Unrestrained inflammation is harmful to tissue repair and regeneration. Immune cell membrane-camouflaged nanoparticles have been proven to show promise as inflammation targets and multitargeted inflammation controls in the treatment of severe inflammation. Prevention and early intervention of inflammation can reduce the risk of irreversible tissue damage and loss of function, but no cell membrane-camouflaged nanotechnology has been reported to achieve stage-specific treatment in these conditions. In this study, we investigated the prophylactic and therapeutic efficacy of fibroblast membrane-camouflaged nanoparticles for topical treatment of early inflammation (early pulpitis as the model) with the help of in-depth bioinformatics and molecular biology investigations in vitro and in vivo. Nanoparticles have been proven to act as sentinels to detect and competitively neutralize invasive Escherichia coli lipopolysaccharide (E. coli LPS) with resident fibroblasts to effectively inhibit the activation of intricate signaling pathways. Moreover, nanoparticles can alleviate the secretion of multiple inflammatory cytokines to achieve multitargeted anti-inflammatory effects, attenuating inflammatory conditions in the early stage. Our work verified the feasibility of fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage, which widens the potential cell types for inflammation regulation.
Escherichia coli ; Fibroblasts ; Humans ; Inflammation/drug therapy* ; Nanoparticles

Objective To investigate the correlations between the FBN1 gene mutation types and the clinical phenotype . Methods 87 probands with Marfan or Marfan-like syndromes and their family members were enrolled in this study ( total 300 cases).The clinical manifestations of each patients involving the ocular, cardiovascular system, skeletal system and other im-plicated systems were collected and evaluated .According to the clinical manifestations , these patients were divided into two groups, namely aortic dissection group and aortic root aneurysm group.Blood samples were taken from patients and DNA se-quencing was performed on each patient by the genetic aortic disease gene Panel .The detected single nucleotide variants ( SNVs)/indel were interpreted according to the ACMG guidelines, and the pathogenic variation was confirmed through Sanger sequencing.The aortic wall tissue was obtained from MFS patients who underwent surgery .The correlations between genotypes and clinical phenotypes were further explored by comparing the aortic wall tissue histological specimens of each genotype pa-tient.Results A total of 92 FBN1 mutations(31％) were detected in 300 people with Marfan syndromes or Marfan-like syn-dromes, 18 of which were undiscovered mutations.There were 49 missense mutations(53.26％), 13 splicing mutations (14.13％), 17 frameshift mutations(18.48％), and 13 nonsense mutations(14.13％).In this cohort, 24 cases had aortic dissection and 25 cases were aortic root aneurysm.Statistical analysis revealed that patients with aortic dissection mostly ap-peared in frameshift mutations(29.17％ vs.4.00％, P =0.017).However, patients with aortic root aneurysm mostly ap-peared in missense mutations(72.00％ vs.37.50％, P =0.015), and accompanied with ectopia lentis(41.67％ vs. 8.33％, P=0.008).Pathological specimens staining found that elastic fibers in the aortic wall of patients with frameshift mu-tations are sparser, and the smooth muscle cells are more deficient and more disorganized than patients with missense muta-tions.Conclusion FBN1 gene frameshift mutations result a lack of elastic fibers and disorganized smooth muscle cells in aor-tic wall and are presented more in patients with aortic dissection than aortic root aneurysm .

Objectives To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza.Methods This was a randomized,double-blind,double-dummy,placebo and positive control,multicenter clinical trial,comparing peramivir trihydrate with oseltamivir and placebo.The inclusive criteria were 15-70 years old,onset within 48 h,positive rapid influenza antigen test,and febrile(＞38℃) accompanied with at least two associated symptoms.The severe cases complicated with chronic pulmonary and cardiac diseases,malignancies,organ transplantation,hemodialysis,uncontrolled diabetes,immunocompromised status,pregnancy and coexistence of bacterium infections were excluded.All patients were randomized 2:2:1 to receive peramivir,oseltamivir and placebo respectively.The primary endpoint was the disease duration,the secondary endpoints included time to normal axillary temperature and normal living activities,viral response,and adverse effects.Results Following informed consent,133 patients were included in this study.Four patients were exclude due to missing medical records,not fitting inclusion or exclusion criteria and poor compliance.A total of 129 patients were finally analyzed,including 49 cases,54 cases and 26 cases in peramivir group,oseltamivir group and placebo group.The median disease duration were 96 (76,120)hours,105(90,124) hours,and 124 (104,172)hours in three groups respectively(P＞0.05).The time to normal axillary temperature,normal living activities and viral response were not significantly different in three groups(P＞0.05).Conclusion The value of antiviral therapy in patients with mild influenza needs to be further determined.

