Protective effects of Salvianic acid A against multiple-organ ischemia-reperfusion injury: a review.

Ischemia-reperfusion (I/R) injury refers to a new injury caused by reperfusion after the restoration of ischemic tissue or organ blood supply. Salvianic acid A (danshensu) is a primary active ingredient extracted from Salvia miltiorrhiza. It has a protective function against I/R injury in the cardiovascular system, brain, liver, kidney, gastrointestinal tract, and other organs. This article reviews evidence of the protective effects of Salvianic acid A and its potential mechanisms of action in organ I/R injury protection. The aim of this review is to investigate the role of Salvianic acid A in the treatment of I/R injury, providing a reference resource that could facilitate subsequent studies.

Recent Advances in Anti-Atherosclerosis and Potential Therapeutic Targets for Nanomaterial-Derived Drug Formulations.

Atherosclerosis, the leading cause of death worldwide, is responsible for ≈17.6 million deaths globally each year. Most therapeutic drugs for atherosclerosis have low delivery efficiencies and significant side effects, and this has hampered the development of effective treatment strategies. Diversified nanomaterials can improve drug properties and are considered to be key for the development of improved treatment strategies for atherosclerosis. The pathological mechanisms underlying atherosclerosis is summarized, rationally designed nanoparticle-mediated therapeutic strategies, and potential future therapeutic targets for nanodelivery. The content of this study reveals the potential and challenges of nanoparticle use for the treatment of atherosclerosis and highlights new effective design ideas.

Discovery of novel danshensu derivatives bearing pyrazolone moiety as potential anti-ischemic stroke agents with antioxidant activity.

Neuroprotective agents with attenuation of oxidative stress by directly scavenging ROS and indirectly through Keap1-Nrf2 signal pathway activation may be a promising cerebral ischemic stroke therapeutic strategy. In this study, a series of novel danshensu derivatives bearing pyrazolone moieties with dual antioxidant effects were synthesized for the treatment of ischemic stroke. Most compounds exhibited considerable DPPH free radical scavenging ability and neuroprotective activity against H2O2-induced oxidative injury in PC12 neuronal cells, without cytotoxicity. Among these target compounds, Del03 displayed the strongest dose-dependent neuroprotective activity in vitro, directly downregulated intracellular ROS levels, and improved the oxidative stress parameters MDA, SOD, and LDH. Del03 also promoted Nrf2 translocation to the nucleus, subsequently increasing the expression of the Nrf2 downstream target HO-1. Molecular docking analysis revealed that Del03 could anchor to the key site of Keap1. Del03 possessed the ability to penetrate blood-brain barrier and displayed good ability on pharmacokinetic properties in rats Del03 possessed good BBB penetration efficiency, suitable pharmacokinetic properties in vivo. Del03 reduced cerebral infarction volume and promoted neurological function in a middle cerebral artery occlusion (MCAO) mouse model at a dose of 20 mg/kg by intravenous injection. The characteristics of Del03 detailed in this study demonstrate its potential as a therapeutic agent in the treatment of ischemic stroke.

Design, synthesis, and biological evaluation of novel NO-releasing 4-chromanone derivatives as potential vasodilator agents.

The nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway is an effective mechanism involved in the treatment of hypertension. In our search for potential antihypertensive agents, a series of novel NO-donor derivatives of the 4-chromanone skeleton were designed and synthesized by coupling furoxans or nitrooxy NO-donor moieties. All derivatives showed enhanced nitric oxide releasing capacity and vasodilator activity with EC50 values ranging from 0.0215 µM to 1.46 µM, obviously superior to those of precursor 3. These biological evaluations indicated that all compounds displayed an important vasorelaxant effect, and several compounds (9c, 14b, 14c, 14d) presented good vasodilator activity, with 14c being the best. Furthermore, molecular modeling studies revealed that compound 14c occupied the pocket well with the phosphodiesterase 5 domain in a favorable conformation. In conclusion, we observed that these novel compounds can act as structural templates for the design and subsequent development of new vasodilators and antihypertensive drugs.

Recent Advances in Targeted Nanotherapies for Ischemic Stroke.

