Obiective:To investigate whether"Fuzheng Qingretonglin"decoction can reduce urinary tract damage caused by complex urinary tract infection caused by drug resistant Escherichia coli by regulating Nod-like rec...Obiective:To investigate whether"Fuzheng Qingretonglin"decoction can reduce urinary tract damage caused by complex urinary tract infection caused by drug resistant Escherichia coli by regulating Nod-like receptor pyrin domain3 inflammasome,and to explore the feasibility of this decoction combined with levofloxacin in the treatment of complex urinary tract infection caused by drug resistant bacteria.Methods:SD rats were divided into five groups:sham group,model group,levofloxacin group(Lev group),levofloxacin+Fuzheng Qingre Tonglin decoction group(FZ+lev group),and Fuzheng Qingre Tonglin decoction group(FZQRTL group).After the experiment,urine was taken for bacterial culture to determine the urinary tract infection of rats in each group;HE staining was used to observe the pathological changes of kidney and bladder tissues in rats;The expression of NLRP3 in kidney and bladder tissues was detected by immunohistochemistry;The expression of IL-1βand IL-18 in serum of rats was detected by ELISA;The expressions of NLRP3,ASC and Caspase-1 were detected by Western blotting.Results:The positive rate of urine bacteria culture in the sham group was 0%,the positive rate of urine bacteria culture in the model group was 100%;and the positive rate of urine bacteria culture in the FZ+lev group was 37.50%,which was statistically different from that in the model group(P<0.05).A large number of inflammatory cells were observed in the kidney and bladder tissues of the model group by HE staining,while the number of inflammatory cells in the kidney and bladder tissues of the Lev group and FZQRTL group was significantly reduced compared with that of the model group.The FZ+lev group in the number and structure of inflammatory cells in kidney and bladder were similar to the sham group.The NLRP3 immunohistochemistry of kidney and bladder tissue in FZ+lev groups and FZQRTL groups was significantly different from that in model group(P<0.001).The levels of IL-1βand IL-18 in serum of Lev group,FZQRTL group and FZ+lev group were significantly decreased by ELISA compared with model group(P<0.001).The levels of IL-1βand IL-18 in the FZ+lev groups were significantly lower than in the Lev group and FZQRTL group,and the differences were statistically significant(P<0.05).The protein expressions of NLRP3,ASC and Caspase-1 in the Lev group,FZQRTL group and FZ+lev group were significantly lower than those in the model group(P<0.001).The protein expressions of NLRP3,ASC and Caspase-1 in the FZ+lev groups were significantly lower than in the Lev group and FZQRTL group,and the differences were statistically significant(P<0.05).Conclusions:"Fuzheng Qingretonglin"decoction may have a protective effect on the kidney and bladder of rats with complex urinary tract infection caused by drug-resistant Escherichia coli by inhibiting the activation of NLRP3 inflammatory bodies,and TCM combined with levofloxacin has a better therapeutic effect than TCM or levofloxacin alone.展开更多
Objective To investigate the effect of low concentration of Wenyang Tonglin Decoction(WTD)on the binding conditions of R45 plasmid conjugative transfer under liquid phase conjugation and its mechanism.Methods Escheric...Objective To investigate the effect of low concentration of Wenyang Tonglin Decoction(WTD)on the binding conditions of R45 plasmid conjugative transfer under liquid phase conjugation and its mechanism.Methods Escherichia coli CP9(R45)and Staphylococcus aureus RN450RF were cultured in medium containing WTD,and their minimum inhibitory concentration(MIC)values were obtained.Using promoter fusion technology,E.coli CP9(R45)containing a promoter fusion was obtained.β-Galactosidase activity of TrfAp and TrbBp was tested,and the mRNA expression of regulatory factors(TrbA,KorA,and KorB)was detected by real-time fluorescent quantitative polymerase chain reaction.Results The MIC of E.coli CP9(R45)was 400 g/L and that of S.aureus RN450RF was 200 g/L.When the drug concentration in the culture medium was 200 g/L,the highest number of conjugants was(3.47±0.20)×10^(7) CFU/mL At 90 h of conjugation,the maximum number of conjugants was(1.15±0.06)×10^(8) CFU/mL When the initial bacterial concentration was 10^(8) CFU/mL,the maximum number of conjugants was(3.47±0.20)×10^(7) CFU/mL.When the drug concentration was 200 g/L,theβ-galactosidase activity of TrfAp and TrbBp significantly increased;the relative quantification of TrbA,KorA and KorB were significantly inhibited.Conclusion Low concentration of WTD promoted the development of bacterial resistance by affecting promoters and inhibiting the expression of regulatory factors.展开更多
