Objective To evaluate the application of fractional exhaled nitric oxide (FeNO) in the reducing treatment of bronchial asthma.Methods From October 2015 to September 2016,60 asthmatic patients with FeNO＞25 ppb were randomized into FeNO group and control group with 30 cases in each group.Patients in both groups were treated with combined inhaled corticosteroids and long-acting beta 2 agonist (ICS/LABA) starting with low doses;the dosage was adjusted according to the symptom control alone in control group,while in FeNO group the dosage was adjusted according to the symptom control and FeNO level.After 1 year-follow up,the Asthma Control Test (ACT) scores,Asthma Life Questionnaire (mini AQLQ)scores,pulmonary function,FeNO levels,blood eosinophil counts,total IgE,hierarchical control level,cumulative corticosteroid use and cumulative months of leukotriene receptor antagonists (LTRA) use were compared before and after treatment within group,and between two groups.Stratified analysis was carried out in the patients complicated with allergic rhinitis.Results After treatment,ACT scores,mini AQLQ scores and FEV1/pred (％) were significantly higher than those before treatmentin both groups (t=10.755,10.189,8.632 and 13.311,8.102,12.456,respectively,all P＜0.05),while the FeNO,EOS and total IgE levels were significantly lower than those before treatment (t=8.005,3.313,3.924 and 8.967,3.885,3.270,respectively,all P＜0.05),and the numbers of patients with good control were significantly increased (Z=-5.035 and-4.976 respectively,P＜0.05).Compared with control group,FeNO level was lower,mini AQLQ scores of symptom scores and emotional scores were higher and the average numbers of asthma attacks per patient per year were less after treatment in FeNO group (t=2.912,4.214,4.589,U=2.154,all P＜0.05).However,there was no significant difference in cumulative corticosteroid use and cumulative months of LTRA use between two groups (U=564.000 t=1.921 and 0.165,respectively,P＞0.05).For patients complicated with allergic rhinitis,the numbers of acute asthma attack were increased and the cumulative dosage of systemic corticosteroid use was higher in control group than those in FeNO group (both P＜0.05).Conclusion The reducing treatment strategy based on FeNO level and symptom control is of clinical value for patients with bronchial asthma,especially for those complicated with allergic rhinitis.

Panic disorder (PD) is an acute paroxysmal anxiety disorder with poorly understood pathophysiology. The dorsal periaqueductal gray (dPAG) is involved in the genesis of PD. However, the downstream neurofunctional changes of the dPAG during panic attacks have yet to be evaluated in vivo. In this study, optogenetic stimulation to the dPAG was performed to induce panic-like behaviors, and in vivo positron emission tomography (PET) imaging with F-flurodeoxyglucose (F-FDG) was conducted to evaluate neurofunctional changes before and after the optogenetic stimulation. Compared with the baseline, post-optogenetic stimulation PET imaging demonstrated that the glucose metabolism significantly increased (P < 0.001) in dPAG, the cuneiform nucleus, the cerebellar lobule, the cingulate cortex, the alveus of the hippocampus, the primary visual cortex, the septohypothalamic nucleus, and the retrosplenial granular cortex but significantly decreased (P < 0.001) in the basal ganglia, the frontal cortex, the forceps minor corpus callosum, the primary somatosensory cortex, the primary motor cortex, the secondary visual cortex, and the dorsal lateral geniculate nucleus. Taken together, these data indicated that in vivo PET imaging can successfully detect downstream neurofunctional changes involved in the panic attacks after optogenetic stimulation to the dPAG.