Ischemic stroke (IS) is a severe neurological disease caused by the narrowing or occlusion of cerebral blood vessels and is known for high morbidity, disability, and mortality rates. Clinically available treatments of stroke include the surgical removal of the thrombus and thrombolysis with tissue fibrinogen activator. Pharmaceuticals targeting IS are uncommon, and the development of new therapies is hindered by the low bioavailability and stability of many drugs. Nanomedicine provides new opportunities for the development of novel neuroprotective and thrombolytic strategies for the diagnosis and treatment of IS. Numerous nanotherapeutics with different physicochemical properties are currently being developed to facilitate drug delivery by accumulation and controlled release and to improve their restorative properties. In this review, we discuss recent developments in IS therapy, including assisted drug delivery and targeting, neuroprotection through regulation of the neuron environment, and sources of endogenous biomimetic specific targeting. In addition, we discuss the role and neurotoxic effects of inorganic metal nanoparticles in IS therapy. This study provides a theoretical basis for the utilization of nano-IS therapies that may contribute to the development of new strategies for a range of embolic diseases.

Curcumin Scaffold as a Multifunctional Tool for Alzheimer's Disease Research.

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, which is caused by multi-factors and characterized by two histopathological hallmarks: amyloid-ß (Aß) plaques and neurofibrillary tangles of Tau proteins. Thus, researchers have been devoting tremendous efforts to developing and designing new molecules for the early diagnosis of AD and curative purposes. Curcumin and its scaffold have fluorescent and photochemical properties. Mounting evidence showed that curcumin scaffold had neuroprotective effects on AD such as anti-amyloidogenic, anti-inflammatory, anti-oxidative and metal chelating. In this review, we summarized different curcumin derivatives and analyzed the in vitro and in vivo results in order to exhibit the applications in AD diagnosis, therapeutic monitoring and therapy. The analysis results showed that, although curcumin and its analogues have some disadvantages such as short wavelength and low bioavailability, these shortcomings can be conquered by modifying the structures. Curcumin scaffold still has the potential to be a multifunctional tool for AD research, including AD diagnosis and therapy.

Characteristic diversity and antimicrobial resistance of Salmonella from gastroenteritis.

Salmonella is a leading cause of foodborne disease worldwide and may cause to gastroenteritis. The aim of this study was to determine the prevalence, serotypes, virulence genes, molecular subtyping, and antibiotic resistance phenotype of Salmonella from gastroenteritis in Hubei, China. Of 500 patients stools samples collected from January 2015 to January 2016, 52 (10.40%) samples were contaminated by Salmonella. The results showed that most of the isolates were positive for eight virulence genes that appear on pathogenicity islands, prophages, plasmid, and fimbrial. A total of twelve serotypes were found. Antimicrobial susceptibility results indicated that most strains were resistant to ampicillin (57.69%), kanamycin (53.85%), and tetracycline (40.38%). There were 33 STs on MLST types, and were grouped into two clusters. Thus, our findings provided insights into the dissemination of antibiotic resistant strains, genetic diversity, and improved our knowledge of microbiological risk assessment in Salmonella from gastroenteritis.

[Effects of vasoactive intestinal peptide on airway inflammation and Th17/Treg balance in asthmatic mice].

OBJECTIVE: To investigate the effects of vasoactive intestinal peptide (VIP) on the airway inflammation and its regulatory effect on Th17/Treg imbalance in asthmatic mice. METHODS: A total of 30 BALB/c mice were equally and randomly divided into three groups: control, asthma, and VIP. An acute asthmatic mouse model was established by sensitization and challenge with ovalbumin (OVA). The control group received normal saline instead of OVA. Before the challenge with OVA, the VIP group was administered VIP (20 µg/mL) by aerosol inhalation for 30 minutes. The bronchoalveolar lavage fluid (BALF) and the lung tissue were collected from mice. The pathological changes in the lung tissue were observed by hematoxylin and eosin staining. The levels of Th17/Treg-related cytokines in BALF were measured by enzyme-linked immunosorbent assay. The expression of retinoid-related orphan receptor gamma t (RORγt) and forkhead box P3 (Foxp3) were measured by real-time fluorescence quantitative PCR and immunohistochemistry. RESULTS: The histopathological results showed that the VIP group had milder symptoms of airway inflammation than the asthma group. The level of IL-17 in BALF in the asthma group was significantly higher than that in the control group and the VIP group (P<0.01), but the level of IL-17 in the control group was significantly lower than that in the VIP group (P<0.01). The level of IL-10 in BALF in the asthma group was significantly lower than that in the control group and the VIP group (P<0.01, but the level of IL-10 in the VIP group was significantly higher than that in the control group (P<0.01). The asthma group showed significantly higher expression levels of RORγt mRNA and protein in the lung tissue and significantly lower expression levels of Foxp3 mRNA and protein than the control group (P<0.01). The VIP group had significantly lower expression levels of RORγt mRNA and protein in the lung tissue and significantly higher expression levels of Foxp3 mRNA and protein than the asthma group (P<0.05). CONCLUSIONS: The Th17/Treg imbalance may be closely related to the airway inflammation in asthmatic mice. VIP can improve airway inflammation by regulating the Th17/Treg imbalance in asthmatic mice.

