Objective To conduct an in vitro study of the growth of Pseudomonas aeruginosa,Staphylococcus aureus and Acin- etobacter spp.,and evaluate their response to various concentrations of tumor necrosis factor(TNF)-?,interleukin (IL)-1?, and IL-6.Methods To monitor the growth of bacteria incubated with the cytokines TNF?,IL-1?and IL-6 that were added to RPMI 1640 medium in various concentrations (10,50.100,500 pg,1 and 10 ng) at 2,4 to 6,8 and 16-18 h.The bacterial concentration was estimated when the mixtures of cytokines and specific neutralizing monoclonal antibodies (MoAbs) were in- cubated.Results We found that all three bacterial species showed concentration-dependent growth enhancement when incubated with one or more tested cytokines.Blockade by specific neutralizing cytokine significantly inhibited cytokine-induced growth. When compared with control,the 6 h growth response was maximal with IL-1?for Staphylococcus aureus and Acinetobacter spp.,and with IL-6 for Pseudomonas aeruginosa.Conclusions In this study we provide additional evidence for a newly de- scribed mechanism for bacterial proliferation in the presence of exaggerated and protracted inflammation.The effect that cyto kine-induced growth enhancement inhibited by specific neutralizing cytokine MoAbs may be useful for antimicrobial therapy.

BACKGROUNDPneumonia has become the predominant cause of death for the elderly. It is critical to determine the status of oropharyngeal pathogen colonization in the elderly when treating pneumonia. To explore the efficient approaches to treat age-related pneumonia, we determined the status of oropharyngeal pathogenic colonization in the elderly community.

METHODSThroat swab cultures were used to isolate oropharyngeal pathogens from 706 residents older than 65 years living in the community of Shenyang City. Characteristics of bacterial strains were sorted and identified using drug sensitivity tests.

RESULTSResults of bacterial identification showed that 265 out of 706 samples were positive, thereby exhibiting a 37.5% positive rate. There were 290 bacterial strains isolated from the elderly community in total, of which 248 strains were gram-negative bacilli (GNB) and 42 strains were gram-positive cocci (GNC), accounting for 85.5% and 14.5%, respectively. There were 158 Klebsiella pneumoniae strains, representing 54.4% of the all GNB.

CONCLUSIONThe rate of oropharyngeal GNB colonization in the elderly community increases and Klebsiella pneumoniae is the most common strain.

Aged ; Aged, 80 and over ; Bacteria ; classification ; drug effects ; isolation & purification ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Oropharynx ; microbiology

OBJECTIVETo study the effects of carbamazepine on serum metabolic profiles in rats using nuclear magnetic resonance (NMR) spectroscopy.

METHODSTwenty-four healthy male Wistar rats were randomized into 4 groups (n=6) for daily intragastric administration of high-, medium- or low-dose carbamazepine or distilled water (control) for 7 days. Blood samples were collected from the abdominal aortic under anesthesia after the treatment to determine serum carbamazepine concentration using high-performance liquid chromatography. ¹H nuclear magnetic resonance (¹H NMR) spectra were acquired for pattern recognition analysis. Histopathological changes of the renal and liver tissues of the rats were also examined.

RESULTSSteady-state blood concentration of carbamazepine in high-, medium- and low-dose groups were 14.64 ± 1.41, 8.54 ± 1.19, and 4.56 ± 0.64 µg/ml, respectively. Slight liver swelling was found in high-dose group, but none of the groups showed renal pathologies. Compared with the control group, the high-dose carbamazepine group showed lowered serum concentrations of 1,3-diaminopropane, deoxycorticosterone, 7-dehydrocholesterol, betaine, beta-alanine, L-cystathionine, 4-methyl-2-oxovaleric acid, and creatine with increased levels of saccharides, lactate, succinic acid, acetyl phosphate, and adipic acid. Principal component analysis revealed significant differences of the metabolites between carbamazepine-treated groups and the control group. The metabolic profiles showed no differences in the kinds of metabolites although the concentrations of the metabolites varied between the carbamazepine groups.