Objective·To analyze changes in the type distribution and drug resistance of pathogenic bacteria isolated from burn wards and to provide evidence for rational use of antibiotics, reduction of drug-resistant isolates, and hospital infection control. Methods·Isolates from burn patients were collected from January 2011 to December 2014. Statistical analysis of infection sources, type distribution, and changes in resistance rates of main pathogens during the four year period was performed. Results·A total of 2399 isolates were collected, including 1286 (53.61%) gram-negative bacilli (G-b), 1088 (45.35%) gram-positive cocci (G+c), and 25 (1.04%) fungi. The most common G-b pathogens were Pseudomonas aeruginosa (447, 34.76%) and Acinetobacter baumannii (369, 28.69%). The most common G+c pathogen and fungus were Staphylococcus aureus (489, 44.94%) and Candida albicans (8, 33.33%), respectively. In the last two years, the detection rates of S.aureus and A.baumannii were significantly lower and the detection rate of P.aeruginosa was significantly higher than those in the first two years (P<0.05). P.aeruginosa and A.baumannii showed high resistance (>80%) to the third and fourth generation cephalosporins, carbapenems, aminoglycosides and quinolones, but the changes were not statistically significant (P>0.05). S.aureus was only highly resistant to penicillin (97.58%) and was 100% susceptible to vancomycin. Its resistance rates toward cefazolin, ampicillin/sulbactam, gentamicin, levofloxacin, and rifampin decreased significantly (P<0.05). The detection rate of methicillin-resistant S. aureus (MRSA) dropped from 72.28% to 63.00%. Conclusion·Many types of drug resistant bacteria were detected in burn wards. The drug resistance problem was serious. Improving management and rational use of antibiotics can reduce the occurrence of drug-resistant bacteria and increase the efficacy of clinical anti-infective treatment and nosocomial infection control.

Objective To investigate antimicrobial resistance among nosocomial gram-negative bacilli in 2016 across China.Methods About 1 394 consecutive and non-repetitive gram-negative bacilli were isolated from 14 teaching hospitals from March to August in 2016 across China.All of these isolates were sent to the central laboratory for reidentification and susceptibility testing.The minimal inhibitory concentration(MICs)of meropenem and other antibacterial agents were determined by agar dilution method.The data were analyzed by using WHONET-5.6 software.Results The activity of antimicrobial agents against Enterobacteriaceae was as follows in descending order of susceptible rate: meropenem (95.2%,891/936), amikacin (94.6%,885/936), ertapenem (92.1%,862/936), piperacillin/tazobactam (88.1%,825/936), imipenem (88.0%,823/936), cefoperazone-sulbactam (83.1%,778/936), cefepime (72.2%,676/936), cefiazidime (72.2%,676/936), levofloxacin(68.8%,644/936), ciprofloxacin (63.2%,592/936), minocyline (62.9%,589/936), cefiriaxone (54.9%,514/936), cefotaxime (54.0%,505/936), cefoxitin (44.3%,415/936).The sensitivities of E.coli to carbapenems, amikacin, piperacillin-tazobactam, polymyxin B and cefoperazone-sulbactam were over 80%.The more sensitive antibiotic to Klebsiella pneumoniae was polymyxin B (99.0%), followed by amikacin (84.9%), meropenem (84.4%) and imipenem (82.0%).The prevalence of extended-spectrum β-lactamase was 62.8%(137/218)in Escherichia coli and 28.3%(58/205)in Klebsiella pneumonia.The activity of antimicrobial agents against E.cloacae, E.aerogenes and Citrobacter freundii was as follows in descending order of susceptible rate: meropenem (97.0%-98.5%), amikacin (95.8%-98.3%), imipenem (94.5%-97.5%), polymyxin B (96.4%-100%), cefoperazone-sulbactam (76.5%-90.0%), ertapenem (73.3%-90.1%), piperacillin/tazobactam (82.4%-88.3%).The most active agents against Pseudomonas aeruginosa were polymyxinB (100%), followed by amikacin (89.3%) and ciprofloxacin (82.4%).The most active agents against Acinetobacter baumannii were polymyxinB (100%).The sensitivities of Acinetobacter baumannii to meropenem, imipenem, minocycline and cefoperazone-sulbactam were 20.3%(39/202), 19.3%(41/202), 66.3%(134/202) and 24.8%(50/202), respectively.Conclusions Carbapenems remain high sensitive against Enterobacteriaceae.Controlling carbapenem resistant Klebsiella pneumoniae is urgent.Drug antimicrobial resistance in A.baumanni is a still serious problem.