[Clinical analysis of hemolytic-uremic syndrome associated with Streptococcus pneumoniae serotype 3 infection in a child].

OBJECTIVE: To study the clinical characteristics of Streptococcus pneumonia-associated hemolytic uremic syndrome (SP-HUS) in children. METHOD: Clinical and laboratory data of a pediatric case of SP-HUS were retrospectively analyzed and the key points of diagnosis and therapy were reviewed. RESULT: An 18-month old girl was admitted with chief complaint of fever and cough for 5 days combined with mild labored breath. Breath sound was found weakened in right lung with lower lobe dullness on percussion. Laboratory tests revealed: WBC 3.7×10(9)/L, Hb 83 g/L, PLT 11×10(9)/L, C-reactive protein (CRP) > 180 mg/L. Morphological study of the RBCs showed marked anisocytosis and schistocytosis. Urinalysis showed 42.66 RBCs per high-power field, occult blood (+++), proteinura (++++). Streptococcus pneumoniae was isolated from blood, pleural fluid and sputum. Serotyping with simplified chessboard system was 3. The direct Coombs test was positive. Serum complement levels (C3 and C4) were depressed at 0.699 g/L, 0.064 g/L, respectively. Chest X-ray showed pleural effusion and infection of the right hemothorax. The computerized tomographic scan of the chest revealed pneumatoceles in the right lower lobe. The diagnosis on admission we considered was SP-HUS. Intravenous antibiotic therapy (vancomycin + cefoperazone/sulbactam) was administered. The renal replacement theraphy was administered to maintain electrolyte and fluid balances and adequate nutrition. Transfusions of washed red blood cells were administered to correct the anemia. One month after admission the patient was good with recovery. Liver and renal function recovered and the pneumonia was resolving, anemia and platelets were corrected. The direct Coombs test turned to be negative. Serum complement levels (C3 and C4) were normal. After 3-month follow-up, no clinical anomalies were detected. CONCLUSION: SP-HUS should be suspected when the following occurs in the context of pneumococcal infections: microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure and a positive Coombs test result. Serotype 3 of SP was associated with HUS.

[Epidemiological characteristics of Mycoplasma pneumoniae pneumonia in children].

OBJECTIVE: To study the epidemiological characteristics of Mycoplasma pneumoniae pneumonia (MPP) in children, and to provide a basis for diagnosis and treatment. METHODS: The serum level of Mycoplasma pneumoniae antibody IgM (MP-IgM) was measured by enzyme-linked immunosorbent assay for 3156 hospitalized children with confirmed community acquired pneumonia from February 2011 to January 2012. The antigens of seven respiratory viruses were detected in the nasopharyngeal secretions of children with MPP. RESULTS: MP-IgM was detected in 427 of the 3156 patients, with a positive rate of 13.53%. The infection rate in female patients was significantly higher than in male patients (16.30% vs 11.70%; P<0.01). The MP-IgM detection rates were 3.6%, 12.5%, 19.2%, and 24.4% in children aged under 1 year, 1-3 years, 3-6 years and 6-14 years respectively (P<0.01), and the total MP-IgM detection rate in children aged under 3 years was significantly lower than in children over 3 years (P<0.01). The MP-IgM detection rate varied with the seasons and was significantly higher in summer and autumn than in winter and spring (19.18% vs 9.61%; P<0.01). Of the 427 MP-IgM-positive children, 60 (14.1%) were infected with respiratory viruses, and the highest proportion of which was respiratory syncytial virus. CONCLUSIONS: MPP is sporadic throughout the whole year, with a higher incidence in summer and autumn. MPP occurs mostly in preschool and school-age children, and there is mixed infection of MP and respiratory viruses.

[Viral etiology of acute respiratory infection in children from Wenzhou between 2007 and 2008].