CONCLUSIONSCarbamazepine significantly affects metabolism in normal rats. This finding provides evidence for clinical drug monitoring and drug safety of carbamazepine. NMR technique has important values for pharmacodynamic and toxicological evaluation of drugs.

Animals ; Carbamazepine ; blood ; Kidney ; pathology ; Liver ; pathology ; Magnetic Resonance Spectroscopy ; Male ; Metabolomics ; Principal Component Analysis ; Rats ; Rats, Wistar

Objective To investigate pathogenic bacteria distribution and drug resistance of the bacteria isolated from Chinese young and mid-age patients (14-65 years).Methods Collect and monitor the isolates from young and mid-aged patients (14-65 years) in 557 mem-ber hospitals of Grade three between January 1 and December 31 in 2012.Disk diffusion and automatic machine method are applied to anti-biotic resistance test.The data were analyzed and processed with software WHONET 5.6.Results There are 383443 isolates from young and mid-aged patients in 557 hospitals of Grade three.Gram-negative bac-teria is account for 69.33%, the major strains are Escherichia coli of 78915, Klebsiella pneumoniae of 48698, Pseudomonas aeruginosa of 36239 and Acinetobacter baumannii of 27858, respectively;Gram-posi-tive bacteria is account for 30.67%, Staphylococcus aureus of 33328, Staphylococcus epidermidis of 18818, Enterococcus faecalis of 13114 and Enterococcus faecium of 8517 are the top four.It was not found that Staphylococcus spp.were resistant to vancomycin and linezolid, and there were teicoplanin resistant oagulase -negative Staphylococcus account for 3.4%, Vancomycin resistant Enterococcus faecium 3.2%, Vancomycin resistant Enterococcus faecalis 1.5%.Frequen-cy of extended spectrum beta lactamase ( ESBLs) in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis are separately 58.4%, 33.6%and 24.9%, which increase resistance to imipenem as 2.8%, 6.5%and 4.1%contrast to last year.Rate of carbapenem resistant to Acinetobacter baumannii was about 50%, only polymixin B has better ac-tivity 96.7%.Haemophilus were isolated less among the young and mid-aged patients, but were sensitive to most an-tibiotic.Conclusion Antibiotic resistant rate of young and mid-aged patients in China are more serious, especially increase of ESBLs producing Enterobacteriaceae, multi drug resistant non-fermenting bacteria and vancomycin resistant Enterococcus.Meanwhile, the resistant trend is various by time, so that it is important and tedious work to monitor the antibiotic resistance.

In ischemic stroke, increased level of neuronal complex of nitric oxide synthase (nNOS)-postsynaptic density protein-95 (PSD-95) plays an important role in neuronal damage. We aimed to establish a screening model to identify compounds capable of uncoupling nNOS interaction with PSD-95. In this model, human embryonic kidney-293T (HEK-293T) cells were transfected with either pCDH-Flag-nNOS or pcDNA3.1-PSD-95 plasmid to obtain the protein of Flag-nNOS or PSD-95. Incubating Flag-nNOS with PSD-95 causes formation of the nNOS-PSD-95 complex. ZL006, a known uncoupler of nNOS-PSD-95 interaction, can disturb the interaction between Flag-nNOS and PSD-95, serving as a positive control. The method coupling antibodies to magnetic beads with glutaraldehyde was used to decrease the cost and increase the efficiency. To establish that our model is suitable for selecting nNOS-PSD-95 uncouplers, we evaluated the ability of IC87201, another reported uncoupler of nNOS-PSD-95 interaction, and structural analogs of ZL006. IC87201 and one structure analog of ZL006 showed uncoupling effect, supporting that our model can be used to select different types uncoupler blocking nNOS-PSD-95 interaction.

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.