b>OBJECTIVE</b>Asthma is a chronic respiratory tract disorder characterized by airway hyperreaction (AHR), persistent airway inflammation, high serum IgE, overproduction of IL-4, IL-5 and IL-13 by allergen-specific Th2 cells. The morbidity and mortality of asthma have continued to increase despite the use of currently available therapeutic agents. The reputed effects of traditional Chinese medicines (TCMs) have led to increasing use of TCMs for treatment of asthma throughout the world. The aims of this study were to investigate in asthma model of young rat the mRNA expressions of apoptotic gene fas and bcl-2, eosinophils (EOS) apoptosis in airway, and effects of achyranthes bidentata polysaccharides (ABPS), a group of polysaccharides extracted from TCM Achyranthes bidentata blume, on treatment of asthma.</p><p><b>METHODS</b>Fifty Sprague-Dawley (SD) rats were divided into five groups, 10 rats per group. Asthma in rats was induced by intraperitioneal sensitization and challenge with nebulized ovalbumin (OVA). A pretreatment with ABPS [50 mg/(kg x d)] was done according to three different schedules: consecutively 3 days at sensitization (T1), at challenge (T2) or both of the two periods (T3). Sham-treated rats (A) and naive rats (C) served as controls. The animals were sacrificed 24 hours after the last challenge. The mRNA expression of bcl-2 and fas in eosinophils presenting in airway and the apoptosis of eosinophils in airway were assessed by using in situ hybridization with oligonucleotide probe and TUNEL methods, respectively.</p><p><b>RESULTS</b>(1) Twenty-four hours after the last antigen challenge, the mRNA expression of fas in eosinophils presenting in airway significantly decreased in group A [(43.4 +/- 10.0)%] compared with that in group C [(73.2 +/- 11.9)%] (P < 0.01). ABPS could increase the fas mRNA expression significantly in all the three groups [(59.0 +/- 8.1)%, (57.5 +/- 9.6)%, (76.2 +/- 2.7)%], compared with that in group A (P < 0.05, P < 0.05, P < 0.01, respectively). The expression of the bcl-2 mRNA in group C was (47.9 +/- 8.7)%, it was elevated to (67.4 +/- 7.3)% in group A (P < 0.01). The expression of the bcl-2 mRNA in ABPS treated T1 and T3 groups was significantly lowered [(57.7 +/- 12.7)%, (57.3 +/- 6.8)%, P < 0.05], but not in T2 group [(72.4 +/- 6.7)%]. (2) In group A, the EOS presenting in the airway increased significantly, but there were few apoptotic EOS; the percentage of apoptotic eosinophil was distinctly lower in group A than that in group C [(5.3 +/- 2.2)% vs. (15.9 +/- 2.4)%, P < 0.01]. Compared with that in group A, the eosinophil apoptosis ratio in those ABPS treated groups T1, T3 was evidently elevated [(8.7 +/- 2.9)%, (9.8 +/- 2.2)%, P < 0.05, P < 0.05], but ABPS treated at challenge (T2) could not change the eosinophil apoptosis ratio significantly (P > 0.05).</p><p><b>CONCLUSION</b>(1) In asthmatic rat, the expressions of the genes fas and bcl-2 mRNA in EOS were changed evidently and the ratio of EOS apoptotosis reduced greatly. (2) ABPS could enhance the apoptosis of EOS by upregulating the expression of the genes fas and bcl-2 mRNA.</p>

Effect of shenmai injection on diaphragmatic fatigue in children with respiratory failure / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Shenmai injection (SMI) on diaphragmatic fatigue in children with respiratory failure.</p><p><b>METHODS</b>Thirty-five cases of children respiratory failure with diaphragmatic fatigue were divided into two groups. The control group was treated with comprehensive therapy including anti-infection, oxygen inhalation and parenteral nutrition, etc. The SMI group was treated with SMI intravenously, besides the comprehensive therapy as in the control group. Taking electrical impedance respirogram (IRG) as criterion of therapeutic effect, the effective cases after 30 min medication, time for diaphragmatic fatigue disappearance, as well as arterial blood gas analysis before and after treatment were analyzed.</p><p><b>RESULTS</b>(1) In 30 min after medication, the effective cases in the SMI group (15/18) were more than that in the control group (4/17, P < 0.01); (2) Blood pH increased and PaCO2 decreased in both groups after treatment, but the decrease of PaCO2 was more significant in the SMI group (P < 0.05); (3) Time of diaphragmatic fatigue disappearance in the SMI group was shorter than that in the control group (P < 0.01).</p><p><b>CONCLUSION</b>SMI is an effective drug for treatment of diaphragmatic fatigue in children with less adverse effect, and worthwhile for spreading in clinical practice.</p>

Respiratory Function Tests of 102 Cases of Healthy Children with Impulse Oscillometry / 实用儿科临床杂志

Objective To study the respiratory function tests reference values of healthy children in China with impulse oscillometry(IOS).Methods The respiratory function tests reference values of 102 children were measured by using masterscreen IOS and analysed it.Results Impedance and airway resistance reference values decreased as age and body height increased step by step,at the same time capacitance decreased.The difference was significant while the predicted values compared to the measured data.Conclusion We shall use respiratory function tests reference values which are established by us,and the difference is significant compared with the foreign predicted(values.)