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Objective:High-throughput screening to obtain small molecular compounds against Gram-negative bacilli by targeting BamA outer membrane protein.Methods:The sybyl-X2.1 software was used to perform high-throughput virtual screening of small molecular compounds in Chemdiv compound library based on the molecular docking. The top 150 hits by high-throughput screening were re-screened through in vitro biological experiments. The top 4 small molecules with obvious antibacterial activity were selected for in-depth molecular docking analysis, and the small molecule 8308-0401 with the highest docking score was selected for further experiments. The antibacterial effect of 8308-0401 combined with rifampicin was tested by checkerboard assay. Finally, the affinity between 8308-0401 and BamA was tested by plasma surface resonance assay. Results:The docking score of the top 150 hits calculated by high-throughput virtual screening had a mean value of 5.63. In vitro biological experiments showed that small molecules 8308-0401, 8365-1335, C066-2507 and L582-0346 exhibited strong antibacterial activity. Among those molecules, 8308-0401 showed the highest molecular docking score, and synergistic antibacterial activity against both types of strains and clinical isolates when combined with rifampicin. 8308-0401 has a strong affinity to BamA with binding a constant of 182 μmol/L. Conclusion:The small molecule 8308-0401 exerts antibacterial activity against Gram negative bacilli by targeting the outer membrane protein BamA.
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Objective@#To analyze the clinical characteristics of patients with asthma-chronic obstructive pulmonary overlap syndrome (ACOS).@*Methods@#From January 2015 to December 2017, 40 patients with ACOS, 40 patients with asthma and 40 patients with chronic obstructive pulmonary disease(COPD) in Zhoushan Hospital were collected.The general information, laboratory test indicators, lung function test indicators and FEV1 mutation after bronchodilator test were compared among the three groups.@*Results@#There were statistically significant differences in age[(45.36±5.27) vs. (54.45±4.69) vs. (67.57±5.18), F=9.334, P=0.004], the proportion of smoking patients (92.50% vs. 75.00% vs. 60.00%, χ2=11.550, P=0.003), and the proportion of family history of asthma (7.50% vs. 20.00% vs. 30.00%, χ2=6.562, P=0.038) among the patients with ACOS, asthma and COPD.The percentage of eosinophils in peripheral blood [(8.46±0.94)% vs. (6.13±0.78)% vs. (3.75±0.45)%, F=11.626, P=0.001] and the serum IgE levels [(353.41±45.74)IU/mL vs. (252.65±30.45)IU/mL vs. (155.26±22.77)IU/mL, F=7.605, P=0.001] were decreased in turn, the differences were statistically significant.The FEV1/FVC% and FEV1% pred in the ACOS group were lower than those in the asthma group [(54.26±6.86)% vs. (72.43±8.52)%, t=10.506, P=0.001 and (50.35±6.22)% vs. (62.60±7.52)%, t=7.939, P=0.001], however, there were no significant differences compared with the COPD group[(54.26±6.86)% vs. (53.88±7.25)%, t=0.241, P=0.810 and (50.35±6.22)% vs. (50.56±6.46)%, t=0.148, P=0.883]. The proportion of small airway dysfunction in the ACOS group was higher than that in the asthma group (82.50% vs. 57.50%, χ2=5.952, P=0.015), however, there was no statistically significant difference compared with COPD group(82.50% vs. 85.00%, χ2=0.092, P=0.762). The RV/TLC% in the ACOS group was higher than that in the asthma group [(46.71±5.31)% vs. (32.46±4.52)%, t=12.924, P=0.001], however, there was no statistically significant difference compared with the COPD group [(46.71±5.31)% vs. (46.92±5.75)%, t=0.170, P=0.866]. The DLCO% in the ACOS group was lower than that in the asthma group [(64.37±4.66)% vs (82.62±4.53)%, t=17.760, P=0.001], but higher than that of the COPD group [(64.37±4.66)% vs. (51.25±4.35)%, t=13.017, P=0.001]. After bronchodilator test, the FEV1 mutation rate of the ACOS group was higher than that of the COPD group [(20.86±2.05)% vs. (6.52±0.55)%, t=42.730, P=0.001], but there was no statistically significant difference compared with the asthma group [(20.86±2.05)% vs. (21.13±2.14)%, t=0.576, P=0.566].@*Conclusion@#Compared with asthma patients, the age of ACOS patients is older, the percentage of peripheral blood eosinophils and the level of serum IgE are lower, the pulmonary ventilation function is lower, the airway dysfunction is more significant, the residual volume is more significant, the lung diffuse function is lower, acidic granulocyte airway inflammation is mild.But compared with patients with COPD, the age of ACOS patients is younger, the percentage of peripheral blood eosinophils and serum IgE levels are higher, the lung diffuse function is higher, and acidic granulocyte airway inflammation is heavier.