Objective: To investigate the effects of p38 mitogen-activated protein kinases (p38 MAPK) inhibitor (SB203580) on airway inflammation in a mouse model of asthma. Methods: Forty-eight female BALB/c mice were randomly divided into four groups (n=12): control group, asthma group, dexamethasone group (2 mg/kg) and SB203580 group (5 mg/kg). Within 24 hours after the last ovalbumin (OVA) challenge, airway responsiveness was measured by lung resistance (RL) and dynamic compliance (Cdyn). Bronchoalveolar lavage fluid (BALF) was collected for counting total cells, eosinophils, lymphocytes, neutrophils and macrophages. IgE and OVA-specific IgE in serum and IL-4, IL-5, IL-13 and IFN-γ in BALF were detected by ELISA. Lung tissues were stained with hematoxylin and eosin (HE) and alcian blue-periodic acid-Schiff (AB-PAS) to observe histopathological changes. Expression of p38 MAPK and phosphorylated p38 (p-p38) MAPK was detected by immunohistochemical staining and Western blot, respectively. Results: (1) The mice in the asthma group showed typical symptoms of acute asthma after inhaling aerosolized OVA, while the symptoms were alleviated in those treated with dexamethasone or SB203580. (2) When challenged with the methacholine at the doses of 0.050 mg/kg, 0.100 mg/kg and 0.200 mg/kg, asthmatic mice treated with dexamethasone or SB203580 showed significantly decreased RL and increased Cdyn as compared with those in the asthma group (all P<0.05). (3) The concentrations of total IgE and OVA-specific IgE in serum in both dexamethasone and SB203580 groups were lower than those in the asthma group (all P<0.05). (4) Compared with the asthma group, the numbers of the total cells, eosinophil, lymphocytes and neutrophils in BALF were decreased in dexamethasone and SB203580 groups (all P<0.05). (5) Compared with the asthma group, the dexamethasone and SB203580 groups showed lower levels of IL-4, IL-5 and IL-13, but higher levels of IFN-γ in BALF (all P<0.05). (6) Dexamethasone or SB203580 significantly decreased the hyperemia and edema in airway mucosa, reduced the infiltration of inflammatory cells in the peribronchial areas and alleviated the tracheal epithelium goblet cell metaplasia in asthmatic mice. (7) Treatment with dexamethasone or SB203580 inhibited OVA-induced phosphorylation of p38 MAPK in asthmatic mice as revealed by immunohistochemical staining (both P<0.05). No significant difference in the expression of p38 MAPK was observed among the four groups (all P>0.05). (8) Expression of p-p38 MAPK at protein level in both dexamethasone and SB203580 groups was lower than that in asthma group (both P<0.05). Conclusion SB203580 regulated the Th1/Th2 balance through inhibiting the activation of p38 MAPK signaling pathway to alleviate OVA-induced airway inflammation.

In view of the characteristics of the computerized system,the key points in the quality assurance (QA) of the computerized system was discussed and summarized combined with the requirements of the GLP laboratory in Europe and America.The validation of computerized system,the control during the use of computerized system,period maintenance and safety protection of computerized system,archives of electronic data was discussed,expecting to provide reference for the management of computerized system in Chinese GLP laboratory which is generally not high currently.The experiences were obtained as follow:Through repeated inspection and review,the problem was found and set as the risk point;a targeted QA inspection plan was made focusing on the risk-based inspection and the QA inspection plan was timely adjusted according to the problems,which ensures the pertinence and validity of the QA inspection.

Objective To investigate the effects of 4.1N expression in lung cancer A549 cell line on cell proliferation, invasion and migration. Methods A549 cells were cultured in vitro and transfected with lipofectamine 2000 mediation. Three groups were employed: transfection with pEGFP-4.1N plasmid, pEGFP vector plasmid, and blank control, respectively. The mRNA and protein expression differences of 4.1N was examined by semi-quantitative RT-PCR and Western blot in every group after 48 h. The proliferation capability was determined by MTT assay. Invasion capability was evaluated by scratches, adhesion experiments and Transwell chamber model. Results After the transfection, the expression of 4.1N mRNA and protein in pEGFP-4.1N plasmid transfection group was significantly enhanced (P<0.05). The proliferation capability of A549 cells descended extremely (P<0.05). The migration and invasion capability of A549 cells in vitro decreased substantially (P<0.05). Conclusions Transfected with 4.1N gene can significantly increases the expression levels of 4.1N mRNA and protein in A549 cells which are highly metastatic in human. Cell behavior in vitro studies showed that 4.1N gene can inhibit the proliferation, adhesion, invasion and migration of A549 cells, which plays an important role in the metastasis of lung cancer and it may become a molecular marker for metastasis of lung cancer.