OBJECTIVE: To study the viral etiology of acute respiratory infection (ARI)in children from Wenzhou, Zhejiang between 2007 and 2008. METHODS: The nasopharyngeal aspirate samples were obtained from 5 097 hospitalized children with ARI. Seven common respiratory viruses, including respiratory syncytial virus (RSV), influenza virus A and B, parainfluenza viruses 1, 2 and 3 and adenovirus, were detected using direct immunofluorescence. RESULTS: Viral agents were identified in 2 209 cases (43.3%).Of the 2 209, RSV was the most frequent (78.1%), followed by parainfluenza 3 (12.4%), influenza virus A (3.0%), adenovirus (2.8%), parainfluenza 1 (1.7%), influenza B (0.5%) and parainfluenza 2 (0.3%). The infants at ages of <3 months and <6 months had higher detection rate of viruses (53.6% and 49.2%, respectively). A highest detection rate of viruses was found in winter. CONCLUSIONS: RSV is the leading pathogen of ARI in children from Wenzhou, Zhejiang between 2007 and 2008. The children at age of less than 6 months are susceptible to respiratory viruses. The viral activity peaks in winter.

[Clinical analysis of 234 cases with congenital malformations of respiratory system].

OBJECTIVE: To explore clinical characteristics, radiographic findings and diagnostic methods of patients with congenital malformations of respiratory system for enhancing the diagnosis of congenital malformations of respiratory system in children. METHOD: Totally 234 patients with congenital malformations of respiratory system were chosen from the inpatient department of Yuying Children's Hospital Affiliated to Wenzhou Medical College from July 2003 to June 2008. The clinical presentations and radiographic findings of these children were analyzed. RESULT: Of the 234 patients with congenital malformations of respiratory system, the age at diagnosis was between the first day and 14 years of age, mean age was 1.12 years. The main symptoms were persistent laryngeal stridor, recurrent wheezing, recurrent respiratory tract infections and dyspnea. Through the use of chest X-ray, spiral CT 3D reconstructions, fiberoptic bronchoscopy and other laboratory techniques, 213 cases were diagnosed as having single malformation and 21 cases were found to have multiple malformations. Of the 213 cases with single malformation, 97 cases had laryngeal malformation (congenital laryngeal stridor in 90 cases, congenital laryngeal webs in 5 cases and congenital laryngeal cyst in 2 cases), 35 cases had tracheal-bronchial malformation (congenital tracheobronchial stenosis in 17 cases, congenital abnormal bronchial origin in 7 cases, tracheobronchomalacia in 10 cases and tracheoesophageal fistula in 1 case), 43 cases had lung malformation (pulmonary sequestration in 5 cases, congenital lung cysts in 22 cases, congenital lobar emphysema in 1 case, agenesis of lung and hypoplasia of lung in 8 cases and congenital cystic adenomatoid malformation in 7 cases), 38 cases had diaphragm malformation, 28 cases had congenital tracheal-bronchial stenosis as confirmed by spiral CT 3D reconstructions and fiberoptic bronchoscopy. Ten cases with congenital abnormal bronchial origin were diagnosed with spiral CT 3D reconstructions. Laryngeal stridor and tracheobronchomalacia were diagnosed by fiberoptic laryngoscope and fiberoptic bronchoscopy. The accuracy rates of preoperative diagnosis through clinical and radiographic examinations of 37 cases with lung malformation and 36 cases with diaphragm malformation were 83.78% and 91.67%. CONCLUSION: Congenital malformations of respiratory system are a group of diseases that are important for pediatric respiratory clinicians. Congenital malformations of respiratory system should be considered in children with persistent laryngeal stridor, recurrent wheezing, recurrent respiratory tract infections and dyspnea. The radiographic examination and respiratory endoscope play important roles in the diagnosis of congenital malformations of respiratory system.

[The role of external signal regulated kinase and transforming growth factor beta(1) in asthma airway remodeling and regulation of glucocorticoids].

