1.Fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage.
Lizhong SUN ; Libang HE ; Wei WU ; Li LUO ; Mingyue HAN ; Yifang LIU ; Shijie SHI ; Kaijing ZHONG ; Jiaojiao YANG ; Jiyao LI
International Journal of Oral Science 2021;13(1):39-39
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
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Fibroblasts
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Humans
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Inflammation/drug therapy*
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Nanoparticles
2.A randomized controlled study of peramivir, oseltamivir and placebo in patients with mild influenza
Hongwei FAN ; Yang HAN ; Wei LIU ; Xingwang LI ; Lizhong LI ; Heyun YAO ; Yong WANG ; Zhiqiang SU ; Weixian YE ; Jin HUANG ; Weizhong LU ; Guiwei LI ; Hailing LI ; Shaoyang WANG ; Hao WU ; Qiaofa LU ; Guangfa ZHU ; Shengming LIU ; Gang CHEN ; Wenhong ZHANG ; Taisheng LI
Chinese Journal of Internal Medicine 2019;58(8):560-565
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.
3.Study on the FBN1 gene mutation spectrum and association between genotype and clinical phenotype in 300 Marfan syndrome patients and their relatives
Ming GONG ; Shijun XU ; Yuwei FU ; Xin WANG ; Hairui SUN ; Zining WU ; Lei LI ; Lu HAN ; Feng LAN ; Yihua HE ; Yongmin LIU ; Junming ZHU ; Lizhong SUN ; Hongjia ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2019;35(1):33-40
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 .
4.Analysis of distribution and drug resistance of pathogenic bacteria in burn wards
Zhengpeng XU ; Su WANG ; Lizhong HAN ; Wenkui WANG
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(4):527-531
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.
5.Antimicrobial resistance of gram-negative bacilli isolated from 14 teaching hospitals across China in 2016
Qi WANG ; Ping JI ; Xiuli XU ; Yingchun XU ; Ziyong SUN ; Zhidong HU ; Yunsong YU ; Bin YANG ; Kang LIAO ; Juan LU ; Yunzhuo CHU ; Yaning MEI ; Lizhong HAN ; Xianju FENG ; Hui WANG
Chinese Journal of Laboratory Medicine 2017;40(8):614-622
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.
6.Investigation of antibacterial activity of topical antimicrobials against methicillin-resistant Staphylococcus aureus.
Shengyong CUI ; Lizhong HAN ; Shuzhen XIAO ; Xu CHEN ; Qingxuan CHANG ; Yan LIU ; Xiong ZHANG
Chinese Journal of Burns 2014;30(1):21-24
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
7.Distribution and antimicrobial resistance of pathogens isolated from hospi-talized patients with bloodstream infections
Shengyuan ZHAO ; Shuzhen XIAO ; Lizhong HAN ; Chenrong MI ; Yuxing NI
Chinese Journal of Infection Control 2014;(5):266-270
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.
8.Multicenter study on risk factors for multidrug-resistant organism health-care-associated pneumonia
Yuelun ZHANG ; Lizhong HAN ; Zhirong YANG ; Yonghong XIAO ; Zhen LIN ; Yuxing NI ; Anhua WU ; Renfei FANG ; Siyan ZHAN
Chinese Journal of Infection Control 2014;(9):513-517,523
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 .
9.Relationship between antibiotic use and antimicrobial resistance in Acinetobacter baumannii
Shuzhen XIAO ; Guiting XU ; Jie FANG ; Haiqing CHU ; Lizhong HAN ; Yuxing NI
Chinese Journal of Infection and Chemotherapy 2013;(6):446-449
Objective To investigate the relationship between antibiotic use and antimicrobial resistance in Acinetobacter bau-mannii for rational use of antibiotics.Methods Antibiotic use density (AUD)of common antibiotics in hospitalized patients were collected in a tertiary hospital between 2006 and 2010.Clinical isolates of A.baumannii from those patients were collect-ed.The resistance to common antimicrobial agents were tested by disk diffusion method according to Clinical and Laboratory Standards Institute (CLSI,2012)guidelines.Relationship between antibiotic use and antimicrobial resistance in A.baumannii was analysed by SPSS 16.0.Results The resistant rates of A.baumannii isolated from inpatients were high.Consumption of cephalosporins and quinolones were large.There was a positive correlation between the resistant rate of A.baumannii to imi-penem and AUD of carbapenems (r=0.975,P <0.05).The resistant rate of A.baumannii to meropenem showed significantly positive relation to AUD of carbapenems (r= 0.975,P <0.05).Resistant rates of aminoglycosides,quinolones,cephalospo-rins and beta-lactamase inhibitors was not correlated to AUD of those antibiotics.Conclusions We should pay more attention to the high prevalence of resistant A.baumannnii strains.Application of imipenem and meropenem should be strictly controlled.Amikacin and beta-lactamase inhibitors are better choice for empirical antibiotic therapy in the treatment of infections caused by A. baumannii.
10.The influence of platelet rich plasma gel applied to adipose-derived stem cells repair soft tissue wounds
Huaiwei LIAO ; Chao HAN ; Lizhong LIU ; Minjun CAO
Chongqing Medicine 2013;(32):3859-3862
Objective To explore the role of ADSCs and PRP in soft tissue defect repairing .Methods Harvest adipose tissue from inguinalis fat pad of SD rats ,isolation ,culture ,and identification the ADSCs through three differentiation method .Take 30 male SD rats about 6-7 weeks old randomly .Randomly selected 12 rats been take blood from heart .Preparation the PRP with modi-fied appel method .To count platelet of whole blood and PRP under microscope .Take the remaining rats .Divided the rat into 3 groups(n=6 in each group) randomly ,of which group A treatment with ADSCs and PRP ;Group B treatment with ADSCs ;Group C treatment whit PRP .Selected one side of skin defect wound for test randomly and the relative side skin defect is for control ,Handle all of the control wound to group D ;Observe the grow th of granulation tissue on the wound surface ;observe the inflammatory sur-rounding and the degree about epithelial .statistical analysis and record the wound size ,and calculation the shrinkage rate of wound in different periods .Record the time of completely healing time .Histologic observation of the wound healing tissue .Results Plate-let counting showed platelet of PRP is 5 .21 times than whole blood .The wound completely healed time :group A (18 .25 ± 1 .44 ) days ,group B(19 .13 ± 1 .28)days ,group C(19 .72 ± 0 .87)days ,group D(22 .31 ± 1 .65) days ,The time of each treatment group and control group was significantly obvious(P< 0 .05) .At 3 ,7 ,11 and 15 days after experimental treatment ,compared with the control group the experiment group of wound contraction rate was significantly obvious (P<0 .05) .Conclusion Application of AD-SCs with PRP can enhance the quality and shorten the wound healing time than used them alone .

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