Preliminary study on high throughput screening small molecules targeting Gram-negative bacilli outer membrane protein BamA / 中华检验医学杂志

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.

Huge pyogenic liver abscess (PLA) in an elderly patient with diabetes following the pancreaticoduodenectomy / 中华内分泌外科杂志

We described an elderly female with type 2 diabetes referred to our hospital with fever,nausea and upper abdominal pain.The patient had got duodenal tumor and received the pancreaticoduodenectomy (PD) 12 years ago.The laboratory examinations revealed white blood cells (WBC) increasing and severe hypocalcemia.Abdominal computed tomography (CT) revealed a huge gas-forming pyogenic liver abscess (PLA) in left lobe of the liver.The patient got cured after correction of calcium metabolism disorders,treatment with antibiotic and receiving percutaneous tube drainage.We concluded that we should remain on high alert of those patients with DM and the history of cancer,when he or she gets fever of unknown origin and abdominal tenderness.PLA should be considered.

Evaluation on the capability of CHROMagar orientation medium combined with simple biochemical tests for identificaction of common oxidase-negtive gram-negative bacilli / 中华微生物学和免疫学杂志

Objective To evaluate the practicability of CHROMagar orientation medium combined with simple biochemical tests for identification of common oxidase-negtive gram-negative bacilli.Methods The CHROMagar orientation medium was used together with biochemical tests including indole test , ornithine decarboxylase test and lysine decarboxylase test for identification of common oxidase -negtive gram-negative bacilli.The sensitivity, specificity, likelihood ratio, Youden index and Kappa value of the diagnostic assays were evaluated .McNemar test was performed to evaluate facticity, accuracy and cost of the method in com-parison with the Vitek-2 system as reference method .Results The identification of oxidase-negtive gram-negative bacilli from 318 bacterial strains showed that the sensitivities and specificities of CHROMagar orien-tation mediumm in combination with simple biochemical tests to Serratia marcescens, Stenotrophomonas mal-tophilia and Acinetobacter baumannii reached 100%, and for Escherichia coli, Enterobacter aerogenes and Klebsiella pneumoiae were above 90%.The specificities for identification of Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii and Proteus mirabilis were all above 90%, but the sensitivities were around 75%-90%.Kappa values of the assays were above 0.85, howerer, which was only 0.5947 for Citrobacter freundii.McNemar test showed that all P values were above 0.05, and cost of the assays was reduced by 90%.Conclusion CHROMagar orientation medium in combination with simple biochemical tests is a cost-effective assay for identification of common oxidase-negtive gram-negative bacilli .

Screening early gastric carcinoma and precancerous lesions with narrowband endoscopic imaging / 中国医师杂志

Objective To observe the characteristic of precancerous lesions and early gastric carcinoma with narrow belt imaging technology. Methods The 74 patients were enrolled in this study. The same case was used as self-control. The operation was made in pain-less under anesthesia. When the mirror was advanced to the duodenal descending segment, an ordinary microscope mode was used and the mirror was back to Mallory, the lesions found were recorded, the image was zoomed in with low-fold and observed (1.4,1.6,1.8 times). Suspicious lesions were collected and biopsies were made. Results Chronic gastritis could be commonly found in type A and AB. Mild in-testinalization and mild atypical hyperplasia could be commonly found in mixed type holding type C, type BC and AB. Moderate atypical hy-perplasia could be found in type CD and AC, and heavy atypical hyperplasia in type CD and D. Early gastric cancers (superficial depressed) were seen in type BC and irregular thick type A. Advanced gastric cancers were in type CD, D and C. Helicobacter pylori infection were common in type A and B. Protruded type, sunken type were not easily missed with common endoscopic and NBI. But "for ordinary focus of infection, it was easily missed with common endoscopic, while less with NBI. Conclusion NBI is a simple and safe method, which can be used to find precancerous lesions and early gastric cancer lesions more easily. It will enlaance the diagnosis rate of precancerous lesions and early gastric cancer as positive rate of biopsy was markedly improved.