Objective To investigate the species and drug resistance of pathogens causing bloodstream infections in hospitalized patients,and provide scientific evidence for antimicrobial use and control of healthcare-associated blood-stream infection.Methods From January 1 to December 31,2012,16 428 blood specimens were performed blood culture,pathogens were isolated and performed antimicrobial susceptibility testing.Results Of 16 428 blood speci-mens from 5 546 patients,384 (6.92%)were positive for blood culture,398 pathogenic isolates were detected,of which gram-positive bacteria,gram-negative bacteria,and fungi accounted for 23.62% (n=94),68.34% (n=272),and 8.04% (n=32)respectively,positive rate of blood culture were highest in 61-80 age group(8.26%), the top five departments of positive rate of blood culture were departments of burn,traditional Chinese medicine, cardiac intensive care unit,transplantation and traumatology;gram-positive cocci were highly susceptible to vanco-mycin,teicoplanin and linezolid,one Enterococcus faecium strain was found to be resistant to vancomycin;Among gram-negative bacilli,Enterobacteriaceae were highly susceptible to amikacin and carbapenems;drug resistance rates of Acinetobacterbaumannii and Pseudomonasaeruginosa to carbapenems was 70.97% and 35.90% respective-ly.Conclusion Gram-negative bacteria are the major pathogens causing bloodstream infection,positive rate of blood culture of elderly people is high.It is necessary to conduct regular surveillance on distribution and drug resistance of pathogens.

OBJECTIVETo investigate the antibacterial activity of silver sulfadiazine (SD-Ag), mupirocin, and clotrimazole used alone or in combination against methicillin-resistant Staphylococcus aureus (MRSA) isolated from burn wounds.

METHODSEighteen MRSA isolates from wound excretion of 18 burn patients hospitalized in our unit from July to December 2011 were collected continuously and non-repetitively. (1) Minimum inhibitory concentration (MIC), 50% MIC (MIC50), and 90% MIC (MIC90) of SD-Ag, mupirocin, and clotrimazole used alone, those of SD-Ag and mupirocin used in combination, and those of SD-Ag, mupirocin, and clotrimazole used in combination to MRSA were determined by checkerboard agar dilution method. (2) Fractional inhibitory concentration (FIC) index was calculated to determine the combined effect of SD-Ag plus mupirocin, and SD-Ag plus mupirocin and clotrimazole. Synergy with FIC index less than or equal to 0.5 or additivity with FIC index more than 0.5 and less than or equal to 1.0 was regarded as effective, and indifference with FIC index more than 1.0 and less than or equal to 4.0 or antagonism with FIC index more than 4.0 was regarded as ineffective. The effective ratio was compared with overall ratio (assumed as 0) by unilateral binomial distribution test.

RESULTSThe MIC, MIC50, and MIC90 of SD-Ag, mupirocin, and clotrimazole used alone against 18 MRSA isolates were respectively 8, 8, 16 µg/mL; 2, 16, 64 µg/mL; 2, 2, 2 µg/mL. MIC of antimicrobial agents used in combination decreased from 3.1% to 50.0% as compared with that of individual agent used alone. Compared with those of single application of SD-Ag and mupirocin, MIC50 of SD-Ag and that of mupirocin both decreased 75.0%, and MIC90 of them decreased 87.5% when SD-Ag and mupirocin were used in combination. Compared with those of single application of SD-Ag, mupirocin, and clotrimazole, MIC50 of SD-Ag, mupirocin, and clotrimazole respectively decreased 75.0%, 87.5%, and 50.0%; MIC90 of them respectively decreased 87.5%, 96.9%, and 50.0% when SD-Ag, mupirocin, and clotrimazole were used in combination. Among the 18 MRSA isolates, the combined effect of SD-Ag and mupirocin was synergic in 9 isolates, additive in 7 isolates, indifferent in 2 isolates, and antagonistic in 0 isolate; the combined effect of SD-Ag, mupirocin, and clotrimazole was additive in 16 isolates, indifferent in 2 isolates, and antagonistic in 0 isolate. There were statistically significant differences between effective ratio and overall ratio of 18 MRSA isolates treated with combined antimicrobial agents (P values all above 0.01).