OBJECTIVE: To study role of external signal regulated kinase (ERK) and transforming growth factor beta(1) (TGF-beta1) in asthma airway remodeling and to explore the regulation of glucocorticoids on ERK, TGF-beta1, and airway remodeling. METHODS: Thirty SD rats were randomly divided into 3 equal groups: control group; asthma group, undergoing intra-peritoneal injection of ovalbumin (OVA) on days 1 and 8 and inhalation of OVA every other day for 8 weeks since day 15 to establish chronic asthma models; dexamethasone (DM) intervention group, undergoing intra-peritoneal injection of DM 30 min before every inhalation instigation; and control group, receiving normal saline instead of DM. 1 - 2 hours after the last instigation the left lungs were taken out. The total bronchial wall thickness (Wat) and smooth muscle thickness (Wam) were measured by image analysis system. Phosphorylated ERK (P-ERK) was detected by immunohistochemistry. 1 - 2 hours after the last instigation blood samples were collected from the femoral artery. The concentration of transforming growth factor (TGF)-beta1 in the serum was measured by sandwich ELISA. Rat airway epithelial cells were cultured, stimulated with platelet-derived growth factor-BB (PDGF-BB, 1, 10, 25, or 50 microg/L), U0126 (specific inhibitor of phosphorylation of ERK), or budesonide (BUD). Western blotting was used to detect the P-ERK level. The level of TGF-beta1 in the cell culture supernatant was detected by sandwich ELISA. RESULTS: The Wat and Wam of the asthma group was significantly higher than those of the control group (both P < 0.01), and the Wat and Wam of the DM group were both significantly lower than those of the asthma group (both P < 0.01). The mean optical density of P-ERK and concentration of TGF-beta1 in the serum of the asthma group were 31.1 +/- 2.2 and 28.1 +/- 7.4 microg/L respectively, both significantly higher than those of the control group (12.8 +/- 2.4 and 13.6 +/- 2.7 microg/L respectively, both P < 0.01), and the mean optical density of P-ERK and concentration of TGF-beta1 in the serum of the DM group were 18.7 +/- 3.1 and 15.0 +/- 3.2 microg/L respectively, both significantly lower than those asthma group (both P < 0.01). In the PDGF-BB (25 microg/L) stimulated cells marked phosphorylation of ERK occurred 15 min later, the level of P-ERK remained high up to 8 hour later, and the maximal activation occurred at the period of 2 h - 4 h later, 6.5 +/- 0.4 times that of the control value (P < 0.01). The phosphorylation levels of ERK depended on the concentration of PDGF-BB and the maximal level phosphorylation was detected with the concentration of PDGF-BB of 50 microg/L, which was 4.1 +/- 0.3 times that of the control value (P < 0.01). U0126 and BUD inhibited the phosphorylation of ERK in the cells stimulated by PDGF-BB of the concentration of 25 microg/L. there was no difference in the level of TGF-beta1 in the cell culture supernatant among different groups. CONCLUSION: Phosphorylation of ERK and TGF-beta1 have an important role in asthma airway remodeling; PDGF-BB does not induce normal rat airway epithelial cells to product or release TGF-beta1 by phosphorylation of ERK. Glucocorticoids can inhibit phosphorylation of ERK.

[Role of external signal regulated kinase signal transduction pathway in airway remodeling of rats with asthma and regulation by glucocorticoids].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Effect of Radix Astragali on signal transducer and activator of transcription activator-4 and its mRNA expression in a rat model of asthma].

OBJECTIVE: To study the effect of Radix Astragali (RA) on the expression of signal transducer and activator of transcription-4 (STAT4) and its mRNA in the bronchus of a rat model of asthma. METHODS: Forty male SD rats were randomly divided into four groups: the control group, asthma group, high dosage of RA group and low dosage of RA group. In the experiment, the rat model of asthma was established by the ovalbumin (OVA) challenge methods. The lung tissue was gainedfrom the left lung, bronchoalveolar lavage fluid (BALF) was gained from the right lung. The eosinophils (EOS) numbers and differentiated cell numbers in BALF were counted by different counting fluids; the protein expressions of STAT4 were detected by immunohistochemistry; the mRNA expressions of STAT4 were detected by in situ hybridization. RESULTS: (1) In the BALF of the asthma group, the absolute numbers of EOS, the ratios of EOS to the total cell numbers (EOS%) of asthma group [(35.81 +/- 7.30) x 10(7)/L, (8. 20 +/- 1.75)%] were all significantly higher than those of the control group [(1.51 +/- 1.04) x 10(7)/L, (0.70 +/- 0.48)%] (P < 0.01); the total cell numbers in BALF, the absolute numbers of EOS and EOS% of RA groups [(14.89 +/- 2.35) x 10(7)/L, (4.70 +/- 0.82)%; (10.98 +/- 1.81) x 10(7)/L, (3.56 +/- 0.53)%] were all significantly lower than those of asthma group (P < 0.01); (2) The concentration of IL-4 in BALF of asthma group (25.70 +/- 7.36) was significantly higher than that of the control group (8.55 +/- 2.97) (P < 0.01); the concentration of IL-4 of BALF of RA groups [(31.89 +/- 5.46), (35.26 +/- 6.03)] was significantly lower than that of asthma group (P < 0.01); the concentration of IL-12 of BALF of asthma group (16.10 +/- 3.38) was significantly lower than that of the control group (42.33 +/- 9.66) (P < 0.01); the concentration of IL-12 of BALF of the RA groups [(31.89 +/- 5.46), (35.26 +/- 6.03)] was significantly higher than that of the asthma group (P < 0.01); (3) Immunohistochemistry and in situ hybridization showed that the protein content of STAT4 and the STAT4 mRNA expression around the bronchus of asthma group [(0.096 +/- 0.012), (0.098 +/- 0.011)] were lower than those of the control group [(0.216 +/- 0.034), (0.228 +/- 0.032)], while those of RA groups [(0.176 +/- 0.012), (0.185 +/- 0.023); (0.183 +/- 0.011), (0.201 +/- 0.019)] were all significantly higher than that of the asthma group (P < 0.01), the airway smooth muscle cells, the pulmonary arterial smooth muscle cells and endothelial cells were the chief expression cells; (4) the STAT4 and the STAT4mRNA expression around the bronchus had positive correlation with the concentration of IL-12 in BALF while had negative correlation with the concentration of IL-4, absolute numbers of EOS in BALF. CONCLUSIONS: RA has an inhibitory effect on airway inflammation cells infiltration such as EOS, it raises the STAT4 protein and its mRNA expression in the airway smooth muscle cells, the pulmonary arterial smooth muscle cells and endothelial cells, and the key mechanism may be that the IL-12 composition is increased.