Background Acinetobacter baumanii (A. baumanii ) remains an important microbial pathogen resulting in nosocomialacquired infections with significant morbidity and mortality. The mechanism by which nosocomial bacteri...Background Acinetobacter baumanii (A. baumanii ) remains an important microbial pathogen resulting in nosocomialacquired infections with significant morbidity and mortality. The mechanism by which nosocomial bacteria, like A. baumanii, attain multidrug resistance to antibiotics is of considerable interest. The aim in this study was to investigate the spread status of antibiotic resistance genes, such as multiple 13-1actamase genes and aminoglycoside-modifying enzyme genes, from A. baumanii strains isolated from patients with lower respiratory tract infections (LRTIs). Methods Two thousand six hundred and ninety-eight sputum or the bronchoalveolar lavage samples from inpatients with LRTIs were collected in 21 hospitals in the mainland of China from November 2007 to February 2009. All samples were routinely inoculated. The isolated bacterial strains and their susceptibility were analyzed via VITEK-2 expert system. Several kinds of antibiotic resistant genes were further differentiated via polymerase chain reaction and sequencing methods. Results Totally, 39 A. baumanii strains were isolated from 2698 sputum or bronchoalveolar lavage samples. There was not only a high resistant rate of the isolated A. baumanfi strains to ampicillin and first- and second-generation cephalosporins (94.87%, 100% and 97.44%, respectively), but also to the third-generation cephalosporins (ceftriaxone at 92.31%, ceftazidine at 51.28%) and imipenem (43.59%) as well. The lowest antibiotic resistance rate of 20.51% was found to amikacin. The OXA-23 gene was identified in 17 strains of A. baumanii, and the AmpC gene in 23 strains. The TEM-1 gene was carried in 15 strains. PER-1 and SHV-2 genes were detected in two different strains. Aminoglycoside-modifying enzyme gene aac-3-1a was found in 23 strains, and the aac-6"lb gene in 19 strains, aac-3-1a and aac-6"lb genes hibernated in three A. baumanfi strains that showed no drug-resistant phenotype. Conclusions A. baumanii can carry multiple drug-resistant genes at the same time and result in multi-drug resistance. Aminoglycoside-modifying enzyme genes could be hibernating in aminoglycoside sensitive strains without expressing their phenotype.展开更多
The mounting threat of antibiotic-resistant bacterial infections has made it imperative to develop innovative antibacterial strategies.Here we propose a novel antibacterial nanoplatform of silver nanoparticles-decorat...The mounting threat of antibiotic-resistant bacterial infections has made it imperative to develop innovative antibacterial strategies.Here we propose a novel antibacterial nanoplatform of silver nanoparticles-decorated and mesoporous silica coated single-walled carbon nanotubes constructed via a N-[3-(trimethoxysiltyl)propyl]ethylene diamine(TSD)-mediated method(SWCNTs@mSiO2-TSD@Ag).In this system,the outer mesoporous silica shells are able to improve the dispersibility of SWCNTs,which will increase their contact area with bacteria cell walls.Meanwhile,the large number of mesopores in silica layers act as microreactors for in situ synthesis of Ag NPs with controlled small size and uniform distribution,which induces an enhanced antibacterial activity.Compared with TSD modified mesoporous silica coated single-walled carbon nanotubes(SWCNTs@mSiO2-TSD)and commercialAg NPs,this combination nanosystem of SWCNTs@mSiO2-TSD@Ag exhibits much stronger antibacterial performance against multi-drug-resistant bacteria Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)in vitro through damaging the bacterial cell membranes and a fast release of silver ions.Furthermore,the in vivo rat skin infection model verifies that SWCNTS@mSiO2-TSD@Ag have remarkably improved abilities of bacterial clearance,wound healing promoting as well as outstanding biocompatibility.Therefore,this novel nanoplatform indicates promising potentials as a safe and powerful tool for the treatment of clinical drug-resistant infections.展开更多