CONCLUSIONSFor burn wounds at middle and late stages infected with Staphylococcus aureus or Staphylococcus aureus and Fungus, low dose of SD-Ag or combination of above-mentioned antimicrobial agents can effectively control infection and decrease the adverse effect of antimicrobial agents on wound healing.

Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; administration & dosage ; adverse effects ; pharmacology ; Burns ; microbiology ; Child ; Child, Preschool ; Clotrimazole ; administration & dosage ; adverse effects ; pharmacology ; Drug Therapy, Combination ; Female ; Humans ; Infant ; Male ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; isolation & purification ; Middle Aged ; Mupirocin ; administration & dosage ; adverse effects ; pharmacology ; Silver Sulfadiazine ; administration & dosage ; adverse effects ; pharmacology ; Young Adult

Objective To assess the risk factors of multidrug-resistant organism(MDRO)healthcare-associated pneumonia(HCAP).Methods The case-control study was conducted in patients admitted to 22 hospitals in 4 cities between April 1 ,2013 and December 31 ,2013,patients with HCAP caused by MDRO (MRSA,MDRPA,MDRAB, ESBL KP,ESBL E.coli)(drug-resistant group )and drug-sensitive organisms (MSSA,PA,AB,KP,E.coli)(drug-sensitive group )were surveyed .Univariate and multivariate statistical analysis methods were used to evaluate the risk factors for MDRO HCAP.The prognosis,cost and length of hospital stay between drug-resistant group and drug-sensitive group were compared .Results A total of 1 656 patients were included in the study ,including 43 pa-tients (2.60%)with mixed infection caused by both drug-resistant and drug-sensitive organisms ;there were 927 ca-ses (55.98%)in drug-resistant group and 772 cases(46.62%)in drug-sensitive group .Logistic regression model re-vealed that admission to ICUs (OR 95%CI :1 .55[1 .14-2.11]),mechanical ventilation (OR 95%CI :1 .45[1 .15-1 .84]),arteriovenous catheterization (OR 95%CI :1 .29 [1 .02 - 1 .63 ]),fiberbronchoscopy (OR 95%CI :1 .46 [1 .02-2.09]),antimicrobial use(OR 95%CI :1 .63[1 .20-2.22]),chronic lung diseases (OR 95%CI :1 .54[1 .13-2.10]),and chronic cardiovascular and cerebrovascular diseases (OR 95%CI :1 .42[1 .15-1 .74])were independ-ent risk factors for MDRO HCAP .Compared with drug-sensitive group ,drug-resistant group prolonged length of hospital stay by an average of 5.89 days,increased hospitalization and antimicrobial expense by ￥40 739.30 and￥2 805.80 respectively;prognoses was worse,risk factor was 1 .66-fold of drug-sensitive group(OR 95%CI :1 .16-2.35).Conclusion Admission to ICUs,invasive operations,antimicrobial use,chronic lung diseases and chronic cardiovascular and cerebrovascular diseases can increase the risk of MDRO HCAP .

Objective To evaluate the capability of three tests used alone or in combination for identification of Staphylococcus aureus.Methods Identification of Staphylococcus aureus by the detection of spa gene with PCR and the Vitek-2 system were selected as the reference methods.Comparison of three phenotypic tests including DNase,mannitol fermentation and tube coagulase test was carried out to analyze the sensitivity,specificity,positive/negative predictive value,positive/negative likelihood ratio and Youden index.The consistency,cost and related indexes of the assays were analyzed between the combined phenotypic tests and the reference methods.Results In the present study,324 isolates of Staphylococci,including 293 Staphylococcus aureus and 31 non-Staphylococcus aureus,were collected.Single biochemical test could not identify Staphylococcus aureus efficiently.Comparison between the reference methods and the combined three biochemical tests by Kappa statistic analysis indicated that an overall Kappa value was 0.9441,and the algorithm of combined test was less costly.The sensitivity and specificity of this algorithm were 100％ and 90.3％,respectively.Conclusion The cost-effective algorithm of combined DNase,mannitol fermentation and tube coagulase test could efficiently distinguish Staphylococcus aureus from other Staphylococcus species.

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 .