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Objective To analyze the clinical characteristics of patients with asthma-chronic obstructive pulmonary overlap syndrome (ACOS).Methods From January 2015 to December 2017,40 patients with ACOS,40 patients with asthma and 40 patients with chronic obstructive pulmonary disease (COPD) in Zhoushan Hospital were collected.The general information,laboratory test indicators,lung function test indicators and FEV1 mutation after bronchodilator test were compared among the three groups.Results There were statistically significant differences in age[(45.36 ±5.27) vs.(54.45 ±4.69) vs.(67.57 ±5.18),F=9.334,P=0.004],the proportion of smoking patients (92.50％ vs.75.00％ vs.60.00％,x2 =11.550,P =0.003),and the proportion of family history of asthma (7.50％ vs.20.00％ vs.30.00％,x2 =6.562,P =0.038) among the patients with ACOS,asthma and COPD.The percentage of eosinophils in peripheral blood [(8.46 ± 0.94) ％ vs.(6.13 ± 0.78) ％ vs.(3.75 ±0.45) ％,F =11.626,P =0.001] and the serum IgE levels [(353.41 ± 45.74) IU/mL vs.(252.65 ± 30.45) IU/ mL vs.(155.26 ± 22.77) IU/mL,F =7.605,P =0.001] were decreased in turn,the differences were statistically significant.The FEV1/FVC％ and FEV1％ pred in the ACOS group were lower than those in the asthma group [(54.26 ± 6.86) ％ vs.(72.43 ± 8.52) ％,t =10.506,P =0.001 and (50.35 ± 6.22) ％ vs.(62.60 ± 7.52) ％,t =7.939,P =0.001],however,there were no significant differences compared with the COPD group [(54.26 ± 6.86)％ vs.(53.88 ±7.25)％,t =0.241,P =0.810 and (50.35 ±6.22)％ vs.(50.56 ±6.46)％,t =0.148,P =0.883].The proportion of small airway dysfunction in the ACOS group was higher than that in the asthma group (82.50％ vs.57.50％,x2 =5.952,P =0.015),however,there was no statistically significant difference compared with COPD group(82.50％ vs.85.00％,x2 =0.092,P =0.762).The RV/TLC％ in the ACOS group was higher than that in the asthma group [(46.71 ± 5.31) ％ vs.(32.46 ± 4.52) ％,t =12.924,P =0.001],however,there was no statistically significant difference compared with the COPD group [(46.71 ± 5.31)％ vs.(46.92 ± 5.75)％,t =0.170,P =0.866].The DLCO％ in the ACOS group was lower than that in the asthma group [(64.37 ±4.66) ％ vs (82.62 ± 4.53) ％,t =17.760,P =0.001],but higher than that of the COPD group [(64.37 ± 4.66) ％ vs.(51.25 ± 4.35) ％,t =13.017,P =0.001].After bronchodilator test,the FEV1 mutation rate of the ACOS group was higher than that of the COPD group [(20.86 ± 2.05) ％ vs.(6.52 ± 0.55) ％,t =42.730,P =0.001],but there was no statistically significant difference compared with the asthma group [(20.86 ± 2.05)％ vs.(21.13 ±2.14)％,t =0.576,P=0.566].Conclusion Compared with asthma patients,the age of ACOS patients is older,the percentage of peripheral blood eosinophils and the level of serum IgE are lower,the pulmonary ventilation function is lower,the airway dysfunction is more significant,the residual volume is more significant,the lung diffuse function is lower,acidic granulocyte airway inflammation is mild.But compared with patients with COPD,the age of ACOS patients is younger,the percentage of peripheral blood eosinophils and serum IgE levels are higher,the lung diffuse function is higher,and acidic granulocyte airway inflammation is heavier.
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Objective Investigated the clinical features and risk factors of pulmonary metastasis in children with papillary thyroid carcinoma aiming to provide guide for clinical work.Methods Collected the informations of 40 patients with under the age of 14,who underwent surgery in the Thyroid surgery of the First Affiliated Hospital of ZhengZhou University and confirmed for the papillary thyroid carcinoma by the postoperative pathology.At the same time,excluded studies with history of head and neck malignancy or lyphoma or secondary thyroid cancer,papillary thyroid carcinoma with hyperthyroidism and cases of imcomplete informations.The age of the 40 patients was 3 to 14 years old,12 were boy and 28 were girl.The largest tumor diameter was 7.5 cm,and the smallest was 0.3 cm.Tumor lesions were solitary in 22 cases and multiple lesions were in 18 cases.There were 33 cases of cervical lymph node metastases and 7 cases of no cervical lymph nodes.There were 10 cases of pulmonary metastasis and 30 cases of non-pulmonary metastasis.This research adopted chi-square test and Logistic regression statistical analysis of related risk factors and clinical features,including patients' age,gender,tumor diameter,number of lesions,surgical methods,neck lymph node metastasis,and pulmonary metastasis.Results The positive rate of plumonary metastsis in children with papillary thyroid carcinoma was 25％ (10/40),statistical analysis found that the positive rate of children with lung metastasis (x2 =8.620,P =0.003),tumor diameter over 2 cm (x2 =5.763,P =5.763) and the difference was statistically significant higher.Logistic regression analysis showed that the number of risk factors was multifocal papillary thyroid carcinoma in children lung metastasis (OR =13.058,P =0.028).Conclusions Higher lung metastasis is a clinical feature of thyroid papillary carcinoma in children.The risk of lung metastasis was significantly higher for children with thyroid papillary carcinoma who had multiple lessions.