Objective To evaluate the performance of modified Hodge test on the detection of carbapenemases among Enterobacteriaceae with decreased susceptibility to carbapenems. Methods Fortynine Enterobacteriaceae isolates with decreased susceptibility to carbapenems ( MIC of imipenem, meropenem or ertapenem was ≥ 2 μg/ml ) were collected from 16 teaching hospitals from 2004 to 2008. MICs of imipenem, meropenem and etapenem were determined by agar dilution method. Carbapenemases were detected by modified Hodge test. Carbepenemase-causing positive results and AmpCs-causing positive results were differentiated by phenyl boronic acid and oxacillin. Beta-lactamases encoding genes including blaNDM-1were detected by PCR and sequencing. Results Thirty-six of 49 isolates were non-susceptible to imipenem (MIC >4 μg/ml), 31 were non-susceptible to meropenem (MIC > 4 μg/ml) and 47 were non-susceptible to ertapenem (MIC > 2 μg/ml). Twenty-three isolates showed positive modified Hodge test result, including 9 weak-positive results and 14 strong-positive results. Through PCR detection and sequencing, 2 out of 9 isolates showing weak-positive results carried blaKPC-2 and other 7 did not carry any carbapenemase genes but AmpCs/ESBLs genes. Among the 14 isolates showing strong-positive results, 4 carried blaKPC-2, 8 carried blaIMP-4 and 2 caried blaIMP-8. All 26 isolates with negative modified Hodge test result didn't carry any carbapenemase genes. No isolate carried blaNDM-1. Carbapenemases genes PCR detection was regarded as a gold standard, and the sensitivity, specificity, positive predictive value and negative predictive value of modified hodge test was 100%, 79%, 70% and 100% on the detection of carbapenemases among Enterobacteriaceae with decreased susceptibility to carbapenems. Conclusions Modified Hodge test revealed great sensitivity but showed a few false positive results. True and false positive results can be effectively differentiated by phynel boronic acid and oxacillin.

Objective To investigate distribution and antimicrobial resistance among nosocomial pathogens from 13 teaching hospitals in China in 2009. Methods Non-repetitive pathogens from nosocomial BSI, HAP and IAI were collected and sent to the central lab for MIC determination by agar dilution method.WHONET5.6 software was used to analyze the data. Results A total of 2 502 clinical isolates were collected. The top three pathogens of BSI were Escherichia coli [27. 1% (285/1 052 )] , coagulase-negutive staphylococcus [12. 6% ( 133/1 052)] and Klebsiella pneumoniae [10. 8% ( 114/1 052)]. The top three pathogens of HAP were Acinetobacter baumannii [28. 8% (226/785)], Pseudomonas aeruginosa [16. 1% (126/785)] and Klebsiella pneumoniae [14.6% (115/785 )] . The top three pathogens of IAI were Escherichia coli[31.0% ( 206/665 )], Klebsiella pneumonia [11.3% ( 75/665 )] and Enterococcus faecium [10. 8% (72/665)]. Against Escherichia coil and Klebsiella spp. , the antimicrobial agents with higher than 80% susceptibility rate included imipenem and meropenem (98. 1%-100% ), tigecycline (95.3%-100% ), piperacillin-tazobactam ( 88.6% -97. 1% ) and amikacin ( 88. 3% -92. 5% ). Against Enterobacter spp. , Citrobacter spp. and Serratia spp. , the susceptibility rates of tigecycline were 93.5% -100% whereas the value of imipenem and meropenem were 92.9% -100%. Other antimicrobial agents with high activity included amikacin ( 85.2% -96. 7% ), pipcracillin-tazobactam ( 82.4% -96.4% ), cefepime ( 79. 6% -96. 7% ) and cefoperazonc-sulbactam (78. 7%-90. 0% ). Polymyxin B showed the highest susceptibility rateagainst Pseudomonas aeruginosa ( 100% ), followed by amikacin ( 81.9% ) and piperacillin-tazobactam (80.1% ). Polymyxin B also showed the highest susceptibility rate against Acinetobacter baumannii (98. 8% ), followed by tigecycline (90. 1% ) and minocycline (72. 0% ). The incidence of carbapenemresistant Acinetobacter baumannii was 60. 1%. The MRSA rate was 60. 2% and the MRSCoN rate was 84. 2%. All Staphylococcus strains were susceptible to tigecycline, vancomycin, teicoplanin and linezolid except for one isolate of Staphylococcus haemolysis with intermediate to teicoplanin. Two Enterococcus faecalis isolates which were intermediate to linezolid and one Enterococcus faecium isolate which was resistant to vancomycin and teicoplanin was found in this surveillance, while the MICs of tigecycline against these three isolates were 0. 032-0. 064 μg/ml. Conclusions Tigecycline, carbapenems, piperacillin-tazobactam,amikacin and cefepime remain relatively high activity against nosocomial Enterobacteriaceae. Pseudomonas aeruginosa exhibite high susceptibility to polymyxin B, while Acinetobacter baumanni shows high susceptibility to polymyxin B and tigecycline. Tigecycline, vancomycin, teicoplanin and linezolid remain high activity against nosocomial gram-positive cocci.

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.