To analyze the differentially expressed proteins which interacted with NF-kappaB in the uterine lower segment smooth muscle tissues under different status of labor onset, and to provide a new foundation on the mechanisms for labor onset.
 Methods: NF-κB P65 protein expression in smooth muscle tissues from the term non-labor group, natural term labor group and drug-induced term labor group was analyzed by Western blot. Co-immunoprecipitation and SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) were performed to detect the proteins interacting with NF-κB p65 in the NF-κB p65 complexes. The components of the complex were identified by LC-ESI-MS/MS (liquid chromatography-tandem electrospray mass spectrometry) and database analysis. The identified differentially expressed proteins were confirmed by Western blot.
 Results: Positive expression of NF-κB was detected in all of the three groups. 10 differentially expressed proteins were identified by LC-ESI-MS/MS in human lower segment myometrium tissues in the term non-labor group and natural term labor group, mean while, 5 differentially expressed proteins were identified in the term non-labor group and the drug-induced labor group. 3 differential expression proteins were detected in all of the 3 groups, including Heat shock 70, Annexin A6 and Desmin, which were verified by Western blot. These proteins were mainly involved in chaperone, signal transduction, cell structure, and energy metabolism process, respectively.
 Conclusion: NF-κB expressed in uterine smooth muscle cells is involved in the process of initiation and regulation of labor onset through a number of proteins relevant to signal transduction, cell structure and energy metabolism.
Blotting, Western ; Electrophoresis, Polyacrylamide Gel ; Energy Metabolism ; genetics ; Female ; Humans ; Immunoprecipitation ; Labor, Obstetric ; genetics ; Molecular Chaperones ; genetics ; Myocytes, Smooth Muscle ; Myometrium ; physiology ; NF-kappa B ; genetics ; physiology ; Pregnancy ; Protein Interaction Mapping ; Proteomics ; Signal Transduction ; genetics ; Tandem Mass Spectrometry ; Transcription Factor RelA

Objective To establish a method for the determination of quetiapine fumarate in human serum by RP‐HPLC and apply it into clinical .Methods Extracting with ethyl ether after serum‐drug was alkalized ,and then determined by RP‐HPLC .The determination was performed on Zorbax Eclipse XDB‐C18 column with mobile phase consisted of methanol‐water (70∶30 ,containing 0 .5% triethylamine and 0 .4% glacial acetic acid) at the flow rate of 0 .6 ml/min .The detection wave‐length was set at 254 nm ,and the column temperature was 35 ℃ .The method would be applied into analysis of clinical medica‐tion .Results Quetiapine fumarate and the impurities could be completely separated ,and the linear range of quetiapine fumar‐ate were 50‐1 000 ng/ml(r=0 .999 5) .The recovery of the method was 98 .2%‐100 .1% and the recovery of extracting was 75 .2%‐84 .6% .RSD of intra‐day was within 0 .8%‐3 .7% and RSD of inter‐day was within 1 .4%‐5 .1% .The limit of quantita‐tion for quetiapine fumarate was 2 .1 ng/ml .This method had been applied into clinical pharmacy and achieved a good effects . Conclusions The method is simple ,accurate ,reproducible ,and sensitive for determination of quetiapine fumarate in human se‐rum .It has important significance on instructing the rational use of clinical medicine and discovering the unreasonable drug combination .