Pyogenic liver abscess and keratitis are aggressive bacterial infections and the treatment has failed to eradicate bacteria in infectious sites completely owing to the currently severe drug resistance to existing anti...Pyogenic liver abscess and keratitis are aggressive bacterial infections and the treatment has failed to eradicate bacteria in infectious sites completely owing to the currently severe drug resistance to existing antibiotics.Here,we report a simple and efficient one-step development of ultrasmall non-antibiotic nanoparticles(ICG-Ga NPs)containing clinically approved gallium(Ⅲ)(Ga^(3+))and liver targeting indocyanine green(ICG)molecules to eradicate multi-drug resistant(MDR)bacteria thought the synergetic effect of photodynamic therapy and iron metabolism blocking.The ICG-Ga NPs induced photodynamic effect could destroy the bacterial membrane,further boost the endocytosis of Ga^(3+),then replace iron in bacteria cells to disrupt bacterial iron metabolism,and demonstrate the synergetic bacterial killing and biofilm disrupting effects.The ICG-Ga NPs show an excellent therapeutic effect against extended spectrumβ-lactamases Escherichia coli(ESBL E.coli)and significantly improve treatment outcomes in infected liver abscess and keratitis.Meanwhile,the ultrasmall size of ICG-Ga NPs could be cleared rapid via renal clearance route,guaranteeing the biocompatibility.The protective effect and good biocompatibility of ICG-Ga NPs will facilitate clinical treatment of bacteria infected diseases and enable the development of next-generation non-antibiotic antibacterial agents.展开更多
Infection prevention and control(IPC)measures to reduce transmission of drug-resistant and drug-sensitive tuberculosis(TB)in health facilities are well described but poorly implemented.The implementation of TB IPC has...Infection prevention and control(IPC)measures to reduce transmission of drug-resistant and drug-sensitive tuberculosis(TB)in health facilities are well described but poorly implemented.The implementation of TB IPC has been assessed primarily through quantitative and structured approaches that treat administrative,environmental,and personal protective measures as discrete entities.We present an on-going project entitled Umoya omuhle(“good air”),conducted in two provinces of South Africa,that adopts an interdisciplinary,‘whole systems’approach to problem analysis and intervention development for reducing nosocomial transmission of Mycobacterium tuberculosis(Mtb)through improved IPC.We suggest that TB IPC represents a complex intervention that is delivered within a dynamic context shaped by policy guidelines,health facility space,infrastructure,organisation of care,and management culture.Methods drawn from epidemiology,anthropology,and health policy and systems research enable rich contextual analysis of how nosocomial Mtb transmission occurs,as well as opportunities to address the problem holistically.A‘whole systems’approach can identify leverage points within the health facility infrastructure and organisation of care that can inform the design of interventions to reduce the risk of nosocomial Mtb transmission.展开更多
BACKGROUND Gastro-thoracic fistula is a serious complication after radical surgery for esophageal cancer,and a conservative approach or endoscopic intervention is commonly applied to treat most cases.CASE SUMMARY Here...BACKGROUND Gastro-thoracic fistula is a serious complication after radical surgery for esophageal cancer,and a conservative approach or endoscopic intervention is commonly applied to treat most cases.CASE SUMMARY Here we describe the case of a patient with a gastro-thoracic fistula which could not be closed during gastroscopy after receiving postoperative radiotherapy,together with severe multiple drug-resistant bacterial infection and chest wall fistula.The abscess was drained and local irrigation applied with ozonated water,together with oral ozonated water,which achieved a good effect and highlighted a new way to cure fistula in such patients.CONCLUSION Patients with gastro-thoracic fistula that cannot be closed and severe infection can be treated by drainage and flushing with ozonated water.展开更多
基金Luzhou People's Government-Science and technology Strategic Cooperation project of Southwest Medical University(2017LZXNYD-T09)。