[Detection of etiologic agents and antibiotic resistance in children with acute lower respiratory tract infection in Wenzhou City].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[The role of alveolar macrophages in airway remodeling in asthmatic rats].

OBJECTIVE: To study the role of alveolar macrophages (AM) in the processes of airway remodeling in asthmatic rats. METHODS: Forty-eight young male Sprague-Dawley rats (Grade II) were divided randomly into a control group (A group), a 3 day asthma group (B group), a 14 day asthma group (C group) and a 30 day asthma group (D group). The rats were sensitized and challenged by ovalbumin to establish the asthmatic model. AM were purified from bronchoalveolar lavage. The content of tumor necrosis factor-alpha (TNF-alpha) in AM was measured by enzyme-linked immunosorbent assay, prostaglandin E2 (PGE2) by radioimmunoassay, matrix metalloproteinase-9 mRNA (MMP-9 mRNA) and tissue inhibitor of metalloproteinase-1 mRNA (TIMP-1 mRNA) by hybridization in situ. The total bronchial wall area (WAt) and the smooth muscle area (WAm) were measured by image analysis system. The WAt and the WAm were quantified per unit length of basement membrane (Pbm). RESULTS: The bronchial wall thickness and the smooth muscle thickness of D group [(85 +/- 9) microm2/microm, (28.6 +/- 4.9) microm2/microm] were significantly higher than those of A group [(67 +/- 10) microm2/microm, (16.8 +/- 2.4) microm2/microm, t = 2.938, 3.227, all P < 0.01]. The contents of TNF-alpha and PGE2 in D group [(0.68 +/- 0.25) microg/L, (0.122 +/- 0.030) microg/L] were significantly higher than those in A group [(0.37 +/- 0.09) microg/L, (0.079 +/- 0.018) microg/L, t = 2.683, 3.016, all P < 0.01]. When A group was compared with B group [(0.74 +/- 0.29) microg/L, (0.120 +/- 0.028) microg/L] and C group [(0.71 +/- 0.23) microg/L, (0.117 +/- 0.028) microg/L], there was no significant difference (t = 1.624, 0.472, all P > 0.05) and (t = 0.935, 0.533, all P > 0.05). The contents (light density) of MMP-9 mRNA and TIMP-1 mRNA in D group (0.346 +/- 0.033, 0.361 +/- 0.040) were significantly higher than C group (0.279 +/- 0.015, 0.259 +/- 0.015, t = 2.574, 2.716, all P < 0.01), and so did D group and B group (0.183 +/- 0.025, 0.136 +/- 0.014, t = 2.913, 3.017, all P < 0.01), D group and A group (0.104 +/- 0.007, 0.109 +/- 0.008, t = 3.632, 3.487, all P < 0.01). There were significant correlations between the contents of MMP-9 mRNA and WAt (r = 0.693, P < 0.01), between MMP-9 mRNA and WAm (r = 0.738, P < 0.01), between TIMP-1 mRNA and WAt (r = 0.823, P < 0.01), and between TIMP-1 mRNA and WAm (r = 0.876, P < 0.01). CONCLUSION: AM and AM-derived cytokines are associated with airway remodeling in asthmatic rats.