Objective To investigate the drug resistance and risk factors of hospital-acquired pneumonia (HAP) induced by imipenem-resistant Acinetobacter baumannii.Methods Clinical data on 114 patients with Acinetobacter baumannii-related HAPs admitted in Wujiang First People' s Hospital in Suzhou during January 2013 and December 2014 were retrospectively analyzed.According to the results of drug sensitivity test,patients were divided into imipenem-resistant group and non imipenem-resistant group.Drug resistance to 20 commonly used antibiotics was observed in two groups,and multivariate Logistic regression analysis was performed to identify the risk factors of imipenem-resistant Acinetobacter baumannii infection.Results Among 114 strains ofAcinetobacter baumannii,66 strains (57.89％) were imipenem-resistant and 48 strains (42.11％) were non-imipenem-resistant.The resistance rates to β-lactams,quinolones and aminoglycosides were significantly higher in imipenem-resistant group than those in non-imipenem-resistant group (P ＜ 0.01),and no tigecycline-resistant strain was found in both groups.Univariate analysis showed that acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score ≥ 15,plasma level of albumin ≤ 25 g/L,intensive care unit (ICU) stay,indwelling gastric tube,deep venous catheterization,establishment of artificial airway,mechanical ventilation time ≥ 7 d,use of broad-spectrum antibiotics ≥ 14 d and combined use of antibiotics were risk factors of imipenem-resistant Acinetobacter baumannii related HAP (x2 =13.06,6.86,25.40,15.09,17.87,21.46,17.94,6.91 and 10.10,P ＜0.01).Multivariate Logistic regression analysis revealed that establishment of artificial airway [OR =72.014,95％ confidetial interval (CI):19.566-265.061,P ＜ 0.01],and use of broad-spectrum antibiotics ≥ 14 d (OR =3.892,95％ CI:1.092-13.879,P ＜ 0.05) were independent risk factors of imipenem-resistant Acinetobacter baumannii related HAP.Conclusion Imipenem-resistant Acinetobacter baumannii strains are highly resistant to most antibiotics.Strict control of invasive procedures and long-term combined use of antibiotics may reduce the occurrence of imipenem-resistant Acinetobacter baumannii related HAPs.

Objective To explore drug resistance and distribution of multidrug-resistant(MDR)Mycobacterium tuberculosis (M.tuberculosis)in a county-level hospital,so as to strengthen the prevention and control of health-care-associated infection with M.tuberculosis .Methods Specimens with positive sputum smear were performed M. tuberculosis culture and drug resistance testing,and distribution of MDR tuberculosis patients in the departments before isolation were investigated retrospectively.Results Of 488 patients with tuberculosis,254 were positive for sputum smear,122 M.tuberculosis strains were isolated from positive sputum smear patients,120 isolates were per-formed drug susceptibility testing,results revealed that 86 isolates were drug-resistant strains,46 of which were monodrug-resistant,40 were MDR.Of MDR strains,16 were all resistant to isoniazide,rifampicin,streptomycin, and ethambutol.The percentage of monodrug-resistance,MDR,pandrug resistance was 9.43%,8.20%,and 3.28% respectively.Medical imaging department,ultrasound department,and respiratory disease department were the main units of M.tuberculosis exposure.Conclusion The percentage of MDR M.tuberculosis is high among M. tuberculosis ,surveillance should be intensified,so as to prevent the transmission in hospital.

Objective To investigate the relationship between risk factors and recurrent respiratory tract infections( RRTI) in children. Methods A case-control study was carried out in 204 children with RRTI,com-pared with 400 children without RRTI in control group. Results Second-hand smoking,breastfeeding,malnutri-tion,zinc deficiency,pet at home,home decoration and use of glucocorticoid were associated with RRTI in chil-dren. But the association between breastfeeding and RRTI was only found in children less than 5 years old. The second hand smoking was associated with RRTI only among boys,rather than girls. Home decoration,zinc defi-ciency,malnutrition and breastfeeding were associated with RRTI only among girls,but not among boys. Conclu-sion Recurrent respiratory tract infections are associated with multiple factors. Different risk factors have differ-ent affections on RRTI on gender.