文摘Obiective:To investigate whether"Fuzheng Qingretonglin"decoction can reduce urinary tract damage caused by complex urinary tract infection caused by drug resistant Escherichia coli by regulating Nod-like receptor pyrin domain3 inflammasome,and to explore the feasibility of this decoction combined with levofloxacin in the treatment of complex urinary tract infection caused by drug resistant bacteria.Methods:SD rats were divided into five groups:sham group,model group,levofloxacin group(Lev group),levofloxacin+Fuzheng Qingre Tonglin decoction group(FZ+lev group),and Fuzheng Qingre Tonglin decoction group(FZQRTL group).After the experiment,urine was taken for bacterial culture to determine the urinary tract infection of rats in each group;HE staining was used to observe the pathological changes of kidney and bladder tissues in rats;The expression of NLRP3 in kidney and bladder tissues was detected by immunohistochemistry;The expression of IL-1βand IL-18 in serum of rats was detected by ELISA;The expressions of NLRP3,ASC and Caspase-1 were detected by Western blotting.Results:The positive rate of urine bacteria culture in the sham group was 0%,the positive rate of urine bacteria culture in the model group was 100%;and the positive rate of urine bacteria culture in the FZ+lev group was 37.50%,which was statistically different from that in the model group(P<0.05).A large number of inflammatory cells were observed in the kidney and bladder tissues of the model group by HE staining,while the number of inflammatory cells in the kidney and bladder tissues of the Lev group and FZQRTL group was significantly reduced compared with that of the model group.The FZ+lev group in the number and structure of inflammatory cells in kidney and bladder were similar to the sham group.The NLRP3 immunohistochemistry of kidney and bladder tissue in FZ+lev groups and FZQRTL groups was significantly different from that in model group(P<0.001).The levels of IL-1βand IL-18 in serum of Lev group,FZQRTL group and FZ+lev group were significantly decreased by ELISA compared with model group(P<0.001).The levels of IL-1βand IL-18 in the FZ+lev groups were significantly lower than in the Lev group and FZQRTL group,and the differences were statistically significant(P<0.05).The protein expressions of NLRP3,ASC and Caspase-1 in the Lev group,FZQRTL group and FZ+lev group were significantly lower than those in the model group(P<0.001).The protein expressions of NLRP3,ASC and Caspase-1 in the FZ+lev groups were significantly lower than in the Lev group and FZQRTL group,and the differences were statistically significant(P<0.05).Conclusions:"Fuzheng Qingretonglin"decoction may have a protective effect on the kidney and bladder of rats with complex urinary tract infection caused by drug-resistant Escherichia coli by inhibiting the activation of NLRP3 inflammatory bodies,and TCM combined with levofloxacin has a better therapeutic effect than TCM or levofloxacin alone.
基金Supported by the National Natural Science Foundation of China(No.81873070)。
文摘Objective To investigate the effect of low concentration of Wenyang Tonglin Decoction(WTD)on the binding conditions of R45 plasmid conjugative transfer under liquid phase conjugation and its mechanism.Methods Escherichia coli CP9(R45)and Staphylococcus aureus RN450RF were cultured in medium containing WTD,and their minimum inhibitory concentration(MIC)values were obtained.Using promoter fusion technology,E.coli CP9(R45)containing a promoter fusion was obtained.β-Galactosidase activity of TrfAp and TrbBp was tested,and the mRNA expression of regulatory factors(TrbA,KorA,and KorB)was detected by real-time fluorescent quantitative polymerase chain reaction.Results The MIC of E.coli CP9(R45)was 400 g/L and that of S.aureus RN450RF was 200 g/L.When the drug concentration in the culture medium was 200 g/L,the highest number of conjugants was(3.47±0.20)×10^(7) CFU/mL At 90 h of conjugation,the maximum number of conjugants was(1.15±0.06)×10^(8) CFU/mL When the initial bacterial concentration was 10^(8) CFU/mL,the maximum number of conjugants was(3.47±0.20)×10^(7) CFU/mL.When the drug concentration was 200 g/L,theβ-galactosidase activity of TrfAp and TrbBp significantly increased;the relative quantification of TrbA,KorA and KorB were significantly inhibited.Conclusion Low concentration of WTD promoted the development of bacterial resistance by affecting promoters and inhibiting the expression of regulatory factors.
文摘Background Acinetobacter baumanii (A. baumanii ) remains an important microbial pathogen resulting in nosocomialacquired infections with significant morbidity and mortality. The mechanism by which nosocomial bacteria, like A. baumanii, attain multidrug resistance to antibiotics is of considerable interest. The aim in this study was to investigate the spread status of antibiotic resistance genes, such as multiple 13-1actamase genes and aminoglycoside-modifying enzyme genes, from A. baumanii strains isolated from patients with lower respiratory tract infections (LRTIs). Methods Two thousand six hundred and ninety-eight sputum or the bronchoalveolar lavage samples from inpatients with LRTIs were collected in 21 hospitals in the mainland of China from November 2007 to February 2009. All samples were routinely inoculated. The isolated bacterial strains and their susceptibility were analyzed via VITEK-2 expert system. Several kinds of antibiotic resistant genes were further differentiated via polymerase chain reaction and sequencing methods. Results Totally, 39 A. baumanii strains were isolated from 2698 sputum or bronchoalveolar lavage samples. There was not only a high resistant rate of the isolated A. baumanfi strains to ampicillin and first- and second-generation cephalosporins (94.87%, 100% and 97.44%, respectively), but also to the third-generation cephalosporins (ceftriaxone at 92.31%, ceftazidine at 51.28%) and imipenem (43.59%) as well. The lowest antibiotic resistance rate of 20.51% was found to amikacin. The OXA-23 gene was identified in 17 strains of A. baumanii, and the AmpC gene in 23 strains. The TEM-1 gene was carried in 15 strains. PER-1 and SHV-2 genes were detected in two different strains. Aminoglycoside-modifying enzyme gene aac-3-1a was found in 23 strains, and the aac-6"lb gene in 19 strains, aac-3-1a and aac-6"lb genes hibernated in three A. baumanfi strains that showed no drug-resistant phenotype. Conclusions A. baumanii can carry multiple drug-resistant genes at the same time and result in multi-drug resistance. Aminoglycoside-modifying enzyme genes could be hibernating in aminoglycoside sensitive strains without expressing their phenotype.
基金This work is supported by the National Natural Science Foundation of China(Nos.51802192,81802156,and 81772338)the Interdisciplinary Program of Shanghai Jiao Tong University(No.YG2017ZD05)+2 种基金Natural Science Foundation of Shanghai(No.19ZR1474800)Shanghai Sailing Program(No.18YF1410700)Innovation Research Plan supported by Shanghai Municipal Education Commission(No.ZXWF082101).
文摘The mounting threat of antibiotic-resistant bacterial infections has made it imperative to develop innovative antibacterial strategies.Here we propose a novel antibacterial nanoplatform of silver nanoparticles-decorated and mesoporous silica coated single-walled carbon nanotubes constructed via a N-[3-(trimethoxysiltyl)propyl]ethylene diamine(TSD)-mediated method(SWCNTs@mSiO2-TSD@Ag).In this system,the outer mesoporous silica shells are able to improve the dispersibility of SWCNTs,which will increase their contact area with bacteria cell walls.Meanwhile,the large number of mesopores in silica layers act as microreactors for in situ synthesis of Ag NPs with controlled small size and uniform distribution,which induces an enhanced antibacterial activity.Compared with TSD modified mesoporous silica coated single-walled carbon nanotubes(SWCNTs@mSiO2-TSD)and commercialAg NPs,this combination nanosystem of SWCNTs@mSiO2-TSD@Ag exhibits much stronger antibacterial performance against multi-drug-resistant bacteria Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)in vitro through damaging the bacterial cell membranes and a fast release of silver ions.Furthermore,the in vivo rat skin infection model verifies that SWCNTS@mSiO2-TSD@Ag have remarkably improved abilities of bacterial clearance,wound healing promoting as well as outstanding biocompatibility.Therefore,this novel nanoplatform indicates promising potentials as a safe and powerful tool for the treatment of clinical drug-resistant infections.
基金the National Natural Science Foundation of China(No.81971667 and 81671748 and)the Key Research and Development Projection of Zhejiang Province(No.2020C03035).
文摘Pyogenic liver abscess and keratitis are aggressive bacterial infections and the treatment has failed to eradicate bacteria in infectious sites completely owing to the currently severe drug resistance to existing antibiotics.Here,we report a simple and efficient one-step development of ultrasmall non-antibiotic nanoparticles(ICG-Ga NPs)containing clinically approved gallium(Ⅲ)(Ga^(3+))and liver targeting indocyanine green(ICG)molecules to eradicate multi-drug resistant(MDR)bacteria thought the synergetic effect of photodynamic therapy and iron metabolism blocking.The ICG-Ga NPs induced photodynamic effect could destroy the bacterial membrane,further boost the endocytosis of Ga^(3+),then replace iron in bacteria cells to disrupt bacterial iron metabolism,and demonstrate the synergetic bacterial killing and biofilm disrupting effects.The ICG-Ga NPs show an excellent therapeutic effect against extended spectrumβ-lactamases Escherichia coli(ESBL E.coli)and significantly improve treatment outcomes in infected liver abscess and keratitis.Meanwhile,the ultrasmall size of ICG-Ga NPs could be cleared rapid via renal clearance route,guaranteeing the biocompatibility.The protective effect and good biocompatibility of ICG-Ga NPs will facilitate clinical treatment of bacteria infected diseases and enable the development of next-generation non-antibiotic antibacterial agents.
基金It is funded through the UK Econom ic and Social Research Council(Grant#ES/P008011/1),one of seven research councils underpinning the Antimicrobial Resistance Cross Council Initiative.
文摘Infection prevention and control(IPC)measures to reduce transmission of drug-resistant and drug-sensitive tuberculosis(TB)in health facilities are well described but poorly implemented.The implementation of TB IPC has been assessed primarily through quantitative and structured approaches that treat administrative,environmental,and personal protective measures as discrete entities.We present an on-going project entitled Umoya omuhle(“good air”),conducted in two provinces of South Africa,that adopts an interdisciplinary,‘whole systems’approach to problem analysis and intervention development for reducing nosocomial transmission of Mycobacterium tuberculosis(Mtb)through improved IPC.We suggest that TB IPC represents a complex intervention that is delivered within a dynamic context shaped by policy guidelines,health facility space,infrastructure,organisation of care,and management culture.Methods drawn from epidemiology,anthropology,and health policy and systems research enable rich contextual analysis of how nosocomial Mtb transmission occurs,as well as opportunities to address the problem holistically.A‘whole systems’approach can identify leverage points within the health facility infrastructure and organisation of care that can inform the design of interventions to reduce the risk of nosocomial Mtb transmission.
基金Foundation of President of Nanfang Hospital,Southern Medical University.
文摘BACKGROUND Gastro-thoracic fistula is a serious complication after radical surgery for esophageal cancer,and a conservative approach or endoscopic intervention is commonly applied to treat most cases.CASE SUMMARY Here we describe the case of a patient with a gastro-thoracic fistula which could not be closed during gastroscopy after receiving postoperative radiotherapy,together with severe multiple drug-resistant bacterial infection and chest wall fistula.The abscess was drained and local irrigation applied with ozonated water,together with oral ozonated water,which achieved a good effect and highlighted a new way to cure fistula in such patients.CONCLUSION Patients with gastro-thoracic fistula that cannot be closed and severe infection can be treated by drainage and flushing with ozonated water.